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Sample records for allogeneic split-skin grafting

  1. Allogeneic split-skin grafting in stem cell transplanted patients

    DEFF Research Database (Denmark)

    Olsen, Jan Kyrre Berg; Vindeløv, Lars; Schmidt, G.

    2008-01-01

    SUMMARY: We present a unique case of a bone marrow stem cell transplanted (BMT) patient with cutaneous chronic Graft versus Host Disease (cGvHD) who underwent successful allogeneic split-thickness skin graft (STSG) transplantation. BMT had previously been carried out due to myelodysplasia and non......). Allogeneic skin grafts are known to be acutely rejected. Successful allogeneic STSG has only been reported in sporadic cases of identical twins (isotransplantation). This case is the first to demonstrate what works in theory: the immune system of a stem cell transplanted patient with 100% or mixed stable...... to a full thickness ulceration on the entire scalp. From the femoral region of the donating sister a STSG was harvested under local analgesia and transplanted without analgesia to the prepared scalp ulcer of the recipient. The result was full and permanent take of the allogeneic STSG (follow up: three years...

  2. Meshed split skin graft for extensive vitiligo

    Directory of Open Access Journals (Sweden)

    Srinivas C

    2004-05-01

    Full Text Available A 30 year old female presented with generalized stable vitiligo involving large areas of the body. Since large areas were to be treated it was decided to do meshed split skin graft. A phototoxic blister over recipient site was induced by applying 8 MOP solution followed by exposure to UVA. The split skin graft was harvested from donor area by Padgett dermatome which was meshed by an ampligreffe to increase the size of the graft by 4 times. Significant pigmentation of the depigmented skin was seen after 5 months. This procedure helps to cover large recipient areas, when pigmented donor skin is limited with minimal risk of scarring. Phototoxic blister enables easy separation of epidermis thus saving time required for dermabrasion from recipient site.

  3. SPLIT SKIN GRAFT HARVESTING UNDER LOCAL ANESTHESIA INFILTRATION VERSUS TOPICAL LOCAL ANESTHESIA

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    Shahi

    2014-04-01

    Full Text Available OBJECTIVE: To compare the effectiveness of topical local anesthesia using PRILOX cream versus local anesthesia infiltration using lignocaine and adrenaline in harvesting split skin graft. METHODS: A prospective study of 58 patients requiring split skin graft was carried. One group comprising 29 patients underwent harvesting of split skin graft under topical local anesthesia using PRILOX cream while the other group had local anesthesia infiltration using lignocaine and adrenaline. RESULTS: There were no significant differences between the 2 groups in terms of operating time, per operative pain, post-operative pain and post-operative requirement of analgesia. There was significant difference in time and pain during administration of local anesthesia and patient’s acceptability/ satisfaction with method of anesthesia. CONCLUSION: Topical local anesthesia using PRILOX cream can be used effectively for harvesting of split skin graft and is good alternative to local anesthesia infiltration.

  4. Calcium alginate dressings promote healing of split skin graft donor sites.

    LENUS (Irish Health Repository)

    O'Donoghue, J M

    2012-02-03

    A prospective controlled trial was carried out to assess the healing efficacy of calcium alginate and paraffin gauze on split skin graft donor sites. Thirty patients were randomised to the calcium alginate group and 21 to the paraffin gauze group. The donor sites were assessed at 10 days post harvesting to determine if they were completely healed (100%) or not. Twenty one of the 30 patients dressed with calcium alginate were completely healed at day 10, while only 7\\/21 in the paraffin gauze group were healed (p < 0.05). There were two infections in the study, both occurring in the alginate group while there was no difference in dressing slippage between the two groups. Calcium alginate dressings provide a significant improvement in healing split skin graft donor sites.

  5. Preprosthetic mandibular vestibuloplasty with split-skin graft. A 2-year follow-up study.

    Science.gov (United States)

    Hillerup, S

    1987-06-01

    17 patients with lower denture malfunction problems related to insufficient residual ridges had a vestibuloplasty with split-skin graft performed in the mandible under local analgesia on an out-patient basis. The patients were followed-up for 2 years and records of vestibular extension showed a maximum of relapse at the 1-month control (24%). Most of the lost extension was regained at the 6-month check, and the 2-year outcome was 92% of the surgically-created vestibular sulcus extension as a mean value of records obtained at the midline and canine regions. A comparison with a previous study on buccal mucosal graft vestibuloplasty led to the conclusion that free grafts of skin and buccal mucosa prevent a relapse equally well under the same circumstances. 13 patients were satisfied with the improvement achieved, 3 reported fair, and 1 was dissatisfied with the result of the operation. The split-skin graft underwent a change of appearance in 5 cases interpreted as a skin graft candidosis. Indication of this condition accelerating the residual ridge resorption is discussed.

  6. Effects of a silicone-coated polyamide net dressing and calcium alginate on the healing of split skin graft donor sites: a prospective randomised trial.

    LENUS (Irish Health Repository)

    O'Donoghue, J M

    2012-02-03

    An open randomised prospectively controlled trial was performed to assess the healing efficacy, slippage rate and degree of discomfort on removal of calcium alginate and a silicone-coated polyamide net dressing on split skin graft donor sites. Sixteen patients were randomised to the calcium alginate group and 14 to the silicone-coated group. The donor sites were assessed at days 7, 10, 14 and up to day 21. The mean time to healing in the calcium alginate group was 8.75 +\\/- 0.78 days (range 7 to 14 days) compared to 12 +\\/- 0.62 days (range 7 to 16 days) for the silicone-coated group (p < 0.01). Although more silicone-coated dressings slipped (5 versus 1), the difference was not statistically significant. Pain during the first dressing change was assessed using a visual analogue pain scale. Although no significant differences were found between the groups, it was necessary to change the dressing protocol in the silicone-coated arm of the trial after entering the first two patients. Overlaid absorbent gauze adhered to the donor site through the fenestrations in the dressing necessitating the placement of paraffin gauze between the experimental dressing and the overlying cotton gauze. There was one infection in the study, occurring in the alginate group. Based on these results we recommend calcium alginate as the dressing of choice for split skin graft donor sites.

  7. Allogenic bone grafts in post-traumatic juxta-articular defects: Need for allogenic bone banking.

    Science.gov (United States)

    Mishra, Anil Kumar; Vikas, Rohit; Agrawal, H S

    2017-07-01

    Allogenic bone banking provide both structural and granular bone grafts for various orthopaedic, spinal, oncological and dental surgeries. However allogenic bones, presently, are not readily available. This article discusses the clinical applications of the allogenic grafts, the screening criteria and procedure for maintenance of such a bone banking facility. This article demonstrates the effective role of allogenic bone in a case of post-traumatic bone loss situation and discusses the growing need and present situation of bone banking in our country.

  8. [Treatment of tibial pseudoarthrosis. Complications after intramedullary, allogeneic fibular grafting].

    Science.gov (United States)

    Helfen, T; Prall, W C; Mutschler, W; Thaller, P H

    2015-04-01

    A 24-year-old woman underwent cosmetic bilateral tibial lengthening with severe complications. In all, 15 operations, including allogeneic fibular grafting of both tibia, were required to treat unstable bilateral non-union, malalignment, and osteomyelitis of the right tibia.The present article describes the surgical strategy of revision to achieve good recovery with full consolidation and proper alignment of the lower leg. Furthermore, the indications for allogeneic bone grafting, which was described by Erich Lexer 100 years ago, are discussed. For surgical revision, a T-external fixator was used on the right leg, while a customized tibial nail was used on the left leg. Using these techniques, full consolidation and proper alignment was achieved. Allogeneic bone grafts in upper extremity defects cannot be recommended.

  9. The treatment of deep dermal hand burns: How do we achieve better results? Should we use allogeneic keratinocytes or skin grafts?

    Science.gov (United States)

    Haslik, W; Kamolz, L-P; Lumenta, D B; Hladik, M; Beck, H; Frey, M

    2010-05-01

    The treatment of deep dermal burns has a broad spectrum and has been subject to discussion over the past years. The treatment of hand burns is challenging due to the high requirements to aesthetic and functional outcome. 27 patients, 7 women and 20 men with deep dermal hand burns with a mean age of 41.3+/-16.5 and a mean TBSA of 15%+/-19.6% were treated either with allogeneic cryopreserved keratinocytes or with split skin grafts. Long-term follow-up revealed no statistical significant differences between the two groups concerning Vancouver Scar Scale as well as hand function judged by the DASH score; however there was a tendency to higher VSS scores and impaired aesthetic results in the keratinocyte group. Allogeneic keratinocytes are a suitable armentarium for the treatment of deep dermal hand burns; and, if used correctly, they can produce a timely healing comparable to split-thickness skin grafts. Limited availability, high costs as well as the need for special skills are key factors, which render application of this technique outside specialist burn centres virtually impossible. In our opinion, the cultivation and use of keratinocytes should be reserved to these centres in order to facilitate a sensible application for a full range of indications. We recommend usage of allogeneic keratinocytes for deep dermal hand burns only in severely burned patients with a lack of donor sites. Patients with unrestricted availability of donor sites seem to profit from the application of split-thickness skin grafts according to our results. Copyright 2009 Elsevier Ltd and ISBI. All rights reserved.

  10. A Unique Case of Allogeneic Fat Grafting Between Brothers

    Science.gov (United States)

    Kim, Samuel; Edelson, Richard L.; Sumpio, Brandon; Kwei, Stephanie

    2016-01-01

    Summary: We present a case of a 65-year-old man with cutaneous T-cell lymphoma treated with radiation therapy and an allogeneic hematopoietic stem cell transplant from his human leukocyte antigen-matched brother. Engraftment was successful, but the patient went on to develop painful, radiation-induced ulcers. The ulcers were fat-allografted using liposuctioned fat from his brother because of the patient’s unique chimeric state. Postprocedure follow-up revealed epithelialization of the ulcer sites and significant improvement in neuropathic pain. Our unique case study supports the use of fat grafting for its restorative purposes and for its ability to alleviate chronic neuropathic pain. Additionally, it appears that our case provides a basis of a general approach to the treatment of radiation-induced ulcers in chimeric patients with lymphoid malignancies.

  11. Chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor promotes sciatic nerve repair

    Institute of Scientific and Technical Information of China (English)

    Yanru Zhang; Hui Zhang; Kaka Katiella; Wenhua Huang

    2014-01-01

    A chemically extracted acellular allogeneic nerve graft can reduce postoperative immune re-jection, similar to an autologous nerve graft, and can guide neural regeneration. However, it remains poorly understood whether a chemically extracted acellular allogeneic nerve graft combined with neurotrophic factors provides a good local environment for neural regenera-tion. This study investigated the repair of injured rat sciatic nerve using a chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor. An autologous nerve anastomosis group and a chemical acellular allogeneic nerve bridging group were prepared as controls. At 8 weeks after repair, sciatic functional index, evoked potential amplitude of the soleus muscle, triceps wet weight recovery rate, total number of myelinated nerve fibers and myelin sheath thickness were measured. For these indices, values in the three groups showed the autologous nerve anastomosis group > chemically extracted acellular nerve graft + ciliary neurotrophic factor group > chemical acellular allogeneic nerve bridging group. These results suggest that chemically extracted acellular nerve grafts combined with ciliary neurotrophic factor can repair sciatic nerve defects, and that this repair is inferior to autologous nerve anasto-mosis, but superior to chemically extracted acellular allogeneic nerve bridging alone.

  12. Current and future approaches to treat graft failure after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Locatelli, Franco; Lucarelli, Barbarella; Merli, Pietro

    2014-01-01

    One significant obstacle to the success of allogeneic hematopoietic stem cell transplantation (HSCT) is represented by graft failure, defined as either lack of initial engraftment of donor cells (primary graft failure) or loss of donor cells after initial engraftment (secondary graft failure). Graft failure mediated by host immune cells attacking donor stem cells is named graft rejection. Factors associated with graft failure include HLA disparity in the donor/recipient pair, underlying disease, viral infections, type of conditioning regimen and stem cell source employed. In this article, the experts summarize current approaches to treat graft failure/rejection after HSCT, and they discuss new strategies of graft manipulation and immune therapy of particular interest for preventing/treating this complication. A limited array of options is available to treat graft failure. The experts believe that re-transplantation from another donor or the same donor (if there is no evidence of immunologically mediated graft failure) is the treatment of choice for patients with primary graft failure or acute graft rejection. The experts think that strategies based on innovative approaches of graft manipulation, new agents or cellular therapies could render in the future graft failure a much less relevant problem for HSCT recipients.

  13. Functional changes of dendritic cells derived from allogeneic partial liver graft undergoing acute rejection in rats

    Institute of Scientific and Technical Information of China (English)

    Ming-Qing Xu; Zhen-Xiang Yao

    2003-01-01

    AIM: To investigate functional change of dendritic cells (DCs)derived from allogeneic partial liver graft undergoing acuterejection in rats.METHODS: Allogeneic (SD rat to LEW rat) whole and 50 %partial liver transplantation were performed. DCs from livergrafts 0 hr and 4 days after transplantation were isolated andpropagated in the presence of GM-CSFin vitro. Morphologicalcharacteristics of DCs propagated for 4 days and 10 dayswere observed by electron rmicroscopy. Phenotypical featuresof DCs propagated for 10 days were analyzed by flowcytometry. Expression of IL-12 protein and IL-12 receptormRNA in DCs propagated for 10 days was also measured byWestern blotting and semiquantitative RT-PCR, respectively.Histological grading of rejection were determined.RESULTS: Allogeneic whole liver grafts showed no featuresof rejection at day 4 after transplantation. In contrast,allogeneic partial liver grafts demonstrated moderate tosevere rejection at day 4 after transplantation. DCs derivedfrom allogeneic partial liver graft 4 days after transplantationexhibited typical morphological characteristics of DC after 4days' culture in the presence of GM-CSF. DCs from allogeneicwhole liver graft 0 hr and 4 days after transplantation didnot exhibit typical morphological characteristics of DC untilafter 10 days' culture in the presence of GM-CSF. After 10days' propagationin vitro, DCs derived from allogeneic wholeliver graft exhibited features of immature DC, with absenceof CD40, CD80 and CD86 surface expression, and low levelsof IL-12 proteins (IL-12 p35 and IL-12 p40) and IL-12receptor (IL-12Rβ1 and IL-12Rβ2) mRNA, whereas DCs fromallogeneic partial liver graft 4 days after transplantationdisplayed features of mature DC, with high levels of CD40,CD80 and CD86 surface expression, and as a consequence,higher expression of IL-12 proteins (IL-12 p35 and IL-12 p40)and IL-12 receptors (IL-12Rβ1 and IL-12Rβ2) mRNA thanthose of DCs both from partial liver graft 0 hr and whole livergraft

  14. Storage of allogeneic vascular grafts: experience from a high-volume liver transplant institute.

    Science.gov (United States)

    Aydin, Cemalettin; Ince, Volkan; Otan, Emrah; Akbulut, Sami; Koc, Cemalettin; Kayaalp, Cuneyt; Yilmaz, Sezai

    2013-01-01

    Allogeneic vascular grafts are often required for vascular reconstruction during living donor liver transplantation. Such grafts are obtained prior to use, making storage conditions a critical issue for maintaining the integrity of the tissue to ensure a successful transplantation. This study describes an optimized storage protocol currently in use at a high-volume liver transplant center. Twenty-nine allogeneic vascular graft tissues obtained during cardiovascular surgery or from cadaveric donors were stored respectively in sterile 50 mL of Ringer lactate solution, without any preservation solutions or antimicrobials, at -22°C for a maximum of 3 months. Prior to use in vascular reconstruction, grafts were thawed in 0.9% NaCl solution at 37°C, and 1 × 0.5-cm(2) tissue samples were collected for microbial culturing and viral serology. ABO compatibility was not performed for any patients receiving vascular grafts. During this prospective study, all 29 allogeneic vascular grafts were used for back-table vascular reconstruction in living donor liver transplantation procedures. A total of 16 grafts were from the saphenous vein, 10 were from the iliac vein, and 3 were from the iliac artery. Bacterial growth was not detected in any tissue samples taken from the stored grafts. No vascular graft-related complications occurred during the 5 months of follow-up. The successful vascular reconstructions achieved with all 29 study grafts demonstrate that the simple, inexpensive storage method described herein is feasible and safe. Randomized, controlled studies should be carried out to further optimize and standardize the technique.

  15. Voriconazole-Induced Periostitis Mimicking Chronic Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation.

    Science.gov (United States)

    Sweiss, Karen; Oh, Annie; Rondelli, Damiano; Patel, Pritesh

    2016-01-01

    Voriconazole is an established first-line agent for treatment of invasive fungal infections in patients undergoing allogeneic stem cell transplantation (ASCT). It is associated with the uncommon complication of periostitis. We report this complication in a 58-year-old female undergoing HSCT. She was treated with corticosteroids with minimal improvement. The symptoms related to periostitis can mimic chronic graft-versus-host disease in patients undergoing HSCT and clinicians should differentiate this from other diagnoses and promptly discontinue therapy.

  16. Efficacy of Allogenic Cultured Keratinocyte Grafts for Burn Wounds

    Science.gov (United States)

    1993-06-01

    antigen expression induced by interferon gamma on C57BL/6 cultured keratinocytes. Notably, this antigen appears in vivo whether or not the animal has been...exposed to interferon gamma . This is extremely important because there is spontaneous generation of this antigen after grafting. Examples of this

  17. Immunomodulation with dendritic cells and donor lymphocyte infusion converge to induce graft vs neuroblastoma reactions without GVHD after allogeneic bone marrow transplantation

    OpenAIRE

    Ash, S.; Stein, J.; Askenasy, N; Yaniv, I.

    2010-01-01

    Background: Mounting evidence points to the efficacy of donor lymphocyte infusion (DLI) and immunisation with tumour-pulsed dendritic cells (DC) in generating graft vs leukaemia reactions after allogeneic bone marrow transplantation (BMT). We assessed the efficacy of DLI and DC in generating potent graft vs neuroblastoma tumour (GVT) reactions following allogeneic BMT. Methods: Mice bearing congenic (H2Ka) Neuro-2a tumours were grafted with allogeneic (H2Kb) T-cell-depleted bone marrow cells....

  18. Graft-versus-host disease and graft-versus-tumor effects after allogeneic hematopoietic cell transplantation

    DEFF Research Database (Denmark)

    Storb, Rainer; Gyurkocza, Boglarka; Storer, Barry E

    2013-01-01

    We designed a minimal-intensity conditioning regimen for allogeneic hematopoietic cell transplantation (HCT) in patients with advanced hematologic malignancies unable to tolerate high-intensity regimens because of age, serious comorbidities, or previous high-dose HCT. The regimen allows the pures...

  19. Mandibular Reconstruction in Ameloblastoma Using Allogeneic Cord Stem Cells and Alloplastic Graft Material - Case Report.

    Science.gov (United States)

    Manimaran, K; Chandramohan, M; Kannan, R; Sankaranarayanan, S; Ravi, V R; Sharma, Rohini

    Ameloblastoma is a histologically benign odontogenic tumour and has a tendency of locally aggressive behaviour. This is second most prevalent odontogenic tumour and most common in the molar-ramus-angle region and surgical resection is only treatment option. In this article, we propose an innovative approach to deal with these cases by using alloplastic graft with cord stem cells. Over 2.5 years follow-up, we could demonstrate bone regeneration using this technique with no recurrence. To the best of our knowledge, this is the first report of successful regeneration of part of ramus and body of mandible using allogeneic cord stem cells in cases of Ameloblastoma.

  20. Voriconazole-Induced Periostitis Mimicking Chronic Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Karen Sweiss

    2016-01-01

    Full Text Available Voriconazole is an established first-line agent for treatment of invasive fungal infections in patients undergoing allogeneic stem cell transplantation (ASCT. It is associated with the uncommon complication of periostitis. We report this complication in a 58-year-old female undergoing HSCT. She was treated with corticosteroids with minimal improvement. The symptoms related to periostitis can mimic chronic graft-versus-host disease in patients undergoing HSCT and clinicians should differentiate this from other diagnoses and promptly discontinue therapy.

  1. Ceacam1 separates graft-versus-host-disease from graft-versus-tumor activity after experimental allogeneic bone marrow transplantation.

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    Sydney X Lu

    Full Text Available Allogeneic bone marrow transplantation (allo-BMT is a potentially curative therapy for a variety of hematologic diseases, but benefits, including graft-versus-tumor (GVT activity are limited by graft-versus-host-disease (GVHD. Carcinoembryonic antigen related cell adhesion molecule 1 (Ceacam1 is a transmembrane glycoprotein found on epithelium, T cells, and many tumors. It regulates a variety of physiologic and pathological processes such as tumor biology, leukocyte activation, and energy homeostasis. Previous studies suggest that Ceacam1 negatively regulates inflammation in inflammatory bowel disease models.We studied Ceacam1 as a regulator of GVHD and GVT after allogeneic bone marrow transplantation (allo-BMT in mouse models. In vivo, Ceacam1(-/- T cells caused increased GVHD mortality and GVHD of the colon, and greater numbers of donor T cells were positive for activation markers (CD25(hi, CD62L(lo. Additionally, Ceacam1(-/- CD8 T cells had greater expression of the gut-trafficking integrin α(4β(7, though both CD4 and CD8 T cells were found increased numbers in the gut post-transplant. Ceacam1(-/- recipients also experienced increased GVHD mortality and GVHD of the colon, and alloreactive T cells displayed increased activation. Additionally, Ceacam1(-/- mice had increased mortality and decreased numbers of regenerating small intestinal crypts upon radiation exposure. Conversely, Ceacam1-overexpressing T cells caused attenuated target-organ and systemic GVHD, which correlated with decreased donor T cell numbers in target tissues, and mortality. Finally, graft-versus-tumor survival in a Ceacam1(+ lymphoma model was improved in animals receiving Ceacam1(-/- vs. control T cells.We conclude that Ceacam1 regulates T cell activation, GVHD target organ damage, and numbers of donor T cells in lymphoid organs and GVHD target tissues. In recipients of allo-BMT, Ceacam1 may also regulate tissue radiosensitivity. Because of its expression on both the

  2. Acellular allogeneic nerve grafting combined with bone marrow mesenchymal stem cell transplantation for the repair of long-segment sciatic nerve defects: biomechanics and validation of mathematical models

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    Ya-jun Li

    2016-01-01

    Full Text Available We hypothesized that a chemically extracted acellular allogeneic nerve graft used in combination with bone marrow mesenchymal stem cell transplantation would be an effective treatment for long-segment sciatic nerve defects. To test this, we established rabbit models of 30 mm sciatic nerve defects, and treated them using either an autograft or a chemically decellularized allogeneic nerve graft with or without simultaneous transplantation of bone marrow mesenchymal stem cells. We compared the tensile properties, electrophysiological function and morphology of the damaged nerve in each group. Sciatic nerves repaired by the allogeneic nerve graft combined with stem cell transplantation showed better recovery than those repaired by the acellular allogeneic nerve graft alone, and produced similar results to those observed with the autograft. These findings confirm that a chemically extracted acellular allogeneic nerve graft combined with transplantation of bone marrow mesenchymal stem cells is an effective method of repairing long-segment sciatic nerve defects.

  3. Liver Graft versus Host Disease after Allogeneic Peripheral Stem Cell Transplantation: Update on Etiopathogenesis and Diagnosis.

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    Mihăilă, R-G

    2016-01-01

    Graft versus host disease (GVHD) is the main complication of allogeneic hematopoietic cell transplantation and is more frequent after peripheral stem cell transplants. Graft versus leukemia or lymphoma component of them is beneficial to eradicate residual tumor mass after previous treatment and conditioning regimen. A severe GVHD may endanger the patient's life. The most important liver manifestations of GVHD are increased serum alkaline phosphatase and bilirubin values. The last allows to estimate the GVHD severity. Sometimes, an increase of aminotransferases can mimic an acute hepatitis. Donor-derived hematopoietic cells appeared to turn in mesenchymal liver cells. Activated CD4(+) T cells, humoral and complement activation, a large number of cytokines and cytokine receptors are involved in GVHD development. Correct and early recognition of GVHD and its differentiation from the other liver diseases are essential for the medical practice.

  4. Primary Graft Failure after Myeloablative Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies

    Science.gov (United States)

    Olsson, Richard F.; Logan, Brent R.; Chaudhury, Sonali; Zhu, Xiaochun; Akpek, Görgün; Bolwell, Brian J.; Bredeson, Christopher N.; Dvorak, Christopher C.; Gupta, Vikas; Ho, Vincent T.; Lazarus, Hillard M.; Marks, David I.; Ringdén, Olle T.H.; Pasquini, Marcelo C.; Schriber, Jeffrey R.; Cooke, Kenneth R.

    2015-01-01

    Clinical outcomes after primary graft failure (PGF) remain poor. Here we present a large retrospective analysis (n=23,272) which investigates means to prevent PGF and early detection of patients at high risk. In patients with hematologic malignancies, who underwent their first myeloablative allogeneic hematopoietic cell transplantation, PGF was reported in 1,278 (5.5%), and there was a marked difference in PGFs using peripheral blood stem cell compared to bone marrow grafts (2.5 vs. 7.3%; Pmarrow transplants, total nucleated cell doses ≤2.4 × 108/kg were associated with PGF (OR 1.39; Ptransplant may provide the rationale for an early request for additional hematopoietic stem cells. PMID:25772027

  5. Acute renal graft-versus-host disease in a murine model of allogeneic bone marrow transplantation.

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    Schmid, Peter M; Bouazzaoui, Abdellatif; Schmid, Karin; Birner, Christoph; Schach, Christian; Maier, Lars S; Holler, Ernst; Endemann, Dierk H

    2017-03-23

    Acute kidney injury (AKI) is a very common complication after allogeneic bone marrow transplantation (BMT) and associated with poor prognosis. Generally kidneys are assumed to be no direct target of Graft-versus-Host Disease (GvHD), and renal impairment is often attributed to several other factors occurring in the early phase after BMT. Our study aimed to prove the existence of renal GvHD in a fully MHC-mismatched model of BALB/c mice conditioned and transplanted according to two different intensity protocols. Syngeneically transplanted and untreated animals served as controls. 4 weeks after transplantation, allogeneic animals developed acute GvHD that was more pronounced in the high-intensity protocol (HIP) group than in the low-intensity protocol (LIP) group. Urea and creatinine as classic serum markers of renal function could not verify renal impairment 4 weeks after BMT. Creatinine levels were even reduced as a result of catabolic metabolism and loss of muscle mass due to acute GvHD. Proteinuria, albuminuria, and urinary N-acetyl-beta-Dglucosaminidase (NAG) levels were measured as additional renal markers before and after transplantation. Albuminuria and NAG were only significantly increased after allogeneic transplantation, correlating with disease severity between HIP and LIP animals. Histological investigations of the kidneys showed renal infiltration of T-cells and macrophages with endarteriitis, interstitial nephritis, tubulitis, and glomerulitis. T-cells consisted of CD4+, CD8+, and FoxP3+ cells. Renal expression analysis of allogeneic animals showed increases in indoleamine-2,3 dioxygenase (IDO), different cytokines (TNFα, IFN-γ, IL-1α, IL2, IL-6, and IL-10), and adhesion molecules (ICAM-1 and VCAM-1), resembling findings from other tissues in acute GvHD. In summary, our study supports the entity of renal GvHD with histological features suggestive of cell-mediated renal injury. Albuminuria and urinary NAG levels may serve as early markers of renal

  6. Emerging drugs for prevention of graft failure after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Servais, Sophie; Beguin, Yves; Baron, Frédéric

    2013-06-01

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the treatment of choice for many patients suffering from hematological malignancies, severe hemoglobinopathies, bone marrow failures or severe primary immunodeficiencies. Graft rejection/failure (GF) is a life-threatening complication following allo-HSCT that is most commonly caused by the reactivity of recipient T cells, natural killer (NK) cells or antibodies against donor grafted hematopoietic cells. The increasing use of allo-HSCT following reduced-intensity conditioning (RIC) and the increasing use of alternative donors (unrelated cord blood and human leukocyte antigen (HLA)-mismatched donor) have resulted in higher frequency of GF. This review describes the pathogenesis and current prevention and treatment of GF as well as agents in development for GF prevention or treatment. The risk of GF may be reduced in the future by optimizing the conditioning regimens and post-grafting immunosuppression, increasing the number of hematopoietic stem cells (HSCs) and/or immune cells transplanted, optimizing HSC homing and better detecting patients at high risk of GF by searching for pre-transplant donor-specific anti-HLA antibodies in patients given grafts from HLA-mismatched donors, or by closely monitoring donor T- and/or NK-cell chimerism after allo-HSCT following RIC.

  7. Rehabilitation of atrophic maxilla using the combination of autogenous and allogeneic bone grafts followed by protocol-type prosthesis.

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    Margonar, Rogério; dos Santos, Pâmela Letícia; Queiroz, Thallita Pereira; Marcantonio, Elcio

    2010-11-01

    Currently, there are several techniques for the rehabilitation of atrophic maxillary ridges in literature. The grafting procedure using autogenous bone is considered ideal by many researchers, as it shows osteogenic capability and causes no antigenic reaction. However, this type of bone graft has some shortcomings, mainly the restricted availability of donor sites. In recent years, several alternatives have been investigated to supply the disadvantages of autogenous bone grafts. In such studies, allogeneic bone grafts, which are obtained from individuals with different genetic load, but from the same species, have been extensively used. They can be indicated in cases of arthroplasty, surgical knee reconstruction, large bone defects, and in oral and maxillofacial reconstruction. Besides showing great applicability and biocompatibility, this type of bone is available in unlimited quantities. On the other hand, allogeneic bone may have the disadvantage of transmitting infectious diseases. Atrophic maxillae can be treated with bone grafts followed by osseointegrated implants to obtain aesthetic and functional oral rehabilitation. This study aimed to show the viability of allogeneic bone grafting in an atrophic maxilla, followed by oral rehabilitation with dental implant and protocol-type prosthesis within a 3-year follow-up period by means of a clinical case report.

  8. Pericardial effusion and cardiac tamponade: clinical manifestation of chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

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    Ferreira, David Cavalcanti; de Oliveira, José Salvador Rodrigues; Parísio, Katya; Ramalho, Fernanda Maria Morselli

    2014-03-01

    The authors report a case with pericardial effusion and cardiac tamponade as a rare clinical manifestation of chronic graft-versus-host disease in a young man with acute myelogenous leukemia submitted to an allogeneic hematopoietic stem cell transplantation from a related donor.

  9. Analyses of risk factors for intestinal acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    燕法红

    2014-01-01

    Objective To investigate the risk factors of intestinal acute graft-versus-host disease(aGVHD)after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods The clinical data of 534 cases of 533 patients undergoing allo-HSCT during Jan 2004 and Sep 2012were retrospectively analyzed.The effects of donor-recipient HLA

  10. Agonistic CD200R1 DNA Aptamers Are Potent Immunosuppressants That Prolong Allogeneic Skin Graft Survival

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    Aaron Prodeus

    2014-01-01

    Full Text Available CD200R1 expressed on the surface of myeloid and lymphoid cells delivers immune inhibitory signals to modulate inflammation when engaged with its ligand CD200. Signalling through CD200/CD200R1 has been implicated in a number of immune-related diseases including allergy, infection, cancer and transplantation, as well as several autoimmune disorders including arthritis, systemic lupus erythematosus, and multiple sclerosis. We report the development and characterization of DNA aptamers, which bind to murine CD200R1 and act as potent signalling molecules in the absence of exogenous CD200. These agonistic aptamers suppress cytotoxic T-lymphocyte induction in 5-day allogeneic mixed leukocyte culture and induce rapid phosphorylation of the CD200R1 cytoplasmic tail thereby initiating immune inhibitory signalling. PEGylated conjugates of these aptamers show significant in vivo immunosuppression and enhance survival of allogeneic skin grafts as effectively as soluble CD200Fc. As DNA aptamers exhibit inherent advantages over conventional protein-based therapeutics including low immunogenicity, ease of synthesis, low cost, and long shelf life, such CD200R1 agonistic aptamers may emerge as useful and safe nonsteroidal anti-inflammatory therapeutic agents.

  11. Distraction arthrodesis of the subtalar joint using allogeneic bone graft: a review of 15 cases.

    Science.gov (United States)

    Lee, Michael S; Tallerico, Valerie

    2010-01-01

    Distraction arthrodesis of the subtalar joint is often used for the correction of neglected calcaneal fractures. Although different techniques have been advocated, there remains some debate as to the optimal type of bone graft for this purpose. This study retrospectively reviewed one surgeon's results for distraction arthrodesis of the talocalcaneal joint for 15 consecutive feet in 15 patients using 12 frozen femoral head and 3 freeze-dried iliac crest allografts. Indications for distraction arthrodesis in this series included neglected calcaneal fracture (n = 10), failed open reduction with internal fixation (n = 3), malunion after ankle fusion (n = 1), and subtalar joint arthritis with deformity (n = 1). The mean patient age was 47.5 (range 29 to 66) years, and the mean duration of follow-up was 20.6 (range 13 to 31) months. Complete union was achieved in 14 (93.33%) feet. Orthobiological agents were used in every case, including 7 (46.67%) platelet-rich plasma, 5 (33.33%) demineralized bone matrix combined with platelet-rich plasma, 2 (13.33%) platelet-rich plasma combined with an implantable electrical bone growth stimulator, and 1 (6.67%) demineralized bone matrix only. One (6.67%) patient developed a nonunion with collapse of the allogeneic graft, requiring revision with autogenous iliac crest bone graft. There were 8 (53.33%) minor complications, including 4 (26.66%) cases with inferior heel irritation, 2 (13.33%) with sural nerve paresthesia, and 2 (13.33%) with wound dehiscence. In conclusion, the use of allograft for subtalar joint distraction arthrodesis results in similar union rates as autogenous iliac crest grafting previously reported in the literature. Copyright 2010 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  12. Use of allogenic (iliac) corticocancellous graft for Le Fort I interpositional defects: technique and results.

    Science.gov (United States)

    Posnick, Jeffrey C; Sami, Ali

    2015-01-01

    We performed a retrospective review of a consecutive series of 50 patients who had undergone Le Fort I with interpositional grafting during a 3-year period. Maxillary repositioning included horizontal advancement and vertical and transverse change to the extent that an interpositional graft was considered necessary. Allogenic (iliac) corticocancellous bone was used in all cases. Each patient underwent analytic model planning to document the maxillary vector change data points. The recorded data served as an indicator of the osteotomy site gaps requiring grafting. Standardized photographs in centric relation at a minimum of 12 months after treatment were analyzed to measure overjet, overbite, midline position, and first molar lateral occlusion. Specific maxillary region wound healing parameters were reviewed. The patients' mean age at surgery was 32 years (range 15 to 60). Analytic model planning clarified that the study patients had an average of 8 mm horizontal advancement, 2 mm vertical lengthening, and 2 mm of transverse expansion. The data confirmed a favorable occlusion at a minimum of 1 year after surgery with maintenance of a normal overjet (49 of 50 patients, 98%), normal overbite (48 of 50 patients, 96%), planned dental midline positioning (45 of 50 patients, 90%), and ideal first molar lateral occlusion (48 of 50 patients, 96%) for most patients. None of the study patients sustained wound healing complications. Also, no cases of postoperative sepsis or viral illness developed. The results of the present study have confirmed that iliac corticocancellous allograft has minimal systemic or recipient site complications and can be safely used to fill complex 3-dimensional interpositional defects associated with Le Fort I osteotomy and/or repositioning. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  13. Possible Implication of Bacterial Infection in Acute Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

    Science.gov (United States)

    Fuji, Shigeo; Kapp, Markus; Einsele, Hermann

    2014-01-01

    Graft-versus-host disease (GVHD) is still one of the major causes of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (HSCT). In the pathogenesis of acute GVHD, it has been established that donor-derived T-cells activated in the recipient play a major role in GVHD in initiation and maintenance within an inflammatory cascade. To reduce the risk of GVHD, intensification of GVHD prophylaxis like T-cell depletion is effective, but it inevitably increases the risk of infectious diseases and abrogates beneficial graft-versus-leukemia effects. Although various cytokines are considered to play an important role in the pathogenesis of GVHD, GVHD initiation is such a complex process that cannot be prevented by means of single inflammatory cytokine inhibition. Thus, efficient methods to control the whole inflammatory milieu both on cellular and humoral view are needed. In this context, infectious diseases can theoretically contribute to an elevation of inflammatory cytokines after allogeneic HSCT and activation of various subtypes of immune effector cells, which might in summary lead to an aggravation of acute GVHD. The appropriate treatments or prophylaxis of bacterial infection during the early phase after allogeneic HSCT might be beneficial to reduce not only infectious-related but also GVHD-related mortality. Here, we aim to review the literature addressing the interactions of bacterial infections and GVHD after allogeneic HSCT. PMID:24795865

  14. Possible implication of bacterial infection in acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Shigeo eFuji

    2014-04-01

    Full Text Available Graft-versus-host disease (GVHD is still one of the major causes of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (HSCT. In the pathogenesis of acute GVHD, it has been established that donor-derived T cells activated in the recipient play a major role in GVHD in initiation and maintenance within an inflammatory cascade. To reduce the risk of GVHD, intensification of GVHD prophylaxis like T cell depletion is effective, but it inevitably increases the risk of infectious diseases and abrogates beneficial graft-versus-leukemia effects. Although various cytokines are considered to play an important role in the pathogenesis of GVHD, GVHD initiation is such a complex process that cannot be prevented by means of single inflammatory cytokine inhibition. Thus, efficient methods to control the whole inflammatory milieu both on cellular and humoral view are needed. In this context, infectious diseases can theoretically contribute to an elevation of inflammatory cytokines after allogeneic HSCT and activation of various subtypes of immune effector cells, which might in summary lead to an aggravation of acute GVHD. The appropriate treatments or prophylaxis of bacterial infection during the early phase after allogeneic HSCT might be beneficial to reduce not only infectious-related but also GVHD-related mortality. Here, we aim to review the literature addressing the interactions of bacterial infections and GVHD after allogeneic HSCT.

  15. Invariant Natural Killer T Cells As Suppressors of Graft-versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Melissa Mavers

    2017-07-01

    Full Text Available Invariant natural killer T (iNKT cells serve as a bridge between innate and adaptive immunity and have been shown to play an important role in immune regulation, defense against pathogens, and cancer immunity. Recent data also suggest that this compartment of the immune system plays a significant role in reducing graft-versus-host disease (GVHD in the setting of allogeneic hematopoietic stem cell transplantation. Murine studies have shown that boosting iNKT numbers through certain conditioning regimens or adoptive transfer leads to suppression of acute or chronic GVHD. Preclinical work reveals that iNKT cells exert their suppressive function by expanding regulatory T cells in vivo, though the exact mechanism by which this occurs has yet to be fully elucidated. Human studies have demonstrated that a higher number of iNKT cells in the graft or in the peripheral blood of the recipient post-transplantation are associated with a reduction in GVHD risk, importantly without a loss of graft-versus-tumor effect. In two separate analyses of many immune cell subsets in allogeneic grafts, iNKT cell dose was the only parameter associated with a significant improvement in GVHD or in GVHD-free progression-free survival. Failure to reconstitute iNKT cells following allogeneic transplantation has also been associated with an increased risk of relapse. These data demonstrate that iNKT cells hold promise for future clinical application in the prevention of GVHD in allogeneic stem cell transplantation and warrant further study of the immunoregulatory functions of iNKT cells in this setting.

  16. Lethal graft-versus-host disease: modification with allogeneic cultured donor cells.

    Science.gov (United States)

    Mauch, P; Lipton, J M; Hamilton, B; Obbagy, J; Kudisch, M; Nathan, D; Hellman, S

    1984-05-01

    The use of the bone marrow culture technique was studied as a means to prepare donor marrow for bone marrow transplantation to avoid lethal graft-versus-host disease (GVHD). Preliminary experiments demonstrated the rapid loss of theta-positive cells in such cultures, so that theta-positive cells were not detected after 6 days. Initial experiments in C3H/HeJ (H-2k, Hbbd) recipients prepared with 900 rad demonstrated improved survival when 3-day cultured C57BL/6 (H-2b, Hbbs) donor cells were used in place of hind limb marrow for transplantation. However, hemoglobin typing of recipient animals revealed only short-term donor engraftment, with competitive repopulation of recipient marrow occurring. Subsequent experiments were done in 1,200-rad prepared recipients, with long-term donor engraftment demonstrated. The majority of 1,200-rad prepared animals receiving cultured allogeneic cells died of GVHD, but animals receiving 28-day cultured cells had an improved 90-day survival and a delay in GVHD development over animals receiving hind limb marrow or marrow from shorter times in culture. In addition, animals receiving anti-theta-treated, 3-day nonadherent cells had an improved survival (44%) over animals receiving anti-theta-treated hind limb marrow (20%). These experiments demonstrate modest benefit for the use of cultured cells in bone marrow transplantation across major H-2 histocompatibility complex differences.

  17. Graft-versus-leukemia effects from donor lymphocyte infusion after nonmyeloablative allogeneic bone marrow transplantation in mice

    Institute of Scientific and Technical Information of China (English)

    DU Bing; LI De-peng; XU Kai-lin; PAN Xiu-ying

    2005-01-01

    Background Nonmyeloablative allogeneic bone marrow transplantation has been used since the 1990s as a new hematological stem cell transplantation strategy for treating hematological diseases. The purpose of this study was to explore the graft-versus-leukemia (GVL) effects of donor lymphocyte infusions (DLIs) after nonmyeloablative allogeneic bone marrow transplantations, while assessing the declines in treatment-associated morbidity, mortality, and graft-versus-host disease (GVHD).Methods A total of 615 (H-2k) mice were injected with L615 tumor cells and received 500 cGy (60Coγ-ray) irradiation three days later, followed by an allogeneic bone marrow transplantation (allo-BMT). The allo-grafts consisted of 3×107 bone marrow cells and 1×107 spleen cells from BALB/C (H-2d) donor mice. Two days after the allo-BMT, the recipient mice were given 200 mg/kg of cyclophosphamide. Subsequently, recipient mice were infused with either donor spleen cells (2×107) on day 14 or 21, or donor spleen cells (5×107) pretreated with hydrocortisone and cyclosporin A (CsA) in vitro on day 14 post-BMT.Results The median survival time of mice that received DLI on day 21 and pretreated DLI on day 14 post-BMT was longer than that of controls and the day 14 DLI group (P<0.01). No evidence of severe GVHD was observed in the day 21 DLI group nor in the day 14 treated DLI group. Mixed chimerism was confirmed in the day 14 DLI group, the day 14 treated DLI group, and the day 21 DLI group on the thirteenth day post-transplantation; full donor chimerism was observed two weeks after DLI.Conclusion Donor lymphocyte infusion after nonmyeloablative bone marrow transplantation may reduce transplantation-associated morbidity and mortality while strengthening graft-versus-leukemia effects.

  18. Graft-versus-lymphoma effect in a 64-year-old caucasian woman after allogeneic stem-cell transplantation: a case report

    Directory of Open Access Journals (Sweden)

    Behre Gerhard

    2009-01-01

    Full Text Available Abstract Introduction The existence of a graft-versus-lymphoma effect is well established. When lacking a firm diagnosis, however, the clinician is challenged to to weigh the potential benefits of the graft-versus-lymphoma effect against potential dangers of graft-versus-host disease as well as against generalized (viral infections. Case presentation We present evidence for a graft-versus-lymphoma effect in a 64-year-old caucasian woman with a transplanted peripheral blood-stem-cell graft from her Human Leukocyte Antigen-identical sister, and propose diagnostic measures to distinguish between graft-versus-host effect, and against viral disease or drug-induced reactions. Conclusion We were able to identify an allogeneic graft-reaction against progressive lymphoma alongside an erythema consistent with acute graft-versus-host disease of the skin. Establishing a firm diagnosis enabled us to decide against T-cell suppression (such as by using cyclosporine. Anti-lymphoma activity was favoured, by means of the allogeneic graft, local radiation and immunotherapy. This illustrates the importance of a sound differential diagnosis of erythema after allogeneic stem-cell transplantation, including assessment of viral disease of the affected tissue.

  19. Graft versus neuroblastoma reaction is efficiently elicited by allogeneic bone marrow transplantation through cytolytic activity in the absence of GVHD.

    Science.gov (United States)

    Ash, Shifra; Gigi, Vered; Askenasy, Nadir; Fabian, Ina; Stein, Jerry; Yaniv, Isaac

    2009-12-01

    Continuous efforts are dedicated to develop immunotherapeutic approaches to neuroblastoma (NB), a tumor that relapses at high rates following high-dose conventional cytotoxic therapy and autologous bone marrow cell (BMC) reconstitution. This study presents a series of transplant experiments aiming to evaluate the efficacy of allogeneic BMC transplantation. Neuro-2a cells were found to express low levels of class I major histocompatibility complex (MHC) antigens. While radiation and syngeneic bone marrow transplantation (BMT) reduced tumor growth (P < 0.001), allogeneic BMT further impaired subcutaneous development of Neuro-2a cells (P < 0.001). Allogeneic donor-derived T cells displayed direct cytotoxic activity against Neuro-2a in vitro, a mechanism of immune-mediated suppression of tumor growth. The proliferation of lymphocytes from congenic mice bearing subcutaneous tumors was inhibited by tumor lysate, suggesting that a soluble factor suppresses cytotoxic activity of syngeneic lymphocytes. However, the growth of Neuro-2a cells was impaired when implanted into chimeric mice at various times after syngeneic and allogeneic BMT. F1 (donor-host) splenocytes were infused attempting to foster immune reconstitution, however they engrafted transiently and had no effect on tumor growth. Taken together, these data indicate: (1) Neuro-2a cells express MHC antigens and immunogenic tumor associated antigens. (2) Allogeneic BMT is a significantly better platform to develop graft versus tumor (GVT) immunotherapy to NB as compared to syngeneic (autologous) immuno-hematopoietic reconstitution. (3) An effective GVT reaction in tumor bearing mice is primed by MHC disparity and targets tumor associated antigens.

  20. Histomorhological and clinical evaluation of maxillary alveolar ridge reconstruction after craniofacial trauma by applying combination of allogeneic and autogenous bone graft.

    Science.gov (United States)

    De Ponte, Francesco Saverio; Falzea, Roberto; Runci, Michele; Siniscalchi, Enrico Nastro; Lauritano, Floriana; Bramanti, Ennio; Cervino, Gabriele; Cicciu, Marco

    2017-02-01

    A variety of techniques and materials for the rehabilitation and reconstruction of traumatized maxillary ridges prior to dental implants placement have been described in literature. Autogenous bone grafting is considered ideal by many researchers and it still remains the most predictable and documented method. The aim of this report is to underline the effectiveness of using allogeneic bone graft for managing maxillofacial trauma. A case of a 30-year-old male with severely atrophic maxillary ridge as a consequence of complex craniofacial injury is presented here. Augmentation procedure in two stages was performed using allogeneic and autogenous bone grafts in different areas of the osseous defect. Four months after grafting, during the implants placement surgery, samples of both sectors were withdrawn and submitted to histological evaluation. On the examination of the specimens, treated by hematoxylin and eosin staining, the morphology of integrated allogeneic bone grafts was revealed to be similar to the autologous bone. Our clinical experience shows how the allogeneic bone graft presented normal bone tissue architecture and is highly vascularized, and it can be used for reconstruction of severe trauma of the maxilla.

  1. Histomorhological and clinical evaluation of maxillary alveolar ridge reconstruction after craniofacial trauma by applying combination of allogeneic and autogenous bone graft

    Directory of Open Access Journals (Sweden)

    Francesco Saverio De Ponte

    2017-02-01

    Full Text Available A variety of techniques and materials for the rehabilitation and reconstruction of traumatized maxillary ridges prior to dental implants placement have been described in literature. Autogenous bone grafting is considered ideal by many researchers and it still remains the most predictable and documented method. The aim of this report is to underline the effectiveness of using allogeneic bone graft for managing maxillofacial trauma. A case of a 30-year-old male with severely atrophic maxillary ridge as a consequence of complex craniofacial injury is presented here. Augmentation procedure in two stages was performed using allogeneic and autogenous bone grafts in different areas of the osseous defect. Four months after grafting, during the implants placement surgery, samples of both sectors were withdrawn and submitted to histological evaluation. On the examination of the specimens, treated by hematoxylin and eosin staining, the morphology of integrated allogeneic bone grafts was revealed to be similar to the autologous bone. Our clinical experience shows how the allogeneic bone graft presented normal bone tissue architecture and is highly vascularized, and it can be used for reconstruction of severe trauma of the maxilla.

  2. Allogeneic versus autologous derived cell sources for use in engineered bone-ligament-bone grafts in sheep anterior cruciate ligament repair.

    Science.gov (United States)

    Mahalingam, Vasudevan D; Behbahani-Nejad, Nilofar; Horine, Storm V; Olsen, Tyler J; Smietana, Michael J; Wojtys, Edward M; Wellik, Deneen M; Arruda, Ellen M; Larkin, Lisa M

    2015-03-01

    The use of autografts versus allografts for anterior cruciate ligament (ACL) reconstruction is controversial. The current popular options for ACL reconstruction are patellar tendon or hamstring autografts, yet advances in allograft technologies have made allogeneic grafts a favorable option for repair tissue. Despite this, the mismatched biomechanical properties and risk of osteoarthritis resulting from the current graft technologies have prompted the investigation of new tissue sources for ACL reconstruction. Previous work by our lab has demonstrated that tissue-engineered bone-ligament-bone (BLB) constructs generated from an allogeneic cell source develop structural and functional properties similar to those of native ACL and vascular and neural structures that exceed those of autologous patellar tendon grafts. In this study, we investigated the effectiveness of our tissue-engineered ligament constructs fabricated from autologous versus allogeneic cell sources. Our preliminary results demonstrate that 6 months postimplantation, our tissue-engineered auto- and allogeneic BLB grafts show similar histological and mechanical outcomes indicating that the autologous grafts are a viable option for ACL reconstruction. These data indicate that our tissue-engineered autologous ligament graft could be used in clinical situations where immune rejection and disease transmission may preclude allograft use.

  3. Impact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia

    DEFF Research Database (Denmark)

    Baron, F; Labopin, M; Niederwieser, D;

    2012-01-01

    This report investigated the impact of graft-versus-host disease (GVHD) on transplantation outcomes in 1859 acute myeloid leukemia patients given allogeneic peripheral blood stem cells after reduced-intensity conditioning (RIC allo-SCT). Grade I acute GVHD was associated with a lower risk of rela...... of relapse (hazards ratio (HR)=0.7, P=0.02) translating into a trend for better overall survival (OS; HR=1.3; P=0.07). Grade II acute GVHD had no net impact on OS, while grade III-IV acute GVHD was associated with a worse OS (HR=0.4, P...

  4. Acellular allogeneic nerve grafting combined with bone marrow mesenchymal stem cell transplantation for the repair of long-segment sciatic nerve defects:biomechanics and validation of mathematical models

    Institute of Scientific and Technical Information of China (English)

    Ya-jun Li; Bao-lin Zhao; Hao-ze Lv; Zhi-gang Qin; Min Luo

    2016-01-01

    We hypothesized that a chemically extracted acellular allogeneic nerve graft used in combination with bone marrow mesenchymal stem cell transplantation would be an effective treatment for long-segment sciatic nerve defects. To test this, we established rabbit models of 30 mm sciatic nerve defects, and treated them using either an autograft or a chemically decellularized allogeneic nerve graft with or without simultaneous transplantation of bone marrow mesenchymal stem cells. We compared the tensile properties, electrophysiological function and morphology of the damaged nerve in each group. Sciatic nerves repaired by the allogeneic nerve graft combined with stem cell trans-plantation showed better recovery than those repaired by the acellular allogeneic nerve graft alone, and produced similar results to those observed with the autograft. These ifndings conifrm that a chemically extracted acellular allogeneic nerve graft combined with transplanta-tion of bone marrow mesenchymal stem cells is an effective method of repairing long-segment sciatic nerve defects.

  5. Induction of graft versus malignancy effect after unrelated allogeneic PBSCT using donor lymphocyte infusions derived from frozen aliquots of the original graft.

    Science.gov (United States)

    Hasskarl, J; Zerweck, A; Wäsch, R; Ihorst, G; Bertz, H; Finke, J

    2012-02-01

    To evaluate safety and efficacy of donor lymphocyte infusions (DLI), derived from frozen aliquots of the original G-CSF-stimulated graft after allogeneic PBSCT from unrelated donors, data of 121 patients with hematological malignancies treated with DLIs were retrospectively analyzed. Indications for PBSCT were AML/myelodysplastic syndrome (n=63/8), ALL (n=17), lymphoma (n=13), multiple myeloma (n=10) and myeloproliferative syndrome (n=10). Reasons for DLI were hematological relapse (n=81), molecular and/or cytogenetic relapse (n=5), mixed chimerism (n=22) and prophylactic DLI in high-risk patients (n=13). DLIs were well tolerated with no acute adverse reactions. DLI-induced acute-type GvHD (aGvHD) was observed in 19 patients and chronic-type GvHD (cGvHD) developed in 14 patients. Three patients died of GvHD complications. DLI induced CR, complete chimerism or PR in 34 patients; 24 patients had stable disease, 50 patients progressed and 13 patients were not evaluable for response. Objective response was more obvious for molecular relapse (5/5) or mixed chimerism (14/22) compared with hematological relapse (13/81). Median survival after first DLI was 10.4 months (95% confidence interval: 4.4-26.0). Cryopreserved G-CSF-stimulated DLI, derived from allogeneic grafts are safe and immunoreactive, and can be applied early in case of mixed chimerism and molecular or cytogenetic relapse.

  6. Immunization of allogeneic bone marrow transplant recipients with tumor cell vaccines enhances graft-versus-tumor activity without exacerbating graft-versus-host disease.

    Science.gov (United States)

    Anderson, L D; Savary, C A; Mullen, C A

    2000-04-01

    Allogeneic bone marrow transplantation (BMT) induces 2 closely associated immune responses: graft-versus-tumor (GVT) activity and graft-versus-host disease (GVHD). We have previously shown that pretransplant immunization of allogeneic BMT donors with a recipient-derived tumor cell vaccine increases both GVT activity and lethal GVHD because of the priming of donor T cells against putative minor histocompatibility antigens (mHAgs) on the tumor vaccine cells. The work reported here tested the hypothesis that tumor cell vaccination after BMT would produce an increase in GVT activity without exacerbating GVHD. C3H.SW donor bone marrow and splenocytes were transplanted into major histocompatibility complex-matched, mHAg-mismatched C57BL/6 recipients. One month after BMT, recipients were immunized against either a C57BL/6 myeloid leukemia (C1498) or fibrosarcoma (205). Immunized recipients had a significant increase in survival and protection against tumor growth in both tumor models, and significant tumor protection was seen even in recipients with preexisting micrometastatic cancer before immunization. Alloreactivity appeared to contribute to the in vitro anti-tumor cytolytic activity, but in vivo immunity was tumor specific, and no exacerbation of GVHD was observed. Although the immunodominant mHAg B6(dom1) was shown to be expressed by all B6 tumors tested and was largely responsible for the alloreactivity resulting from tumor immunization of donors, the in vitro alloreactivity of immune recipients was more restricted and was not mediated by recognition of B6(dom1). In conclusion, post-transplant tumor immunization of allogeneic BMT recipients against either a leukemia or a solid tumor can increase GVT activity and survival without exacerbating GVHD.

  7. T-cell chimerism is valuable in predicting early mortality in steroid-resistant acute graft-versus-host disease after myeloablative allogeneic cell transplantation

    DEFF Research Database (Denmark)

    Minculescu, Lia; Madsen, Hans O.; Sengeløv, Henrik

    2014-01-01

    The main aim of this study was to evaluate the impact of early T-cell chimerism status on the incidence and clinical course of acute graft-versus-host disease (aGVHD) in allogeneic transplant recipients after myeloablative conditioning. Of 62 patients, 38 (61%) had complete T-cell donor chimerism...

  8. Bim is required for T-cell allogeneic responses and graft-versus-host disease in vivo.

    Science.gov (United States)

    Yu, Yu; Yu, Jing; Iclozan, Cristina; Kaosaard, Kane; Anasetti, Claudio; Yu, Xue-Zhong

    2012-01-01

    Bim, a BH3-only Bcl-2-family protein, is essential for T-cell negative selection in the thymus as well as for the death of activated T cells in the periphery. The role of Bim has been extensively studied in T-cell responses to self-antigens and viral infections. Recent findings on Bim in autoimmunity triggered our interest in investigating whether Bim may play a role in another disease with inflammatory symptoms as graft-versus-host disease (GVHD). Here we report that Bim is required for optimal T-cell responses to alloantigens in vivo and for the development of GVHD. Using murine models of allogeneic bone marrow transplantation (BMT), we found that donor T cells deficient for Bim are impaired in the induction of GVHD primarily due to a significant defect in T cell activation and expansion in vivo. Upon TCR engagement, Bim(-/-) T cells exhibited selective defects in CD69 expression and phosphorylation of PLCγ1. Our studies uncover a novel aspect of Bim function in T-cell activation with important implications in understanding the mechanisms of T-cell activation and tolerance under allogeneic transplantation.

  9. The prevalence and prognostic value of concomitant eosinophilia in chronic graft-versus-host disease after allogeneic stem cell transplantation.

    Science.gov (United States)

    Mortensen, Katrine Brandt; Gerds, Thomas Alexander; Bjerrum, Ole Weis; Lindmark, Anders; Sengeløv, Henrik; Andersen, Christen Lykkegaard

    2014-03-01

    The prognostic significance of eosinophilia after myeloablative allogeneic stem cell transplantation (ASCT) remains to be established. Patients, whom developed chronic graft-versus-host disease (cGVHD) after ASCT, were included (n = 142). Eosinophil count was analyzed at cGVHD onset. We observed no significant association between EO and the grade of cGVHD, thrombocytopenia, nor extensive skin involvement. Importantly, we observed no significant association between cGVHD with concomitant eosinophilia and long-term clinical outcomes, and subgroup analyses revealed a considerable confounding effect of ongoing steroid treatment. In conclusion, we advocate that prognostic conclusions regarding cGVHD with concomitant eosinophilia after ASCT should be interpreted with caution. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. The prevalence and prognostic value of concomitant eosinophilia in chronic graft-versus-host disease after allogeneic stem cell transplantation

    DEFF Research Database (Denmark)

    Mortensen, Katrine Brandt; Gerds, Thomas Alexander; Bjerrum, Ole Weis

    2014-01-01

    The prognostic significance of eosinophilia after myeloablative allogeneic stem cell transplantation (ASCT) remains to be established. Patients, whom developed chronic graft-versus-host disease (cGVHD) after ASCT, were included (n = 142). Eosinophil count was analyzed at cGVHD onset. We observed...... no significant association between EO and the grade of cGVHD, thrombocytopenia, nor extensive skin involvement. Importantly, we observed no significant association between cGVHD with concomitant eosinophilia and long-term clinical outcomes, and subgroup analyses revealed a considerable confounding effect...... of ongoing steroid treatment. In conclusion, we advocate that prognostic conclusions regarding cGVHD with concomitant eosinophilia after ASCT should be interpreted with caution....

  11. Ocular Surface Rreconstruction with Allogeneic Limbal Stem Cell and Autologous Oral Mucosal Graft: Two Cases

    Directory of Open Access Journals (Sweden)

    Gözde Orman

    2013-04-01

    Full Text Available Two patients with severe ocular surface damage in both eyes are presented. In the patient with limbal stem cell deficiency, allogeneic limbal stem cell transplantation was performed. In the other patient with recurrent pterygium and symblepharon, autogenic oral mucosa transplantation was performed to manage the symblepharon. In this study, we discuss the methods that can be performed for reconstruction in patients with ocular surface disorder in both eyes. (Turk J Ophthalmol 2013; 43: 129-31

  12. The role of pattern-recognition receptors in graft-versus-host disease and graft-versus-leukemia after allogeneic stem cell transplantation.

    Science.gov (United States)

    Heidegger, Simon; van den Brink, Marcel R M; Haas, Tobias; Poeck, Hendrik

    2014-01-01

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only treatment with curative potential for certain aggressive hematopoietic malignancies. Its success is limited by acute graft-versus-host disease (GVHD), a life-threatening complication that occurs when allo-reactive donor T cells attack recipient organs. There is growing evidence that microbes and innate pattern-recognition receptors (PRRs) such as toll-like receptors (TLR) and nod-like receptors (NLR) are critically involved in the pathogenesis of acute GVHD. Currently, a widely accepted model postulates that intensive chemotherapy and/or total-body irradiation during pre-transplant conditioning results in tissue damage and a loss of epithelial barrier function. Subsequent translocation of bacterial components as well as release of endogenous danger molecules stimulate PRRs of host antigen-presenting cells to trigger the production of pro-inflammatory cytokines (cytokine storm) that modulate T cell allo-reactivity against host tissues, but eventually also the beneficial graft-versus-leukemia (GVL) effect. Given the limitations of existing immunosuppressive therapies, a better understanding of the molecular mechanisms that govern GVHD versus GVL is urgently needed. This may ultimately allow to design modulators, which protect from GvHD but preserve donor T-cell attack on hematologic malignancies. Here, we will briefly summarize current knowledge about the role of innate immunity in the pathogenesis of GVHD and GVL following allo-HSCT.

  13. The role of pattern-recognition receptors in Graft-versus-host disease and Graft-versus-leukemia after allogeneic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Simon eHeidegger

    2014-07-01

    Full Text Available Allogeneic hematopoietic stem cell transplantation (allo-HSCT is the only treatment with curative potential for certain aggressive hematopoietic malignancies. Its success is limited by acute graft-versus-host disease (GVHD, a life-threatening complication that occurs when alloreactive donor T cells attack recipient organs. There is growing evidence that microbes and innate pattern-recognition receptors (PRRs such as toll-like (TLR and nod-like receptors (NLR are critically involved in the pathogenesis of acute GVHD. A now widely accepted model postulates that intensive chemotherapy and / or total-body irradiation during pre-transplant conditioning result in tissue damage and a loss of epithelial barrier function. Subsequent translocation of bacterial components as well as release of endogenous danger molecules stimulate PRRs of host antigen-presenting cells (APCs to trigger the production of pro-inflammatory cytokines (‘cytokine storm’ that modulate T cell alloreactivity against host tissues, but eventually also the beneficial graft-versus-leukemia (GVL effect. Given the limitations of existing immunosuppressive therapies, a better understanding of the molecular mechanisms which govern GVHD vs GVL is urgently needed. This may ultimately allow to design modulators which protect from GvHD but preserve donor T-cell attack on hematologic malignancies. Here, we will briefly summarize current knowledge about the role of innate immunity in the pathogenesis of GVHD and GVL following allo-HSCT.

  14. Thoracic air-leakage syndrome in allogeneic stem cell transplant recipients as a late complication of chronic graft-versus-host disease: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jae Wook; Kim, Song Soo; Jo, Daeg Yeon; Yun, Hwan Jung; Lee, Hyo Jin; Kim, Jin Hwan [Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon (Korea, Republic of)

    2016-08-15

    Air-leakage syndrome associated with graft-versus-host disease (GVHD) is a rare complication, but it is also reported as an independent predictor of a worse survival rate after stem cell transplantation. We report two cases of air-leakage syndrome associated with GVHD after allogeneic stem cell transplantation in acute leukemia patients who presented with spontaneous pneumomediastinum and subcutaneous emphysema, and finally death due to respiratory failure seven to eight months later.

  15. Postmortem examination of the kidney in allogeneic hematopoietic stem cell transplantation recipients: possible involvement of graft-versus-host disease.

    Science.gov (United States)

    Kusumi, Eiji; Kami, Masahiro; Hara, Shigeo; Hoshino, Junichi; Yamaguchi, Yutaka; Murashige, Naoko; Kishi, Yukiko; Shibagaki, Yugo; Shibata, Taro; Matsumura, Tomoko; Yuji, Koichiro; Masuoka, Kazuhiro; Wake, Atsushi; Miyakoshi, Shigesaburo; Taniguchi, Shuichi

    2008-03-01

    To investigate the association between graft-versus-host disease (GVHD) and renal injury after allogeneic stem cell transplantation (allo-SCT), we compared autopsy findings of 26 consecutive allo-SCT recipients with two control groups: patients with hematologic malignancies who received cytotoxic chemotherapy alone (Control 1, n = 21) and those with non-hematologic diseases (Control 2, n = 12). We evaluated the following renal pathology; renal tubulitis, allograft glomerulitis, intimal arteritis, allograft nephropathy, and peritubular capillaritis. These changes were found in 11 allo-SCT recipients and 10 patients in Control 1, but none in Control 2. While overall frequency of renal impairments was similar between allo-SCT recipients and Control 1 (3/26 vs. 1/21), allo-SCT recipients were more likely to have renal tubulitis and peritubular capillaritis compared to Control 1 (5/26 vs. 1/21), but less likely to present with glomerulitis (1/26 vs. 6/21). Grade III-IV acute or extensive-type chronic GVHD were seen in all of the three patients with renal tubulitis and four of the five patients with peritubular capillaritis. Allo-SCT recipients with severe GVHD tended to have tubulitis and peritubular capillaritis. These findings have implications of some renal impairment attributable to GVHD.

  16. Magnetic resonance enterography for assessment of intestinal graft-versus-host disease after allogeneic stem cell transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Derlin, Thorsten [University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); Hanover Medical School, Department of Nuclear Medicine, Hanover (Germany); Laqmani, Azien; Adam, Gerhard; Bannas, Peter [University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); Veldhoen, Simon [University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); University Medical Center Wuerzburg, Department of Diagnostic and Interventional Radiology, Wuerzburg (Germany); Apostolova, Ivayla [Otto-von-Guericke University, Department of Radiology and Nuclear Medicine, Magdeburg (Germany); Ayuk, Francis; Kroeger, Nicolaus [University Medical Center Hamburg-Eppendorf, Department of Stem Cell Transplantation, Hamburg (Germany)

    2015-05-01

    To determine the diagnostic performance of MR enterography (MRE) for detection and grading of gastrointestinal graft-versus-host disease (GI GvHD) after hematopoietic stem cell transplantation (SCT). Forty-one patients with known GvHD or suspected GvHD underwent MRE and GI endoscopy with multi-level biopsies. MRE images were reviewed for presence of intestinal wall inflammation. Clinical grading of GI GvHD was performed. Histopathological evaluation (HPE) served as the reference standard. Overall, MRE demonstrated a per-patient sensitivity of 81.5 % for detection of GI GvHD. The most common findings were intestinal wall thickening (81.5 % of GvHD patients), luminal stenosis (81.5 %), mural contrast enhancement (70.4 %), and ascites (59.3 %). These findings were also observed in other conditions than GvHD. The most frequently involved intestinal segment was the sigmoid colon (63.0 %), followed by the ileum (59.3 %) and the jejeunum (51.9 %). The number of involved segments (r{sub s} =0.54, p =0.009) correlated significantly with clinical severity as determined by GvHD grading. After allogeneic stem cell transplantation, MRE may (1) contribute to detection and localization of GI GvHD, and (2) add information indicating the clinical severity of disease, but findings are unspecific. False negative results may be observed not only in low-grade GI GvHD. (orig.)

  17. Glomerular diseases associated with chronic graft-versus-host disease after allogeneic peripheral blood stem cell transplantation: case reports.

    Science.gov (United States)

    Chanswangphuwana, C; Townamchai, N; Intragumtornchai, T; Bunworasate, U

    2014-12-01

    Chronic graft-versus-host disease (cGVHD) is the major complication following allogeneic stem cell transplantation (allo-SCT). Nephrotic syndrome (NS) and other types of glomerulonephritis have been proposed to be the very rare forms of renal cGVHD. From 1991 to 2011, 253 patients underwent allo-SCT at our center. We report here 4 cases (1.6%) presenting with varieties of glomerular manifestations associated with cGVHD. The first case was typical NS. The renal pathology showed membranous nephropathy (MN). The second case was also MN, but this patient also had the pathology of focal segmental glomerulosclrosis (FSGS) and acute tubular necrosis (ATN). The third case showed lupus nephritis-like glomerular lesions with a high anti-nuclear antibody (ANA) titer. The fourth case presented with rapidly progressive glomerulonephritis (RPGN)-like symptoms. The kidney histology in this case was not available. The patient responded well to immunosuppressive therapy, but NS later recurred. Therefore, overt glomerular diseases after allo-SCT in Thai patients are not very rare. Monitoring urinalysis during withdrawal of immunosuppressive drugs and also during follow-up of patients with cGVHD may be considered.

  18. Mycophenolate mofetil and cyclosporine for graft-versus-host disease prophylaxis following reduced intensity conditioning allogeneic stem cell transplantation.

    Science.gov (United States)

    Mohty, M; de Lavallade, H; Faucher, C; Bilger, K; Vey, N; Stoppa, A-M; Gravis, G; Coso, D; Viens, P; Gastaut, J-A; Blaise, D

    2004-09-01

    The use of reduced intensity conditioning (RIC) regimens for allogeneic stem cell transplantation (allo-SCT) can result in a significant decrease in early procedure-related toxicity in patients not eligible for standard myeloablative regimens. However, acute graft-versus-host disease (aGVHD) remains a matter of concern after RIC allo-SCT, and its incidence might be expected to be higher in elderly and high-risk patients. This report investigated mycophenolate mofetil (MMF) and cyclosporin A (CsA) combination (n=14) in comparison to CsA alone (n=20) for GVHD prophylaxis in cancer patients aged over 50 years (27 haematological malignancies and seven solid tumours) receiving an HLA-identical sibling antithymocyte-globulin (ATG)-based RIC allo-SCT. Baseline demographic characteristics and risk factors for aGVHD were comparable between both groups. Although MMF administration was not associated with any significant toxicity, the cumulative incidence of any form of GVHD was comparable between both groups (cumulative incidence of grade II-IV aGVHD, 50% (95% CI, 28-72%) for CsA alone, as compared to 64% (95% CI, 39-89%) to CsA and MMF, P=NS), suggesting that adjunction of MMF to CsA is feasible, but does not translate towards a significant reduction of aGVHD, at least in the context ATG-based RIC allo-SCT.

  19. A case of upper gingiva carcinoma with chronic graft-versus-host disease after allogenic bone marrow transplantation.

    Science.gov (United States)

    Tsushima, F; Sakurai, J; Harada, H

    2015-09-01

    Oral squamous cell carcinoma (OSCC) is one of the most common solid tumours occurring after haematopoietic stem cell transplantation (HSCT), especially in patients with chronic graft-versus-host-disease (cGVHD). We describe a case of OSCC that developed in a 51-year-old male 22 years after he had received allogeneic HSCT from his human leukocyte antigen-identical sister as a treatment for acute myelocytic leukaemia. The patient had presented with multiple white patchy lesions on the palatal gingiva and mucosa 16 years after HSCT; these lesions were consistent with the clinical features of cGVHD. Six years later, oral examination and biopsy revealed upper gingival squamous cell carcinoma (SCC) in areas of cGVHD, and he underwent tumour excision. Follow-up examination at 2 years and 4 months after the operation revealed no evidence of recurrence of local SCC or metastasis of the cervical lymph node. The current case highlights the susceptibility of patients with cGVHD to the development of OSCC even two decades after HSCT. Therefore, we recommend careful long-term follow-up of the oral cavity for patients with cGVHD. © 2015 Australian Dental Association.

  20. Innate immune activation by the viral PAMP poly I:C potentiates pulmonary graft-versus-host disease after allogeneic hematopoietic cell transplant.

    Science.gov (United States)

    Kinnier, Christine V; Martinu, Tereza; Gowdy, Kymberly M; Nugent, Julia L; Kelly, Francine L; Palmer, Scott M

    2011-01-15

    Respiratory viral infections cause significant morbidity and increase the risk for chronic pulmonary graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT). Our overall hypothesis is that local innate immune activation potentiates adaptive alloimmunity. In this study, we hypothesized that a viral pathogen-associated molecular pattern (PAMP) alone can potentiate pulmonary GVHD after allogeneic HCT. We, therefore, examined the effect of pulmonary exposure to polyinosinic:polycytidylic acid (poly I:C), a viral mimetic that activates innate immunity, in an established murine HCT model. Poly I:C-induced a marked pulmonary T cell response in allogeneic HCT mice as compared to syngeneic HCT, with increased CD4+ cells in the lung fluid and tissue. This lymphocytic inflammation persisted at 2 weeks post poly I:C exposure in allogeneic mice and was associated with CD3+ cell infiltration into the bronchiolar epithelium and features of epithelial injury. In vitro, poly I:C enhanced allospecific proliferation in a mixed lymphocyte reaction. In vivo, poly I:C exposure was associated with an early increase in pulmonary monocyte recruitment and activation as well as a decrease in CD4+FOXP3+ regulatory T cells in allogeneic mice as compared to syngeneic. In contrast, intrapulmonary poly I:C did not alter the extent of systemic GVHD in either syngeneic or allogeneic mice. Collectively, our results suggest that local activation of pulmonary innate immunity by a viral molecular pattern represents a novel pathway that contributes to pulmonary GVHD after allogeneic HCT, through a mechanism that includes increased recruitment and maturation of intrapulmonary monocytes.

  1. Effect of acute and chronic graft-versus-host disease on relapse and survival after reduced-intensity conditioning allogeneic transplantation for myeloma

    Science.gov (United States)

    Ringdén, Olle; Shrestha, Smriti; da Silva, Gisela Tunes; Zhang, Mei-Jie; Dispenzieri, Angela; Remberger, Mats; Kamble, Rammurti; Freytes, Cesar O.; Gale, Robert Peter; Gibson, John; Gupta, Vikas; Holmberg, Leona; Lazarus, Hillard; McCarthy, Philip; Meehan, Kenneth; Schouten, Harry; Milone, Gustavo A.; Lonial, Sagar; Hari, Parameswaran N

    2011-01-01

    We evaluated the effect of acute and chronic graft-versus-host disease (GVHD) on relapse and survival after allogeneic haematopoietic stem cell transplantation (HSCT) for multiple myeloma (MM) using non-myeloablative conditioning (NMA) and reduced-intensity conditioning (RIC). The outcomes of 177 HLA-identical sibling HSCT recipients between 1997 and 2005 following NMA (n=98) or RIC (n=79) were analyzed. In 105 patients, autografting was followed by planned NMA/RIC allogeneic transplantation. The impact of GVHD was assessed as a time-dependent covariate using Cox models. The incidence of acute GVHD (grades I–IV) was 42% (95% confidence interval (CI) 35 – 49%) and of chronic GVHD at five years was 59% (95% CI 49 – 69%), with 70% developing extensive chronic GVHD. In multivariate analysis, acute GVHD (≥ grade I) was associated with an increased risk of TRM (relative risk (RR)=2.42; p=0.016), whereas limited chronic GVHD significantly decreased the risk of myeloma relapse (RR=0.35, p=0.035) and was associated with superior event-free survival (RR=0.40, p=0.027). Acute GVHD had a detrimental effect on survival, especially in those receiving autologous followed by allogeneic HSCT (RR=3.52; p=0.001). The reduction in relapse risk associated with chronic GVHD is consistent with a beneficial graft-versus-myeloma effect, but this did not translate into a survival advantage. PMID:21946381

  2. CD34 selected cells for the treatment of poor graft function after allogeneic stem cell transplantation.

    Science.gov (United States)

    Stasia, Alessandra; Ghiso, Anna; Galaverna, Federica; Raiola, Anna Maria; Gualandi, Francesca; Luchetti, Silvia; Pozzi, Sarah; Varaldo, Riccardo; Lamparelli, Teresa; Bregante, Stefania; Van Lint, Maria Teresa; di Grazia, Carmen; Bacigalupo, Andrea

    2014-09-01

    Poor graft function (PGF) is characterized by pancytopenia and a hypoplastic marrow, with complete donor chimerism, usually without severe graft-versus-host disease (GVHD). We report 41 patients with PGF, treated with granulocyte colony-stimulating factor-mobilized CD34 selected cells, at a median interval from transplant of 140 days, without conditioning and without GVHD prophylaxis. Donors were HLA matched siblings (n = 12), unrelated donors (n = 18), or mismatched family members (n = 11). The median number of infused CD34(+) cells was 3.4 × 10(6)/kg. The rate of trilineage recovery was 75%: 83% for HLA matched siblings and 72% for unrelated and mismatched family members (P = .3). The cumulative incidence of acute grade II GVHD was 15%, and no patient developed de novo chronic GVHD. The actuarial 3-year survival is 63%: 76% and 25% for patients with or without trilineage recovery. These data confirm the role of CD34(+) selected cells from the same donor in the treatment of PGF and warrant the request for a second donation also when the donor is unrelated.

  3. Allogenous bone grafts improved by bone marrow stem cells and platelet growth factors: clinical case reports.

    Science.gov (United States)

    Filho Cerruti, Humberto; Kerkis, Irina; Kerkis, Alexandre; Tatsui, Nelson Hidekazu; da Costa Neves, Adriana; Bueno, Daniela Franco; da Silva, Marcelo Cavenaghi Pereira

    2007-04-01

    In order to increase the amount of available bone where dental implants must be placed, the present study has associated platelet-rich plasma (PRP) and mononuclear cells (MNCs) from bone marrow aspirate and bone scaffold (BS) in 32 patients aged between 45 and 75 years old. The MNC attainment and the adherence to the BS were confirmed through histology, cell culture, and scanning electron microscopy. The clinical results, analyzed by computed tomography, have showed that the scaffolds were well integrated and adapted to the cortical bone. We can conclude that the process of healing observed in the patients was due to the presence of mesenchymal stem cell in MNC fraction in the bone grafts.

  4. Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multi-center survey

    Science.gov (United States)

    Zeiser, Robert; Burchert, Andreas; Lengerke, Claudia; Verbeek, Mareike; Maas-Bauer, Kristina; Metzelder, Stephan K.; Spoerl, Silvia; Ditschkowski, Markus; Ecsedi, Matyas; Sockel, Katja; Ayuk, Francis; Ajib, Salem; de Fontbrune, Flore Sicre; Na, Il-Kang; Penter, Livius; Holtick, Udo; Wolf, Dominik; Schuler, Esther; Meyer, Everett; Apostolova, Petya; Bertz, Hartmut; Marks, Reinhard; Lübbert, Michael; Wäsch, Ralph; Scheid, Christof; Stölzel, Friedrich; Ordemann, Rainer; Bug, Gesine; Kobbe, Guido; Negrin, Robert; Brune, Mats; Spyridonidis, Alexandros; Schmitt-Gräff, Annette; van der Velden, Walter; Huls, Gerwin; Mielke, Stephan; Grigoleit, Götz Ulrich; Kuball, Jürgen; Flynn, Ryan; Ihorst, Gabriele; Du, Jing; Blazar, Bruce R; Arnold, Renate; Kröger, Nicolaus; Passweg, Jakob; Halter, Jörg; Socié, Gerard; Beelen, Dietrich; Peschel, Christian; Neubauer, Andreas; Finke, Jürgen; Duyster, Justus; von Bubnoff, Nikolas

    2016-01-01

    Despite major improvements in allogeneic hematopoietic cell transplantation over the last decades, corticosteroid-refractory (SR) acute (a) and chronic (c) graft-versus-host disease (GVHD) cause high mortality. Pre-clinical evidence indicates the potent anti-inflammatory properties of the JAK1/2 inhibitor ruxolitinib. In this retrospective survey, 19 stem cell transplant centers in Europe and the United States reported outcome data from 95 patients who had received ruxolitinib as salvage-therapy for SR-GVHD. Patients were classified as having SR-aGVHD (n=54, all grade III or IV) or SR-cGVHD (n=41, all moderate or severe). The median number of previous GVHD-therapies was 3 for both SR-aGVHD (1–7) and SR-cGVHD (1–10). The ORR was 81.5% (44/54) in SR-aGVHD including 25 CRs (46.3%), while for SR-cGVHD the ORR was 85.4% (35/41). Of those patients responding to ruxolitinib, the rate of GVHD-relapse was 6.8% (3/44) and 5.7% (2/35) for SR-aGVHD and SR-cGVHD, respectively. The 6-month-survival was 79% (67.3%–90.7%,95% CI) and 97.4% (92.3%–100%,95% CI) for SR-aGVHD and SR-cGVHD, respectively. Cytopenia and CMV-reactivation were observed during ruxolitinib-treatment in both SR-aGVHD (30/54, 55.6% and 18/54, 33.3%) and SR-cGVHD (7/41, 17.1% and 6/41, 14.6%) patients. Ruxolitinib may constitute a promising new treatment option for SR-aGVHD and SR-cGVHD that should be validated in a prospective trial. PMID:26228813

  5. Colonoscopy in the diagnosis of intestinal graft versus host disease and cytomegalovirus enteritis following allogeneic haematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    HE Jin-de; LIU Yu-lan; WANG Zhi-feng; LIU Dai-hong; CHEN Huan; CHEN Yu-hong

    2008-01-01

    Background Gastrointestinal graft versus host disease (GI-GVHD) and cytomegalovirus (CMV) enteritis are important complications following allogeneic haematopoietic stem cell transplantation (alIo-HSCT). We explored the role of colonoscopy in the diagnosis of GI-GVHD and CMV enteritis following alIo-HSCT to identify the endoscopic manifestations of GI-GVHD and CMV enteritis was made.Methods A retrospective analysis of the colonoscopic manifestations of GI-GVHD, CMV enteritis and GI-GVHD with concurrent CMV enteritis (GconC) and their related clinical issues.Results Forty-seven patients underwent 50 colonoscopies with diagnoses of 32 GI-GVHD, 7 CMV enteritis and 11 GconC. Both GI-GVHD and CMV enteritis had colonic mucosal lesions with various manifestations under colonoscopy. Tortoise shell like changes of the mucosa (12 of 32) and deep ulcers (2 of 7) were specific endoscopic manifestations for GI-GVHD and CMV enteritis, respectively, while mucosal oedema, erythema, congestion, erosion and shallow ulcers could not be used to differentiate GI-GVHD from CMV enteritis. GconC patients were prone to have oozing bleeding of the end ileal mucosa and typhlodicliditis. Of the biopsed specimens for GI-GVHD, CMV enteritis and GconC, 64%, 70% and 44% were taken from the rectum and sigmoid colon respectively.Conclusions Following alIo-HSCT, tortoise shell like changes and deep ulcers of the colonic mucosa are characteristic changes for Gl-GVHD and CMV enteritis, respectively, while the other lesions are not. Most of the GI-GVHDs and CMV enteritis cases can be diagnosed by left colon examination and tissue biopsy, but total colon examination to the terminal ileum is preferred.

  6. Bismuth 213-labeled anti-CD45 radioimmunoconjugate to condition dogs for nonmyeloablative allogeneic marrow grafts

    Energy Technology Data Exchange (ETDEWEB)

    Sandmaier, B M.(Fred Hutchinson Cancer Research Center, Seattle, WA); Bethge, W A.(Fred Hutchinson Cancer Research Center, Seattle, WA); Wilbur, D. Scott (Washington, Univ Of); Hamlin, Donald K.(Washington, Univ Of); Santos, E B.(Fred Hutchinson Cancer Research Center, Seattle, WA); Brechbiel, M W.(National Cancer Institute, National Institutes of Health, Bethesda, MD); Fisher, Darrell R.(BATTELLE (PACIFIC NW LAB)); Storb, R. (Fred Hutchinson Cancer Research Center)

    2002-01-01

    To lower treatment-related mortality and toxicity of conventional marrow transplantation, a nonmyeloablative regimen using 200 cGy total-body irradiation (TBI) and mycophenolate mofetil (MMF) combined with cyclosporine (CSP) for postgrafting immunosuppression was developed. To circumvent possible toxic effects of external- beam gamma irradiation, strategies for targeted radiation therapy were investigated. We tested whether the short-lived (46 minutes) alpha-emitter Bi-213 conjugated to an anti-CD45 monoclonal antibody (mAb) could replace 200 cGy TBI and selectively target hematopoietic tissues in a canine model of nonmyeloablative DLA-identical marrow transplantation. Biodistribution studies using iodine 123-labeled anti-CD45 mAb showed uptake in blood, marrow, lymph nodes, spleen, and liver. In a dose-escalation study, 7 dogs treated with the Bi-213-anti-CD45 conjugate (Bi-213 dose, 0.1-5.9 mCi/kg[3.7-218 MBq/kg]) without marrow grafts had no toxic effects other than a mild, reversible suppression of blood counts. On the basis of these studies, 3 dogs were treated with 0.5 mg/kg Bi-213-labeled anti-CD45 mAb (Bi-213 doses, 3.6, 4.6, and 8.8 mCi/kg[133, 170, and 326 MBq/kg]) given in 6 injections 3 and 2 days before grafting of marrow from DLA-identical littermates. The dogs also received MMF (10 mg/kg subcutaneously twice daily the day of transplantation until day 27 afterward) and CSP (15 mg/kg orally twice daily the day before transplantation until 35 days afterward). Therapy was well tolerated except for transient elevations in levels of transaminases in 3 dogs, followed by, in one dog, ascites. All dogs achieved prompt engraftment and stable mixed hematopoietic chimerism, with donor contributions ranging from 30% to 70% after more than 27 weeks of follow-up. These results form the basis for additional studies in animals and the design of clinical trials using Bi-213 as a nonmyeloablative conditioning regimen with minimal toxicity.

  7. Methotrexate for the Treatment of Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Amr Nassar

    2014-01-01

    Full Text Available Glucocorticoids have been the primary treatment of graft-versus-host disease (GVHD over the past decade. Complete responses to steroid therapy are usually expected in almost one-third of aGVHD cases and partial response is anticipated in another one-third of patients. However, for those patients not responding to corticosteroid treatment, there is no standard second-line therapy for acute or chronic GVHD. Methotrexate (MTX for treatment of steroid refractory GVHD has been evaluated in a number of studies. Results from peer-reviewed original articles were identified and the pooled data analyzed. Despite several limitations in data collection and analysis, weekly administration of methotrexate at a median dose of 7.5 mg/m2 seems to be safe with minimal toxicities in the context of both aGVHD and cGVHD treatments. The observed overall response (OR in patients with aGVHD to MTX treatment in the published studies was 69.9%, with complete response (CR in 59.2% and PR in 10.6%. In cGVHD the OR was 77.6%, with CR reported in 49.6% and PR in 28% of patients. Predictors of better responses were lower grade GVHD, cutaneous involvement, and isolated organ involvement. MTX as a steroid sparing agent might reduce long-term complications and improve the quality of life of GVHD affected individuals.

  8. Post-Transplant Cyclophosphamide and Tacrolimus-Mycophenolate Mofetil Combination Prevents Graft-versus-Host Disease in Allogeneic Peripheral Blood Hematopoietic Cell Transplantation from HLA-Matched Donors.

    Science.gov (United States)

    Carnevale-Schianca, Fabrizio; Caravelli, Daniela; Gallo, Susanna; Coha, Valentina; D'Ambrosio, Lorenzo; Vassallo, Elena; Fizzotti, Marco; Nesi, Francesca; Gioeni, Luisa; Berger, Massimo; Polo, Alessandra; Gammaitoni, Loretta; Becco, Paolo; Giraudo, Lidia; Mangioni, Monica; Sangiolo, Dario; Grignani, Giovanni; Rota-Scalabrini, Delia; Sottile, Antonino; Fagioli, Franca; Aglietta, Massimo

    2017-03-01

    Allogeneic hematopoietic cell transplant (HCT) remains the only curative therapy for many hematologic malignancies but it is limited by high nonrelapse mortality (NRM), primarily from unpredictable control of graft-versus-host disease (GVHD). Recently, post-transplant cyclophosphamide demonstrated improved GVHD control in allogeneic bone marrow HCT. Here we explore cyclophosphamide in allogeneic peripheral blood stem cell transplantation (alloPBSCT). Patients with high-risk hematologic malignancies received alloPBSCT from HLA-matched unrelated/related donors. GVHD prophylaxis included combination post-HCT cyclophosphamide 50 mg/kg (days +3 and +4) and tacrolimus/mofetil mycophenolate (T/MMF) (day +5 forward). The primary objective was the cumulative incidence of acute and chronic GVHD. Between March 2011 and May 2015, 35 consecutive patients received the proposed regimen. MMF was stopped in all patients at day +28; the median discontinuation of tacrolimus was day +113. Acute and chronic GVHD cumulative incidences were 17% and 7%, respectively, with no grade IV GVHD events, only 2 patients requiring chronic GVHD immunosuppression control, and no deaths from GVHD. Two-year NRM, overall survival, event-free survival, and chronic GVHD event-free survival rates were 3%, 77%, 54%, and 49%, respectively. The graft-versus-tumor effect was maintained as 5 of 15 patients (33%) who received HCT with evidence of disease experienced further disease response. A post-transplant cyclophosphamide + T/MMF combination strategy effectively prevented acute and chronic GVHD after alloPBSCT from HLA-matched donors and achieved an unprecedented low NRM without losing efficacy in disease control or impaired development of the graft-versus-tumor effect. This trial is registered at clinicaltrials.gov as NCT02300571.

  9. Graft monocytic myeloid-derived suppressor cell content predicts the risk of acute graft-versus-host disease after allogeneic transplantation of granulocyte colony-stimulating factor-mobilized peripheral blood stem cells.

    Science.gov (United States)

    Vendramin, Antonio; Gimondi, Silvia; Bermema, Anisa; Longoni, Paolo; Rizzitano, Sara; Corradini, Paolo; Carniti, Cristiana

    2014-12-01

    Myeloid-derived suppressor cells (MDSCs) are powerful immunomodulatory cells that in mice play a role in infectious and inflammatory disorders, including acute graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. Their relevance in clinical acute GVHD is poorly known. We analyzed whether granulocyte colony-stimulating factor (G-CSF) administration, used to mobilize hematopoietic stem cells, affected the frequency of MDSCs in the peripheral blood stem cell grafts of 60 unrelated donors. In addition, we evaluated whether the MDSC content in the peripheral blood stem cell grafts affected the occurrence of acute GVHD in patients undergoing unrelated donor allogeneic stem cell transplantation. Systemic treatment with G-CSF induces an expansion of myeloid cells displaying the phenotype of monocytic MDSCs (Lin(low/neg)HLA-DR(-)CD11b(+)CD33(+)CD14(+)) with the ability to suppress alloreactive T cells in vitro, therefore meeting the definition of MDSCs. Monocytic MDSC dose was the only graft parameter to predict acute GVHD. The cumulative incidence of acute GVHD at 180 days after transplantation for recipients receiving monocytic MDSC doses below and above the median was 63% and 22%, respectively (P = .02). The number of monocytic MDSCs infused did not impact the relapse rate or the transplant-related mortality rate (P > .05). Although further prospective studies involving larger sample size are needed to validate the exact monocytic MDSC graft dose that protects from acute GVHD, our results strongly suggest the modulation of G-CSF might be used to affect monocytic MDSCs graft cell doses for prevention of acute GVHD.

  10. Effect and mechanism of acute graft versus host disease on early diffuse murine lung injury following allogeneic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    To explore the effect and pathogenssis of acute graft-versus-host disease (aGVHD) on early diffuse lung injury in allogeneic hematopoietic stem cell transplantation (allo-HSCT), we established an aGVHD model of C57BL/6→BALB/c mice. Chest computed tomography (CT) scans, histopathology and the levels of cytokines including tumor necrosis factor α (TNFα) and Interferon (IFNγ) in lungs were dynamically detected in recipient mice after transplantation. The incidence of aGVHD was respectively 0%, 0% and 100% in simple irradiation group (A), syngeneic transplant group(B) and allogeneic transplant group (C). Chest CT scans of recipient mice were normal in 3 groups on days +3 and +7 after transplantation. CT showed that two of ten mice had bilateral lung diffuse infiltrate on day +12 (on the brink of death) in group A and 6 of 10 mice had bilateral lung diffuse infiltrate on day +14 (3 d after aGVHD occurring) in group C, and were normal on days +12 and +14 in group B after transplantation. Histopathology of lungs in the 3 groups was similar, consisting of minor interstitial pneumonitis on day +3. Group A showed edema, hyperplasia of epithelial cells and widened alveolar interval on day +7, and epithelial cell necrosis, lymphocyte infiltration, hemorrhage, protein leakage, and local consolidation on day +12. The histopathology of group B showed slight edema of epithelial cells on +7 day, which were slighter than that on day +3, and virtually normal on day +14. The histopathology in group C was characterized by the significant expansion and congestion of capillaries, and lymphocyte infiltration on day +7, the acute pneumonitis was present involving tissue edema, lymphocyte and macrophage infiltration, protein leakage and perivascular inflammation on day +14. In group A, the levels of TNFα were lower on day +7 than on day +3. In group B, the levels of TNFα attained a peak on day +3, which decreased on days +7 and +14. In group C, the levels of TNFα were highest on day

  11. Correlation of lung abnormalities on high-resolution CT with clinical graft-versus-host disease after allogeneic versus autologous bone marrow transplantation in children

    Energy Technology Data Exchange (ETDEWEB)

    Merlini, Laura; Borzani, Irene Maria Olivia; Anooshiravani, Mehrak; Hanquinet, Sylviane [University of Geneva Children' s Hospital, Paediatric Radiology Unit, Geneva (Switzerland); Rochat, Isabelle [University of Geneva Children' s Hospital, Paediatric Pneumology Unit, Geneva (Switzerland); Ozsahin, Ayse Hulya [University of Geneva Children' s Hospital, Paediatric Oncology Unit, Geneva (Switzerland)

    2008-11-15

    Late-onset noninfectious pulmonary complications (LONIPCs) are life-threatening complications of bone marrow transplantation (BMT). Several pathological patterns are described in the literature with different prognoses, and with different relationships to graft-versus-host disease (GVHD). The role of high-resolution CT (HRCT) is not yet well established. To illustrate different patterns of LONIPCs on HRCT in allogeneic versus autologous BMT in order to investigate the correlation with chronic GVHD (cGVHD). A total of 67 HRCT scans were performed in 24 patients with noninfectious pulmonary disease at least 3 months after BMT (16 allogeneic, 8 autologous). Abnormality patterns and extension on HRCT images were correlated with the clinical outcome and with the severity of cGVHD. Of 24 patients, 9 showed LONIPCs (1 autologous, 8 allogeneic). There was a significant association between abnormalities on HRCT and severe cGVHD (P = 0.038), with no specific pattern. Prognosis seemed to be related to the severity of cGVHD and not to the extent of abnormalities on HRCT. The significant association between abnormalities on HRCT and severe GVHD suggests that LONIPCs can be a pulmonary manifestation of the disease. HRCT is a useful tool when combined with clinical data. (orig.)

  12. The Activating NKG2C Receptor Is Significantly Reduced in NK Cells after Allogeneic Stem Cell Transplantation in Patients with Severe Graft-versus-Host Disease

    Directory of Open Access Journals (Sweden)

    Lambros Kordelas

    2016-10-01

    Full Text Available Natural killer (NK cells play a central role in the innate immune system. In allogeneic stem cell transplantation (alloSCT, alloreactive NK cells derived by the graft are discussed to mediate the elimination of leukemic cells and dendritic cells in the patient and thereby to reduce the risk for leukemic relapses and graft-versus-host reactions. The alloreactivity of NK cells is determined by various receptors including the activating CD94/NKG2C and the inhibitory CD94/NKG2A receptors, which both recognize the non-classical human leukocyte antigen E (HLA-E. Here we analyze the contribution of these receptors to NK cell alloreactivity in 26 patients over the course of the first year after alloSCT due to acute myeloid leukemia, myelodysplastic syndrome and T cell Non-Hodgkin-Lymphoma. Our results show that NK cells expressing the activating CD94/NKG2C receptor are significantly reduced in patients after alloSCT with severe acute and chronic graft-versus-host disease (GvHD. Moreover, the ratio of CD94/NKG2C to CD94/NKG2A was reduced in patients with severe acute and chronic GvHD after receiving an HLA-mismatched graft. Collectively, these results provide evidence for the first time that CD94/NKG2C is involved in GvHD prevention.

  13. All-trans retinoid acid promotes allogeneic corneal graft survival in mice by regulating Treg-Th17 balance in the presence of TGF-β.

    Science.gov (United States)

    Wang, Xin; Wang, Wentao; Xu, Jianjiang; Wu, Suqian; Le, Qihua

    2015-03-19

    All-trans retinoid acid (ATRA) has been proven to skew Regulatory T cell-T helper 17 cell (Treg-Th17) balance toward Treg in vitro, favoring graft acceptance. However, its in vivo effect after solid organ transplantation is under investigation. BALB/c mice were given orthotopic corneal grafts from C57BL/6 donors, and recipient mice were administered with ATRA, TGF-β, and the combination of both agents for 8 weeks after surgery. We found that a mixed treatment of ATRA and TGF-β significantly promoted graft survival. Moreover, with the presence of TGF-β, ATRA upregulated CD4(+)CD25(+)Foxp3(+)Treg cells and suppressed Th17 cells in the blood, spleen and draining lymph nodes of recipient mice, as well as enhanced the Foxp3 expression and inhibited the RORγt expression in grafts and peripheral blood mononuclear cells (PBMCs). Simultaneously, increased number of Foxp3+ cells and decreased number of IL-17+ cells in conjunctiva were found in recipients with mixed treatment, along with reduced IL-17 level in serum and aqueous humor and increased IL-10 level in aqueous humor. Tregs isolated from recipient mice treated with ATRA + TGF-β presented the strongest suppressive activity in vitro. Combined application of ATRA and TGF-β may shift the Th17-Treg balance toward Tregs, hence facilitating the induction of immunological tolerance after allogenic corneal transplantation and representing a potential therapeutic approach in the treatment of posttransplant rejection.

  14. The Activating NKG2C Receptor Is Significantly Reduced in NK Cells after Allogeneic Stem Cell Transplantation in Patients with Severe Graft-versus-Host Disease

    Science.gov (United States)

    Kordelas, Lambros; Steckel, Nina-Kristin; Horn, Peter A.; Beelen, Dietrich W.; Rebmann, Vera

    2016-01-01

    Natural killer (NK) cells play a central role in the innate immune system. In allogeneic stem cell transplantation (alloSCT), alloreactive NK cells derived by the graft are discussed to mediate the elimination of leukemic cells and dendritic cells in the patient and thereby to reduce the risk for leukemic relapses and graft-versus-host reactions. The alloreactivity of NK cells is determined by various receptors including the activating CD94/NKG2C and the inhibitory CD94/NKG2A receptors, which both recognize the non-classical human leukocyte antigen E (HLA-E). Here we analyze the contribution of these receptors to NK cell alloreactivity in 26 patients over the course of the first year after alloSCT due to acute myeloid leukemia, myelodysplastic syndrome and T cell Non-Hodgkin-Lymphoma. Our results show that NK cells expressing the activating CD94/NKG2C receptor are significantly reduced in patients after alloSCT with severe acute and chronic graft-versus-host disease (GvHD). Moreover, the ratio of CD94/NKG2C to CD94/NKG2A was reduced in patients with severe acute and chronic GvHD after receiving an HLA-mismatched graft. Collectively, these results provide evidence for the first time that CD94/NKG2C is involved in GvHD prevention. PMID:27801784

  15. NCI first International Workshop on the biology, prevention, and treatment of relapse after allogeneic hematopoietic stem cell transplantation: report from the committee on the biological considerations of hematological relapse following allogeneic stem cell transplantation unrelated to graft-versus-tumor effects: state of the science.

    Science.gov (United States)

    Cairo, Mitchell S; Jordan, Craig T; Maley, Carlo C; Chao, Clifford; Melnick, Ari; Armstrong, Scott A; Shlomchik, Warren; Molldrem, Jeff; Ferrone, Soldano; Mackall, Crystal; Zitvogel, Laurence; Bishop, Michael R; Giralt, Sergio A; June, Carl H

    2010-06-01

    Hematopoietic malignant relapse still remains the major cause of death following allogeneic hematopoietic stem cell transplantation (HSCT). Although there has been a large focus on the immunologic mechanisms responsible for the graft-versus-tumor (GVT) effect or lack thereof, there has been little attention paid to investigating the biologic basis of hematologic malignant disease relapse following allogeneic HSCT. There are a large number of factors that are responsible for the biologic resistance of hematopoietic tumors following allogeneic HSCT. We have focused on 5 major areas including clonal evolution of cancer drug resistance, cancer radiation resistance, genomic basis of leukemia resistance, cancer epigenetics, and resistant leukemia stem cells. We recommend increased funding to pursue 3 broad areas that will significantly enhance our understanding of the biologic basis of malignant relapse after allogeneic HSCT, including: (1) genomic and epigenetic alterations, (2) cancer stem cell biology, and (3) clonal cancer drug and radiation resistance.

  16. Vorinostat plus tacrolimus and mycophenolate to prevent graft-versus-host disease after related-donor reduced-intensity conditioning allogeneic haemopoietic stem-cell transplantation: a phase 1/2 trial

    NARCIS (Netherlands)

    Choi, S.W.; Braun, T.; Chang, L.; Ferrara, J.L.; Pawarode, A.; Magenau, J.M.; Hou, G.; Beumer, J.H.; Levine, J.E.; Goldstein, S.; Couriel, D.R.; Stockerl-Goldstein, K.; Krijanovski, O.I.; Kitko, C.; Yanik, G.A.; Lehmann, M.H.; Tawara, I.; Sun, Y; Paczesny, S.; Mapara, M.Y.; Dinarello, C.A.; Dipersio, J.F.; Reddy, P.

    2014-01-01

    BACKGROUND: Acute graft-versus-host disease (GVHD) remains a barrier to more widespread application of allogeneic haemopoietic stem-cell transplantation. Vorinostat is an inhibitor of histone deacetylases and was shown to attenuate GVHD in preclinical models. We aimed to study the safety and activit

  17. Influence of chronic L-DOPA treatment on immune response following allogeneic and xenogeneic graft in a rat model of Parkinson's disease.

    Science.gov (United States)

    Breger, Ludivine S; Kienle, Korbinian; Smith, Gaynor A; Dunnett, Stephen B; Lane, Emma L

    2017-03-01

    Although intrastriatal transplantation of fetal cells for the treatment of Parkinson's disease had shown encouraging results in initial open-label clinical trials, subsequent double-blind studies reported more debatable outcomes. These studies highlighted the need for greater preclinical analysis of the parameters that may influence the success of cell therapy. While much of this has focused on the cells and location of the transplants, few have attempted to replicate potentially critical patient centered factors. Of particular relevance is that patients will be under continued L-DOPA treatment prior to and following transplantation, and that typically the grafts will not be immunologically compatible with the host. The aim of this study was therefore to determine the effect of chronic L-DOPA administered during different phases of the transplantation process on the survival and function of grafts with differing degrees of immunological compatibility. To that end, unilaterally 6-OHDA lesioned rats received sham surgery, allogeneic or xenogeneic transplants, while being treated with L-DOPA before and/or after transplantation. Irrespective of the L-DOPA treatment, dopaminergic grafts improved function and reduced the onset of L-DOPA induced dyskinesia. Importantly, although L-DOPA administered post transplantation was found to have no detrimental effect on graft survival, it did significantly promote the immune response around xenogeneic transplants, despite the administration of immunosuppressive treatment (cyclosporine). This study is the first to systematically examine the effect of L-DOPA on graft tolerance, which is dependent on the donor-host compatibility. These findings emphasize the importance of using animal models that adequately represent the patient paradigm.

  18. Application of MultiStem(®) Allogeneic Cells for Immunomodulatory Therapy: Clinical Progress and Pre-Clinical Challenges in Prophylaxis for Graft Versus Host Disease.

    Science.gov (United States)

    Vaes, Bart; Van't Hof, Wouter; Deans, Robert; Pinxteren, Jef

    2012-01-01

    The last decade has seen much progress in adjunctive cell therapy for immune disorders. Both corporate and institutional Phase III studies have been run using mesenchymal stromal cells (MSC) for treatment of Graft versus Host Disease (GvHD), and product approval has been achieved for treatment of pediatric GvHD in Canada and New Zealand (Prochymal(®); Osiris Therapeutics). This effectiveness has prompted the prophylactic use of adherent stem cells at the time of allogeneic hematopoietic stem cell transplantation (HSCT) to prevent occurrence of GvHD and possibly provide stromal support for hematopoietic recovery. The MultiStem(®) product is an adult adherent stem cell product derived from bone marrow which has significant clinical exposure. MultiStem cells are currently in phase II clinical studies for treatment of ischemic stroke and ulcerative colitis, with Phase I studies completed in acute myocardial infarction and for GvHD prophylaxis in allogeneic HSCT, demonstrating that MultiStem administration was well tolerated while the incidence and severity of GvHD was reduced. In advancing this clinical approach, it is important to recognize that alternate models exist based on clinical manufacturing strategies. Corporate sponsors exploit the universal donor properties of adherent stem cells and manufacture at large scale, with many products obtained from one or limited donors and used across many patients. In Europe, institutional sponsors often produce allogeneic product in a patient designated context. For this approach, disposable bioreactors producing <10 products/donor in a closed system manner are very well suited. In this review, the use of adherent stem cells for GvHD prophylaxis is summarized and the suitability of disposable bioreactors for MultiStem production is presented, with an emphasis on quality control parameters, which are critical with a multiple donor approach for manufacturing.

  19. Application of MultiStem® allogeneic cells for immunomodulatory therapy: clinical progress and pre-clinical challenges in prophylaxis for graft vs host disease

    Directory of Open Access Journals (Sweden)

    Bart eVaes

    2012-11-01

    Full Text Available The last decade has seen much progress in adjunctive cell therapy for immune disorders. Both corporate and institutional Phase III studies have been run using mesenchymal stromal cells (MSC for treatment of Graft vs Host Disease (GvHD, and product approval has been achieved for treatment of pediatric GvHD in Canada and New Zealand (Prochymal®; Osiris Therapeutics. This effectiveness has prompted the prophylactic use of adherent stem cells at the time of allogeneic hematopoietic stem cell transplantation (HSCT to prevent occurrence of GvHD and possibly provide stromal support for hematopoietic recovery. The MultiStem® product is an adult adherent stem cell product derived from bone marrow which has significant clinical exposure. MultiStem cells are currently in phase II clinical studies for treatment of ischemic stroke and ulcerative colitis, with Phase I studies completed in acute myocardial infarction and for GvHD prophylaxis in allogeneic HSCT, demonstrating that MultiStem administration was well tolerated while the incidence and severity of GvHD was reduced. In advancing this clinical approach, it is important to recognize that alternate models exist based on clinical manufacturing strategies. Corporate sponsors exploit the universal donor properties of adherent stem cells and manufacture at large scale, with many products obtained from one or limited donors and used across many patients. In Europe, institutional sponsors often produce allogeneic product in a patient designated context. For this approach, disposable bioreactors producing <10 products per donor in a closed system manner are very well suited. In this review, the use of adherent stem cells for GvHD prophylaxis is summarized and the suitability of disposable bioreactors for MultiStem production is presented, with an emphasis on quality control parameters, which are critical with a multiple donor approach for manufacturing.

  20. [Management of graft failure and erythroblastopenia in patients undergoing allogeneic hematopoietic stem cell transplantation: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)].

    Science.gov (United States)

    Cornillon, Jérôme; Sicre de Fontbrune, Flore; Chantepie, Sylvain; Coiteux, Valérie; Gauthier, Jordan; Masouridi-Levrat, Stavroula; Pochon, Cécile; Terriou, Louis; Yakoub-Agha, Ibrahim; Dalle, Jean-Hugues

    2016-11-01

    Success of allogeneic hematopoietic stem cells transplantation requires both the underlying disease eradication and satisfying reconstitution of hematopoiesis from donor cells. However, reconstitution delays, secondary development or persistence of cytopenia are regularly observed and are potential causes of failure after allogeneic transplantation. These graft dysfunctions should be distinguished from non-engraftment/engraftment failure. Although these situations are relatively common, there is no consensus in the literature for their management. During the workshop of the SFGM-TC, the working group proposed recommendations from an analysis of the literature. Copyright © 2016. Published by Elsevier Masson SAS.

  1. Variables Affecting Fusion Rates in the Rat Posterolateral Spinal Fusion Model with Autogenic/Allogenic Bone Grafts: A Meta-analysis.

    Science.gov (United States)

    Ishida, Wataru; Elder, Benjamin D; Holmes, Christina; Lo, Sheng-Fu L; Witham, Timothy F

    2016-11-01

    The rat posterolateral spinal fusion model with autogenic/allogenic bone graft (rat PFABG) has been increasingly utilized as an experimental model to assess the efficacy of novel fusion treatments. The objective of this study was to investigate the reliability of the rat PFABG model and examine the effects of different variables on spinal fusion. A web-based literature search from January, 1970 to September, 2015, yielded 26 studies, which included 40 rat PFABG control groups and 449 rats. Data regarding age, weight, sex, and strain of rats, graft volume, graft type, decorticated levels, surgical approach, institution, the number of control rats, fusion rate, methods of fusion assessment, and timing of fusion assessment were collected and analyzed. The primary outcome variable of interest was fusion rate, as evaluated by manual palpation. Fusion rates varied widely, from 0 to 96%. The calculated overall fusion rate was 46.1% with an I (2) value of 62.4, which indicated moderate heterogeneity. Weight >300 g, age >14 weeks, male rat, Sprague-Dawley strain, and autogenic coccyx grafts increased fusion rates with statistical significance. Additionally, an assessment time-point ≥8 weeks had a trend towards statistical significance (p = 0.070). Multi-regression analysis demonstrated that timing of assessment and age as continuous variables, as well as sex as a categorical variable, can predict the fusion rate with R (2) = 0.82. In an inter-institution reliability analysis, the pooled overall fusion rate was 50.0% [44.8, 55.3%], with statistically significant differences among fusion outcomes at different institutions (p fusion outcomes, the reliability of the rat PFABG model was relatively limited. However, selection of adequate variables can optimize its use as a control group in studies evaluating the efficacy of novel fusion therapies.

  2. The addition of sirolimus to the graft-versus-host disease prophylaxis regimen in reduced intensity allogeneic stem cell transplantation for lymphoma: a multicentre randomized trial.

    Science.gov (United States)

    Armand, Philippe; Kim, Haesook T; Sainvil, Marie-Michele; Lange, Paulina B; Giardino, Angela A; Bachanova, Veronika; Devine, Steven M; Waller, Edmund K; Jagirdar, Neera; Herrera, Alex F; Cutler, Corey; Ho, Vincent T; Koreth, John; Alyea, Edwin P; McAfee, Steven L; Soiffer, Robert J; Chen, Yi-Bin; Antin, Joseph H

    2016-04-01

    Inhibition of the mechanistic target of rapamycin (mTOR) pathway has clinical activity in lymphoma. The mTOR inhibitor sirolimus has been used in the prevention and treatment of graft-versus-host disease (GVHD) after allogeneic haematopoietic stem cell transplantation (HSCT). A retrospective study suggested that patients with lymphoma undergoing reduced intensity conditioning (RIC) HSCT who received sirolimus as part of their GVHD prophylaxis regimen had a lower rate of relapse. We therefore performed a multicentre randomized trial comparing tacrolimus, sirolimus and methotrexate to standard regimens in adult patients undergoing RIC HSCT for lymphoma in order to assess the possible benefit of sirolimus on HSCT outcome. 139 patients were randomized. There was no difference overall in 2-year overall survival, progression-free survival, relapse, non-relapse mortality or chronic GVHD. However, the sirolimus-containing arm had a significantly lower incidence of grade II-IV acute GVHD (9% vs. 25%, P = 0·015), which was more marked for unrelated donor grafts. In conclusion, the addition of sirolimus for GVHD prophylaxis in RIC HSCT is associated with no increased overall toxicity and a lower risk of acute GVHD, although it does not improve survival; this regimen is an acceptable option for GVHD prevention in RIC HSCT. This trial is registered at clinicaltrials.gov (NCT00928018).

  3. Increase of bone marrow macrophages and CD8(+) T lymphocytes predict graft failure after allogeneic bone marrow or cord blood transplantation.

    Science.gov (United States)

    Kawashima, N; Terakura, S; Nishiwaki, S; Koyama, D; Ozawa, Y; Ito, M; Miyamura, K

    2017-08-01

    Graft failure (GF) remains an obstacle to survival after allogeneic hematopoietic stem cell transplantation. However, differentiating GF from delayed engraftment (DE) can be difficult. Host CD8(+) lymphocytes have been reported to mediate graft rejection, but the impact of macrophages on DE or GF is yet to be clarified. Peri-engraftment bone marrow (BM) specimens of 32 adult patients with normal engraftment, DE or GF were retrospectively evaluated to identify the potential associations of CD163(+) macrophage and CD8(+) lymphocyte infiltration into BM. The macrophage or CD8(+) lymphocyte number/total nucleated cell number was defined as the Mac ratio and CD8 ratio, respectively. Both DE and GF groups had significantly higher Mac ratios at day 14 than the normal group (PGF groups (P=1.000). The CD8 ratio at day 14 was significantly higher in the GF than in the normal group (P=0.005), whereas the CD8 ratios of the DE and normal groups were similar (P=0.07). A high Mac ratio at day 14 was associated with a risk of DE or subsequent GF. Patients with increased CD8 ratio at day 14 had a further risk of GF. The Mac ratio and the CD8 ratio appear to be well suited for predicting engraftment status.

  4. B-Cell-Based and Soluble Biomarkers in Body Liquids for Predicting Acute/Chronic Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

    Science.gov (United States)

    Juric, Mateja Kralj; Shevtsov, Maxim; Mozes, Petra; Ogonek, Justyna; Crossland, Rachel E.; Dickinson, Anne M.; Greinix, Hildegard T.; Holler, Ernst; Weissinger, Eva M.; Multhoff, Gabriele

    2017-01-01

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the main curative therapy for hematological malignancy such as leukemias, lymphomas, or multiple myelomas and some other hematological disorders. In this therapy, cure of hematological diseases relies on graft-versus-malignancy effects by allogenic immune cells. However, severe posttransplant treatment-associated complications such as acute graft-versus-host disease (aGvHD) and chronic graft-versus-host disease (cGvHD) limit this approach. Most research into GvHD has concentrated on the aGvHD, while the more complex and multifaceted chronic form has been largely poorly investigated. cGvHD is a multi-organ autoimmune disorder and is the major cause of non-relapse morbidity and mortality following allo-HSCT, occurring in about 50% of patients, or 13,000–15,000 patients per year worldwide. Therefore, there is a high medical need for an early prediction of these therapy-associated toxicities. Biomarkers have gained importance over the last decade in diagnosis, in prognosis, and in prediction of pending diseases or side effects. Biomarkers can be cells, factors isolated from target tissues, or soluble factors that can be detected in body fluids. In this review, we aim to summarize some of the recent developments of biomarkers in the field of allo-HSCT. We will focus on cell-based biomarkers (B-cell subsets) for cGvHD and soluble factors including microRNA (miRNA), which are excreted into serum/plasma and urine. We also discuss the potential role of cytosolic and extracellular 70 kDa heat shock proteins (HSP70) as potential biomarkers for aGvHD and their role in preclinical models. Proteomic biomarkers in the blood have been used as predictors of treatment responses in patients with aGvHD for many years. More recently, miRNAs have been found to serve as a biomarker to diagnose aGvHD in the plasma. Another development relates to urine-based biomarkers that are usually detected by capillary

  5. OMISSION OF DAY +11 METHOTREXATE DOES NOT APPEAR TO INFLUENCE INCIDENCE AND SEVERITY OF GRAFT-VERSUS-HOST DISEASE AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION

    Institute of Scientific and Technical Information of China (English)

    朱康儿; 张涛; 陈盛亭; 钟隽; 曾慧兰

    2004-01-01

    Objective: To explore the influence of omission of the day +11 dose of methotrexate (MIX) on the incidence and severity of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: From April 1997 to October 2002, 80 leukemia patients (46 men and 34 women aged from 12 to 56 years with a median age of 35) underwent allo-HSCT at our BMT unit. Among them, 58 patients received grafts from HLA-identical siblings, 8 from HLA one major antigen mismatched siblings and 14 from HLA-matched unrelated donors. All patients received a modified cyclosporine and short-course MTX regimen for GVHD prophylaxis, which included MTX 15 mg on day +1, and 10 mg on days +3 and +6 (MTX day +11 dose omitted) and cyclosporine given daily. Results: The overall incidence of grade I~IV acute GVHD was 57.5% (46/80 patients), with grade II~IV acute GVHD in 28 patients (35%) and grade III~IV acute GVHD in 7 patients (8.8%). Among 58 patients receiving grafts from HLA-identical siblings, 24 patients developed grade I~IV acute GVHD (41.4%), with grade II~IV acute GVHD in 13 patients (22.4%) and grade III~IV acute GVHD in 4 patients (6.9%). 2l out of 22 patients receiving grafts from HLA one major antigen mismatched siblings and HLA-matched unrelated donors developed grade I~IV acute GVHD (95.5%), with grade II~IV acute GVHD in 14 patients (63.6%) and grade III~IV acute GVHD in 3 patients (13.6%). Chronic GVHD occurred in 38 out of 56 evaluable patients (67.9%), with extensive form in 15 patients (26.8%) and limited form in 23 patients (41.1%). With a median follow-up of 960 days (range 180~1980 days), the probability of leukemia-free survival at 3 years was 61.3% for all patients. Conclusion: Our results suggest that the day +11 MTX can be omitted without a major deleterious effect on the incidence and severity of graft-versus-host disease after HLA-identical sibling transplantation as well as HLA one major antigen mismatched sibling and HLA

  6. ECZEMATOID GRAFT VERSUS HOST DISEASE IN A SEX MISMATCHED ALLOGENEIC STEM CELL TRANSPLANT REFRACTORY TO TREATMENT: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Abhilasha

    2014-03-01

    Full Text Available A 25 years old gentleman presented with bleeding gums, purpura and fever for 2 months and severe anemia requiring 10 blood transfusions. Baseline hematological investigations and bone marrow examination confirmed aplastic anemia. He underwent allogeneic stem cell transplant as a curative option with HLA identical sister as the donor. Neutrophils engrafted on day +16. On day +115 he showed signs of dyshydrotic eczema and was initiated on local and systemic steroids and topical tacrolimus. As there were features of Cyclosporin induced MAHA, the same was stopped and oral Mycophenolate was initiated on day +129. On day +170 he presented with extensive progression of cutaneous and hepatic GVHD. Subsequent treatment with Cyclophosphamide, Sirolimus and Daclizumab did not show significant response. On day +195, he succumbed to sepsis with multiorgan failure. The diagnosis of ezcematoid GVHD was confirmed by cutaneous manifestations, biopsy, the clinical course and the presence of GVHD in other organs.

  7. Role of Intrinsic (Graft) Versus Extrinsic (Host) Factors in the Growth of Transplanted Organs Following Allogeneic and Xenogeneic Transplantation.

    Science.gov (United States)

    Tanabe, T; Watanabe, H; Shah, J A; Sahara, H; Shimizu, A; Nomura, S; Asfour, A; Danton, M; Boyd, L; Dardenne Meyers, A; Ekanayake-Alper, D K; Sachs, D H; Yamada, K

    2017-01-24

    In our studies of life-supporting α-1,3-galactocyltransferase knockout (GalT-KO) pig-to-baboon kidneys, we found that some recipients developed increased serum creatinine with growth of the grafts, without histological or immunological evidence of rejection. We hypothesized that the rapid growth of orthotopic pig grafts in smaller baboon recipients may have led to deterioration of organ function. To test this hypothesis for both kidneys and lungs, we assessed whether the growth of outbred (Yorkshire) organ transplants in miniature swine was regulated by intrinsic (graft) or extrinsic (host environment) factors. Yorkshire kidneys exhibited persistent growth in miniature swine, reaching 3.7 times their initial volume over 3 mo versus 1.2 times for miniature swine kidneys over the same time period. Similar rapid early growth of lung allografts was observed and, in this case, led to organ dysfunction. For xenograft kidneys, a review of our results suggests that there is a threshold for kidney graft volume of 25 cm(3) /kg of recipient body weight at which cortical ischemia is induced in transplanted GalT-KO kidneys in baboons. These results suggest that intrinsic factors are responsible, at least in part, for growth of donor organs and that this property should be taken into consideration for growth-curve-mismatched transplants, especially for life-supporting organs transplanted into a limited recipient space.

  8. Effects of xenogeneic, allogeneic and isogeneic thymus grafts on lymphocyte populations in peripheral lymphoid organs of the nude rat

    DEFF Research Database (Denmark)

    Hougen, H P; Klausen, B; Stenvang, J P

    1987-01-01

    In order to gain information about the effect of xenografted, allografted and isografted thymic tissue on peripheral lymphoid organs of immune-deficient rats, athymic nude LEW rats of ninth backcross-intercross were grafted with fetal calf and neonatal BDIX and LEW thymus. Adrenalectomy was also...

  9. Association of disparities in known minor histocompatibility antigens with relapse-free survival and graft-versus-host-disease after allogeneic stem cell transplantation

    Science.gov (United States)

    Hobo, Willemijn; Broen, Kelly; van der Velden, Walter J.F.M.; Greupink-Draaisma, Annelies; Adisty, Niken; Wouters, Yannick; Kester, Michel; Fredrix, Hanny; Jansen, Joop H.; van der Reijden, Bert; Falkenburg, J.H. Frederik; de Witte, Theo; Preijers, Frank; Schattenberg, Ton; Feuth, Ton; Blijlevens, Nicole M.; Schaap, Nicolaas; Dolstra, Harry

    2012-01-01

    Allogeneic stem cell transplantation (allo-SCT) can induce remission in patients with hematological malignancies due to graft-versus-tumor (GVT) responses. This immune-mediated anti-tumor effect, however, is often accompanied by detrimental graft-versus-host disease (GVHD). Both GVT and GVHD are mediated by minor histocompatibility antigen (MiHA)-specific T cells recognizing peptide products from polymorphic genes that differ between recipient and donor. In this study, we evaluated whether mismatches in a panel of seventeen MiHA are associated with clinical outcome after partial T cell-depleted allo-SCT. Comprehensive statistical analysis revealed that DNA mismatches for one or more autosomal-encoded MiHA was associated with increased relapse-free survival in sibling transplants, (P =0.04), particularly in patients suffering from multiple myeloma (P =0.02). Moreover, mismatches for the ubiquitous Y chromosome-derived MiHA resulted in a higher incidence of acute GVHD (grade 3–4; P =0.004), while autosomal MiHA mismatches, ubiquitous or restricted to hematopoietic cells, were not associated with severe GVHD. Finally, we demonstrated considerable differences between MiHA in their capability to induce in vivo T cell responses using dual-color tetramer analysis of peripheral blood samples collected post-SCT. Importantly, detection of MiHA-specific T cell responses was associated with improved relapse-free survival in sibling transplants (P =0.01). Our findings provide a rationale to further boost GVT immunity towards autosomal MiHA with a hematopoietic restriction to improve outcome after HLA-matched allo-SCT. PMID:23022467

  10. Graft-versus-host disease following allogeneic transplantation from HLA-identical sibling with antithymocyte globulin-based reduced-intensity preparative regimen.

    Science.gov (United States)

    Mohty, Mohamad; Bay, Jacques-Olivier; Faucher, Catherine; Choufi, Bachra; Bilger, Karin; Tournilhac, Olivier; Vey, Norbert; Stoppa, Anne-Marie; Coso, Diane; Chabannon, Christian; Viens, Patrice; Maraninchi, Dominique; Blaise, Didier

    2003-07-15

    Reduced-intensity conditioning (RIC) regimens are increasingly used for allogeneic stem cell transplantation (allo-SCT). RIC has been shown to allow engraftment with minimal early transplantation-related mortality (TRM). However, in the context of RIC, predictive factors for acute and chronic graft-versus-host disease (aGVHD and cGVHD, respectively) and their effect on outcome remain unknown. In this report, we analyzed the outcome of 101 high-risk patients (70 hematologic and 31 nonhematologic malignancies) who received an HLA-identical sibling allo-SCT after RIC, including fludarabine, busulfan, and antithymocyte globulin (ATG). The cumulative incidence of grade II-IV aGVHD was 36% (95% confidence interval [CI], 27%-45%), whereas the cumulative incidence of cGVHD at 2 years was 43% (95% CI, 33%-53%). In multivariate analysis, the incidence of aGVHD was significantly associated with the ATG dose infused during conditioning (P =.0005), whereas peripheral blood as stem cell source was the only predictive factor for the development of cGVHD (P =.0007). The 1-year cumulative incidences of disease progression or relapse in patients with (n = 69) and without (n = 31) GVHD (whatever its form or grade) were 30% (95% CI, 19%-41%) and 55% (95% CI, 37%-72%), respectively (P =.02), suggesting that a potent graft-versus-tumor (GVT) effect can be achieved in high-risk patients following RIC. Moreover, the GVT effect was closely associated with GVHD without an increased risk of TRM (cumulative incidence of TRM, 18% [95% CI, 10%-25%]). Collectively, these results provide a framework for the refinement of RIC approaches designed to enhance the GVT effect with an acceptable risk of GVHD.

  11. Mesenchymal stem cells provide prophylaxis against acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation: A meta-analysis of animal models.

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    Wang, Li; Zhang, Haiyan; Guan, Lixun; Zhao, Shasha; Gu, Zhenyang; Wei, Huaping; Gao, Zhe; Wang, Feiyan; Yang, Nan; Luo, Lan; Li, Yonghui; Wang, Lili; Liu, Daihong; Gao, Chunji

    2016-09-20

    A meta-analysis of animal models was conducted to evaluate the prophylactic effects of mesenchymal stem cells (MSCs) on acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation. A total of 50 studies involving 1848 animals were included. The pooled results showed that MSCs significantly reduced aGVHD-associated mortality (risk ratio = 0.70, 95% confidence interval 0.62 to 0.79, P = 2.73×10-9) and clinical scores (standardized mean difference = -3.60, 95% confidence interval -4.43 to -2.76, P = 3.61×10-17). In addition, MSCs conferred robust favorable prophylactic effects on aGVHD across recipient species, MSC doses, and administration times, but not MSC sources. Our meta-analysis showed that MSCs significantly prevented mortality and alleviated the clinical manifestations of aGVHD in animal models. These data support further clinical trials aimed at evaluating the efficacy of using MSCs to prevent aGVHD.

  12. Reduced IL-35 levels are associated with increased platelet aggregation and activation in patients with acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

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    Zhang, Xiaohui; Zhou, Yi; Xu, Lanping; Han, Wei; Chen, Huan; Chen, Yuhong; Fu, Haixia; Zhou, Shiyuan; Zhao, Jingzhong; Wang, Qianming; Feng, Feier; Zhu, Xiaolu; Liu, Kaiyan; Huang, Xiaojun

    2015-05-01

    Acute graft-versus-host disease (aGVHD) is a major complication associated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Interleukin (IL)-35 is a novel anti-inflammatory cytokine that suppresses the immune response. This prospective study explored IL-35 plasma levels in 65 patients after HSCT. The results revealed that the peripheral blood of patients with grades III-IV aGVHD (23.46 ng/ml) had reduced IL-35 compared to transplanted patients with grades I-II aGVHD (40.26 ng/ml, p IL-35 levels with respect to aGVHD. The patients who received lower levels of IL-35 cells in the GBM (28.0 ng/ml, p = 0.551) or lower levels of IL-35 in PBPC (53.46 ng/ml, p = 0.03) exhibited a higher incidence of aGVHD. Patients with aGVHD have increased platelet aggregation. IL-35 was added to patient blood in vitro, and platelet aggregation was inhibited by IL-35 in a dose-dependent manner. The markers of platelet activation (CD62P/PAC-1) can also be inhibited by IL-35. The results indicate that IL-35 may affect the development of aGVHD by inhibiting platelet activation and aggregation. Our data suggests that IL-35 represents a potentially effective therapeutic agent against aGVHD after allo-HSCT.

  13. Inhibition of nuclear factor-κB activation in pancreatic β-cells has a protective effect on allogeneic pancreatic islet graft survival.

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    Roy Eldor

    Full Text Available Pancreatic islet transplantation, a treatment for type 1 diabetes, has met significant challenges, as a substantial fraction of the islet mass fails to engraft, partly due to death by apoptosis in the peri- and post-transplantation periods. Previous evidence has suggested that NF-κB activation is involved in cytokine-mediated β-cell apoptosis and regulates the expression of pro-inflammatory and chemokine genes. We therefore sought to explore the effects of β-cell-specific inhibition of NF-κB activation as a means of cytoprotection in an allogeneic model of islet transplantation. To this end, we used islets isolated from the ToI-β transgenic mouse, where NF-κB signalling can specifically and conditionally be inhibited in β-cells by expressing an inducible and non-degradable form of IκBα regulated by the tet-on system. Our results show that β-cell-specific blockade of NF-κB led to a prolonged islet graft survival, with a relative higher preservation of the engrafted endocrine tissue and reduced inflammation. Importantly, a longer delay in allograft rejection was achieved when mice were systemically treated with the proteasome inhibitor, Bortezomib. Our findings emphasize the contribution of NF-κB activation in the allograft rejection process, and suggest an involvement of the CXCL10/IP-10 chemokine. Furthermore, we suggest a potential, readily available therapeutic agent that may temper this process.

  14. Inhibition of nuclear factor-κB activation in pancreatic β-cells has a protective effect on allogeneic pancreatic islet graft survival.

    Science.gov (United States)

    Eldor, Roy; Abel, Roy; Sever, Dror; Sadoun, Gad; Peled, Amnon; Sionov, Ronit; Melloul, Danielle

    2013-01-01

    Pancreatic islet transplantation, a treatment for type 1 diabetes, has met significant challenges, as a substantial fraction of the islet mass fails to engraft, partly due to death by apoptosis in the peri- and post-transplantation periods. Previous evidence has suggested that NF-κB activation is involved in cytokine-mediated β-cell apoptosis and regulates the expression of pro-inflammatory and chemokine genes. We therefore sought to explore the effects of β-cell-specific inhibition of NF-κB activation as a means of cytoprotection in an allogeneic model of islet transplantation. To this end, we used islets isolated from the ToI-β transgenic mouse, where NF-κB signalling can specifically and conditionally be inhibited in β-cells by expressing an inducible and non-degradable form of IκBα regulated by the tet-on system. Our results show that β-cell-specific blockade of NF-κB led to a prolonged islet graft survival, with a relative higher preservation of the engrafted endocrine tissue and reduced inflammation. Importantly, a longer delay in allograft rejection was achieved when mice were systemically treated with the proteasome inhibitor, Bortezomib. Our findings emphasize the contribution of NF-κB activation in the allograft rejection process, and suggest an involvement of the CXCL10/IP-10 chemokine. Furthermore, we suggest a potential, readily available therapeutic agent that may temper this process.

  15. Pretransplant β2-Microglobulin Is Associated with the Risk of Acute Graft-versus-Host-Disease after Allogeneic Hematopoietic Cell Transplant.

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    Costa-Lima, Carolina; Miranda, Eliana Cristina Martins; Colella, Marcos Paulo; Aranha, Francisco Jose Penteado; de Souza, Carmino Antonio; Vigorito, Afonso Celso; De Paula, Erich Vinicius

    2016-07-01

    The risk of acute graft-versus-host disease (aGVHD) can be reliably estimated by the hematopoietic cell transplantation-specific comorbidity index (HCT-CI), which can be further refined by the incorporation of pre-hematopoietic cell transplantation (HCT) serum levels of inflammatory biomarkers such as ferritin and albumin. β2-Microglobulin (β2-m) is a key component of the MHC class I complex, which is independently associated with mortality and frailty in the general population. We took advantage of our institutional protocol that includes measurement of pre-HCT β2-m serum levels in the most patients to investigate whether pre-transplant β2-m levels were associated with the risk of aGVHD. One hundred three consecutive patients submitted to allogeneic HCT, of which 26 developed grades II to IV aGVHD, were included in the analysis. β2-m was significantly associated with age and HCT-CI. Higher levels of β2-m were observed in patients who developed aGVHD (P = .008). In the multivariate Cox regression model, β2-m and HCT-CI remained independently associated with the risk of developing aGVHD. In conclusion, the association between β2-m and the occurrence of aGVHD suggests that the measurement of this protein before HCT might represent an additional element for risk stratification of aGVHD.

  16. A radio-resistant perforin-expressing lymphoid population controls allogeneic T cell engraftment, activation, and onset of graft-versus-host disease in mice.

    Science.gov (United States)

    Davis, Joanne E; Harvey, Michael; Gherardin, Nicholas A; Koldej, Rachel; Huntington, Nicholas; Neeson, Paul; Trapani, Joseph A; Ritchie, David S

    2015-02-01

    Immunosuppressive pretransplantation conditioning is essential for donor cell engraftment in allogeneic bone marrow transplantation (BMT). The role of residual postconditioning recipient immunity in determining engraftment is poorly understood. We examined the role of recipient perforin in the kinetics of donor cell engraftment. MHC-mismatched BMT mouse models demonstrated that both the rate and proportion of donor lymphoid cell engraftment and expansion of effector memory donor T cells in both spleen and BM were significantly increased within 5 to 7 days post-BMT in perforin-deficient (pfn(-/-)) recipients, compared with wild-type. In wild-type recipients, depletion of natural killer (NK) cells before BMT enhanced donor lymphoid cell engraftment to that seen in pfn(-/-) recipients. This demonstrated that a perforin-dependent, NK-mediated, host-versus-graft (HVG) effect limits the rate of donor engraftment and T cell activation. Radiation-resistant natural killer T (NKT) cells survived in the BM of lethally irradiated mice and may drive NK cell activation, resulting in the HVG effect. Furthermore, reduced pretransplant irradiation doses in pfn(-/-) recipients permitted long-term donor lymphoid cell engraftment. These findings suggest that suppression of perforin activity or selective depletion of recipient NK cells before BMT could be used to improve donor stem cell engraftment, in turn allowing for the reduction of pretransplant conditioning.

  17. Risk Factors for Steroid-Refractory Acute Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation from Matched Related or Unrelated Donors.

    Science.gov (United States)

    Calmettes, Claire; Vigouroux, Stéphane; Labopin, Myriam; Tabrizi, Reza; Turlure, Pascal; Lafarge, Xavier; Marit, Gérald; Pigneux, Arnaud; Leguay, Thibaut; Bouabdallah, Krimo; Dilhuydy, Marie-Sarah; Duclos, Cédric; Mohr, Catherine; Lascaux, Axelle; Dumas, Pierre-Yves; Dimicoli-Salazar, Sophie; Saint-Lézer, Arnaud; Milpied, Noël

    2015-05-01

    We performed a retrospective study to identify pretransplantation risk factors for steroid-refractory (SR) acute graft-versus host disease (aGVHD) after allogeneic stem cell transplantation from matched donors in 630 adult patients who underwent transplantation at our center between 2000 and 2012. The cumulative incidence (CI) of SR aGVHD was 11.3% ± 2.3%. The identified independent risk factors were matched unrelated donor (hazard ratio [HR], 2.52; P = .001), female donor for male recipient (HR, 1.84; P = .023) and absence of antithymocyte globulin (HR, 2.02; P = .005). Three risk groups were defined according to the presence of these risk factors. In the whole cohort, the CI of SR aGVHD was 3.5% ± 1.7% in the low-risk group (0 risk factor, n = 115), 9.3% ± 1.6% in the intermediate-risk group (1 risk factor, n = 323), and 19.3% ± 2.9% in the high-risk group (2 or 3 risk factors, n = 192). Our study suggests that pretransplantation characteristics might help identify patients at high risk for SR aGVHD. A risk adapted first-line treatment of aGVHD could be evaluated in those patients.

  18. Dermoscopic Follow-Up of the Skin towards Acute Graft-versus-Host-Disease in Patients after Allogeneic Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Grazyna Kaminska-Winciorek

    2016-01-01

    Full Text Available Background. Acute graft-versus-host disease (aGVHD involving skin is one of the most frequent complications of allogeneic hematopoietic stem cell transplantation (alloHSCT, usually diagnosed based on clinical manifestations. So far, skin biopsy with histopathological evaluation is the only method to confirm the diagnosis. Objective. In this prospective study we monitored alloHSCT recipients by dermoscopy in order to assess its utility as an alternative noninvasive tool to early diagnose acute GVHD. Methods. Thirteen consecutive patients who received alloHSCT were examined clinically and dermoscopically towards aGVHD [days 28 (±7, 56 (±7, and 100 (±7], as well as in each patient who developed cutaneous aGVHD diagnosed according to clinical criteria (Glucksberg scale. Results. Six patients (46% developed symptoms of cutaneous acute GVHD (grade 1, n=3; grade 2, n=3. Dermoscopic evaluation revealed pinkish or reddish background and well-visible, multiple thin telangiectasias. Conclusion. To our knowledge, this is the first report on the use of dermoscopy to evaluate skin involvement in the course of acute GVHD suggesting its role as a diagnostic tool in follow-up of GVHD, which can be also used before clinical symptoms occur.

  19. [Migration and distribution of allogeneic T lymphocytes in organs of graft-versus-host disease mouse model].

    Science.gov (United States)

    Wen, Hong-Sheng; Wang, Jian-Min; Zhou, Hong; Xia, Rong; Qiu, Hui-Ying; Gao, Lei; Hu, Xiao-Xia

    2006-10-01

    This study was aimed to investigate the migration and distribution processes of allogeneic donor T lymphocytes in the organs of recipient mice. GVHD model was established by transfusion of the splenocytes of eGFP transgeneic C57BL/6 mice together with born marrow cells harvested from C57BL/6 mice into BALB/c mice underwent 8.0 Gy total body irradiation. The migration and homing of eGFP(+) cells were tracked by stereo-fluorescent microscopy or inverted fluorescent microscopy and flow cytometry. The enzyme linked immunosorbent assay (ELISA) was performed on supernatants from the tissue homogenates to detect the amount of MIP-1alpha. The results indicated that GVHD clinical manifestation and pathological changes of organs appeared on day 8 post transplantation. eGFP-positive donor T cells in recipient organs were observed by inverted fluorescence microscope in frozen section, or by stereo-fluorescence microscopy in living organs, such as liver, spleen, skin, lungs, bowels, and tongue. The highest expression of MIP-1alpha was on day 7 post transplantation in the liver (491.3 +/- 32.1 pg/ml), and day 3 post transplantation in the spleen (881.5 +/- 45.2 pg/ml), respectively (P liver, skin, bowels, as well as lungs and tongue. MIP-1alpha may be in relation with the infiltration of T lymphocytes in liver and spleen.

  20. Role of acute graft-versus-host disease in the risk of bacteremia and invasive fungal disease after allogeneic hemopoietic stem cell transplantation in children. Results from a single-center observational study.

    Science.gov (United States)

    Castagnola, Elio; Bagnasco, Francesca; Bandettini, Roberto; Caviglia, Ilaria; Morreale, Giuseppe; Lanino, Edoardo; Giardino, Stefano; Moroni, Cristina; Haupt, Riccardo; Faraci, Maura

    2014-07-01

    Data on epidemiology of severe infectious complications, ie, bacteremia or invasive fungal disease (IFD), in children with acute graft-versus-host disease (aGVHD) after allogeneic hemopoietic stem cell transplantation (HSCT) are scarce. In a retrospective, single-center study, we analyzed the risk (hazard ratio [HR]) and the rate (episodes/1000 patients days at risk) of bacteremias and IFD in children receiving allogeneic HSCT, according to the type of donor (matched related [MRD] or alternative [AD]) and presence and grade of aGVHD. From 2000 to 2009, 198 children receiving 217 allogeneic HSCT developed 134 severe infectious episodes (103 bacteremias and 31 IFD). The type of donor (AD versus MRD) was the most important risk factor for the severe infections (P = .0052). In separate multivariable analysis for bacteremia and IFD, children receiving an AD HSCT had increased HR and rate of bacteremia compared with those receiving a MRD transplantation (P = .0171 and P = .0001, respectively), whereas the HR and the rate of IFD were significantly influenced by the grade of aGVHD (P = .0002 and P design management strategies of infections in pediatric allogeneic HSCT.

  1. Effect of Solcoseryl on cadaveric split-skin oxygen consumption during 4 degrees C storage and in frozen biopsies.

    Science.gov (United States)

    Alsbjörn, B F; Jensen, M G; Sørensen, B

    1989-04-01

    Oxygen consumption rate in cadaveric split-skin biopsies was investigated. Biopsies were harvested at different times postmortem and stored at different temperatures in either Solcoseryl (a protein-free bovine hemodialysate) or placebo-containing media. During the first week of storage Solcoseryl had no influence on oxygen consumption. However, in the second and third weeks the oxygen consumption was improved by Solcoseryl.

  2. [The impact of donor naive and memory T cell subsets on patient outcome following allogeneic stem cell transplantation: relationship between infused donor CD4+/CCR7+ T cell subsets and acute graft-versus-host disease].

    Science.gov (United States)

    Choufi, B; Thiant, S; Trauet, J; Cliquennois, M; Cherrel, M; Boulanger, F; Coiteux, V; Magro, L; Labalette, M; Yakoub-Agha, I

    2014-06-01

    In a previous prospective study on 62 patients who underwent an HLA-matched allogeneic stem cell transplantation, we have observed that proportion of donor-derived CCR7(+)/CD4(+) T cells in the graft provided a predictive indicator of acute GVHD without interfering on chronic GVHD and relapse rate. Here we present our results on a confirmatory cohort of 137 consecutive patients. Indeed patients who received more than 76% of CCR7(+)/CD4(+) T cells in the graft developed more often acute GVHD be it of low or high grade than those who did not. Determination of the CCR7(+)/CCR7(neg) ratio of CD4(+) T cells in the graft provides a predictive indicator of acute GVHD and could help to define strategies of partial selective T cell depleted transplantation.

  3. Low-dose alemtuzumab vs. standard policy for prevention of graft-versus-host disease in unrelated and related allogeneic stem cell transplantation-a matched pair analysis.

    Science.gov (United States)

    Busemann, Christoph; Neumann, Thomas; Schulze, Meike; Klenner, Anne; Thiele, Thomas; Greinacher, Andreas; Dölken, Gottfried; Krüger, William H

    2013-07-01

    Antibody-mediated in vivo T cell depletion is common prior to unrelated (URD) or mismatched allogeneic stem cell transplantation (alloSCT) and optional in HLA-identical sibling (FAM) alloSCT. While anti-thymocyte globulin (ATG) is the current standard, alemtuzumab is an alternative. The optimal dose of alemtuzumab has not been defined. This retrospective analysis compares low-dose alemtuzumab with ATG in URD alloSCT and with no antibody in FAM alloSCT. Twenty-eight patients treated with alemtuzumab (10 mg; HLA mismatch, 20 mg) were matched to 28 patients who have either received ATG (URD) or no antibody (noAB) according to disease, disease stage, age, transplant type and risk state. Both groups were compared for engraftment, outcome, disease-free (DFS) and overall survival (OS), graft-versus-host disease (GvHD), freedom from GvHD (ffGvHD) and transplant-related mortality (TRM). No significant differences were found between the groups for leukocyte engraftment, GvHD, ffGvHD, TRM, DFS and OS. There was a trend for reduction of cGvHD by alemtuzumab (p = 0.05). A transplant-type stratified subanalysis consolidated equivalency of alemtuzumab and ATG in URD-SCT and indicates possible superiority of low-dose alemtuzumab compared to noAB in FAM-SCT. Low-dose alemtuzumab, as part of conditioning regimen prior to alloSCT, is safe and comparable to standard ATG. Prospective trials, particularly comparing alemtuzumab vs. noAB in FAM alloSCT, should be conducted.

  4. Graft-versus-leukemia effect with a WT1-specific T-cell response induced by azacitidine and donor lymphocyte infusions after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Ishikawa, Tatsunori; Fujii, Nobuharu; Imada, Masahide; Aoe, Michinori; Meguri, Yusuke; Inomata, Tomoko; Nakashima, Hiromi; Fujii, Keiko; Yoshida, Shohei; Nishimori, Hisakazu; Matsuoka, Ken-Ichi; Kondo, Eisei; Maeda, Yoshinobu; Tanimoto, Mitsune

    2017-04-01

    Azacitidine (Aza) and donor lymphocyte infusion (DLI) therapy has recently been reported as an effective salvage therapy for relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Despite the high response rate and relatively long period of remission, most patients relapse again. The immunologic mechanism of the response and limited efficacy remain unknown. Aza + DLI therapy was performed for a patient with therapy-related MDS (t-MDS), who had relapsed after allogeneic peripheral blood stem cell transplantation. We observed a powerful graft-versus-leukemia (GVL) effect accompanied by an evident Wilms tumor antigen 1 (WT1)-specific CD8 T-cell response. Remission continued for 15 months, but finally the patient relapsed. The kinetics of the WT1-specific CD8 T cells were inversely associated with WT1 messenger RNA (mRNA), suggesting a WT1-driven GVL effect. A difference of T-cell phenotype between the whole T cells and the WT1-specific CD8 T cells was observed. It is of note that the memory phenotype of the WT1-specific T cell was limited and decreased early. The immunoescape mechanism was partly supported by loss of the memory phenotype due to failure of expansion and differentiation. Our data suggested that a WT1-specific T-cell response at least partly contributes to the GVL effect induced by Aza + DLI. A strategy for maximizing and maintaining the memory phenotype of the CTL may be required for durable remission. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  5. Impact of Cyclosporine Levels on the Development of Acute Graft versus Host Disease after Reduced Intensity Conditioning Allogeneic Stem Cell Transplantation

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    Irene García Cadenas

    2014-01-01

    Full Text Available We analyze the impact of cyclosporine (CsA levels in the development of acute graft-versus-host disease (aGVHD after reduced intensity conditioning allogeneic hematopoietic transplantation (allo-RIC. We retrospectively evaluated 156 consecutive patients who underwent HLA-identical sibling allo-RIC at our institution. CsA median blood levels in the 1st, 2nd, 3rd and 4th weeks after allo-RIC were 134 (range: 10–444, 219 (54–656, 253 (53–910 and 224 (30–699 ng/mL; 60%, 16%, 11% and 17% of the patients had median CsA blood levels below 150 ng/mL during these weeks. 53 patients developed grade 2–4 aGVHD for a cumulative incidence of 45% (95% CI 34–50% at a median of 42 days. Low CsA levels on the 3rd week and sex-mismatch were associated with the development of GVHD. Risk factors for 1-year NRM and OS were advanced disease status (HR: 2.2, P=0.02 and development of grade 2–4 aGVHD (HR: 2.5, P<0.01, while there was a trend for higher NRM in patients with a low median CsA concentration on the 3rd week (P=0.06. These results emphasize the relevance of sustaining adequate levels of blood CsA by close monitoring and dose adjustments, particularly when engraftment becomes evident. CsA adequate management will impact on long-term outcomes in the allo-RIC setting.

  6. Strategies for the identification of T cell-recognized tumor antigens in hematological malignancies for improved graft-versus-tumor responses after allogeneic blood and marrow transplantation.

    Science.gov (United States)

    Zilberberg, Jenny; Feinman, Rena; Korngold, Robert

    2015-06-01

    Allogeneic blood and marrow transplantation (allo-BMT) is an effective immunotherapeutic treatment that can provide partial or complete remission for patients with hematological malignancies. Mature donor T cells in the donor inoculum play a central role in mediating graft-versus-tumor (GVT) responses by destroying residual tumor cells that persist after conditioning regimens. Alloreactivity towards minor histocompatibility antigens (miHA), which are varied tissue-related self-peptides presented in the context of major histocompatibility complex (MHC) molecules on recipient cells, some of which may be shared on tumor cells, is a dominant factor for the development of GVT. Potentially, GVT can also be directed to tumor-associated antigens or tumor-specific antigens that are more specific to the tumor cells themselves. The full exploitation of allo-BMT, however, is greatly limited by the development of graft-versus-host disease (GVHD), which is mediated by the donor T cell response against the miHA expressed in the recipient's cells of the intestine, skin, and liver. Because of the significance of GVT and GVHD responses in determining the clinical outcome of patients, miHA and tumor antigens have been intensively studied, and one active immunotherapeutic approach to separate these two responses has been cancer vaccination after allo-BMT. The combination of these two strategies has an advantage over vaccination of the patient without allo-BMT because his or her immune system has already been exposed and rendered unresponsive to the tumor antigens. The conditioning for allo-BMT eliminates the patient's existing immune system, including regulatory elements, and provides a more permissive environment for the newly developing donor immune compartment to selectively target the malignant cells. Utilizing recent technological advances, the identities of many human miHA and tumor antigenic peptides have been defined and are currently being evaluated in clinical and basic

  7. Strategies for the Identification of T Cell–Recognized Tumor Antigens in Hematological Malignancies for Improved Graft-versus-Tumor Responses after Allogeneic Blood and Marrow Transplantation

    Science.gov (United States)

    Zilberberg, Jenny; Feinman, Rena; Korngold, Robert

    2015-01-01

    Allogeneic blood and marrow transplantation (allo-BMT) is an effective immunotherapeutic treatment that can provide partial or complete remission for patients with hematological malignancies. Mature donor T cells in the donor inoculum play a central role in mediating graft-versus-tumor (GVT) responses by destroying residual tumor cells that persist after conditioning regimens. Alloreactivity towards minor histocompatibility antigens (miHA), which are varied tissue-related self-peptides presented in the context of major histocompatibility complex (MHC) molecules on recipient cells, some of which may be shared on tumor cells, is a dominant factor for the development of GVT. Potentially, GVT can also be directed to tumor-associated antigens or tumor-specific antigens that are more specific to the tumor cells themselves. The full exploitation of allo-BMT, however, is greatly limited by the development of graft-versus-host disease (GVHD), which is mediated by the donor T cell response against the miHA expressed in the recipient’s cells of the intestine, skin, and liver. Because of the significance of GVT and GVHD responses in determining the clinical outcome of patients, miHA and tumor antigens have been intensively studied, and one active immunotherapeutic approach to separate these two responses has been cancer vaccination after allo-BMT. The combination of these two strategies has an advantage over vaccination of the patient without allo-BMT because his or her immune system has already been exposed and rendered unresponsive to the tumor antigens. The conditioning for allo-BMT eliminates the patient’s existing immune system, including regulatory elements, and provides a more permissive environment for the newly developing donor immune compartment to selectively target the malignant cells. Utilizing recent technological advances, the identities of many human miHA and tumor antigenic peptides have been defined and are currently being evaluated in clinical and basic

  8. Increasing Incidence of Chronic Graft-versus-Host Disease in Allogeneic Transplantation – A Report from CIBMTR

    Science.gov (United States)

    Arai, Sally; Arora, Mukta; Wang, Tao; Spellman, Stephen R.; He, Wensheng; Couriel, Daniel R.; Urbano-Ispizua, Alvaro; Cutler, Corey S.; Bacigalupo, Andrea A.; Battiwalla, Minoo; Flowers, Mary E.; Juckett, Mark B.; Lee, Stephanie J.; Loren, Alison W.; Klumpp, Thomas R.; Prockup, Susan E.; Ringdén, Olle T.H.; Savani, Bipin N.; Socié, Gérard; Schultz, Kirk R.; Spitzer, Thomas; Teshima, Takanori; Bredeson, Christopher N.; Jacobsohn, David A.; Hayashi, Robert J.; Drobyski, William R.; Frangoul, Haydar A.; Akpek, Görgün; Ho, Vincent T.; Lewis, Victor A.; Gale, Robert Peter; DSc(hon); Koreth, John; Chao, Nelson J.; Aljurf, Mahmoud D.; Cooper, Brenda W.; Laughlin, Mary J.; Hsu, Jack W.; Hematti, Peiman; Verdonck, Leo F.; Solh, Melhelm M.; Norkin, Maxim; Reddy, Vijay; Martino, Rodrigo; Gadalla, Shahinaz; Goldberg, Jenna D.; McCarthy, Philip L.; Pérez-Simón, José A.; Khera, Nandita; Lewis, Ian D.; Atsuta, Yoshiko; Olsson, Richard F.; Saber, Wael; Waller, Edmund K.; Blaise, Didier; Pidala, Joseph A.; Martin, Paul J.; Satwani, Prakash; Bornhäuser, Martin; Inamoto, Yoshihiro; Weisdorf, Daniel J.; Horowitz, Mary M.; Pavletic, Steven Z.

    2015-01-01

    Although transplant practices have changed over the last decades there is no information on trends in incidence and outcome of cGVHD over time. This study utilized the central database of the Center for International Blood and Marrow Transplant Research (CIBMTR) to describe the time trends for cGVHD incidence, non-relapse mortality, and the risk factors for cGVHD. The 12-year period was divided into three intervals: 1995-1999, 2000-2003, 2004-2007, and included 26,563 patients with acute leukemia, chronic myeloid leukemia and myelodysplastic syndrome. In the multivariate analysis, the incidence of cGVHD was shown to be increased in more recent years (odds ratio= 1.19, p<0.0001) and this trend was still seen when adjusting for donor type, graft type, or conditioning intensity. In patients with cGVHD, non-relapse mortality has decreased over time, but at 5-years there were no significant differences among different time periods. Risk factors for cGVHD were in line with previous studies. This is the first comprehensive characterization of the trends in cGVHD incidence and underscores the mounting need for addressing this major late complication of transplantation in future research. PMID:25445023

  9. A glucocorticoid amplifies IL-2-induced selective expansion of CD4+CD25+FOXP3+ regulatory T cells in vivo and suppresses graft-versus-host disease after allogeneic lymphocyte transplantation

    Institute of Scientific and Technical Information of China (English)

    Yanhui Xie; Min Wu; Runhua Song; Jiexian Ma; Yi Shi; Wenming Qin; Youxin Jin

    2009-01-01

    Regulatory T (Treg) cells are a subpopulation of T cells that not only prevent autoimmunity, but also control a wide range of T cell-dependent immune responses. Glucocorticoid treatment (dexamethasone, or Dex) has been reported to amplify IL-2-mediated selective in vivo expansion of Treg cells. We simultaneously adminis-tered Dex and IL-2 to the donor in a murine allogeneic lymphocyte transplantation model to expand functional suppressive CD4+CD25+FOXP3+ T cells in the graft and to raise the regulatory T cell/effector T cell (Treg/ Teff) ratio to prevent graft-versus-host disease (GVHD). After combined treatment of the donor with Dex (5 mg/kg/day) and IL-2 (300,000 IU/mouse/day) for 3 days, grafts were subjected to flow cytometric analy-sis, and transplantation was carried out from male C57BL/6 mice to female BALB/c mice aged 8-12 weeks. Results showed that short-term simultaneous administration of Dex and IL-2 markedly expanded functional suppressive CD4+CD25+FOXP3+ T cells in the murine spleen. In this murine allogeneic transplan-tation model, the grafts from donors with Dex and IL-2 pre-treatment led to a longer survival time for the reci-pients than for the control group (median survival time> 60 day vs. 12 day, P = 0.0002). The ratio of Treg/Teff also increased remarkably (0.43 ±0.15 vs. 0.14± 0.01, P=0.01). This study demonstrated that co-stimulation with Dex and IL-2 selectively expanded functional CD4+CD25+FOXP3+ T cells in vivo, and that grafts from donors pre-treated with Dex and IL-2 led to longer survival time and greater suppression of GVHD after allogeneic transplantation. Thus, GVHD can be suppressed by the specific expansion of regulatory T cells with Dex and IL-2 in graft donors.

  10. Cannabidiol for the Prevention of Graft-versus-Host-Disease after Allogeneic Hematopoietic Cell Transplantation: Results of a Phase II Study.

    Science.gov (United States)

    Yeshurun, Moshe; Shpilberg, Ofer; Herscovici, Corina; Shargian, Liat; Dreyer, Juliet; Peck, Anat; Israeli, Moshe; Levy-Assaraf, Maly; Gruenewald, Tsipora; Mechoulam, Raphael; Raanani, Pia; Ram, Ron

    2015-10-01

    Graft-versus-host-disease (GVHD) is a major obstacle to successful allogeneic hematopoietic cell transplantation (alloHCT). Cannabidiol (CBD), a nonpsychotropic ingredient of Cannabis sativa, possesses potent anti-inflammatory and immunosuppressive properties. We hypothesized that CBD may decrease GVHD incidence and severity after alloHCT. We conducted a phase II study. GVHD prophylaxis consisted of cyclosporine and a short course of methotrexate. Patients transplanted from an unrelated donor were given low-dose anti-T cell globulin. CBD 300 mg/day was given orally starting 7 days before transplantation until day 30. Forty-eight consecutive adult patients undergoing alloHCT were enrolled. Thirty-eight patients (79%) had acute leukemia or myelodysplastic syndrome and 35 patients (73%) were given myeloablative conditioning. The donor was either an HLA-identical sibling (n = 28), a 10/10 matched unrelated donor (n = 16), or a 1-antigen-mismatched unrelated donor (n = 4). The median follow-up was 16 months (range, 7 to 23). No grades 3 to 4 toxicities were attributed to CBD. None of the patients developed acute GVHD while consuming CBD. In an intention-to-treat analysis, we found that the cumulative incidence rates of grades II to IV and grades III to IV acute GVHD by day 100 were 12.1% and 5%, respectively. Compared with 101 historical control subjects given standard GVHD prophylaxis, the hazard ratio of developing grades II to IV acute GVHD among subjects treated with CBD plus standard GVHD prophylaxis was .3 (P = .0002). Rates of nonrelapse mortality at 100 days and at 1 year after transplantation were 8.6% and 13.4%, respectively. Among patients surviving more than 100 days, the cumulative incidences of moderate-to-severe chronic GVHD at 12 and 18 months were 20% and 33%, respectively. The combination of CBD with standard GVHD prophylaxis is a safe and promising strategy to reduce the incidence of acute GVHD. A randomized double-blind controlled study is warranted

  11. Relativity of extensor tendon hood anatomy to allogenic tendon hood grafting: an experimental study%伸肌腱腱帽解剖与异体腱帽移植的相关性实验研究

    Institute of Scientific and Technical Information of China (English)

    朱伟; 王澍寰; 张友乐

    2001-01-01

    Objective To observe the anatomy of the extensor tendon hood and investigate its relation to allogenic tendon hood grafting. Methods 24 fingers from 6 fresh adult cadaver hands were used for dissection. The dynamical and static structures of the extensor tendon hood were observed. The sliding range of the extensor tendon at the site of tendon hood was measured. Results The extensor tendon hood was longer on the radial side than on the ulnar side in all fingers. The excursion scope of extensor tendon hoods ranged from 0.9 cm to 1.5 cm, with the longest in the index finger and the shortest in the small finger. Conclusions Allogenic tendon hood grafting can restore the original structure of the extensor tendon hood and avoid impairment of finger extension caused by sliding down of the tendon following autogenous tendon grafting.%目的 探讨伸肌腱腱帽解剖与异体腱帽移植的相关性研究。方法 对6只新鲜尸手24指指伸肌腱腱帽的动力结构和静力结构进行观察,并测定了各指伸肌腱在腱帽处的滑动范围。结果 各指腱帽桡、尺侧的长度均是桡侧长于尺侧,各指伸肌腱腱帽的滑动范围在0.9 ~ 1.5 cm间,示指最大,小指最小。结论 异体腱帽移植可恢复伸肌腱腱帽的原有结构,可避免自体肌腱移植后的肌腱下滑而影响伸指功能的恢复。

  12. Allogeneic splenocyte transfer and lipopolysaccharide inhalations induce differential T cell expansion and lung injury: a novel model of pulmonary graft-versus-host disease.

    Directory of Open Access Journals (Sweden)

    Tereza Martinu

    Full Text Available BACKGROUND: Pulmonary GVHD (pGVHD is an important complication of hematopoietic cell transplant (HCT and is thought to be a consequence of the HCT conditioning regimen, allogeneic donor cells, and posttransplant lung exposures. We have previously demonstrated that serial inhaled lipopolysaccharide (LPS exposures potentiate the development of pGVHD after murine allogeneic HCT. In the current study we hypothesized that allogeneic lymphocytes and environmental exposures alone, in the absence of a pre-conditioning regimen, would cause features of pGVHD and would lead to a different T cell expansion pattern compared to syngeneic cells. METHODS: Recipient Rag1-/- mice received a transfer of allogeneic (Allo or syngeneic (Syn spleen cells. After 1 week of immune reconstitution, mice received 5 daily inhaled LPS exposures and were sacrificed 72 hours after the last LPS exposure. Lung physiology, histology, and protein levels in bronchoalveolar lavage (BAL were assessed. Lung cells were analyzed by flow cytometry. RESULTS: Both Allo and Syn mice that undergo LPS exposures (AlloLPS and SynLPS have prominent lymphocytic inflammation in their lungs, resembling pGVHD pathology, not seen in LPS-unexposed or non-transplanted controls. Compared to SynLPS, however, AlloLPS have significantly increased levels of BAL protein and enhancement of airway hyperreactivity, consistent with more severe lung injury. This injury in AlloLPS mice is associated with an increase in CD8 T cells and effector CD4 T cells, as well as a decrease in regulatory to effector CD4 T cell ratio. Additionally, cytokine analysis is consistent with a preferential Th1 differentiation and upregulation of pulmonary CCL5 and granzyme B. CONCLUSIONS: Allogeneic lymphocyte transfer into lymphocyte-deficient mice, followed by LPS exposures, causes features of pGVHD and lung injury in the absence of a pre-conditioning HCT regimen. This lung disease associated with an expansion of allogeneic effector

  13. 关节镜下自体腘绳肌和异体胫前肌单束重建前交叉韧带的1年随访比较%Autologous hamstring grafts versus allogeneic anterior tibial muscle tendon grafts for arthroscopic reconstruction of single-bundle anterior cruciate ligament: A one-year follow-up

    Institute of Scientific and Technical Information of China (English)

    王洪; Dhakal Rabi Mohan; 孟春庆; 段德宇; 杨述华; 杜靖远; 唐欣; 李立群; 方青; 汤明

    2011-01-01

    BACKGROUND: Due to artificial ligament has chronic fatigue, mere and mere people use a lie graft for the reconstruction of anterior and the posterior cruciate ligament injury.OBJECTP/E: To compare the curath/e effect aftei aithroscopic reconstruction of single-bundle ante lie t cruciate ligament using autclogous hamstring grafts and allogeneic anterior tibial muscle tendon grafts.METHODS: Cases of anterior cruciate ligament reconstruction which using single-bundle autologous hamstring grafts and allogeneic anterior tibia I muscle tend on grafts under arthrosco pic with 1 year follow up were collected. Totalry 23 cases were used autologous hamstring grafts for anterior cruciate ligament reconstruction, and 13 cases were used anterior tibial muscle tendon allograftfor anterior cruciate ligament reconstruction. The fixation of each reconstructed anterior cruciate Igamentwas done by femoral En do Button and tibial biodegradable interference screw. Using a brace to fix the troubled knee and having the physical training of the troubled knee lately and progress K/ely.RESULTS AND CONCLUSION; All the 43 cases were followed up for sk months after reconstruction. Lysholm score of the autologous tendon group was lower than that of the allogeneic tendon group 0.05). There was no significant difference between the two groups of Lysholm score after six months posto pe ratn/ery. Lysholmscore of the two groups after 6 months and a year construction postoperative showed significant difference as compared with preoperation (P < 005). There was significant difference of the Lysholm score after reconstruction in six months follow up and in one year follow up showing a statistic significance (f < 0.05). The curative effect of anterior cruciate ligament reconstruction using autologous hamstring grafts and allogeneic anterior tibial muscle tendon grafts is equally.%背景:由于人工韧带存在慢性疲劳,越来越多的人采用异体肌腱重建前后交叉韧带损伤.目的:比较

  14. Reparación ósea mediante aloimplantes sometidos a diferentesmétodos de conservación en conejos Allogeneic bone grafts treated with different conservation methodsfor bone repair in rabbits

    Directory of Open Access Journals (Sweden)

    G. Dasso

    1998-01-01

    Full Text Available Debido a las limitantes de los implantes de hueso de origen autogénico y a la ineficiencia de los implantes de hueso fresco de origen alogénico ha sido necesario incursionar en el área de los implantes de hueso alogénico procesados. Con este objetivo se utilizaron 27 conejos raza blanco neozelandés de 3 a 5 meses de edad, quienes recibieron los diferentes tipos de aloimplantes de hueso esponjoso (desproteinizados, congelados o hervidos para evaluar el grado de reparación de una lesión previamente realizada en la tibia. Los animales fueron sacrificados a las dos, cuatro y ocho semanas postcirugía y la evaluación se realizó a través de cortes histológicos. Determinándose que a las dos semanas post-cirugía no hubo mayor diferencia entre los distintos grupos analizados, pero sí lo hubo a las cuatro y ocho semanas post-cirugía, donde se observó claramente una mayor eficiencia de los implantes desproteinizados. Esto se debe a que el hipoclorito de sodio destruye los elementos antigénicos presentes en el implante, lo que disminuye las probabilidades de rechazo por parte del huésped y facilita la llegada de células indiferenciadas que se diferencian a osteoblastos formando así hueso neoformado, por lo tanto, esto se refleja en un mayor grado de reparación en comparación con los implantes tratados por congelación y más aún si lo comparamos con los aloimplantes tratados por ebullición. Esta información puede ser de gran utilidad para la implementación de un banco de huesos destinado a corregir lesiones del sistema esqueléticoDue to limitations in the availability of autogeneic bone and to the inefficiency of the fresh allogeneic bone grafts, it has been necessary to evaluate the use of allogeneic processed bone. Therefore, the ability of three procedures -freezing, boiling and desproteinization of allogeneic bone- to repair experimentally created defects in rabbit tibia was tested. Tibia, 2, 4 and 8 weeks after surgery were

  15. Reduction of mandibular residual ridge after vestibuloplasty. A two-year follow-up study comparing the Edlan flap, mucosal and skin graft operations

    DEFF Research Database (Denmark)

    Hillerup, Søren; Eriksen, Erik; Solow, B

    1989-01-01

    Mandibular residual ridge reduction (RRR) after Edlan flap vestibuloplasty, buccal mucosal graft, and split skin graft vestibuloplasty was measured on lateral cephalometric radiographs obtained 1, 3, 6, 12 and 24 months postsurgery in 50 patients. The ridge reduction was most severe during the im...

  16. Ongoing graft-versus-host disease is a risk factor for azoospermia after allogeneic hematopoietic stem cell transplantation: a survey of the Late Effects Working Party of the European Group for Blood and Marrow Transplantation.

    Science.gov (United States)

    Rovó, Alicia; Aljurf, Mahmoud; Chiodi, Sandra; Spinelli, Simonetta; Salooja, Nina; Sucak, Gülsan; Hunter, Ann; Kim, Tan Swee; Socié, Gérard; van Lint, Maria Teresa; Passweg, Jakob R; Arat, Mutlu; Badoglio, Manuela; Tichelli, André

    2013-03-01

    The aim of this study was to assess the degree of spermatogenesis defects in sperm analysis in long-term male survivors after allogeneic hematopoietic stem cell transplantation in order to identify the risk factors related to potential infertility after hematopoietic stem cell transplantation and to provide data on longitudinal sperm recovery after hematopoietic stem cell transplantation. Here, the Late Effects Working Party of the European Group for Blood and Marrow Transplantation reports data of sperm analysis from 224 males who underwent hematopoietic stem cell transplantation. Median time between transplantation and sperm analysis was 63 months (8-275 months). At last sperm analysis, presence of any degree of spermatozoa was reported in 70 (31%) and complete azoospermia in 154 (69%) patients. In multivariate analysis, being conditioned with total body irradiation (RR 7.1; 95% CI: 3.4-14.8) and age over 25 years at transplantation (RR 2.4; 95% CI: 1.09-5.2) were significantly associated with higher risk for azoospermia. In patients not conditioned with total body irradiation, ongoing chronic graft-versus-host disease is the main adverse factor for sperm recovery (RR of 3.11; 95% CI: 1.02-9.47; P=0.045). Already established risk factors, such as total body irradiation and age older than 25 years at hematopoietic stem cell transplantation, were seen to be the most relevant adverse risk factor for sperm production after hematopoietic stem cell transplantation. Furthermore, for the first time, ongoing graft-versus-host disease has been shown to be the most relevant adverse factor for sperm recovery, particularly in patients conditioned without total body irradiation. We also introduce a useful scoring system to predict the probability of male long-term survivors' azoospermia.

  17. Methotrexate Reduces the Incidence of Severe Acute Graft-versus-Host Disease without Increasing the Risk of Relapse after Reduced-Intensity Allogeneic Stem Cell Transplantation from Unrelated Donors.

    Science.gov (United States)

    Vigouroux, Stéphane; Tabrizi, Reza; Melot, Cyril; Coiffard, Joelle; Lafarge, Xavier; Marit, Gérald; Bouabdallah, Krimo; Pigneux, Arnaud; Leguay, Thibaut; Dilhuydy, Marie-Sarah; Schmitt, Anna; Boiron, Jean-Michel; Milpied, Noël

    2011-01-01

    Optimized prophylaxis against graft-versus-host disease (GVHD) after unrelated reduced-intensity allogeneic transplantation when preceded by a conditioning regimen utilizing antithymocyte globulin (ATG) is poorly defined. To investigate the effects of methotrexate (MTX) in this treatment setting, we conducted a retrospective analysis. Sixty-three patients were selected based on the administration of a total dose of 5 mg/kg of ATG in the conditioning regimen and then separated into either group M+ (n = 39), which received MTX or group M- (n = 24), which did not. All patients received cyclosporine. In the M- and M+ groups, cumulative incidences (CI) of grade III-IV acute GVHD (aGVHD) were 43% and 10%, respectively (P = .002). Multivariate analysis indicated that grade III-IV aGVHD was favored by both the absence of MTX and the provision of a female donor for a male recipient. At 2 years, the M+ and M- groups exhibited, respectively: overall survival of 69% and 40% (P = .06), disease-free survival of 57% and 43% (P = .2), nonrelapse mortality of 20% and 44% (P = .1), and incidence of relapse of 27% and 35% (P = .6). These data suggest that MTX reduces the incidence of severe aGVHD without increasing the risk of relapse but with an accompanying trend toward improved survival after unrelated reduced-intensity transplantation with ATG in the conditioning regimen.

  18. Hospital Length of Stay in the First 100 Days After Allogeneic Hematopoietic Cell Transplantation for Acute Leukemia in Remission: Comparison among Alternative Graft Sources

    Science.gov (United States)

    Ballen, Karen K.; Joffe, Steven; Brazauskas, Ruta; Wang, Zhiwe; Aljurf, Mahmoud D.; Akpek, Görgün; Dandoy, Christopher; Frangoul, Haydar A.; Freytes, César O.; Khera, Nandita; Lazarus, Hillard M.; LeMaistre, Charles F.; Mehta, Paulette; Parsons, Susan K.; Szwajcer, David; Ustun, Celalettin; Wood, William A.; Majhail, Navneet S.

    2014-01-01

    Several studies have shown comparable survival outcomes among different graft sources, but the relative resource needs of hematopoietic cell transplantation (HCT) by graft source have not been well studied. We compared total hospital length of stay in the first 100 days after HCT in 1577 patients with acute leukemia in remission receiving umbilical cord blood (UCB), matched unrelated donor (MUD) or mismatched unrelated donors (MMUD) HCT from 2008–2011. To ensure a relatively homogenous study population, the analysis was limited to patients with acute myeloid leukemia and acute lymphoblastic leukemia in first or second complete remission who received HCT in the United States. To account for early deaths, we compared the number of days alive and out of hospital in the first 100 days. For children receiving myeloablative conditioning, median days alive and out of hospital in the first 100 days were 50, 54 and 60 days for single UCB, double UCB and MUD bone marrow (BM) recipients, respectively. In multivariate analysis, use of UCB was significantly associated with fewer days alive and out of the hospital compared to MUD BM. For adults receiving HCT using myeloablative conditioning, median days alive and out of hospital in first 100 days were 52 for single UCB, 55 for double UCB, 69 for MUD BM, 75 for MUD peripheral blood stem cells (PBSC), 63 for MMUD BM and 67 days MMUD PBSC recipients. In multivariate analysis, UCB and MMUD BM recipients had fewer days alive and out of the hospital compared to other graft sources. For adults receiving a reduced intensity preparative regimen, median days alive and out of hospital during the first 100 days for single UCB, double UCB, MUD PBSC and MMUD PBSC were 65, 63, 79, and 79, respectively. Similar to the other two groups, use of UCB was associated with a fewer days alive and out of the hospital. In conclusion, length of stay in the first 100 days varies by graft source and is greater for UCB HCT recipients. These data provide

  19. Comparative alveolar ridge preservation using allogenous tooth graft versus free-dried bone allograft: A randomized, controlled, prospective, clinical pilot study

    Directory of Open Access Journals (Sweden)

    Chaitanya Pradeep Joshi

    2017-01-01

    Full Text Available Background: For the first time in India, allografts from human extracted teeth were prepared. A randomized, prospective, clinicoradiographical, histological study was conducted to evaluate their efficacy in comparison with freeze-dried bone allograft (FDBA in alveolar ridge preservation. Materials and Methods: Graft preparation: with written consent, teeth were collected from three donors (full mouth extraction cases. Once donors' serums were tested negative for HIV, HBV, HCV, and Venereal disease research laboratory (VDRL, mineralized whole tooth allograft (WTA and dentin allograft (DA were prepared using the standard protocol of Tissue Bank at Tata Memorial Hospital, Mumbai, India. Study Design: In this randomized controlled trial, 15 patients undergoing extraction of at least four teeth were selected. In each patient after atraumatic extractions, one socket was grafted with WTA, second with DA, third with FDBA, and fourth was left ungrafted (control site. All the sites were covered with chorion membrane. To estimate three-dimensional alveolar crest changes, cone beam computed tomography scans were taken immediately after grafting and 4 months postoperatively. Bone biopsies using 3 mm trephine bur were obtained from four patients at the time of implant placement and evaluated histologically. Results: Clinically uneventful healing was observed at all sites. Compared to other sites, WTA and DA consistently showed superior results demonstrating least reduction in alveolar crest height and width which was statistically significant (P < 0.05. Between WTA and DA sites, there was no statistically significant difference. Histological analysis also confirmed more new bone formation at WTA and DA sites. Conclusions: Rather than disposing extracted human teeth as a biomedical waste (common practice, they can be collected from suitable systemically healthy donors. With the help of tissue bank, they can be processed into an allograft, serving as an

  20. Comparative Alveolar Ridge Preservation Using Allogenous Tooth Graft versus Free-dried Bone Allograft: A Randomized, Controlled, Prospective, Clinical Pilot Study.

    Science.gov (United States)

    Joshi, Chaitanya Pradeep; D'Lima, Cynthia Bernardo; Samat, Urmila Chandrashekhar; Karde, Prerna Ashok; Patil, Agraja Ganpat; Dani, Nitin Hemchandra

    2017-01-01

    For the first time in India, allografts from human extracted teeth were prepared. A randomized, prospective, clinicoradiographical, histological study was conducted to evaluate their efficacy in comparison with freeze-dried bone allograft (FDBA) in alveolar ridge preservation. Graft preparation: with written consent, teeth were collected from three donors (full mouth extraction cases). Once donors' serums were tested negative for HIV, HBV, HCV, and Venereal disease research laboratory (VDRL), mineralized whole tooth allograft (WTA) and dentin allograft (DA) were prepared using the standard protocol of Tissue Bank at Tata Memorial Hospital, Mumbai, India. In this randomized controlled trial, 15 patients undergoing extraction of at least four teeth were selected. In each patient after atraumatic extractions, one socket was grafted with WTA, second with DA, third with FDBA, and fourth was left ungrafted (control site). All the sites were covered with chorion membrane. To estimate three-dimensional alveolar crest changes, cone beam computed tomography scans were taken immediately after grafting and 4 months postoperatively. Bone biopsies using 3 mm trephine bur were obtained from four patients at the time of implant placement and evaluated histologically. Clinically uneventful healing was observed at all sites. Compared to other sites, WTA and DA consistently showed superior results demonstrating least reduction in alveolar crest height and width which was statistically significant (P < 0.05). Between WTA and DA sites, there was no statistically significant difference. Histological analysis also confirmed more new bone formation at WTA and DA sites. Rather than disposing extracted human teeth as a biomedical waste (common practice), they can be collected from suitable systemically healthy donors. With the help of tissue bank, they can be processed into an allograft, serving as an excellent alternative to conventional allografts.

  1. Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts From HLA-Matched Related and Unrelated Donors in Preventing GVHD

    Science.gov (United States)

    2016-07-08

    Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Acute Biphenotypic Leukemia; Acute Leukemia of Ambiguous Lineage; Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Blastic Plasmacytoid Dendritic Cell Neoplasm; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Graft Versus Host Disease; Lymphoblastic Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Refractory Anemia With Excess Blasts

  2. Evaluation of risk for graft-versus-host disease in children who receive less than the full doses of mini-dose methotrexate for graft-versus-host disease prophylaxis in allogeneic hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Sook Kyung Yum

    2013-11-01

    Full Text Available Purpose: The use of cyclosporine and mini-dose methotrexate (MTX is a common strategy for graftversus- host disease (GVHD prophylaxis in allogeneic transplants. We investigated whether patients who receive fewer than the planned MTX doses are at increased risk for GVHD. Methods: The study cohort included 103 patients who received allogeneic transplants at the Department of Pediatrics of The Catholic University of Korea College of Medicine, from January 2010 to December 2011. MTX was administered on days 1, 3, 6, and 11 after transplant at a dose of 5 mg/ m2 each. Within the cohort, 76 patients (74% received all 4 doses of MTX [MTX(4 group], while 27 patients (26% received 0&#8211;3 doses [MTX(0–3 group]. Results: Although there was no difference in neutrophil engraftment between the 2 groups, platelet engraftment was significantly faster in the MTX(4 group (median, 15 days, compared to the MTX(0&#8211; 3 group (median, 25 days; P =0.034. The incidence of grades II&#8211;IV acute GVHD was not different between the MTX(4 and MTX(0&#8211;3 groups (P =0.417. In the multivariate study, human leukocyte antigen mismatch was the most significant factor causing grades II&#8211;IV acute GVHD (P =0.002, followed by female donor to male recipient transplant (P =0.034. No difference was found between the MTX(4 and MTX (0&#8211;3 groups regarding grades III&#8211;IV acute GVHD, chronic GVHD, and disease-free survival. Conclusion: Our results indicate that deviations from the full dose schedule of MTX for GVHD prophylaxis do not lead to increased incidence of either acute or chronic GVHD.

  3. Increasing incidence of chronic graft-versus-host disease in allogeneic transplantation: a report from the Center for International Blood and Marrow Transplant Research.

    Science.gov (United States)

    Arai, Sally; Arora, Mukta; Wang, Tao; Spellman, Stephen R; He, Wensheng; Couriel, Daniel R; Urbano-Ispizua, Alvaro; Cutler, Corey S; Bacigalupo, Andrea A; Battiwalla, Minoo; Flowers, Mary E; Juckett, Mark B; Lee, Stephanie J; Loren, Alison W; Klumpp, Thomas R; Prockup, Susan E; Ringdén, Olle T H; Savani, Bipin N; Socié, Gérard; Schultz, Kirk R; Spitzer, Thomas; Teshima, Takanori; Bredeson, Christopher N; Jacobsohn, David A; Hayashi, Robert J; Drobyski, William R; Frangoul, Haydar A; Akpek, Görgün; Ho, Vincent T; Lewis, Victor A; Gale, Robert Peter; Koreth, John; Chao, Nelson J; Aljurf, Mahmoud D; Cooper, Brenda W; Laughlin, Mary J; Hsu, Jack W; Hematti, Peiman; Verdonck, Leo F; Solh, Melhelm M; Norkin, Maxim; Reddy, Vijay; Martino, Rodrigo; Gadalla, Shahinaz; Goldberg, Jenna D; McCarthy, Philip L; Pérez-Simón, José A; Khera, Nandita; Lewis, Ian D; Atsuta, Yoshiko; Olsson, Richard F; Saber, Wael; Waller, Edmund K; Blaise, Didier; Pidala, Joseph A; Martin, Paul J; Satwani, Prakash; Bornhäuser, Martin; Inamoto, Yoshihiro; Weisdorf, Daniel J; Horowitz, Mary M; Pavletic, Steven Z

    2015-02-01

    Although transplant practices have changed over the last decades, no information is available on trends in incidence and outcome of chronic graft-versus-host disease (cGVHD) over time. This study used the central database of the Center for International Blood and Marrow Transplant Research (CIBMTR) to describe time trends for cGVHD incidence, nonrelapse mortality, and risk factors for cGVHD. The 12-year period was divided into 3 intervals, 1995 to 1999, 2000 to 2003, and 2004 to 2007, and included 26,563 patients with acute leukemia, chronic myeloid leukemia, and myelodysplastic syndrome. Multivariate analysis showed an increased incidence of cGVHD in more recent years (odds ratio = 1.19, P < .0001), and this trend was still seen when adjusting for donor type, graft type, or conditioning intensity. In patients with cGVHD, nonrelapse mortality has decreased over time, but at 5 years there were no significant differences among different time periods. Risk factors for cGVHD were in line with previous studies. This is the first comprehensive characterization of the trends in cGVHD incidence and underscores the mounting need for addressing this major late complication of transplantation in future research. Copyright © 2015 American Society for Blood and Marrow Transplantation. All rights reserved.

  4. Ex vivo expansion of regulatory T cells for clinical applications against graft-versus-host disease in allogeneic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    ZHANG Lan-fang; XIA Chang-qing

    2013-01-01

    Objective To review the characteristics of regulatory T cells (Tregs) and ex vivo expansion of Tregs for treatment of graftversus-host disease (GVHD).Data sources The data used in this review were retrieved from PubMed (1970-2013).The terms "ex vivo expansion","regulatory T cell",and "graft-versus-host disease" were used for literature search.Study selection The publications about the characteristics of Tregs,ex vivo expansion of Tregs and clinical applications of Tregs against GVHD were identified,retrieved and reviewed.Results Tregs can be classified as natural Tregs (nTregs) and induced Tregs (iTregs).Both subsets share most Treg features.Given their immunosuppressive property,Tregs have been tested for their capability of preventing GVHD.The bottleneck of Treg therapy is the limited numbers of naturally existing Tregs.To solve this problem,ex vivo expansion of nTregs or iTregs has been executed.The initial data indicate Treg therapy is effective in reducing GVHD without compromising graft-versus-leukemia (GVL).Conclusion Ex vivo expansion of Tregs is a reliable way to prepare sufficient number of Tregs for management of GVHD.

  5. The Pinking Shears: A Novel Tool for Improving Skin Graft Cosmesis

    Directory of Open Access Journals (Sweden)

    Cormac W. Joyce, MB BCh

    2014-12-01

    Full Text Available Summary: A significant aesthetic disadvantage to split skin grafts is the obvious transition between the graft and the normal skin. We report on a novel method to interrupt this transition point by using pinking shears, which are dressmaking scissors with saw-toothed blades that create a chevron pattern instead of a straight edge. We describe a case where the pinking shears were utilized on a split skin graft and Integra for reconstruction of the skin on a volar forearm. This technique allows for breaking-up of the transition point between the skin graft and normal skin and gives rise to an improved aesthetic outcome as the boundary is significantly less well-defined. This novel method shows promise and further study is certainly warranted.

  6. Amalgamation of allogenic bone graft, platelet-rich fibrin gel, and PRF membrane in auto-transplantation of an impacted central incisor

    Directory of Open Access Journals (Sweden)

    Zainab Chaudhary

    2015-01-01

    Full Text Available "Social six" teeth refers to the maxillary incisors and canines that play a vital role in the appearance of an individual and absence of any one of them has a significant psycho-social impact. Hence, early treatment and rehabilitation of the same are extremely important. A multitude of treatment options ranging from orthodontic extrusion, extraction followed by implant placement, fixed partial denture, and auto-transplantation have been advocated. This case report discusses the unique amalgamation of platelet-rich fibrin (PRF, demineralized freeze-dried bone graft with use of PRF membrane during auto-transplantation of an impacted central incisor. The authors have focused on maximum usage of autogenous materials in the most economic and least invasive manner. Furthermore, this amalgamation has been used to provide rehabilitation in the least span of time.

  7. Amalgamation of allogenic bone graft, platelet-rich fibrin gel, and PRF membrane in auto-transplantation of an impacted central incisor.

    Science.gov (United States)

    Chaudhary, Zainab; Kumar, Yuvika Raj; Mohanty, Sujata; Khetrapal, Ambica

    2015-01-01

    "Social six" teeth refers to the maxillary incisors and canines that play a vital role in the appearance of an individual and absence of any one of them has a significant psycho-social impact. Hence, early treatment and rehabilitation of the same are extremely important. A multitude of treatment options ranging from orthodontic extrusion, extraction followed by implant placement, fixed partial denture, and auto-transplantation have been advocated. This case report discusses the unique amalgamation of platelet-rich fibrin (PRF), demineralized freeze-dried bone graft with use of PRF membrane during auto-transplantation of an impacted central incisor. The authors have focused on maximum usage of autogenous materials in the most economic and least invasive manner. Furthermore, this amalgamation has been used to provide rehabilitation in the least span of time.

  8. Application experience of extracorporeal photopheresis for treatment of acute “graft-versus-host” disease after allogeneic hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    A. V. Kozlov

    2014-07-01

    Full Text Available Extracorporeal photopheresis (ECP has been used as a component of combined immunosuppressive therapy in 53 patients with steroid-refractoryacute “graft-versus-host” disease. Overall response was observed in 35 patients (66 %; 95 % CI 52.6–77.3: complete response (CR in 15 pts (28.3 %; 95 % CI 18–41.6 and partial response (PR in 20 pts (37.7 %; 95 % CI 25.9–51.2. 3-year OS was 39 % in patients with clinical response (CR or PR; in the absence of clinical response OS was 8 % during the first year (p < 0.0001. Median methylprednisolone dose before ECP was 2 mg/kg/day, and at the end of ECP course – 0.7 mg/kg/day (p < 0.0001.

  9. Chronic persistent parvovirus B19 bone marrow infection resulting in transfusion-dependent pure red cell aplasia in multiple myeloma after allogeneic haematopoietic stem cell transplantation and severe graft versus host disease.

    Science.gov (United States)

    Karrasch, Matthias; Schmidt, Volker; Hammer, Andreas; Hochhaus, Andreas; Rosée, Paul La; Petersen, Iver; Sauerbrei, Andreas; Baier, Michael; Sayer, Herbert G; Hermann, Beate

    2017-03-01

    We report a chronic persistent Parvovirus B19 (PVB19) infection despite long-term immunoglobulin substitution intravenous immunoglobulin (IVIG) and tapering of immune-suppressive therapy in a 41-year-old patient after allogeneic haematopoietic stem cell transplantation (alloHSCT) and long-term immune-suppressive therapy due to a steroid-refractory graft versus host disease (GvHD). More than 18 month after alloHSCT the patient acquired a de novo transfusion-dependent pure red cell aplasia (PRCA) due to a PVB19 infection. Despite prompt tapering of GvHD-directed therapy and application of various IVIG regimens, transfusion-dependent anaemia (fourerythrocyte concentrates a month) persisted, and a high PVB19 replication is still evident for more than 3.5 years. Virological analysis at different time points showed a very high PVB19 load in the blood (range: 6.79E9-1.56E11), as well as highly elevated PVB19-IgG (range: 1.95-3.34) and -IgM (range: 1.97-9.74) levels in serology testing. Other virological parameters were not significantly elevated. After 30 months, a bone marrow (BM) examination still revealed a highly dysplastic erythropoiesis without any cellular maturation, and a high-grade expression of PVB19 within the dysplastic erythropoietic progenitor cells, consistent with a PRCA due to a PVB19 infection of the BM. We suggest that PRCA was most probably caused by a primary PVB19 infection of unknown source following alloHSCT with a PVB19-negative donor. PRCA due a PVB19 infection of the BM may persist over a long-time, despite prolonged administration of various IVIG regimen and tapering of GvHD-directed therapy. The case emphasizes the importance of PVB19 monitoring in heavily pre-treated haematological patients. Currently, PVB19-directed treatment options are extremely limited and optimized therapeutic strategies are urgently needed.

  10. Potent graft-versus-leukemia effect after reduced-intensity allogeneic SCT for intermediate-risk AML with FLT3-ITD or wild-type NPM1 and CEBPA without FLT3-ITD.

    Science.gov (United States)

    Labouré, Gaëlle; Dulucq, Stéphanie; Labopin, Myriam; Tabrizi, Reza; Guérin, Estelle; Pigneux, Arnaud; Lafarge, Xavier; Leguay, Thibaut; Bouabdallah, Krimo; Dilhuydy, Marie-Sarah; Duclos, Cédric; Lascaux, Axelle; Marit, Gérald; Mahon, François-Xavier; Boiron, Jean-Michel; Milpied, Noël; Vigouroux, Stéphane

    2012-12-01

    To investigate the role of reduced-intensity allogeneic (RIC-allo) stem cell transplant (SCT) as postremission therapy in adult intermediate-risk patients with acute myelogenous leukemia (AML) with FLT3-ITD or wild-type NPM1 and CEBPA without FLT3-ITD, we conducted a single-center retrospective study between January 2001 and December 2010. Sixty-six patients were included: 37 treated with RIC-alloSCT and 29 with nonallogeneic SCT therapies. Both groups were comparable concerning age, WBC count at diagnosis, gender, karyotype, genotype, and number of courses of chemotherapy to reach complete remission (CR1). Median follow-up after CR1 was 37 months (range, 11-112 months) and 48 months (range, 9-83 months) in the allo and no-allo groups, respectively. In the allo versus no-allo groups, the 3-year cumulative incidence of relapse (CIR) rates were 25% ± 8% versus 61% ± 9%; P = .005. The 3-year nonrelapse mortality (NRM), overall survival (OS), and relapse-free survival (RFS) were 22% ± 7% versus 4% ± 4% (P = .005), 52% ± 9% versus 44% ± 10% (P = .75), and 53% ± 9% versus 35% ± 9% (P = .28), respectively. Multivariate analysis indicated that CIR was reduced by allo (hazard ratio [HR], 0.32; P = .01). A landmark analysis performed at day 185 after CR1 confirmed a lower CIR after allo. RIC-allo reduces the risk of relapse, suggesting a potent graft-versus-leukemia (GVL) effect in these patients at a high risk of relapse.

  11. The bone marrow microenvironment is similarly impaired in allogeneic hematopoietic stem cell transplantation patients with early and late poor graft function.

    Science.gov (United States)

    Kong, Y; Wang, Y-T; Hu, Y; Han, W; Chang, Y-J; Zhang, X-H; Jiang, Z-F; Huang, X-J

    2016-02-01

    Poor graft function (PGF), including early and late PGF, is a serious complication following allotransplant. We recently reported that bone marrow microenvironment abnormalities may occur in cases of late PGF. Whether these abnormalities occur in early PGF remains unknown. To answer this question, we performed a nested case-control study comparing cellular elements of the bone marrow microenvironment in 10 subjects with early PGF, 30 subjects with late PGF and 40 subjects without PGF. Bone marrow endosteal cells, perivascular cells and endothelial cells were analyzed by flow cytometry and by hematoxylin-eosin and immunohistochemical staining in situ. Subjects with early and late PGF had similar abnormalities in these cell types compared with transplant recipients without PGF. However, none of the aforementioned elements of the bone marrow microenvironment were significantly different between early and late PGF patients. Our data suggest that similar abnormalities in the bone marrow microenvironment may occur in early and late PGF post allotransplant. Cellular approaches, such as the administration of mesenchymal stem cells, promise to be beneficial therapeutic strategies in patients with early or late PGF.

  12. Gut microbiota and allogeneic transplantation.

    Science.gov (United States)

    Wang, Weilin; Xu, Shaoyan; Ren, Zhigang; Jiang, Jianwen; Zheng, Shusen

    2015-08-23

    The latest high-throughput sequencing technologies show that there are more than 1000 types of microbiota in the human gut. These microbes are not only important to maintain human health, but also closely related to the occurrence and development of various diseases. With the development of transplantation technologies, allogeneic transplantation has become an effective therapy for a variety of end-stage diseases. However, complications after transplantation still restrict its further development. Post-transplantation complications are closely associated with a host's immune system. There is also an interaction between a person's gut microbiota and immune system. Recently, animal and human studies have shown that gut microbial populations and diversity are altered after allogeneic transplantations, such as liver transplantation (LT), small bowel transplantation (SBT), kidney transplantation (KT) and hematopoietic stem cell transplantation (HTCT). Moreover, when complications, such as infection, rejection and graft versus host disease (GVHD) occur, gut microbial populations and diversity present a significant dysbiosis. Several animal and clinical studies have demonstrated that taking probiotics and prebiotics can effectively regulate gut microbiota and reduce the incidence of complications after transplantation. However, the role of intestinal decontamination in allogeneic transplantation is controversial. This paper reviews gut microbial status after transplantation and its relationship with complications. The role of intervention methods, including antibiotics, probiotics and prebiotics, in complications after transplantation are also discussed. Further research in this new field needs to determine the definite relationship between gut microbial dysbiosis and complications after transplantation. Additionally, further research examining gut microbial intervention methods to ameliorate complications after transplantation is warranted. A better understanding of the

  13. Comparison of Subcutaneous versus Intravenous Alemtuzumab for Graft-versus-Host Disease Prophylaxis with Fludarabine/Melphalan-Based Conditioning in Matched Unrelated Donor Allogeneic Stem Cell Transplantation.

    Science.gov (United States)

    Patel, Khilna; Parmar, Sapna; Shah, Shreya; Shore, Tsiporah; Gergis, Usama; Mayer, Sebastian; van Besien, Koen

    2016-03-01

    The objective of this study was to compare infusion-related reactions and outcomes of using subcutaneous (subQ) alemtuzumab versus intravenous (i.v.) alemtuzumab as graft-versus-host disease (GVHD) prophylaxis for matched unrelated donor stem cell transplantations. Outcomes include incidence of cytomegalovirus (CMV)/Epstein-Barr (EBV) viremia, development of CMV disease or post-transplantation lymphoproliferative disorder, fatal infections, acute and chronic GVHD, time to engraftment, relapse rate, and survival. We conducted a retrospective study of all adult matched unrelated donor stem cell transplantations patients who received fludarabine/melphalan with subQ or i.v. alemtuzumab in combination with tacrolimus as part of their conditioning for unrelated donor transplantation at New York-Presbyterian/Weill Cornell Medical Center from January 1, 2012 to March 21, 2014. Alemtuzumab was administered at a total cumulative dose of 100 mg (divided over days -7 to -3). Forty-six patients received an unrelated donor stem cell transplantation with fludarabine/melphalan and either subQ (n = 26) or i.v. (n = 20) alemtuzumab in combination with tacrolimus. Within the evaluable population, 130 subQ and 100 i.v. alemtuzumab doses were administered. For the primary outcome, ≥grade 2 infusion-related reactions occurred in 11 (8%) versus 25 (25%) infusions in the subQ and i.v. cohorts, respectively (P = .001). Overall, 12 injections (9%) in the subQ arm versus 26 infusions (26%) in the i.v. arm experienced an infusion-related reaction of any grade (P = .001). There were no significant differences between the subQ and i.v. arms in rates of reactivation of CMV/EBV, development of CMV disease or post-transplantation lymphoproliferative disorder, fatal infections, acute and chronic GVHD, relapse, or survival. Subcutaneous administration of alemtuzumab for GVHD prophylaxis was associated with fewer infusion-related reactions compared with i.v. administration in the SCT setting

  14. Radiotherapy in allogenic renal transplantation: an indication for local graft irradiation?; Strahlentherapie im Rahmen der allogenen Nierentransplantation: eine Indikation zur lokalen Bestrahlung?

    Energy Technology Data Exchange (ETDEWEB)

    Micke, O.; Bruns, F. U.; Schaefer, U.; Willich, N. [Universitaetsklinikum Muenster (Germany). Klinik und Poliklinik fuer Strahlentherapie; Seegenschmiedt, M.H. [Alfried-Krupp-Krankenhaus Essen (Germany). Klinik fuer Radioonkologie, Strahlentherapie und Nuklearmedizin; Matzkies, F.K. [Universitaetsklinikum Muenster (Germany). Medizinische Klinik und Poliklinik D

    2002-05-01

    Patients and Methods: Between 1979 and 1990, eight patients with biopsy-proven acute renal allograft rejection and failure of all other immunosuppressive measures (corticosteroids, ATG, ALG or OKT3) were treated with LGI. Retrospective analysis was conducted for this control group. Radiotherapy was performed with Co-60 up to a median total dose of 6.0 Gy (single doses: 1.5-2.0 Gy). Six of eight patients were dialysis dependent prior to irradiation. In addition a literature review was performed including most important textbooks, electronic databases (Medline, Embase, Science Citations Index), and the internet. Results: Two of eight patients experienced a clinical reversal of rejection and an improvement of renal function: serum creatinine decreased significantly. One patient remained free of dialysis with a functioning graft, the other had a recurrent rejection 2 months later and became dialysis dependent. The literature review showed, that adjuvant LGI has no advantage over conventional immunosuppression. However, in case of a drug refractory allograft rejection LGI restores long-term stable organ function in 13-60% of cases. (orig.) [German] Patienten und Methode: Zwischen 1979 und 1990 wurden acht Patienten mittels Radiotherapie behandelt (historisches Kollektiv). Bei allen Patienten war die akute Abstossung des Nierentransplantats im 1. Jahr nach Transplantation bioptisch gesichert; andere immunsuppressive Massnahmen hatten versagt. Die Bestrahlung erfolgte mit einer medianen Gesamtdosis von 6,0 Gy (Einzeldosis 1,5-2,0 Gy). Sechs von acht Patienten waren zu Beginn der Bestrahlung dialyseabhaengig. Die Ergebnisse werden diskutiert vor dem Hintergrund eines Reviews der vorhandenen Literatur zur lokalen Transplantatbestrahlung und unter Einbeziehung von Lehrbuechern, elektronischen Datenbanken (Medline, Embase, Science Citations Index) und des Internets. Ergebnisse: Im eigenen Patientengut erreichten zwei der acht Patienten klinisch eine Reversion der Rejektion

  15. 脱细胞异体真皮与自体薄皮片复合移植在老年烧伤整形患者中的应用%Removal of Cell Allogeneic Dermis and Autologous Thin Split Graft in the Elderly Patients with Burn and Plastic Surgery

    Institute of Scientific and Technical Information of China (English)

    丁思奇

    2016-01-01

    目的:研究脱细胞异体真皮与自体薄皮片复合移植在老年烧伤整形患者中的应用。方法选取我院收治的23例老年烧伤整形患者作为研究对象。结果22例患者的复合植皮存活,存活率95.65%;3例患者出现部分组织感染现象,严重导致植皮坏死;其中16例患者植后供皮区域无瘢痕,7例患者植皮与正常皮肤接触部位产生轻微的轮廓瘢痕。12例患者植皮部位存活完好,且弹性正常,肤色光泽,无瘢痕;1例患者出现植皮失败的现象。结论采用脱细胞异体真皮与自体薄皮片复合移植在老年烧伤整形患者中能够提高植皮存活率,降低瘢痕程度。%Objective To study the decellularized allogeneic dermis and autologous thin skin application in elderly patients with burn plastic composite transplantation. Methods Selection of 23 cases admitted in a hospital in elderly patients with burn plastic as the research object. Results 22 cases of composite skin graft survival, survival rate 95.65%; 3 patients appeared some phenomenon of tissue infection, serious cause skin graft necrosis; Including 16 patients after graft for skin area without scar, 7 cases of patients with skin graft and normal skin contact parts produce slight scar of contour. Survive intact, 12 patients with skin graft site and elastic, normal skin gloss, no scar, 1 patients, the phenomenon of the skin graft failure. Conclusion Using decellularized allogeneic dermis and autologous thin piece of composite skin grafting in elderly patients with burn plastic can improve the skin graft survival rate.

  16. Allogeneic hematopoietic stem cell transplantation for chronic myelomonocytic leukemia:a report of 12 patients

    Institute of Scientific and Technical Information of China (English)

    孙于谦

    2013-01-01

    Objective To retrospectively review the efficacy of allogeneic hematopoietic stem cell transplantation(allo-HSCT)for chronic myelomonocytic leukemia(CMML).Methods The engraftment,graft versus host disease(GVHD)

  17. Soluble urokinase plasminogen activator receptor during allogeneic stem cell transplantation

    DEFF Research Database (Denmark)

    Haastrup, E; Andersen, J; Ostrowski, S R

    2011-01-01

    the course of allogeneic stem cell transplantation (SCT). Twenty SCT patients were included in the study. suPAR was measured by ELISA in daily taken plasma samples during the pretransplant conditioning with chemotherapy and weekly for 1 month after infusion of the graft. suPAR levels before the start...

  18. On the Feasibility of Utilizing Allogeneic Bone Blocks for Atrophic Maxillary Augmentation

    Directory of Open Access Journals (Sweden)

    Alberto Monje

    2014-01-01

    Full Text Available Purpose. This systematic review was aimed at assessing the feasibility by means of survival rate, histologic analysis, and causes of failure of allogeneic block grafts for augmenting the atrophic maxilla. Material and Methods. A literature search was conducted by one reviewer in several databases. Articles were included in this systematic review if they were human clinical trials in which outcomes of allogeneic bone block grafts were studied by means of survival rate. In addition other factors were extracted in order to assess their influence upon graft failure. Results. Fifteen articles fulfilled the inclusion criteria and subsequently were analyzed in this systematic review. A total of 361 block grafts could be followed 4 to 9 months after the surgery, of which 9 (2.4% failed within 1 month to 2 months after the surgery. Additionally, a weighed mean 4.79 mm (95% CI: 4.51–5.08 horizontal bone gain was computed from 119 grafted sites in 5 studies. Regarding implant cumulative survival rate, the weighed mean was 96.9% (95% CI: 92.8–98.7%, computed from 228 implants over a mean follow-up period of 23.9 months. Histologic analysis showed that allogeneic block grafts behave differently in the early stages of healing when compared to autogenous block grafts. Conclusion. Atrophied maxillary reconstruction with allogeneic bone block grafts represents a reliable option as shown by low block graft failure rate, minimal resorption, and high implant survival rate.

  19. 同种异体牙源性骨移植材料修复兔颅骨缺损的实验研究%Experimental Study of the Repair of Rabbit Skull Defects with Allogeneic Tooth Derived Bone Graft Material

    Institute of Scientific and Technical Information of China (English)

    王媛; 王稚英; 王明

    2016-01-01

    Objective To evaluate the osteogenesis of rabbit allogeneic tooth derived bone graft material by histological detection ,so as to provide quality and cheap repair materials for the repair of bone defects in dental implants. Methods The bone graft materials were prepared using rab⁃bits allogeneic extracted teeth. A total of 28 adult Japanese healthy rabbits were selected to establish the cranial defect model with three 8 mm diam⁃eter holes. The allogenic tooth derived bone graft material were implanted into the experimental group. The artificial bone repair material was used as the control group,and the control group did not receive any implantion. Tetracycline labeling was performed after operation,the specimens were taken at 4,8 and 12 weeks after operation,and then the gross observation,X⁃ray examination,preparation of hard tissue sections,and HE staining were carried out. Results Histological analysis at 4,8 and 12 weeks after operation showed that there was an increasing trend the new bone for⁃mation in both experimental group and the control group ,and the experimental group was better;the trabecular bone structure of the blank group was scarce and the change was not obvious. Conclusion Allogenic tooth derived bone graft materials can promote the repair of bone defect ,and the effect is better than that of artificial bone repair materials.%目的:通过组织学检测评估兔同种异体牙源性骨移植材料的成骨作用,为口腔种植区骨量不足的修复提供质优价廉的修复材料。方法将兔同种异体离体牙制备成骨移植材料。选用成年健康日本长耳兔28只,建立颅骨缺损模型(3个直径为8 mm的洞形缺损),植入同种异体牙源性骨移植材料作为实验组、人工骨修复材料作为对照组、空白对照组不植入任何材料。取标本前3 d、7 d向兔腹腔注射四环素,分别于术后4、8、12周取标本,进行大体观察、X线检查、制备硬组织

  20. Subdominant H60 antigen-specific CD8 T-cell response precedes dominant H4 antigen-specific response during the initial phase of allogenic skin graft rejection.

    Science.gov (United States)

    Yoo, Kang Il; Jeon, Ji Yeong; Ryu, Su Jeong; Nam, Giri; Youn, Hyewon; Choi, Eun Young

    2015-02-13

    In allogeneic transplantation, including the B6 anti-BALB.B settings, H60 and H4 are two representative dominant minor histocompatibility antigens that induce strong CD8 T-cell responses. With different distribution patterns, H60 expression is restricted to hematopoietic cells, whereas H4 is ubiquitously expressed. H60-specific CD8 T-cell response has been known to be dominant in most cases of B6 anti-BALB.B allo-responses, except in the case of skin transplantation. To understand the mechanism underlying the subdominance of H60 during allogeneic skin transplantation, we investigated the dynamics of the H60-specific CD8 T cells in B6 mice transplanted with allogeneic BALB.B tail skin. Unexpectedly, longitudinal bioluminescence imaging and flow cytometric analyses revealed that H60-specific CD8 T cells were not always subdominant to H4-specific cells but instead showed a brief dominance before the H4 response became predominant. H60-specific CD8 T cells could expand in the draining lymph node and migrate to the BALB.B allografts, indicating their active participation in the anti-BALB.B allo-response. Enhancing the frequencies of H60-reactive CD8 T cells prior to skin transplantation reversed the immune hierarchy between H60 and H4. Additionally, H60 became predominant when antigen presentation was limited to the direct pathway. However, when antigen presentation was restricted to the indirect pathway, the expansion of H60-specific CD8 T cells was limited, whereas H4-specific CD8 T cells expanded significantly, suggesting that the temporary immunodominance and eventual subdominance of H60 could be due to their reliance on the direct antigen presentation pathway. These results enhance our understanding of the immunodominance phenomenon following allogeneic tissue transplantation.

  1. Survival of cultured allogeneic keratinocytes transplanted to deep dermal bed assessed with probe specific for Y chromosome.

    OpenAIRE

    Brain, A.; Purkis, P.; Coates, P; Hackett, M; Navsaria, H; Leigh, I

    1989-01-01

    To determine the survival of cultured allogeneic keratinocytes transplanted to a deep dermal bed 24 tattoos that had been removed by deep shave excision in 19 patients were grafted with sheets of cultured allogeneic keratinocytes from donors of the opposite sex. Cells carrying the Y chromosome were identified in biopsy specimens taken from the graft site by in situ DNA hybridisation with a biotinylated Y probe (pHY 2.1) and visualised with a technique using immunoperoxidase. The cultured allo...

  2. Ibrutinib Effective against Graft-Versus-Host Disease

    Science.gov (United States)

    A Cancer Currents blog post on results from a small clinical trial showing that ibrutinib can effectively treat graft-versus-host-disease, a common and serious complication of allogeneic stem cell transplants.

  3. Isolated extra-medullary relapse of acute leukemia following allogeneic bone marrow transplantation.

    Science.gov (United States)

    Firas, Al Sabty; Demeckova, E; Bojtarova, E; Czako, B; Hrubisko, M; Mistrik, M

    2008-01-01

    Isolated extramedullary relapse (IEMR) of acute leukemia (AL) after allogeneic bone marrow transplantation (BMT) is a rare occurrence. It is seen more commonly after BMT than after conventional chemotherapy (CHT) alone. We describe the natural history and response to treatment in four patients with IEMR following allogeneic BMT. The results indicate a stronger graft-versus-leukemia (GVL) effect in the marrow than in the peripheral tissues (Fig. 4, Ref. 13). Full Text (Free, PDF) www.bmj.sk.

  4. Allogeneic stem cell transplantation in acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Natasha Ali

    2012-11-01

    Full Text Available We report a case series of 12 patients with acute myeloid leukemia who underwent allogeneic stem cell transplant with a matched related donor. Male to female ratio was 1:1. The main complication post-transplant was graft-versus-host disease (n=7 patients. Transplant-related mortality involved one patient; cause of death was multi-organ failure. After a median follow up of 36.0±11.3 months, overall survival was 16%.

  5. Surgical technique for allogeneic uterus transplantation in macaques

    Science.gov (United States)

    Obara, Hideaki; Kisu, Iori; Kato, Yojiro; Yamada, Yohei; Matsubara, Kentaro; Emoto, Katsura; Adachi, Masataka; Matoba, Yusuke; Umene, Kiyoko; Nogami, Yuya; Banno, Kouji; Tsuchiya, Hideaki; Itagaki, Iori; Kawamoto, Ikuo; Nakagawa, Takahiro; Ishigaki, Hirohito; Itoh, Yasushi; Ogasawara, Kazumasa; Saiki, Yoko; Sato, Shin-ichi; Nakagawa, Kenshi; Shiina, Takashi; Aoki, Daisuke; Kitagawa, Yuko

    2016-01-01

    No study has reported an animal model of uterus transplantation (UTx) using cynomolgus macaques. We aimed to establish a surgical technique of allogeneic UTx assuming the recovery of a uterus from a deceased donor in cynomolgus macaques. Four allogeneic UTxs were performed in female cynomolgus macaques. Donor surgeries comprised en bloc recovery of organs with iliac vessels on both sides, and/or abdominal aorta/vena cava after sufficient perfusion from one femoral artery or external iliac artery. Before perfusion, 150 mL of whole blood was obtained from the donor for subsequent blood transfusion to the recipient. Four uterine grafts were orthotopically transplanted to recipients. End-to-side anastomosis was performed to the iliac vessels on one side in case 1 and iliac vessels on both sides in case 2; aorto-aorto/cavo-caval anastomosis was performed in cases 3 and 4. Arterial blood flow of the uterine grafts was determined by intraoperative indocyanine green (ICG) angiography. ICG angiography results showed sufficient blood flow to all uterine grafts, and anaemia did not progress. Under appropriate immune suppression, all recipients survived for more than 90 days post-transplantation, without any surgical complications. We describe a surgical technique for allogeneic UTx in cynomolgus macaques. PMID:27786258

  6. Chronic inflammatory demyelinating polyradiculoneuropathy in chronic graft-versus-host disease following allogeneic hematopoietic stem cell transplantation: case report Polirradiculoneuropatia desmielinizante inflamatória crônica na doença do enxerto contra o hospedeiro após transplante de células hematopoiéticas alogênicas: relato de caso

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    Paulo José Lorenzoni

    2007-09-01

    Full Text Available The chronic inflammatory demyelinating polyradiculoneuropathy (CIDP is an unusual but important complication of hematopoietic stem cell transplantation (HSCT rarely reported to date. We describe a 17-year-old woman with a diagnosis of acute myeloid leukemia due to Fanconi's anemia who was submitted to allogeneic HSCT and developed CIDP as part of graft-versus-host disease. Investigation showed high cerebrospinal fluid protein; electrophysiological studies revealed sensory-motor demyelinating polyradiculoneuropathy; muscle and nerve biopsy were compatible with CIDP.A polirradiculoneuropatia desmielinizante inflamatória crônica (CIDP é uma incomum, porém, importante complicação do transplante de células hematopoiéticas (HSCT raramente relatada até a data. Nós descrevemos uma mulher de 17 anos com diagnóstico de leucemia mielóide aguda por anemia de Fanconi que foi submetida à HSCT e desenvolveu CIDP como parte da doença do enxerto contra o hospedeiro. A investigação mostrou elevação na proteína no líquor; estudo eletrofisiológico revelando polirradiculoneuropatia desmielinizante sensitivo-motora; e biópsia de músculo e nervo compatível com CIDP.

  7. Epigenetic therapy in allogeneic hematopoietic stem cell transplantation

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    Qaiser Bashir

    2013-01-01

    Full Text Available DNA methylation and other epigenetic phenomena appear to be relevant in the pathogenesis of several malignant disorders. DNA methyltransferases add methyl groups to cytosine-phosphate-guanine (CpG islandsleading to gene promoter silencing. The DNA methyltransferases inhibitors azacitidine and decitabine have anti-tumor activity against a broad range of malignancies, but have been investigated mostly in myelodysplastic syndrome. In addition, these agents have immunomodulatory effects that are under investigation in the allogeneic stem cell transplantation scenario. Both drugs have been used in the perioperative period of allogeneic transplantations with varying degrees of success. It has been hypothesized that low dose azacitidine may increase the graftversus-leukemia effect and have a role in the maintenance of remission after allogeneic transplantation for myeloid leukemias. It is also intriguing that this favorable effect might occur while mitigating graft-versus-host disease. Here we present a review of the rapidly growing field of epigenetic manipulation using hypomethylating agents in allogeneic transplantation.

  8. Intractable myoclonic seizures in an allogeneic stem cell transplant recipient: A rare case of myoclonic epilepsy

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    Anna Robuccio

    2015-01-01

    Discussion: Graft versus host disease occurs in 30–50% of allogenic hematopoietic stem cell transplant patients and may cause pharmacoresistant myoclonic epilepsy; however, the mechanisms by which GVHD leads to recurrent myoclonic seizures are not well understood (Lee, 2005 [1]. The paucity of clinical reports of such manifestation makes it difficult to diagnose and effectively manage these patients.

  9. Alloreactivity of Virus-Specific T Cells: Possible Implication of Graft-Versus-Host Disease and Graft-Versus-Leukemia Effects

    Science.gov (United States)

    Fuji, Shigeo; Kapp, Markus; Einsele, Hermann

    2013-01-01

    Immune reconstitution of functional virus-specific T cells after allogeneic hematopoietic stem cell transplantation (HSCT) has been intensively investigated. However, the possible role of crossreactivity of these virus-specific T cells against allogeneic targets is still unclear. Theoretically, as in the field of organ transplantation, virus-specific T cells possess crossreactivity potential after allogeneic HSCT. Such crossreactivity is assumed to play a role in graft-versus-host disease and graft-versus-leukemia effects. In this article, we aim to give a comprehensive overview of current understanding about crossreactivity of virus-specific T cells. PMID:24133497

  10. Survival of cultured allogeneic keratinocytes transplanted to deep dermal bed assessed with probe specific for Y chromosome.

    Science.gov (United States)

    Brain, A; Purkis, P; Coates, P; Hackett, M; Navsaria, H; Leigh, I

    1989-04-08

    To determine the survival of cultured allogeneic keratinocytes transplanted to a deep dermal bed 24 tattoos that had been removed by deep shave excision in 19 patients were grafted with sheets of cultured allogeneic keratinocytes from donors of the opposite sex. Cells carrying the Y chromosome were identified in biopsy specimens taken from the graft site by in situ DNA hybridisation with a biotinylated Y probe (pHY 2.1) and visualised with a technique using immunoperoxidase. The cultured allograft sites were biopsied one, two, and three weeks after transplantation. No male cells were identified in any biopsy specimen from female patients who were given transplants of male cultured keratinocytes, and all biopsy specimens from male patients, who received female cultured keratinocytes, showed percentages of male cells within the normal range for male skin. The beneficial effects of cultivated allogeneic keratinocytes result from effects on wound healing other than forming a successful graft that "takes."

  11. Role of small-dose decitabine in treatment of early recurrence and chronic graft versus host disease after allogeneic hematopoietic stem cell transplantation%小剂量地西他滨在异基因造血干细胞移植后早期复发及cGVHD治疗中的作用

    Institute of Scientific and Technical Information of China (English)

    王晓果; 陈婷; 刘焕凤; 邓天霞; 刘俊; 张诚; 张曦; 孔佩艳

    2016-01-01

    目的 分析小剂量地西他滨(decitabine/dacogen,DAC)治疗异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo-HSCT)后慢性移植物抗宿主病(chronic graft versus host disease,cGVHD)患者的转归情况.方法 收集2013年6月25日至2015年7月7日我院行allo-HSCT术后早期复发及发生cGVHD,并接受小剂量DAC治疗的4例患者,包括急性髓系白血病(acute myeloid leukemia,AML)3例,骨髓增生异常综合征(myelodysplastic syndrome,MDS)1例.对其诊断、移植方式、cGVHD分型及评分、以及DAC治疗后转归进行分析.结果 4例接受小剂量DAC的患者,cGVHD症状减轻,无严重的血液学毒性.1例因严重肺部感染放弃治疗,3例目前病情稳定.结论 小剂量DAC可减轻allo-HSCT术后cGVHD症状,改善患者生存质量,并对早期复发的控制有一定的效果.

  12. Disparity for the minor histocompatibility antigen HA-1 is associated with an increased risk of acute graft-versus-host disease (GvHD) but it does not affect chronic GvHD incidence, disease-free survival or overall survival after allogeneic human leucocyte antigen-identical sibling donor transplantation.

    Science.gov (United States)

    Gallardo, D; Aróstegui, J I; Balas, A; Torres, A; Caballero, D; Carreras, E; Brunet, S; Jiménez, A; Mataix, R; Serrano, D; Vallejo, C; Sanz, G; Solano, C; Rodríguez-Luaces, M; Marín, J; Baro, J; Sanz, C; Román, J; González, M; Martorell, J; Sierra, J; Martín, C; de la Cámara, R; Grañena, A

    2001-09-01

    Disparity for the minor histocompatibility antigen HA-1 between patient and donor has been associated with an increased risk of acute graft-versus-host disease (GvHD) after allogeneic human leucocyte antigen (HLA)-identical sibling donor stem cell transplantation (SCT). However, no data concerning the impact of such disparity on chronic GvHD, relapse or overall survival are available. A retrospective multicentre study was performed on 215 HLA-A2-positive patients who received an HLA-identical sibling SCT, in order to determine the differences in acute and chronic GvHD incidence on the basis of the presence or absence of the HA-1 antigen mismatch. Disease-free survival and overall survival were also analysed. We detected 34 patient-donor pairs mismatched for HA-1 antigen (15.8%). Grades II-IV acute GvHD occurred in 51.6% of the HA-1-mismatched pairs compared with 37.1% of the non-mismatched. The multivariate logistic regression model showed statistical significance (P: 0.035, OR: 2.96, 95% CI: 1.07-8.14). No differences were observed between the two groups for grades III-IV acute GvHD, chronic GvHD, disease-free survival or overall survival. These results confirmed the association between HA-1 mismatch and risk of mild acute GvHD, but HA-1 mismatch was not associated with an increased incidence of chronic GvHD and did not affect relapse or overall survival.

  13. Alemtuzumab in allogeneic hematopoetic stem cell transplantation.

    Science.gov (United States)

    Poiré, Xavier; van Besien, Koen

    2011-08-01

    With the use of reduced-intensity conditioning (RIC), early toxicity of allogeneic stem cell transplantation (SCT) has been much reduced. Graft-versus-host disease (GvHD) causes morbidities and mortality. Alemtuzumab is a mAb directed against CD52. When administered prior to transplant, it leads to T-cell depletion. Incorporation of alemtuzumab in RIC results in low rates of GvHD and treatment-related mortality (TRM) in haematological diseases, even in the setting of mismatched-donor transplantation. The use of alemtuzumab for GvHD prophylaxis in SCT. The benefit of alemtuzumab-based conditioning is partially offset by increased disease relapse due to impaired graft-versus-tumor effect (GvT) and by slower immune reconstitution, necessitating special precautions. While GvHD is prevented with alemtuzumab, post-SCT interventions are often required. Most studies find that alemtuzumab-based conditioning results in decreased chronic GvHD and TRM, but also in decreased progression-free survival. Overall survival after 3 - 5 years is usually equivalent and quality of life may be improved because of a lower incidence of sequelae of chronic GvHD. Many aspects of alemtuzumab treatment are under investigation. Alemtuzumab reduces GvHD and TRM after SCT. Use of alemtuzumab requires awareness and strict management of the risk of opportunistic infections and of an increased risk of disease recurrence.

  14. IL-22 promoted CD3+ T cell infiltration by IL-22R induced STAT3 phosphorylation in murine acute graft versus host disease target organs after allogeneic bone marrow transplantation.

    Science.gov (United States)

    Zhao, Kai; Ruan, Suhong; Tian, Yu; Zhao, Dongmei; Chen, Chong; Pan, Bin; Yan, Zhiling; Yin, Lingling; Zhu, Shengyun; Xu, Kailin

    2016-10-01

    Graft versus host disease (GVHD) is a life threatening complication of bone marrow stem cell transplantation, in which considerable numbers of proinflammatory cytokines secreted by allo-reactive donor T cells are involved. We and other previous studies have found that interleukin-22 (IL-22) was able to aggravate the target organs damage of GVHD. However, the mechanism and the signal pathway of IL-22 in murine acute GVHD was not clear. Here, we observed that compared with GVHD group, more serious pathological damage and more CD3(+) T cells infiltrated in GVHD target organs were detected in the mice injected with IL-22. Meanwhile, transcription factor T-bet, RORγt and AhR respectively associated with Th1, Th17 and Th22 cells changed in varying degrees in different GVHD target organs. Furthermore, the increased expression of IL-22R and its downstream protein P-STAT3 were detected in GVHD mice with IL-22 treated. These results suggested that the pathological role of IL-22 in GVHD target organs contribute to exogenous injected IL-22 as well as secreted IL-22 from the infiltrated allo-reactive effector T cells. In addition, the IL-22R-STAT3 pathway may play important role in GVHD tissue injury and target this way may yield new approaches for reduction of GVHD.

  15. Romiplostim in thrombocytopenia treatment after allogeneic bone marrow transplantation

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    I. A. Lisukov

    2014-07-01

    Full Text Available Persistent thrombocytopenia is a frequent complication after allogeneic bone marrow transplantation (BMT. The major causes of thrombocytopenia include accelerated platelet destruction by antiplatelet antibodies, microangiopathy, viral infection, drug toxicity,graft`s hypofunction with insufficient production of platelets from megakaryocytes. We have evaluated an efficacy of TPO-receptor agonistromiplostim in treatment of 3 patients with refractory thrombocytopenia after allogeneic BMT. The first 30 years old patient received haploidentical allogeneic stem cell transplantation for refractory AML relapse. He developed graft hypofunction due to CMV infection, acute GVHD and thrombotic thrombocytopenic purpura (TTP with platelet counts 5 × 109/l and bleeding complications. After bone marrow “boost” the patient received romiplostim 1 mkg/kg weekly during 2 weeks and 4 mkg/kg during another 2 weeks. Upon reaching platelet counts 50 × 109/l the romiplostim was stopped, but platelet count decreased to 5–7 × 109/l and romiplostim was administered in dose of 4 mkg/kg weekly during 5 weeks. Platelet counts have achieved 150 × 109/l and thrombocytopenia during further follow-up was not revealed. The second 19 years old AML patient received haploidentical allogeneic stem cell transplantation for second remission consolidation. He developed thrombocytopenia (10 × 109/l due to CMV infection and severe TTP. He received romiplostim 4 mkg/kg weekly and 5 weeks later platelet counts was 50 × 109/l. The administration of romiplostim was allowed to avoid bleeding complications and transfusion dependency. The third 18 years old ALL patient received MUD allogeneic stem cell transplantation for second remission consolidation. He developed profound thrombocytopenia (5 × 109/l with severe hemorrhagic complications and platelet transfusions refractory due to TTP and acute GVHD. He received one dose of romiplostim 1 mkg/kg and two doses of 3 mkg

  16. Romiplostim in thrombocytopenia treatment after allogeneic bone marrow transplantation

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    I. A. Lisukov

    2012-01-01

    Full Text Available Persistent thrombocytopenia is a frequent complication after allogeneic bone marrow transplantation (BMT. The major causes of thrombocytopenia include accelerated platelet destruction by antiplatelet antibodies, microangiopathy, viral infection, drug toxicity,graft`s hypofunction with insufficient production of platelets from megakaryocytes. We have evaluated an efficacy of TPO-receptor agonistromiplostim in treatment of 3 patients with refractory thrombocytopenia after allogeneic BMT. The first 30 years old patient received haploidentical allogeneic stem cell transplantation for refractory AML relapse. He developed graft hypofunction due to CMV infection, acute GVHD and thrombotic thrombocytopenic purpura (TTP with platelet counts 5 × 109/l and bleeding complications. After bone marrow “boost” the patient received romiplostim 1 mkg/kg weekly during 2 weeks and 4 mkg/kg during another 2 weeks. Upon reaching platelet counts 50 × 109/l the romiplostim was stopped, but platelet count decreased to 5–7 × 109/l and romiplostim was administered in dose of 4 mkg/kg weekly during 5 weeks. Platelet counts have achieved 150 × 109/l and thrombocytopenia during further follow-up was not revealed. The second 19 years old AML patient received haploidentical allogeneic stem cell transplantation for second remission consolidation. He developed thrombocytopenia (10 × 109/l due to CMV infection and severe TTP. He received romiplostim 4 mkg/kg weekly and 5 weeks later platelet counts was 50 × 109/l. The administration of romiplostim was allowed to avoid bleeding complications and transfusion dependency. The third 18 years old ALL patient received MUD allogeneic stem cell transplantation for second remission consolidation. He developed profound thrombocytopenia (5 × 109/l with severe hemorrhagic complications and platelet transfusions refractory due to TTP and acute GVHD. He received one dose of romiplostim 1 mkg/kg and two doses of 3 mkg

  17. Reduction of mandibular residual ridge after vestibuloplasty. A two-year follow-up study comparing the Edlan flap, mucosal and skin graft operations.

    Science.gov (United States)

    Hillerup, S; Eriksen, E; Solow, B

    1989-10-01

    Mandibular residual ridge reduction (RRR) after Edlan flap vestibuloplasty, buccal mucosal graft, and split skin graft vestibuloplasty was measured on lateral cephalometric radiographs obtained 1, 3, 6, 12 and 24 months postsurgery in 50 patients. The ridge reduction was most severe during the immediate postoperative period. The different operation methods did not give rise to significant variations in the reduction pattern, neither did the sex of the patient appear to be an important factor. The temporary increase of mandibular resorption after vestibuloplasty surgery is of a magnitude comparable to the average RRR during 1 year in full denture wearers with a long denture experience.

  18. Use of lymphokine-activated killer cells to prevent bone marrow graft rejection and lethal graft-vs-host disease

    Energy Technology Data Exchange (ETDEWEB)

    Azuma, E.; Yamamoto, H.; Kaplan, J. (Wayne State Univ. School of Medicine, Detroit, MI (USA))

    1989-09-01

    Prompted by our recent finding that lymphokine-activated killer (LAK) cells mediate both veto and natural suppression, we tested the ability of adoptively transferred LAK cells to block two in vivo alloreactions which complicate bone marrow transplantation: resistance to transplanted allogeneic bone marrow cells, and lethal graft-vs-host disease. Adoptive transfer of either donor type B6D2 or recipient-type B6 lymphokine-activated bone marrow cells, cells found to have strong LAK activity, abrogated or inhibited the resistance of irradiated B6 mice to both B6D2 marrow and third party-unrelated C3H marrow as measured by CFU in spleen on day 7. The ability of lymphokine-activated bone marrow cells to abrogate allogeneic resistance was eliminated by C lysis depletion of cells expressing asialo-GM1, NK1.1, and, to a variable degree, Thy-1, but not by depletion of cells expressing Lyt-2, indicating that the responsible cells had a LAK cell phenotype. Similar findings were obtained by using splenic LAK cells generated by 3 to 7 days of culture with rIL-2. Demonstration that allogeneic resistance could be blocked by a cloned LAK cell line provided direct evidence that LAK cells inhibit allogeneic resistance. In addition to inhibiting allogeneic resistance, adoptively transferred recipient-type LAK cells prevented lethal graft-vs-host disease, and permitted long term engraftment of allogeneic marrow. Irradiation prevented LAK cell inhibition of both allogeneic resistance and lethal graft-vs-host disease. These findings suggest that adoptive immunotherapy with LAK cells may prove useful in preventing graft rejection and graft-versus-host disease in human bone marrow transplant recipients.

  19. [Effect of decitabine on immune regulation in patients with acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation].

    Science.gov (United States)

    Wang, Jing; Zhou, Jin; Zheng, Hui-Fei; Fu, Zheng-Zheng

    2014-10-01

    Based on the representative articles in recent years, the different mechanisms of decitabine on immune regulation in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (HSCT) are summarized. Decitabine improves the expression of WT1 gene to stimulate specific cytotoxic T cells which can enhance graft versus leukemia effect (GVL) and improve the expression of FOXP3 gene to stimulate regulatory T cells so as to inhibit the acute graft versus host disease (GVHD). Through the above-mentimed mechanisms, decitabine can improve both therapeutic effect and quality of life in the patients with AML after allogeneic HSCT.

  20. Cutaneous graft-versus-host disease after hematopoietic stem cell transplant - a review*

    Science.gov (United States)

    Villarreal, Cesar Daniel Villarreal; Alanis, Julio Cesar Salas; Pérez, Jose Carlos Jaime; Candiani, Jorge Ocampo

    2016-01-01

    Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplants (allo-HSCT) associated with significant morbidity and mortality. The earliest and most common manifestation is cutaneous graft-versus-host disease. This review focuses on the pathophysiology, clinical features, prevention and treatment of cutaneous graft-versus-host disease. We discuss various insights into the disease's mechanisms and the different treatments for acute and chronic skin graft-versus-host disease. PMID:27438202

  1. Reconstruction of beagle hemi-mandibular defects with allogenic mandibular scaffolds and autologous mesenchymal stem cells.

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    ChangKui Liu

    Full Text Available Massive bone allografts are frequently used in orthopedic reconstructive surgery, but carry a high failure rate of approximately 25%. We tested whether treatment of graft with mesenchymal stem cells (MSCs can increase the integration of massive allografts (hemi-mandible in a large animal model.Thirty beagle dogs received surgical left-sided hemi-mandibular defects, and then divided into two equal groups. Bony defects of the control group were reconstructed using allografts only. Those of the experimental group were reconstructed using allogenic mandibular scaffold-loaded autologous MSCs. Beagles from each group were killed at 4 (n = 4, 12 (n = 4, 24 (n = 4 or 48 weeks (n = 3 postoperatively. CT and micro-CT scans, histological analyses and the bone mineral density (BMD of transplants were used to evaluate defect reconstruction outcomes.Gross and CT examinations showed that the autologous bone grafts had healed in both groups. At 48 weeks, the allogenic mandibular scaffolds of the experimental group had been completely replaced by new bone, which has a smaller surface area to that of the original allogenic scaffold, whereas the scaffold in control dogs remained the same size as the original allogenic scaffold throughout. At 12 weeks, the BMD of the experimental group was significantly higher than the control group (p<0.05, and all micro-architectural parameters were significantly different between groups (p<0.05. Histological analyses showed almost all transplanted allogeneic bone was replaced by new bone, principally fibrous ossification, in the experimental group, which differed from the control group where little new bone formed.Our study demonstrated the feasibility of MSC-loaded allogenic mandibular scaffolds for the reconstruction of hemi-mandibular defects. Further studies are needed to test whether these results can be surpassed by the use of allogenic mandibular scaffolds loaded with a combination of MSCs and osteoinductive growth

  2. Low levels of allogeneic but not syngeneic hematopoietic chimerism reverse autoimmune insulitis in prediabetic NOD mice.

    Science.gov (United States)

    Kaminitz, Ayelet; Mizrahi, Keren; Yaniv, Isaac; Farkas, Daniel L; Stein, Jerry; Askenasy, Nadir

    2009-09-01

    The relative efficiencies of allogeneic and syngeneic bone marrow transplantation and the threshold levels of donor chimerism required to control autoimmune insulitis were evaluated in prediabetic NOD mice. Male and female NOD mice were conditioned by radiation and grafted with bone marrow cells from allogeneic and syngeneic sex-mismatched donors. Establishment of full allogeneic chimerism in peripheral blood reversed insulitis and restored glucose tolerance despite persistence of residual host immune cells. By contrast, sublethal total body irradiation (with or without syngeneic transplant) reduced the incidence and delayed the onset of diabetes. The latter pattern was also seen in mice that rejected the bone marrow allografts. Low levels of stable allogeneic hematopoietic chimerism (>1%) were sufficient to prevent the evolution of diabetes following allogeneic transplantation. The data indicate that immunomodulation attained at low levels of allogeneic, but not syngeneic, hematopoietic chimerism is effective in resolution of islet inflammation at even relatively late stages in the evolution of the prediabetic state in a preclinical model. However, our data question the efficacy and rationale behind syngeneic (autologous-like) immuno-hematopoietic reconstitution in type 1 diabetes.

  3. ABO血型不合异基因造血干细胞移植后血型转换期的输血策略%Transfusion strategy to ABO-incompatible grafts in allogeneic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    许金华; 李晓丰

    2015-01-01

    BACKGROUND:Hematopoietic stem cel transplantation is an important means for clinical cure of hematologic malignancies, congenital hereditary diseases and autoimmune diseases. Although ABO-incompatibility has no effects on the survival of transplanted hematopoietic stem cels, the transfusion strategy to ABO-incompatible grafts in alogeneic hematopoietic stem cel transplantation is worth studying. OBJECTIVE:To explore the antigen-antibody changes during blood conversion after ABO-incompatible hematopoietic stem cel transplantation as wel as transfusion strategies. METHODS:Blood grouping, antibody detection, antibody titer determination, cross-match test were employed for antigen-antibody monitoring during blood conversion and pre-transfusion compatibility detection in 24 cases undergoing ABO-incompatible alogeneic hematopoietic stem cel transplantation. Another 30 cases undergoing ABO-compatible alogeneic hematopoietic stem cel transplantation were enroled as controls to select the appropriate blood. RESULTS AND CONCLUSION:Al of the 24 ABO-incompatible patients developed the hematopoietic reconstitution after transplantation, but both major and major-minor ABO incompatibility were different from ABO compatibility in the time of erythrocytic recovery (P < 0.05). According to the changes of ABO antigen and antibody during the blood conversion, the patients of major ABO incompatibility were selected the red blood cels of their own type, the patients of minor ABO incompatibility were selected the red blood cels of the blood group from patients to donors gradualy, and the patients of major-minor ABO incompatibility were selected the red blood cels from O-type blood to donor’s type gradualy. None of the 24 recipients presented hemolytic reaction during transplantation and after transfusion. Therefore, the transfusion strategy to ABO-incompatible grafts in alogeneic hematopoietic stem cel transplantation is dynamicaly varied according to the changes of patient’s ABO

  4. Killer immunoglobulin-like receptor (KIR and HLA genotypes affect the outcome of allogeneic kidney transplantation.

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    Izabela Nowak

    Full Text Available BACKGROUND: Recipient NK cells may detect the lack of recipient's (i.e., self HLA antigens on donor renal tissue by means of their killer cell immunoglobulin-like receptors (KIRs. KIR genes are differently distributed in individuals, possibly contributing to differences in response to allogeneic graft. METHODOLOGY/PRINCIPAL FINDINGS: We compared frequencies of 10 KIR genes by PCR-SSP in 93 kidney graft recipients rejecting allogeneic renal transplants with those in 190 recipients accepting grafts and 690 healthy control individuals. HLA matching results were drawn from medical records. We observed associations of both a full-length KIR2DS4 gene and its variant with 22-bp deletion with kidney graft rejection. This effect was modulated by the HLA-B,-DR matching, particularly in recipients who did not have glomerulonephritis but had both forms of KIR2DS4 gene. In contrast, in recipients with glomerulonephritis, HLA compatibility seemed to be much less important for graft rejection than the presence of KIR2DS4 gene. Simultaneous presence of both KIR2DS4 variants strongly increased the probability of rejection. Interestingly, KIR2DS5 seemed to protect the graft in the presence of KIR2DS4fl but in the absence of KIR2DS4del. CONCLUSIONS/SIGNIFICANCE: Our results suggest a protective role of KIR2DS5 in graft rejection and an association of KIR2DS4 with kidney rejection, particularly in recipients with glomerulonephritis.

  5. Recurrent myelitis after allogeneic stem cell transplantation. Report of two cases

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    Voß Martin

    2010-09-01

    Full Text Available Abstract Background Allogeneic and autologous haematopoietic stem cell transplantation are established treatment options for haematological malignancies and may possibly be employed to treat a range of genetic and autoimmune diseases. Case presentation We report two patients who developed an acute myelitis within their thoracic spinal cord after allogeneic stem cell transplantation. Myelitis in these patients was not related to graft versus host disease or immune reconstitution and was responsive to intravenous methylprednisolone and cyclophosphamide. Conclusions Myelitis is a possibly disabling consequence of haematopoietic stem cell transplantation.

  6. Functional Reconstitution Of Natural Killer Cells In Allogeneic Hematopoietic Stem Cell Transplantation

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    Md Ashik eUllah

    2016-04-01

    Full Text Available Natural killer (NK cells are the first lymphocyte population to reconstitute following allogeneic hematopoietic stem cell transplantation (HSCT and are important in mediating immunity against both leukemia and pathogens. Although NK cell numbers generally reconstitute within a month, the acquisition of mature NK cell phenotype and full functional competency can take 6 months or more, and is influenced by graft composition, concurrent pharmacologic immunosuppression, graft-versus-host disease and other clinical factors. In addition, cytomegalovirus infection and reactivation have a dominant effect on NK cell memory imprinting following allogeneic HSCT just as it does in healthy individuals. Our understanding of NK cell education and licensing has evolved in the years since the ‘missing self’ hypothesis for NK-mediated graft-versus-leukemia effect was first put forward. For example, we now know that NK cell ‘re-education’ can occur, and that unlicensed NK cells can be more protective than licensed NK cells in certain settings, thus raising new questions about how best to harness graft-versus-leukemia effect. Here we review current understanding of the functional reconstitution of NK cells and NK cell education following allogeneic HSCT, highlighting a conceptual framework for future research.

  7. Allogeneic hematopoietic stem cell transplantation in children with aplastic anemia.

    Science.gov (United States)

    Xue, H-M; Xu, H-G; Huang, K; Guo, H-X; Li, Y; Zhou, D-H; Huang, S-L; Fang, J-P; Chen, C

    2015-05-18

    The aim of this study was to prospectively investigate the efficacy and safety of fully matched allogeneic hematopoietic stem cell transplants in children with severe aplastic anemia in China. A total of twenty patients with severe aplastic anemia were enrolled in our study. Thirteen cases underwent transplantation with fully human leukocyte antigen (HLA)-matched, granulocyte-colony stimulating factor (G-CSF)-primed bone marrow and peripheral blood stem cells (PBSCs) from matching sibling donors. One patient received fully HLA-matched bone marrow from an unrelated donor. Six patients received fully HLA-matched G-CSF-primed PBSCs from unrelated donors. The conditioning regimen included fludarabine, cyclophosphamide, and rabbit anti-thymocyte globulin. Graft-versus-host disease prophylaxis was conducted with cyclosporin A and short-course methotrexate. The median follow-up duration was 3.08 years (range, 0.83-8.41years). The median time of neutrophil recovery (>0.5 x 10(9)/L) was 14 days (range, 10-20 days), and the median time of platelet recovery (>20 x 10(9)/L) was 19 days (range, 14-31 days). The survival rate at the cutoff point of follow-up was 95.0% (19/20). Initial engraftment rate was 95% (19/20). Late graft failure (graft failures occurring 1 year or longer after transplantation) was observed in one patient. Only one patient developed Grade I acute graft-versus-host disease. Two cases suffered from Epstein- Barr virus (EBV)-associated post-transplant lymphoproliferative disorder and remitted after treatment with rituximab. One patient was diagnosed with hyperthyroidism 2.5 years after transplantation. Our study indicated that allogeneic hematopoietic stem cell transplantation is an effective and safe treatment for children with severe aplastic anemia in China.

  8. Survival Of Cultured Allogeneic Keratinocytes Transplanted To Deep Dermal Bed Assessed With Probe Specific For Y Chromosome

    National Research Council Canada - National Science Library

    Anne Brain; Patricia Purkis; Philip Coates; Michael Hackett; Harshad Navsaria; Irene Leigh

    1989-01-01

    ... of cultured allogeneic keratinocytes from donors of the opposite sex. Cells carrying the Y chromosome were identified in biopsy specimens taken from the graft site by in situ DNA hybridisation with a biotinylated Y probe (pHY 2.1...

  9. Allogeneic Th1 cells home to host bone marrow and spleen and mediate IFNγ-dependent aplasia.

    Science.gov (United States)

    Chewning, Joseph H; Zhang, Weiwei; Randolph, David A; Swindle, C Scott; Schoeb, Trenton R; Weaver, Casey T

    2013-06-01

    Bone marrow graft failure and poor graft function are frequent complications after hematopoietic stem cell transplantation and result in significant morbidity and mortality. Both conditions are associated with graft-versus-host disease (GVHD), although the mechanism remains undefined. Here we show, in 2 distinct murine models of GVHD (complete MHC- and class II-disparate) that mimic human peripheral blood stem cell transplantation, that Th1 CD4(+) cells induce bone marrow failure in allogeneic recipients. Bone marrow failure after transplantation of allogeneic naïve CD4(+) T cells was associated with increased CD4(+) Th1 cell development within bone marrow and lymphoid tissues. Using IFNγ-reporter mice, we found that Th1 cells generated during GVHD induced bone marrow failure after transfers into secondary recipients. Homing studies demonstrated that transferred Th1 cells express CXCR4, which was associated with accumulation within bone marrow and spleen. Allogeneic Th1 cells were activated by radiation-resistant host bone marrow cells and induced bone marrow failure through an IFNγ-dependent mechanism. Thus, allogeneic Th1 CD4(+) cells generated during GVHD traffic to hematopoietic sites and induce bone marrow failure via IFNγ-mediated toxicity. These results have important implications for prevention and treatment of bone marrow graft failure after hematopoietic stem cell transplantation. Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  10. Tetanus after allogeneic bone-marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Kendra, J.R.; Halil, O.; Barrett, A.J.; Selwyn, S. (Westminster Medical School, London (UK))

    1982-11-13

    A brief report is presented of a case of tetanus after allogeneic bone-marrow transplantation complicated by radiation-induced pneumonitis. A 30-year-old army sergeant received a bone-marrow transplant from his brother for the treatment of a granulocytic sarcoma after local radiotherapy to the tumour. Six years earlier he had sustained an open, compound fracture of the left tibia and fibula while on army exercise. At the time a pin and plate had been inserted and booster anti-tetanus administered. Bone-marrow transplantation was performed after total body irradiation. Cyclosporin A was given against graft-versus-host disease. Fifty four days after transplantation tetanus was diagnosed and death followed 14 days later. Necropsy disclosed radiation-induced pneumonitis, but no organisms were cultured from the lungs or the old fracture site. It is suggested that spores were incorporated into the wound site before surgery and that oxygenation around the plate became compromised after transplantation, permitting germination of dormant spores, immunosuppression allowing development of the disease.

  11. One-sheet spiraling full thickness skin graft for penile resurfacing after paraffinoma excision

    Directory of Open Access Journals (Sweden)

    Theddeus O.H. Prasetyono

    2011-08-01

    Full Text Available In the midst of on-going non-illicit practice of silicone or paraffin injection to enlarge penis, the author reported 3 cases of surgical treatment to resurface the body of the penis after excision of the destructed penile skin using full thickness skin graft. The skin excision was performed technically through penile body degloving procedure. Full thickness skin graft was then applied as a single sheet donor tissue to cover the denuded penile body spirally. The full thickness graft, which is relatively easy to be performed, is no doubt much thinner than a skin flap, while it also bears a smaller degree of secondary contraction than split skin graft. The color of the skin is considerably matched as it comes from the groin, which is a nearby area of penis. The size and skin sensitization of the penis looks to be natural. The only disadvantage is the common possibility of either spiral or circular junctional scar in between graft edges and between the graft and the penile mucosa and skin to develop hypertrophic scar. However, this possible scar problem applies also to any other surgical scar with any donor tissue. Fortunately, the 3 cases posed no scar problem and normal appearance. All the patients have also regained their normal sexual function. (Med J Indones 2011; 20:222-5Keywords: full thickness skin graft, paraffinoma, siliconoma, sexual function

  12. Informed consent: cultural and religious issues associated with the use of allogeneic and xenogeneic mesh products.

    Science.gov (United States)

    Jenkins, Eric D; Yip, Michael; Melman, Lora; Frisella, Margaret M; Matthews, Brent D

    2010-04-01

    Our aim was to investigate the views of major religions and cultural groups regarding the use of allogeneic and xenogeneic mesh for soft tissue repair. We contacted representatives from Judaism, Islam, Buddhism, Hinduism, Scientology, and Christianity (Baptists, Methodists, Seventh-Day Adventists, Catholics, Lutherans, Church of Jesus Christ of Latter-Day Saints, Evangelical, and Jehovah's Witnesses). We also contacted American Vegan and People for the Ethical Treatment of Animals (PETA). Standardized questionnaires were distributed to the religious and cultural authorities. Questions solicited views on the consumption of beef and pork products and the acceptability of human-, bovine-, or porcine-derived acellular grafts. Dietary restrictions among Jews and Muslims do not translate to tissue implantation restriction. Approximately 50% of Seventh-day Adventists and 40% of Buddhists practice vegetarianism, which may translate into a refusal of the use of xenogeneic tissue. Some Hindus categorically prohibit the use of human tissue and animal products; others allow the donation and receipt of human organs and tissues. PETA is opposed to all uses of animals, but not to human acellular grafts or organ transplantation. Some vegans prefer allogeneic to xenogeneic tissue. Allogeneic and xenogeneic acellular grafts are acceptable among Scientologists, Baptists, Lutherans, Evangelicals, and Catholics. Methodists, Jehovah's Witnesses, and The Church of Jesus Christ of Latter-Day Saints leave the decision up to the individual. Knowledge of religious and cultural preferences regarding biologic mesh assists the surgeon in obtaining a culturally sensitive informed consent for procedures involving acellular allogeneic or xenogeneic grafts. Copyright (c) 2010 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  13. Nachweis von Punktmutationen im TNF-alpha- und INF-gamma-Promotor bei Patienten nach allogener Stammzelltransplantation oder Knochenmarktransplantation

    OpenAIRE

    2008-01-01

    Allogene stammzelltransplantierte Patienten sind einem höherem Risiko für opportunistische Infektionen und andere Komplikationen ausgesetzt. Dabei spielt CMV eine wichtige Rolle und trägt zur Mortalität bei. Eine weitere gefürchtete Komplikation nach allogener Stammzelltransplantation ist die akute und chronische Graft-versus-Host-Disease. Angesichts der Rolle der Zytokine als Mediatorstoffe der Immunantwort ist es wichtig, ihren Einfluß auf den Auftritt und Verlauf der CMV-Infektionen und Gv...

  14. Autologous and allogeneic hematopoietic stem cell transplantation in follicular lymphoma.

    Science.gov (United States)

    Bhatt, V R; Armitage, J O

    2016-01-01

    High-dose chemotherapy and autologous stem cell transplantation (ASCT) improve survival in follicular lymphoma; however, relapse remains the most common cause of death. The lower risk of relapse with allogeneic SCT (alloSCT) is offset by a high transplant-related mortality (TRM). English articles indexed in the MEDLINE database were reviewed to discuss the role of graft purging, rituximab maintenance after ASCT, reduced-intensity conditioning (RIC) alloSCT, T-cell depletion, donor lymphocyte infusion (DLI) and alternate donor sources. Optimal salvage consolidation strategy may utilize ASCT following non-total body irradiation-based conditioning regimen in second remission. Rituximab maintenance after ASCT may improve molecular remission but is not yet shown to improve overall survival. RIC alloSCT permits its use in older and less-fit patients. Studies with T-cell depleted graft failed to reduce TRM despite a decline in graft-versus-host disease; however, these studies did demonstrate a therapeutic role of DLI in post-transplant relapses. In recent years, haploidentical and umbilical cord blood donors have emerged as alternative donor sources, with outcomes comparable to matched unrelated donor SCT. In the future, incorporation of novel therapeutic agents, improved risk-adapted treatment strategies, and advancement of transplant techniques may provide a better chance of survival.

  15. Kidney dysfunction after allogeneic stem cell transplantation

    NARCIS (Netherlands)

    Kersting, S.

    2008-01-01

    Allogeneic stem cell transplantation (SCT) is a widely accepted approach for malignant and nonmalignant hematopoietic diseases. Unfortunately complications can occur because of the treatment, leading to treatment-related mortality. We studied kidney dysfunction after allogeneic SCT in 2 cohorts of

  16. Migration of human antigen-presenting cells in a human skin graft onto nude mice model after contact sensitization

    NARCIS (Netherlands)

    Hoefakker, S.; Balk, H.P.; Boersma, W.J.A.; Joost, T. van; Notten, W.R.F.; Claassen, E.

    1995-01-01

    Fluorescent contact chemical allergens provoke sensitization after application on both syngeneic and allogeneic skin grafts in mice. We attempted to determine whether the functional activity in a contact sensitization response of human skin graft was affected at the level of antigen uptake and

  17. Endocrinopathies after Allogeneic and Autologous Transplantation of Hematopoietic Stem Cells

    Directory of Open Access Journals (Sweden)

    Francesco Orio

    2014-01-01

    Full Text Available Early and late endocrine disorders are among the most common complications in survivors after hematopoietic allogeneic- (allo- and autologous- (auto- stem cell transplant (HSCT. This review summarizes main endocrine disorders reported in literature and observed in our center as consequence of auto- and allo-HSCT and outlines current options for their management. Gonadal impairment has been found early in approximately two-thirds of auto- and allo-HSCT patients: 90–99% of women and 60–90% of men. Dysfunctions of the hypothalamus-pituitary-growth hormone/insulin growth factor-I axis, hypothalamus-pituitary-thyroid axis, and hypothalamus-pituitary-adrenal axis were documented as later complicances, occurring in about 10, 30, and 40–50% of transplanted patients, respectively. Moreover, overt or subclinical thyroid complications (including persistent low-T3 syndrome, chronic thyroiditis, subclinical hypo- or hyperthyroidism, and thyroid carcinoma, gonadal failure, and adrenal insufficiency may persist many years after HSCT. Our analysis further provides evidence that main recognized risk factors for endocrine complications after HSCT are the underlying disease, previous pretransplant therapies, the age at HSCT, gender, total body irradiation, posttransplant derangement of immune system, and in the allogeneic setting, the presence of graft-versus-host disease requiring prolonged steroid treatment. Early identification of endocrine complications can greatly improve the quality of life of long-term survivors after HSCT.

  18. Second Unrelated Donor Hematopoietic Cell Transplantation for Primary Graft Failure

    Science.gov (United States)

    Schriber, Jeffrey; Agovi, Manza-A.; Ho, Vincent; Ballen, Karen K.; Bacigalupo, Andrea; Lazarus, Hillard M.; Bredeson, Christopher N.; Gupta, Vikas; Maziarz, Richard T.; Hale, Gregory A.; Litzow, Mark R.; Logan, Brent; Bornhauser, Martin; Giller, Roger H.; Isola, Luis; Marks, David I.; Rizzo, J. Douglas; Pasquini, Marcelo C.

    2010-01-01

    Failure to engraft donor cells is a devastating complication after allogeneic hematopoietic cell transplantation (HCT). We describe the results of 122 patients reported to the National Marrow Donor Program between 1990 and 2005, who received a second unrelated donor HCT after failing to achieve an absolute neutrophil count of ≥ 500/ μL without recurrent disease. Patients were transplanted for leukemia (n=83), myelodysplastic disorders (n=16), severe aplastic anemia (n=20) and other diseases (n=3). The median age was 29 years. Twenty-four patients received second grafts from a different unrelated donor. Among 98 patients who received a second graft from the same donor, 28 received products that were previously collected and cryopreserved for the first transplantation. One-year overall survival after second transplant was 11% with 10 patients alive at last follow up. We observed no differences between patients who received grafts from the same or different donors, or in those who received fresh or cryopreserved product. The outcomes after a second allogeneic HCT for primary graft failure are dismal. Identifying risk factors for primary graft failure can decrease the incidence of this complication. Further studies are needed to test whether early recognition and hastened procurement of alternative grafts can improve transplant outcomes for primary graft failure. PMID:20172038

  19. Effect of intrathymic injection of allogene antigen on immune response to sciatic nerve transplantation in allogenic mice

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    motor nerve conduction velocity. ② Transplanted nerve was stained with histochemical staining and observed light microscope and electron microscope. ③ Mice received mixed lymphocyte culture and delayed-typed hypersensitiveness to observe absorbency and measure depth of soles.RESULTS: All 76 mice were involved in the final analysis. ① Motor nerve conduction velocity: The nerve recovery in MHC (H-2b) antigen injection group was higher than that in allogenous nerve transplantation group, equal to immunosuppressive agent group and lower than autogenous nerve transplantation group.There were significant differences among them (P < 0.05). ② Histological changes of transplanted nerve:Light and electron microscopes demonstrated that there were a lot of regenerative nerve fibers in autogenous nerve transplantation group, immunosuppressive agent group and MHC (H-2b) antigen injection group, and all nerve fibers passed grafts. ③ Immunological examination: There was no significant difference in mixed lymphocyte culture among allogenous nerve transplantation group, autogenous nerve transplantation group and MHC (H-2b) antigen injection group (P < 0.05). Depth of soles in other groups was deeper than that in the MHC (H-2b) antigen injection group, and there was significant difference (P < 0.05); that was to say,delayed-typed hypersensitiveness was remarkable.CONCLUSION: The intrathymic injection of allogene MHC antigen may induce specific immune tolerance to allogenous sciatic nerve transplantation and promote nerve survival and functional recovery.

  20. Preliminary study on IL-7Rα intervening acute graft-versus-host disease after mice allogeneic bone marrow transplantation%白细胞介素7受体α干预小鼠异基因骨髓移植后急性移植物抗宿主病的初步研究

    Institute of Scientific and Technical Information of China (English)

    卫芬; 马梁明; 龚旭东; 任连生; 朱镭; 郭慧敏; 张华屏

    2013-01-01

    Objective To establish a mouse model of acute graft-versus-host disease (aGVHD) after allogeneic bone marrow transplantation,and using exogenous interleukin-7 receptor alpha (IL-7Rα) intervene mice aGVHD and analyse its possible mechanism.Methods The BALB/C (H-2d) female mice as recipients were grouped by rat: the irradiation group (group A),irradiation transplantation group (group B) and IL-7Rα in the intervention group (group C),each 10.ALL mice were accepted 9 Gy60Co total body irradiation.1×107 bone marrow cells and 2×107 spleen cells of donor C57BL/6 (H-2b) via the tail vein were infused to recipient mice.The signs of the recipient mice,hematopoietic functional recovery and survival time of change,and pathology,chimerism and cytokine levels in checkwere observed.Results Mice in A group after irradiation were gradually death,in group B and group C mice after transplantation had typical aGVHD symptoms,but lighter signs and a longer survival time of Group C than in group B.WBC count in Group C was +14 d (4.53± 0.21) ×109/L,+21 d (3.63±0.06) ×109/L,+28 d (4.31±0.04) ×109/L,was hematopoietic recovery compared with Group B [+14 d (1.81±0.05) ×109/L,+21 d (1.32±0.04) ×109/L,+28 d (1.76±0.04) ×109/L],the difference was statistically significant (t =0.237,0.108,0.359,P < 0.05).The pathological results of liver,spleen,skin histopathology in group C were better than group B.Chimera implants,plasma IL-7 levels after transplant +7 d,concentration was significantly increased.IL-7 concentration in group C was +14 d (194.32±1.02) pg/ml,+21 d (131.63±1.54) pg/ml and in group B was +14 d (330.24±8.08) pg/ml,+21 d (184.09±2.05) pg/ml,the difference was statistically significant (t =1.590,1.285,P <0.05).Conclusion The stable aGVHD mouse model was established.In aGVHD early,plasma IL-7 levels were significantly increased.Exogenous IL-7Rαcan reduce the plasma IL-7 levels,thereby reducing the incidence of aGVHD after allogeneic bone marrow transplantation

  1. Effective management of pulmonary aspergillosis invading the thoracic spine in a child with high risk ALL requiring allogeneic bone marrow transplantation.

    Science.gov (United States)

    Dornbusch, Hans Jürgen; Sovinz, Petra; Lackner, Herwig; Schwinger, Wolfgang; Benesch, Martin; Strenger, Volker; Urban, Christian

    2008-08-01

    Due to unacceptably high mortality, invasive fungal infections (IFI) have long been considered a contraindication against allogeneic stem cell transplantation. Despite severe immunosuppression an 11-year-old girl requiring allogeneic bone marrow transplant (BMT) for relapsed acute lymphoblastic leukemia was cured of a concurrent invasive pulmonary aspergillosis. Treatment comprised combinations of liposomal amphotericin B, caspofungin and voriconazole with donor granulocyte transfusions. This therapeutic regimen, including the choice of reduced intensity conditioning (RIC), allowed the patient to receive an allogeneic BMT. In hematological remission the child later developed fatal chronic graft-versus-host disease. Combined antifungal treatment and granulocyte support allow for effective management of IFI even in allogeneic stem cell transplant recipients. However, short-term benefits of RIC may be outweighed by late complications.

  2. Allogeneic Immunotherapy for Relapsed Multiple Myeloma:Role of Matched Unrelated Donors

    Institute of Scientific and Technical Information of China (English)

    M.Goerner; S.Hoepfner; 等

    2002-01-01

    Existence of a graft-versus-myeloma effect has been well documented by responses to donor lymphocyte infusions and long-term survival after allogeneic bone marrow transplantation.The development of non-myeloablative conditioning regimens allows utilization of allogeneic effects in patients usually not suitable for myeloablative allogeneic transplantation,such as older and heavily pretreated pa-tients.In a small series of 11 patients with multiple myeloma relapsing after autologous transplantation,we show that conditioning with low-dose total body irradiation in combination with fludarabine allows stable engraftment after matched unrelated donor transplantation and is tolerated with acceptable transplant-related morbidity and mortality.With a short median follow-up of 225 days,disease control was achieved only for patients responding to conventional treatment prior to allografting .Future studies with longer follow-up have to define the role of non-myeloablative allogeneic transplantation from unrelated donors as consolidation for patients responding to salvage therapy.

  3. Specific Factors Influence the Success of Autologous and Allogeneic Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Thissiane L. Gonçalves

    2009-01-01

    Full Text Available Successful hematopoietic stem cell transplantation (HSCT, both autologous and allogeneic, requires a rapid and durable engraftment, with neutrophil (>500/µL and platelet (>20,000/µL reconstitution. Factors influencing engraftment after autologous or allogeneic HSCT were investigated in 65 patients: 25 autologous peripheral stem cell transplantation (PBSCT and 40 allogeneic bone marrow transplantation (BMT patients. The major factor affecting engraftment was the graft source for HSCT. Neutrophil and platelet recovery were more rapid in autologous PBSCT than in allogeneic BMT [neutrophil occurring in median on day 10.00 (09.00/11.00 and 19.00 (16.00/23.00 and platelet on day 11.00 (10.00/13.00 and 21.00 (18.00/25.00, respectively; p < 0.0001]. The type of disease also affected engraftment, where multiple myeloma (MM and lymphoma showed faster engraftment when compared with leukemia, syndrome myelodysplastic (SMD and aplastic anemia (AA and MM presented the best overall survival (OS in a period of 12 months. Other factors included the drug used in the conditioning regimen (CR, where CBV, melphalan (M-200 and FluCy showed faster engraftment and M-200 presented the best OS, in a period of 12 months and age, where 50–59 years demonstrated faster engraftment. Sex did not influence neutrophil and platelet recovery.

  4. (GT)n Repeat Polymorphism in Heme Oxygenase-1 (HO-1) Correlates with Clinical Outcome after Myeloablative or Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation

    DEFF Research Database (Denmark)

    Køllgaard, Tania; Kornblit, Brian; Petersen, Jesper;

    2016-01-01

    Allogeneic hematopoietic cell transplantation (HCT) is a treatment for various hematologic diseases where efficacy of treatment is in part based on the graft versus tumour (GVT) activity of cells in the transplant. The cytoprotective enzyme heme oxygenase-1 (HO-1) is a rate-limiting enzyme in heme...

  5. Bone graft

    Science.gov (United States)

    ... around the area. The bone graft can be held in place with pins, plates, or screws. Why ... Orthopaedic Surgery, San Francosco, CA. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the ...

  6. Securing aesthetic outcomes for composite grafts to alar margin and columellar defects: A long term experience.

    Science.gov (United States)

    Ahuja, Rajeev B; Gupta, Rajat; Chatterjee, Pallab; Shrivastava, Prabhat

    2014-01-01

    Composite grafts for nasal reconstruction have been around for over a century but the opinion on its virtues and failings keeps vacillating with a huge difference on the safe size of the graft for transfer. Alar margin and columellar defects are more distinct than dorsal nasal defects in greater difficulty in ensuring a good aesthetic outcome. We report our series of 19 consecutive patients in whom a composite graft was used to reconstruct a defect of alar margin (8 patients), alar base (7 patients) or columella (4 patients). Patient ages ranged from 3-35 years with 5 males and 14 females. The grafts to alar margin and base ranged 0.6-1 cm in width, while grafts to columella were 0.7-1.2 cm. The maximum dimension of the graft in this series was 0.9 mm x 10 mm. Composite grafts were sculpted to be two layered (skin + cartilage), three layered wedges (skin + cartilage + skin) or their combination (two layered in a portion and three layered in another portion). All grafts were cooled in postoperative period for three days by applying an indigenous ice pack of surgical glove. The follow up ranged from 3-9 months with an average of 4.5 months. All of our 19 composite grafts survived completely but they all shrank by a small percentage of their bulk. Eleven patients rated the outcome between 90-95% improvement. We noticed that composite grafts tended to show varied pigmentation in our patients, akin to split skin grafts. In our opinion, most critical to graft survival is its size and the ratio of the marginal raw area to the graft bulk. We recommend that graft width should not exceed 1 cm to ensure complete survival even though larger sized grafts have been reported to survive. We recommend cooling of the graft and justify it on the analogy of 'warm ischemia time' for a replantation, especially in warmer climes like ours in India. We have outlined several considerations in the technique, with an analysis of differing opinions that should facilitate a surgeon in making an

  7. Prevention of cyclosporine A combined with Cobalt protoporphyrin against murine graft-versus-host disease after allogeneic hematopoietic stem cell transplantation%环孢素A联合钴原卟啉预防小鼠HSCT后移植物抗宿主病

    Institute of Scientific and Technical Information of China (English)

    王祥民; 潘秀英; 曾令宇; 安立才; 陈伟; 张翠平; 潘彬; 徐开林

    2012-01-01

    Objective To explore prevention of cyclosporine A (CsA) combined with Cobalt protoporphyrin (CoPP) against murine graft versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods C57BL/6 (H-2Kb) mice were used as donors and BALB/c (H-2Kd) mice as recipients,which were randomly divided into 4 groups.The mice in total body irradiation group (TBI group) were lethally irradiated and injected intravenously with PBS; The mice in Allo-HSCT group (BS group) were lethally irradiated and injected intravenously with bone marrow cells and spleen cells; The mice in CsA intervention group (CsA group) were injected with CsA intraperitoneally after allo-HSCT; The mice in CsA combine with CoPP intervention group (combination group) received both CsA and CoPP intraperitoneally after alloHSCT.Recipients were monitored for condition,survival rate and weight.The liver,small intestine and skin in the recipients were gained and pathological changes of GVHD were assessed.The kidney was stained with Masson staining dye to observe the tissue fibrosis.The expression levels of renal HO-1 mRNA in the recipients were detected.Results In contrast to BS and CsA groups,GVHD degree in combination group was mild,with less reduction and quick recovery of weight.On the day 30 after HSCT,survival rate in BS group was 36.8%,and that in combination group and CsA group was 69.6% and 53.5% respectively (P<0.05).In comparison with BS and CsA groups,pathological changes in combination group were mild,cellular edema and degeneration degree of the liver,small intestine and skin were slight,and few necrosis and infiltrated inflammatory cells were observed.Tubulointerstitial fibrosis hardly occurred in combination group,but it occurred in CsA group abundantly.As compared with BS group,the expression levels of HO-1 mRNA was increased in combination group,while decreased in CsA group (P<0.05).Conclusion CsA combined with CoPP enhanced the protective effect of

  8. Association between acute graft versus host disease and lung injury after allogenic hematopoietic stem cell transplantation%异基因造血干细胞移植后急性移植物抗宿主病与肺损伤的关系

    Institute of Scientific and Technical Information of China (English)

    刘启发; 罗晓丹; 范志平; 宁涓; 徐丹; 孙竞; 张钰; 徐兵; 魏永强

    2009-01-01

    Objective To investigate the characteristics of chest hiigh-resolution computed tomography(HRCT)and pathogenesis of acute graft versus host disease(aGVHD)-induced lung injury after allogenic hematopoietic stem cell transplantation(allo-HSCT).Methods Chest HRCT was performed in 47 patients with aGVHD of grade Ⅱ-Ⅳ after allo-HSCT.Twenty-four of the patients underwent different treatment regimens against aGVHD.Before the treatment peripheral blood samples were collected to detect the serum interferon-γ(IFN-γ)and tumor necrosis factor-α(TNF-α).Transbronchial biopsy was performed in 4 patients that failed to recover completely after treatment.Pulmonary function was examined in the patients who survived more than 6 months in every 3 months.Resuits Twenty of tlle 47 patients showed abnormal images by chest HRCT and 17 of the 20 patients were suspected to be witll aGVHD-induced lung iniury.The HRCT images were characterized by diffused interstitial infiltrate in 5 cases.diflused intemtitial and alveolar infiltrate in 7 cases.and diffused interstitial and segmental lobar alveolar infiltrate in 5 cases.Nine cases had bilateral pleural effusion and hydropericardium,including 4 eases accompanied by myocardial hypertrophy.The levels of serum IFN-γ and TNF-α of the patients with lung injury were(6.9±1.8)μg/L and(400±102)μg/L respectively,both not significantly different from those of the patients without lung injury[(6.3±1.2)μg/L and(428±83)μg/L respectively,P=0.202,0.306].The histopathology of the lung tissue was characterized by disorganization,epithelial cell damage,interstitial fibroplasias,and interstitial T lymphocyte or macrophage infiltrate.The effective rate of treatment for aGVHD-induced lung iniury was positively correlated witll that for aGVHD(r=0.771,P=0.01).Eleven of the 24 patients who survived more than 6 months had abnormal pulmonary function.including 7 out of tlle 9 patients with aGVHD-induced lung injury and 4 out the 15 patients without a

  9. Effects of immature dendritic cells to express CCR7 on graft-versus-host disease in allogeneic bone marrow transplant mouse model%趋化因子受体7基因修饰的未成熟树突细胞对小鼠移植物抗宿主病的作用研究

    Institute of Scientific and Technical Information of China (English)

    李德鹏; 武家庆; 黄一虹; 宋立孝; 谷红红; 高彩玲; 李振宇; 潘秀英; 徐开林

    2013-01-01

    Objective To investigate the effects of immature dendritic cells (imDC) expressing chemokine receptor-7 (CCR7) on acute graft-versus-host disease (aGVHD)in allogeneic bone marrow transped (allo-BMT) mouse model.Methods We constructed the lentiviral vectors carrying mouse CCR7 gene and infect imDC effectively in vitro.GVHD model was established with C57BL/6(H-2b) donor mice and BALB/c (H-2d) recipient mice.After irradiation,recipients were injected with donor bone marrow and spleen cells along with CCR7-modified dendritic cells.Mice were randomized into irradiation,transplant control,pXZ9-imDC (empty vector control) and CCR7-imDC groups.Survival,GVHD score,histopathological analysis and plasma levels of inflammatory cytokines were observed.Results The mean survival in irradiation,transplantation,pXZ9-imDC and CCR7-imDC groups were (8.20± 1.48)d,(12.20± 2.78) d,(20.70 ± 6.01)d and (27.5 ± 7.55)d respectively.The survival in CCR7-imDC group was significantly improved compared with other groups (P<0.05).GVHD scores in transplantation,pXZ9-imDC and CCR7-imDC groups were (6.90± 1.66),(5.60±0.97) and (4.10± 1.79) respectively.CCR7-imDC group had significantly lower GVHD score and minor tissue damages shown by histopathological analysis than the other groups.Plasma IFN-γ level increased and reached the peak at +10 day in transplant group,while it gradually decreased in pXZ9-imDC and CCR7-imDC groups,and then reached the nadir at +20 day post-allo-BMT,with the lowest level in CCR7-imDC group (P<0.01).Plasma IL-4 decreased in transplant group,while it gradually increased in pXZ9-imDC and CCR7-imDC groups and reached the highest level at + 10 day in CCR7-imDC group (P<0.01).The 95%-100% of H-2b positive cells in recipient mice on + 30 day post-allo-BMT demonstrated the complete donor-type implantation.Conclusion Genetically modified immature DC by CCR7 gene could alleviate damages by GVHD and prolong survival of recipient mice after allo-BMT.%目的

  10. TLR5激动剂鞭毛蛋白预防小鼠异基因造血干细胞移植后急性移植物抗宿主病的初步研究%Prophylactic Effect of TLR5 Agonist Flagellin on Acute Graft versus Host Disease after Allogeneic Hematopietic Stem Cell Transplantation and Its Mechanism

    Institute of Scientific and Technical Information of China (English)

    龚旭东; 马梁明; 朱镭; 郭慧敏; 任连生; 任瑞瑞; 张华屏; 卫芬; 牛燕燕

    2012-01-01

    本研究旨在探讨Toll样受体(TLR5)激动剂鞭毛蛋白(flagellin)对小鼠异基因造血干细胞移植(allo-HSCT)后急性移植物抗宿主病(aGVHD)的预防作用和可能作用机制.用主要组织相容性抗原完全不合的纯种近交系小鼠[供体鼠:雄性C57BL/6鼠;受体鼠:雌性BALB/c鼠]建立allo-HSCT的aGVHD动物模型.受鼠随机分为3组:鞭毛蛋白组,于移植前后2次尾静脉注射高纯度(纯度≥95%)的鞭毛蛋白50μl[5μg/(只·次)]预防aGVHD;单纯移植组,移植后仅给予等容量PBS;单纯照射组,仅照射不移植,亦给予等容量PBS.观察比较移植后aGVHD的表现.结果表明,移植小鼠均出现典型的aGVHD症状,单纯移植组小鼠死亡高峰在移植后第4-5天.用鞭毛蛋白作为aGVHD预防方案小鼠的aGVHD症状明显减轻,平均生存时间较单纯移植组显著延长(P<0.05).三组小鼠移植前外周血白细胞数比较均无显著性差异,但在照射后第14、21天,鞭毛蛋白组较单纯移植组外周血白细胞数显著性升高(P<0.05).鞭毛蛋白预防组移植小鼠aGVHD病理表现较单纯移植组明显减轻.流式细胞仪检测鞭毛蛋白组与单纯移植组移植前后不同时间点Treg细胞/CD4+T细胞含量结果也表明,移植后2-4周鞭毛蛋白组小鼠的Treg细胞数较单纯移植组明显增加(P<0.05).结论:鞭毛蛋白对小鼠allo-HSCT后发生aGVHD有预防作用,能减轻其症状和病理损害程度,显著延长其平均生存时间,其机制有可能通过增加移植后小鼠的Treg细胞含量,从而有效改善并减轻移植后小鼠aGVHD.%This study was aimed to investigate the prophylactic effect of Toll like receptor (TLR)5 agonist flagellin on acute graft versus host disease (aGVHD) after allogeneic hematopietic stem cell transplantation (allo-HSCT) and its possible mechemism. The animal model with allo-HSCT aGVHD was established by using purebreed mice (male mouse C57BL/6 as donor, femal mouse BALB/c as recipient

  11. Histologic evaluation of an allogeneic mineralized bone matrix in the treatment of periodontal osseous defects.

    Science.gov (United States)

    Koylass, Jana-Marie; Valderrama, Pilar; Mellonig, James T

    2012-08-01

    The aim of this study was to evaluate the potential of an allogeneic bone matrix to regenerate new bone, cementum, and periodontal ligament around a previously diseased root surface. Four patients with severe chronic periodontitis and teeth with hopeless periodontal or restorative prognoses participated in this study. One tooth with a severe intraosseous defect was selected per patient. At baseline, measurements of probing depth, gingival recession, and clinical attachment level were obtained. Following flap reflection, a root notch was placed at the apical extent of the calculus; the root was debrided, and the allogeneic bone graft material was placed into the defect. After a minimum of 6 months of healing, the teeth were removed en bloc and prepared for histologic examination. Two of four teeth demonstrated regeneration of new bone, cementum, and periodontal ligament. One tooth healed by new connective tissue attachment, and another by junctional epthelium.

  12. Lung function after allogeneic bone marrow transplantation for leukaemia or lymphoma

    DEFF Research Database (Denmark)

    Nysom, K; Holm, K; Hesse, B

    1996-01-01

    Longitudinal data were analysed on the lung function of 25 of 29 survivors of childhood leukaemia or lymphoma, who had been conditioned with cyclophosphamide and total body irradiation before allogeneic bone marrow transplantation, to test whether children are particularly vulnerable to pulmonary...... damage after transplantation. None developed chronic graft-versus-host disease. Transfer factor and lung volumes were reduced immediately after bone marrow transplantation, but increased during the following years. However, at the last follow up, 4-13 years (median 8) after transplantation, patients had...... to their age at bone marrow transplantation. In conclusion, patients had subclinical restrictive pulmonary disease at a median of eight years after total body irradiation and allogeneic bone marrow transplantation....

  13. Alternative donor allogeneic hematopoietic cell transplantation for hemoglobinopathies.

    Science.gov (United States)

    Alfraih, Feras; Aljurf, Mahmoud; Fitzhugh, Courtney D; Kassim, Adetola A

    2016-04-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) offers a curative therapy for patients with hemoglobinopathies, mainly severe sickle cell disease (SCD) and thalassemia (TM). However, the applicability of HSCT has been limited mainly by donor availability, with a less than 25%-30% of eligible patients having human leukocyte antigen (HLA)-matched sibling donors. Previous outcomes using alternate donor options have been markedly inferior due to increased regimen-related toxicity, transplant-related mortality, graft failure, and graft-versus-host disease (GVHD). Advances in transplant technology, including high-resolution HLA typing, improved GVHD prophylactic approaches with tolerance induction, and better supportive care over the last decade, are addressing these historical challenges, resulting in increasing donor options. Herein, we review alternate donor HSCT approaches for severe SCD and TM using unrelated donors, umbilical cord blood units, or related haploidentical donors. Though this is an emerging field, early results are promising and in selected patients, this may be the preferred option to mitigate against the age-related morbidity and early mortality associated with these disorders.

  14. Treatment with mPEG-SPA improves the survival of corneal grafts in rats by immune camouflage.

    Science.gov (United States)

    Wang, Shuangyong; Li, Liangliang; Liu, Ying; Li, Chaoyang; Zhang, Min; Wang, Bowen; Huang, Zheqian; Gao, Xinbo; Wang, Zhichong

    2015-03-01

    We investigated the immune camouflage effects of methoxy polyethylene glycol succinimidyl propionate (mPEG-SPA) on corneal antigens and explored a novel approach for reducing corneal antigenicity, thereby decreasing corneal graft rejection. Importantly, this approach did not alter normal local immunity. Corneal grafts were treated with mPEG-SPA 5KD or 20KD (3% W/V), which could shield major histocompatibility antigen class I molecules (RT1-A) of corneal grafts. Skin grafts of Wistar rats were transplanted to SD rats. Then the splenic lymphocytes were isolated from SD rats. Subsequently, the lymphocytes were co-cultured with autologous corneal grafts or untreated corneal grafts and PEGylated grafts treated with mPEG-SPA 5KD or 20KD obtained from the counterpart skin donors, which were used as autologous control, allogeneic control, mPEG-SPA 5KD group and mPEG-SPA 20KD group, respectively. Lymphocyte proliferation was lower in mPEG-SPA 5KD group and mPEG-SPA 20KD group than in the allogeneic control. SD rats with corneal neovascularisation were used as recipients for high-risk corneal transplantation and were randomly divided into four groups: autologous control, allogeneic control, mPEG-SPA 5KD group and mPEG-SPA 20KD group. The recipients received corneal grafts from Wistar rats. Corneal graft survival was prolonged and graft rejection was reduced in the mPEG-SPA 5KD group and the mPEG-SPA 20KD group compared to the allogeneic control. Thus, we think that mPEG-SPA could immunologically camouflage corneal antigens to prolong corneal grafts survival in high-risk transplantation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Direct imaging of immune rejection and memory induction by allogeneic mesenchymal stromal cells.

    Science.gov (United States)

    Zangi, Lior; Margalit, Raanan; Reich-Zeliger, Shlomit; Bachar-Lustig, Esther; Beilhack, Andreas; Negrin, Robert; Reisner, Yair

    2009-11-01

    Although mesenchymal stromal cells (MSCs) exhibit marked immunoregulatory activity through multiple mechanisms, their potential to completely evade rejection upon transplantation into allogeneic recipients is controversial. To directly address this controversy, the survival of luciferase-labeled MSCs (Luc(+) MSCs) was evaluated by imaging in allogeneic recipients. This analysis showed that although MSCs exhibited longer survival compared to fibroblasts (Fib), their survival was significantly shorter compared to that exhibited in syngeneic or in immune-deficient Balb-Nude or non-obese diabetic severe combined immunodeficiency (NOD-SCID) recipients. Graft rejection in re-challenge experiments infusing Luc(+) Fib into mice, which had previously rejected Luc(+) MSCs, indicated potential induction of immune memory by the MSCs. This was further analyzed in T-cell antigen receptor (TCR) transgeneic mice in which either CD4 TEA mice or CD8 T cells (2C mice) bear a TCR transgene against a specific MHC I or MHC II, respectively. Thus, following a re-challenge with MSCs expressing the cognate MHC haplotype, an enhanced percentage of 2C CD8(+) or TEA CD4(+) T cells exhibited a memory phenotype (CD122(+), CD44(+), and CD62L(low)). Collectively, these results demonstrate that MSCs are not intrinsically immune-privileged, and under allogeneic settings, these cells induce rejection, which is followed by an immune memory. Considering that the use of allogeneic or even a third party ("off the shelf") MSCs is commonly advocated for a variety of clinical applications, our results strongly suggest that long-term survival of allogeneic MSCs likely represents a major challenge.

  16. US and MRI of gastrointestinal graft-versus-host disease

    Energy Technology Data Exchange (ETDEWEB)

    Mentzel, Hans-Joachim; Vogt, Susanna; Behrendt, Werner; Kaiser, Werner A. [Institute for Diagnostic and Interventional Radiology, University of Jena (Germany); Kentouche, Karim; Gruhn, Bemd; Sauerbrey, Axel; Fuchs, Dietlinde; Zintl, Felix [Department of Paediatrics, University of Jena (Germany); Kosmehl, Hartwig [Department of Pathology, University of Jena (Germany)

    2002-03-01

    Abdominal problems often complicate the clinical course after bone marrow transplantation. Graft-versus-host disease occurs as a complication of allogenic bone marrow transplantation. In this report, the findings of intestinal involvement are described and correlated with histopathological findings. Increased bowel-wall thickness and increased vascularity were shown by US. MRI demonstrated generalised increased bowel-wall thickness associated with bowel-wall enhancement after administration of IV gadolinium. (orig.)

  17. Targeting the IL17 Pathway for the Prevention of Graft-Versus-Host Disease

    NARCIS (Netherlands)

    Waart, A.B. van der; Velden, W.J.F.M. van der; Blijlevens, N.M.A.; Dolstra, H.

    2014-01-01

    Graft-versus-host disease (GVHD) is still a major complication of allogeneic stem cell transplantation (allo-SCT). The pathophysiology of GVHD is a multistep process initiated by tissue damage and proinflammatory cytokine cascades induced by the pretransplantation conditioning therapy. This eventual

  18. Emerging pathogen in immunocompromised hosts: Exophiala dermatitidis mycosis in graft-versus-host disease.

    Science.gov (United States)

    Chalkias, S; Alonso, C D; Levine, J D; Wong, M T

    2014-08-01

    Infection with the dematiaceous environmental fungus Exophiala, an emerging pathogen in immunocompromised individuals, poses a diagnostic and therapeutic challenge. Herein, we report the first Exophiala dermatitidis fungemia case, to our knowledge, in an allogeneic hematopoietic stem cell transplant patient with graft-versus-host disease, expanding the clinical setting where Exophiala species mycosis should be suspected.

  19. Lymphadenectomy prior to rat hind limb allotransplantation prevents graft-versus-host disease in chimeric hosts

    NARCIS (Netherlands)

    Brouha, PCR; Perez-Abadia, G; Francois, CG; Laurentin-Perez, LA; Gorantla, [No Value; Vossen, M; Tai, C; Pidwell, D; Anderson, GL; Stadelmann, WK; Hewitt, CW; Kon, M; Barker, JH; Maldonado, C

    2004-01-01

    In previous rat studies, the use of mixed allogeneic chimerism (MAC) to induce host tolerance to hind limb allografts has resulted in severe graft-versus-host disease (GVHD). The purpose of this study was to determine if immunocompetent cells in bone marrow (BM) and/or lymph nodes (LNs) of transplan

  20. Stent graft placement for dysfunctional arteriovenous grafts

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, Gyeong Sik [Dept. of Radiology, CHA Bundang Medical Center, College of Medicine, CHA University, Seongnam (Korea, Republic of); Shin, Byung Seok; Ohm, Joon Young; Ahn, Moon Sang [Chungnam National University Hospital, Daejeon (Korea, Republic of)

    2015-07-15

    This study aimed to evaluate the usefulness and outcomes of stent graft use in dysfunctional arteriovenous grafts. Eleven patients who underwent stent graft placement for a dysfunctional hemodialysis graft were included in this retrospective study. Expanded polytetrafluoroethylene covered stent grafts were placed at the venous anastomosis site in case of pseudoaneurysm, venous laceration, elastic recoil or residual restenosis despite the repeated angioplasty. The patency of the arteriovenous graft was evaluated using Kaplan-Meier analysis. Primary and secondary mean patency was 363 days and 741 days. Primary patency at 3, 6, and 12 months was 82%, 73%, and 32%, respectively. Secondary patency at the 3, 6, 12, 24, and 36 months was improved to 91%, 82%, 82%, 50%, and 25%, respectively. Fractures of the stent graft were observed in 2 patients, but had no effect on the patency. Stent graft placement in dysfunctional arteriovenous graft is useful and effective in prolonging graft patency.

  1. Allogeneic bone marrow transplantation with co-stimulatory blockade induces macrochimerism and tolerance without cytoreductive host treatment.

    Science.gov (United States)

    Wekerle, T; Kurtz, J; Ito, H; Ronquillo, J V; Dong, V; Zhao, G; Shaffer, J; Sayegh, M H; Sykes, M

    2000-04-01

    Allogeneic bone marrow transplantation (in immunocompetent adults) has always required cytoreductive treatment of recipients with irradiation or cytotoxic drugs to achieve lasting engraftment at levels detectable by non-PCR-based techniques ('macrochimerism' or 'mixed chimerism'). Only syngeneic marrow engraftment at such levels has been achieved in unconditioned hosts. This requirement for potentially toxic myelosuppressive host pre-conditioning has precluded the clinical use of allogeneic bone marrow transplantation for many indications other than malignancies, including tolerance induction. We demonstrate here that treatment of naive mice with a high dose of fully major histocompatibility complex-mismatched allogeneic bone marrow, followed by one injection each of monoclonal antibody against CD154 and cytotoxic T-lymphocyte antigen 4 immunoglobulin, resulted in multi-lineage hematopoietic macrochimerism (of about 15%) that persisted for up to 34 weeks. Long-term chimeras developed donor-specific tolerance (donor skin graft survival of more than 145 days) and demonstrated ongoing intrathymic deletion of donor-reactive T cells. A protocol of high-dose bone marrow transplantation and co-stimulatory blockade can thus achieve allogeneic bone marrow engraftment without cytoreduction or T-cell depletion of the host, and eliminates a principal barrier to the more widespread use of allogeneic bone marrow transplantation. Although efforts have been made to minimize host pre-treatment for allogeneic bone marrow transplantation for tolerance induction, so far none have succeeded in eliminating pre-treatment completely. Our demonstration that this can be achieved provides the rationale for a safe approach for inducing robust transplantation tolerance in large animals and humans.

  2. 异基因造血干细胞移植受者外周血单核细胞趋化蛋白-2和IL-12水平变化与急性移植物抗宿主病的相关性%Chan ges of monocyte chemoattractant protein-2 and IL-12 levels in peripheral blood of recipients of allogeneic hemapoietic stem cell transplantation and their correlation with acute graft versus host disease

    Institute of Scientific and Technical Information of China (English)

    费晓莉; 刘林

    2012-01-01

    Objective To investigate the changes of monocyte chemoattractant protein-2 / C-C motif ligand 8 ( MCP-2 / CCL8 ) and IL-12 levels in peripheral blood of recipients of allogeneic hemapoietic stem cell transplantation (allo-HSCT) as well as their correlation with acute graft versus host disease (aGVHD), and provide reliable indexes for early diagnosis of aGVHD in clinic. Methods Twenty recipients of allo-HSCT were served as trial group, while those of autoplastic HSCT as control group. The MCP-2 and IL-12 levels in sera were determined 14(before pre-treatment) and 1 d(after pre-treatment and before stem cell reinfusion) before transplantation, and once a week after transplantation for 8 weeks, while those of patients with aGVHD were determined twice a week after appearance of clinical symptoms. Results In both trial and control groups, no significant differences were observed between the MCP-2 and IL-12 levels in sera 14 and 1 d before transplantation (P > 0. 05), or between those 7 after and 1 d before transplantation (P > 0. 05). Six cases of aGVHD were observed in trial group, of which clinical symptoms appeared 16 ~ 52 d after transplantation, and the time when serum MCP-2 and IL-12 levels increased firstly as compared with those 7 d after transplantation was earlier than that when the clinical symptoms appeared. The serum MCP-2 and IL-12 levels of the patients at time of diagnosis increased significantly as compared with those 7 d after transplantation (P 0. 05). Conclusion MCP-2 and IL-12 were correlated with aGVHD, of which the levels changed earlier than the appearance of clinical symptoms. The determination of serum MCP-2 and IL-12 levels was helpful to the early diagnosis of aGVHD.%目的 探讨异基因造血干细胞移植(allogeneic hemapoietic stem cell transplantation,allo-HSCT)受者外周血单核细胞趋化蛋白-2(Monocyte chemoattractant protein-2/C-C motif ligand 8,MCP-2/CCL8)和白细胞介素- 12( Interleukin- 12,IL-12)水平变化与

  3. Autologous stem cell transplantation versus alternative allogeneic donor transplants in adult acute leukemias.

    Science.gov (United States)

    Claude Gorin, Norbert

    2016-04-01

    The availability of alternative sources of stem cells including most recently T-replete haploidentical marrow or peripheral blood, and the increasing use of reduced-intensity conditioning (RIC), renders feasible an allogeneic transplant to almost all patients with acute leukemia up to 70 years of age. Autologous stem cell transplantation (ASCT) for consolidation of complete remission (CR), however, offers in some circumstances an alternative option. Although associated with a higher relapse rate, autologous transplant benefits from a lower non-relapse mortality, the absence of graft-versus-host disease (GVHD), and a better quality of life for long-term survivors. The recent use of intravenous busulfan (IVBU) with high-dose melphalan, better monitoring of minimal residual disease (MRD), and maintenance therapy post autografting bring new interest. Few retrospective studies compared the outcome following alternative donor versus autologous transplants for remission consolidation. Genoidentical and phenoidentical allogeneic stem cell transplantations are undisputed gold standards, but there are no data showing the superiority of alternative allogeneic donor over autologous transplantation, at the time of undetectable MRD, in patients with good- and intermediate-1 risk acute myelocytic leukemia (AML) in first complete remission (CR1), acute promyelocytic leukemia in second complete remission (CR2), and Philadelphia chromosome-positive (Ph(+)) acute lymphocytic leukemia (ALL).

  4. Retrospective Study of Incidence and Prognostic Significance of Eosinophilia after Allogeneic Hematopoietic Stem Cell Transplantation: Influence of Corticosteroid Therapy

    Directory of Open Access Journals (Sweden)

    Wataru Yamamoto

    2016-08-01

    Full Text Available Objective: The clinical significance of eosinophilia after allogeneic hematopoietic stem cell transplantation is controversial. This study aimed to retrospectively study the impact of eosinophilia on the outcome of allogeneic hematopoietic stem cell transplantation by taking into account the influence of corticosteroid therapy. Materials and Methods: We retrospectively studied 204 patients with acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndrome who underwent allogeneic hematopoietic stem cell transplantation from January 2001 to December 2010. Results: The median age was 43 years (minimum-maximum: 17- 65 years. Myeloablative conditioning was used in 153 patients and reduced intensity conditioning was employed in 51 patients. Donor cells were from bone marrow in 132 patients, peripheral blood in 34, and cord blood in 38. Eosinophilia was detected in 71 patients and there was no significant predictor of eosinophilia by multivariate analysis. There was no relationship between occurrence of eosinophilia and the incidence or grade of acute graft-versus-host disease when the patients were stratified according to corticosteroid treatment. Although eosinophilia was a prognostic factor for 5-year overall survival by univariate analysis, it was not a significant indicator by multivariate analysis. Conclusion: These results suggest that the clinical significance of eosinophilia in patients receiving allogeneic hematopoietic stem cell transplantation should be assessed with consideration of systemic corticosteroid administration.

  5. Retrospective Study of Incidence and Prognostic Significance of Eosinophilia after Allogeneic Hematopoietic Stem Cell Transplantation: Influence of Corticosteroid Therapy.

    Science.gov (United States)

    Yamamoto, Wataru; Ogusa, Eriko; Matsumoto, Kenji; Maruta, Atsuo; Ishigatsubo, Yoshiaki; Kanamori, Heiwa

    2016-09-05

    The clinical significance of eosinophilia after allogeneic hematopoietic stem cell transplantation is controversial. This study aimed to retrospectively study the impact of eosinophilia on the outcome of allogeneic hematopoietic stem cell transplantation by taking into account the influence of corticosteroid therapy. We retrospectively studied 204 patients with acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndrome who underwent allogeneic hematopoietic stem cell transplantation from January 2001 to December 2010. The median age was 43 years (minimum-maximum: 17-65 years). Myeloablative conditioning was used in 153 patients and reduced intensity conditioning was employed in 51 patients. Donor cells were from bone marrow in 132 patients, peripheral blood in 34, and cord blood in 38. Eosinophilia was detected in 71 patients and there was no significant predictor of eosinophilia by multivariate analysis. There was no relationship between occurrence of eosinophilia and the incidence or grade of acute graft-versus-host disease when the patients were stratified according to corticosteroid treatment. Although eosinophilia was a prognostic factor for 5-year overall survival by univariate analysis, it was not a significant indicator by multivariate analysis. These results suggest that the clinical significance of eosinophilia in patients receiving allogeneic hematopoietic stem cell transplantation should be assessed with consideration of systemic corticosteroid administration.

  6. The demanding attention of tuberculosis in allogeneic hematopoietic stem cell transplantation recipients: High incidence compared with general population

    Science.gov (United States)

    Lee, Hyo-Jin; Lee, Dong-Gun; Choi, Su-Mi; Park, Sun Hee; Cho, Sung-Yeon; Choi, Jae-Ki; Kim, Si-Hyun; Choi, Jung-Hyun; Yoo, Jin-Hong; Cho, Byung-Sik; Eom, Ki-Seong; Lee, Seok; Kim, Yoo-Jin; Kim, Hee-Je; Min, Chang-Ki; Kim, Dong-Wook; Lee, Jong-Wook; Min, Woo-Sung; Jung, Jung Im

    2017-01-01

    Background The risk of developing tuberculosis (TB) in allogeneic hematopoietic stem cell transplantation (HSCT) recipients is expected to be relatively high in an intermediate TB burden country. This single-center retrospective study was conducted to investigate risk factors and the incidence of TB after allogeneic HSCT. Methods From January 2004 to March 2011, 845 adult patients were enrolled. Starting April 2009, patients were given isoniazid (INH) prophylaxis based on interferon-γ release assay results. The incidence of TB was analyzed before and after April 2009, and compared it with that of the general population in Korea. Results TB was diagnosed in 21 (2.49%) of the 845 allogeneic HSCT patients. The median time to the development of TB was 386 days after transplantation (range, 49–886). Compared with the general population, the standardized incidence ratio of TB was 9.10 (95% CI; 5.59–14.79). Extensive chronic graft-versus-host disease (GVHD) was associated with the development of TB (P = 0.003). Acute GVHD, conditioning regimen with total body irradiation and conditioning intensity were not significantly related. INH prophylaxis did not reduce the incidence of TB (P = 0.548). Among 21 TB patients, one patient had INH prophylaxis. Conclusion Allogeneic HSCT recipients especially those who suffer from extensive chronic GVHD are at a high risk of developing TB. INH prophylaxis did not statistically change the incidence of TB, however, further well-designed prospective studies are needed. PMID:28278166

  7. Storage and allogeneic transplantation of peripheral nerve using a green tea polyphenol solution in a canine model

    Directory of Open Access Journals (Sweden)

    Noguchi Takashi

    2010-11-01

    Full Text Available Abstract Background In our previous study, allogeneic-transplanted peripheral nerve segments preserved for one month in a polyphenol solution at 4°C could regenerate nerves in rodents demonstrated the same extent of nerve regeneration as isogeneic fresh nerve grafts. The present study investigated whether the same results could be obtained in a canine model. Methods A sciatic nerve was harvested from a male beagle dog, divided into fascicules of Sry and β-actin to investigate whether cells of donor origin remained in the allogeneic nerve segments. FK506 concentration was measured in blood samples taken before the animals were killed. Results The total myelinated axon numbers and amplitudes of the muscle action potentials correlated significantly with the blood FK506 concentration. Few axons were observed in the allogeneic-transplanted nerve segments in the PA0.025 group. PCR showed clear Sry-specific bands in specimens from the PA0.1 and PA0.05 groups but not from the PA0.025 group. Conclusions Successful nerve regeneration was observed in the polyphenol-treated nerve allografts when transplanted in association with a therapeutic dose of FK506. The data indicate that polyphenols can protect nerve tissue from ischemic damage for one month; however, the effects of immune suppression seem insufficient to permit allogeneic transplantation of peripheral nerves in a canine model.

  8. Dichotomous role of interferon-gamma in allogeneic bone marrow transplant.

    Science.gov (United States)

    Lu, Ying; Waller, Edmund K

    2009-11-01

    Interferon (IFN)-gamma is a pleiotropic cytokine with a central role in innate and adaptive immunity. As a potent pro-inflammatory and antitumor cytokine, IFN-gamma is conventionally thought to be responsible for driving cellular immune response. On the other hand, accumulating evidence suggests that IFN-gamma also has immunosuppressive activity. An important role for IFN-gamma in inhibiting graft-versus-host disease (GVHD) has been demonstrated in murine models, despite IFN-gamma being one of the key factors amplifying T cell activation during the process of acute GVHD (aGVHD), the major complication and cause of post-transplant mortality in allogeneic bone marrow transplantation (BMT). At the same time, IFN-gamma facilitates graft-versus-leukemia (GVL) activity. Dissociation of GVL effects from GVHD has been the ultimate goal of allogeneic BMT in the treatment of hematologic malignancies. This paradoxic role of IFN-gamma makes modulating its activity a promising strategy to maximize GVL while minimizing GVHD and improve clinical outcomes in BMT. In this review, the effects of IFN-gamma on GVHD and GVL are discussed with consideration of the mechanism of IFN-gamma action.

  9. Dyslipidemia after allogeneic hematopoietic stem cell transplantation: evaluation and management.

    Science.gov (United States)

    Griffith, Michelle L; Savani, Bipin N; Boord, Jeffrey B

    2010-08-26

    Currently, approximately 15,000 to 20,000 patients undergo allogeneic hematopoietic stem cell transplantation (HSCT) annually throughout the world, with the number of long-term survivors increasing rapidly. In long-term follow-up after transplantation, the focus of care moves beyond cure of the original disease to the identification and treatment of late effects after HSCT. One of the more serious complications is therapy-related cardiovascular disease. Long-term survivors after HSCT probably have an increased risk of premature cardiovascular events. Cardiovascular complications related to dyslipidemia and other risk factors account for a significant proportion of late nonrelapse morbidity and mortality. This review addresses the risk and causes of dyslipidemia and impact on cardiovascular complications after HSCT. Immunosuppressive therapy, chronic graft-versus-host disease, and other long-term complications influence the management of dyslipidemia. There are currently no established guidelines for evaluation and management of dyslipidemia in HSCT patients; in this review, we have summarized our suggested approach in the HSCT population.

  10. T cell reconstitution in allogeneic haematopoietic stem cell transplantation

    DEFF Research Database (Denmark)

    Kielsen, K; Jordan, K K; Uhlving, H H

    2015-01-01

    Infections and acute graft-versus-host disease (aGVHD) are major causes of treatment-related mortality and morbidity following allogeneic haematopoietic stem cell transplantation (HSCT). Both complications depend on reconstitution of the T-lymphocyte population based on donor T cells. Although...... it is well established that Interleukin-7 (IL-7) is a cytokine essential for de novo T cell development in the thymus and homoeostatic peripheral expansion of T cells, associations between circulating levels of IL-7 and T cell reconstitution following HSCT have not been investigated previously. We...... in patients treated with anti-thymocyte globulin (ATG) compared with those not treated with ATG (P = 0.0079). IL-7 levels at day +7 were negatively associated with T cell counts at day +30 to +60 (at day +60: CD3(+) : β = -10.6 × 10(6) cells/l, P = 0.0030; CD8(+) : β = -8.4 × 10(6) cells/l, P = 0.061; CD4...

  11. Allogeneic anorectal transplantation in rats: technical considerations and preliminary results

    Science.gov (United States)

    Galvão, Flavio H. F.; Waisberg, Daniel R.; Seid, Victor E.; Costa, Anderson C. L.; Chaib, Eleazar; Baptista, Rachel Rossini; Capelozzi, Vera Luiza; Lanchotte, Cinthia; Cruz, Ruy J.; Araki, Jun; D’Albuquerque, Luiz Carneiro

    2016-01-01

    Fecal incontinence is a challenging condition with numerous available treatment modalities. Success rates vary across these modalities, and permanent colostomy is often indicated when they fail. For these cases, a novel potential therapeutic strategy is anorectal transplantation (ATx). We performed four isogeneic (Lewis-to-Lewis) and seven allogeneic (Wistar-to-Lewis) ATx procedures. The anorectum was retrieved with a vascular pedicle containing the aorta in continuity with the inferior mesenteric artery and portal vein in continuity with the inferior mesenteric vein. In the recipient, the native anorectal segment was removed and the graft was transplanted by end-to-side aorta-aorta and porto-cava anastomoses and end-to-end colorectal anastomosis. Recipients were sacrificed at the experimental endpoint on postoperative day 30. Surviving animals resumed normal body weight gain and clinical performance within 5 days of surgery. Isografts and 42.9% of allografts achieved normal clinical evolution up to the experimental endpoint. In 57.1% of allografts, signs of immunological rejection (abdominal distention, diarrhea, and anal mucosa inflammation) were observed three weeks after transplantation. Histology revealed moderate to severe rejection in allografts and no signs of rejection in isografts. We describe a feasible model of ATx in rats, which may allow further physiological and immunologic studies. PMID:27488366

  12. CYTOMEGALOVIRUS INTERSTITIAL PNEUMONITIS FOLLOWING ALLOGENEIC PERIPHERAL BLOOD STEM CELL TRANSPLANTATION

    Institute of Scientific and Technical Information of China (English)

    XU Xiao-hua; HUANG Lian-sheng; ZHANG Xiao-hong; ZHU Kang-er; XU Yang; WU Dong; ZHAO Xiao-ying

    2005-01-01

    Objective: To explore the risk factors and prophylaxis and treatment of cytomegalovirus interstitial pneumonitis(CMV-IP) after allogeneic peripheral blood stem cell transplantation (allo-PBSCT). Methods: 43 patients who received allo-PBSCT were allocated to either a Gancyclovir(GCV)-prophylaxis group (n=19) or a non-GCV prophylaxis group (n=24).A comparison was made of the incidence of CMV-IP in patients given or not given prophylactic gancyclovir. Results: 9patients in non-GCV prophylaxis group developed late CMV-IP (P<0.05). Graft-versus-host-disease (GVHD) may be associated with a high risk of CMV-IP. 5 cases of CMV-IP were successfully treated with GCV, but 3 cases died of CMV-IP.The most common adverse event of GCV was neutropenia, but was reversible. Conclusion: CMV infection was a major cause of interstitial pneumonitis after allo-PBSCT, which correlated strongly with the severity of GVHD. Gancyclovir was shown to be effective in both prophylaxis and treatment of CMV-IP.

  13. Pneumatosis intestinalis in children after allogeneic bone marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Yeager, A.M.; Kanof, M.E.; Lake, A.M.; Kramer, S.S.; Jones, B.; Saral, R.; Santos, G.W.

    1987-01-01

    Four children, ages 3 to 8 years, developed pneumatosis intestinalis (PI) after allogeneic bone marrow transplantation (BMT) for acute leukemia or severe aplastic anemia. PI was detected at a median of 48 days (range, 10-63 days) after BMT and was associated with abdominal symptoms and clinical signs. All patients had severe systemic and/or highgrade cutaneous acute graft-versus-host disease (AGVHD) at some time after BMT and were receiving corticosteroids at the time of development of PI; however, PI was associated with concomitant severe AGVHD in only one patient. One patient with PI had Hafnia alvei bacteremia and another patient had gastroenteritis due to rotavirus and adenovirus. All patients were treated with supportive care and systemic broad-spectrum antibiotics, and PI resolved 2-16 days after onset. Two patients died with BMT-associated complications unrelated to PI. Multiple factors contribute to the development of PI after BMT, and the prognosis for recovery from PI is good with medical management alone. Overall survival in these patients is dependent on the frequency and severity of other conditions, such as AGVHD and opportunistic infections, after BMT.

  14. Minimal change disease in graft versus host disease: a podocyte response to the graft?

    Science.gov (United States)

    Huskey, Janna; Rivard, Chris; Myint, Han; Lucia, Scott; Smith, Maxwell; Shimada, Michiko; Ishimoto, Takuji; Araya, Carlos; Garin, Eduardo H; Johnson, Richard J

    2013-12-01

    Nephrotic syndrome is a rare complication of hematopoietic cell transplantation. It has been suggested that nephrotic syndrome may represent a limited form of graft-versus-host disease although the pathological link between these two entities remains unclear. In this paper, we report a case of a 61-year-old female who underwent nonmyeloablative allogenic stem cell transplantation for T-cell prolymphocytic leukemia and subsequently developed biopsy proven minimal change disease shortly after cessation of her immunosuppression therapy. Urinary CD80 was markedly elevated during active disease and disappeared following corticosteroid-induced remission. We hypothesize that alloreactive donor T cells target the kidney and induce podocyte expression of CD80 that results in proteinuria from limited 'graft versus host' disease.

  15. Bone marrow-derived hematopoietic stem and progenitor cells infiltrate allogeneic and syngeneic transplants.

    Science.gov (United States)

    Fan, Z; Enjoji, K; Tigges, J C; Toxavidis, V; Tchipashivili, V; Gong, W; Strom, T B; Koulmanda, M

    2014-12-01

    Lineage (CD3e, CD11b, GR1, B220 and Ly-76) negative hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) infiltrate islet allografts within 24 h posttransplantation. In fact, lineage(negative) Sca-1(+) cKit(+) ("LSK") cells, a classic signature for HSCs, were also detected among these graft infiltrating cells. Lineage negative graft infiltrating cells are functionally multi-potential as determined by a standard competitive bone marrow transplant (BMT) assay. By 3 months post-BMT, both CD45.1 congenic, lineage negative HSCs/HPCs and classic "LSK" HSCs purified from islet allograft infiltrating cells, differentiate and repopulate multiple mature blood cell phenotypes in peripheral blood, lymph nodes, spleen, bone marrow and thymus of CD45.2 hosts. Interestingly, "LSK" HSCs also rapidly infiltrate syngeneic islet transplants as well as allogeneic cardiac transplants and sham surgery sites. It seems likely that an inflammatory response, not an adaptive immune response to allo-antigen, is responsible for the rapid infiltration of islet and cardiac transplants by biologically active HSCs/HPCs. The pattern of hematopoietic differentiation obtained from graft infiltrating HSCs/HPCs, cells that are recovered from inflammatory sites, as noted in the competitive BMT assay, is not precisely the same as that of intramedullary HSCs. This does not refute the obvious multi-lineage potential of graft infiltrating HSCs/HPCs.

  16. Novel regulatory therapies for prevention of Graft-versus-host disease

    Directory of Open Access Journals (Sweden)

    Leventhal Joseph

    2012-05-01

    Full Text Available Abstract Graft-versus-host disease is one of the major transplant-related complications in allogeneic hematopoietic stem cell transplantation. Continued efforts have been made to prevent the occurrence of severe graft-versus-host disease by eliminating or suppressing donor-derived effector T cells. Conventional immunosuppression does not adequately prevent graft-versus-host disease, especially in mismatched transplants. Unfortunately, elimination of donor-derived T cells impairs stem cell engraftment, and delays immunologic reconstitution, rendering the recipient susceptible to post-transplant infections and disease relapse, with potentially lethal consequences. In this review, we discuss the role of dynamic immune regulation in controlling graft-versus-host disease, and how cell-based therapies are being developed using regulatory T cells and other tolerogenic cells for the prevention and treatment of graft-versus-host disease. In addition, advances in the design of cytoreductive conditioning regimens to selectively target graft-versus-host disease-inducing donor-derived T cells that have improved the safety of allogeneic stem cell transplantation are reviewed. Finally, we discuss advances in our understanding of the tolerogenic facilitating cell population, a phenotypically and functionally distinct population of bone marrow-derived cells which promote hematopoietic stem cell engraftment while reducing the risk of graft-versus-host disease.

  17. Sustained disease-free survival achieved with withdrawal of immunosuppression after rapid relapse of myelodysplastic syndrome following myeloablative allogeneic hematopoietic transplantation: a case report

    Directory of Open Access Journals (Sweden)

    Hamilton Betty K

    2013-01-01

    Full Text Available Abstract Introduction Relapse after allogeneic hematopoietic stem cell transplantation in patients with myelodysplasia is a challenging problem with limited treatment options. Attempts to induce a graft-versus-leukemia effect have been used with limited success. In patients with myelodysplasia, sustained complete remissions have generally been limited to patients with long-term remission after transplant and those with low numbers of marrow blasts. Case presentation We report the case of a 41-year-old Caucasian woman with relapsed myelodysplastic syndrome and a high blast percentage six months after undergoing an allogeneic transplant who achieved a sustained complete remission after withdrawal of immunosuppression alone. Conclusion This case highlights the importance of a reasonable period of observation after withdrawing immunosuppression to induce graft-versus-leukemia, and the potential effectiveness of that approach.

  18. Regression of the tumor after withdrawal of cyclosporine in relapsed extranodal natural killer/T cell lymphoma following allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Kako, Shinichi; Izutsu, Koji; Oshima, Kumi; Sato, Hiroyuki; Kanda, Yoshinobu; Motokura, Toru; Chiba, Shigeru; Kurokawa, Mineo

    2007-10-01

    The prognosis of patients with advanced-stage extranodal natural killer/T cell lymphoma, nasal type (ENKL) has been generally poor, and several anecdotal reports have suggested the role of allogeneic hematopoietic stem cell transplantation (HSCT). A potential advantage of allogeneic HSCT may be the graft-versus-lymphoma (GVL) effect. The susceptibility to the GVL effect, however, has been shown to vary according to histologic subtypes, and it has been hardly documented yet whether ENKL is susceptible to the GVL effect. Here we report a patient with advanced-stage ENKL who underwent allogeneic HSCT from an HLA one-allele mismatched related donor, whose clinical course after HSCT suggested the potent GVL effect against ENKL. A 43-year-old female underwent allogeneic HSCT for advanced-stage, chemorefractory ENKL, and achieved complete response. In 4 months after the transplantation, however, the ENKL relapsed in multiple sites. These lesions markedly responded to the discontinuation of immunosuppressive agents and disappeared. Except for a temporal exacerbation of bronchiolitis obliterans organizing pneumonia, she has been free from disease for more than a year without other treatments against lymphoma. The clinical course of the current patient suggests the potent GVL effect against ENKL. Allogeneic HSCT, including that with reduced-intensity regimens, is a promising treatment option for high-risk ENKL.

  19. Associação dos níveis de citocinas no pós-transplante de células-tronco hematopoiéticas com a Doença do Enxerto Contra o Hospedeiro aguda Association of cytokine levels with acute graft versus host disease following full match allogeneic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Jeane E. L. Visentainer

    2005-09-01

    Full Text Available Este estudo foi realizado para investigar se os níveis séricos de sIL-2R, TNF-alfa, IFN-gama, IL-6, IL-10 e TGF-beta1 estavam associados com o desenvolvimento de DECH (Doença do Enxerto Contra o Hospedeiro aguda. Os níveis de citocinas foram seqüencialmente mensurados por Elisa em 13 pacientes que haviam sido submetidos ao transplante alogênico de células progenitoras hematopoiéticas. Os níveis de sIL-2R e IL-10 da 1ª a 15ª semanas pós-transplante foram significativamente maiores no grupo que desenvolveu DECH aguda que naquele sem a doença. Os níveis de sIL-2R aumentaram em direta correlação com a pega do enxerto e ao tempo do DECH aguda, enquanto os níveis de IL-10 aumentaram transitoriamente pós-transplante. A média da concentração de TNF-alfa nas primeiras semanas após o transplante foi maior no grupo que desenvolveu DECH aguda. Além disso, uma queda dos níveis de TGF-beta1 após a pega esteve significativamente associada à DECH aguda. Nenhuma correlação foi encontrada entre DECH aguda e as outras citocinas investigadas. Estes resultados suportam a idéia de que um balanço entre as citocinas derivadas de linfócitos T auxiliadores do tipo 1 e 2 pode ser importante no desenvolvimento e controle da DECH aguda. Embora os níveis de sIL-2R, TNF-alfa, IL-10 e TGF-beta1 tenham sido correlacionados com a DECH aguda, os níveis de sIL-2R ao tempo da pega podem prover um melhor parâmetro para a detecção precoce de DECH aguda após o transplante alogênico.This study was performed to investigate whether the serum levels of sIL-2R, TNF-alpha, IFN-gamma, IL-6, IL-10, and TGF-beta1 are associated with the development of acute GVHD. Serum cytokine levels were sequentially measured by sandwich Enzyme Linked-Immuno-Sorbent Assay (Elisa in 13 patients who had received full match allogeneic stem cell transplantation. Serum sIL-2R and IL-10 levels from the 1st to the 15th week post transplantation were significantly higher in the

  20. No benefit of intraoperative whole blood sequestration and autotransfusion during coronary artery bypass grafting : results of a randomized clinical trial

    NARCIS (Netherlands)

    Ramnath, A N; Naber, H R; de Boer, A; Leusink, J A

    2003-01-01

    OBJECTIVES: In a randomized clinical trial of patients undergoing elective coronary artery bypass grafting, we evaluated the effect of intraoperative whole blood sequestration and autotransfusion on postoperative blood loss and the use of allogeneic blood products. METHODS: Male patients were includ

  1. Function, Adjustment, Quality of Life and Symptoms (FAQS in Allogeneic Hematopoietic Stem Cell Transplantation (HSCT Survivors: A Study Protocol

    Directory of Open Access Journals (Sweden)

    Krumlauf Michael

    2011-04-01

    Full Text Available Abstract Background The population of survivors following allogeneic HSCT continues to increase, and yet their experiences of recovery and long-term survivorship have not been fully characterized. This paper presents a study protocol examining over time the functional status, psychosocial adjustment, health-related quality of life, and symptom experience of survivors who have undergone allogeneic transplantation. The aims of the study are to: 1 explore the patterns of change in these health outcomes during the survivorship phase; 2 characterize subgroups of survivors experiencing adverse outcomes; and 3 examine relationships among outcomes and demographic and clinical factors (such as age, graft-versus-host disease (GVHD, and disease relapse. Methods In this longitudinal observational study, adults who survive a minimum of 3 years from date of allogeneic transplantation complete a series of questionnaires annually. Demographic and clinical data are collected along with a series of patient-reported outcome measures, specifically: 1 Medical Outcomes Study SF- 36; 2 Functional Assessment of Chronic Illness Therapy (FACIT - General, 3 FACIT-Fatigue; 4 FACIT- Spiritual; 5 Psychosocial Adjustment to Illness Scale; 6 Rotterdam Symptom Checklist-Revised; and 7 Pittsburgh Sleep Quality Index. Conclusions This study will provide multidimensional patient-reported outcomes data to expand the understanding of the survivorship experience across the trajectory of allogeneic transplantation recovery. There are a number of inherent challenges in recruiting and retaining a diverse and representative sample of long-term transplant survivors. Study results will contribute to an understanding of outcomes experienced by transplant survivors, including those with chronic GVHD, malignant disease relapse, and other late effects following allogeneic transplantation. Trial Registration ClinicalTrials.gov: NCT00128960

  2. Bone grafting: An overview

    Directory of Open Access Journals (Sweden)

    D. O. Joshi

    2010-08-01

    Full Text Available Bone grafting is the process by which bone is transferred from a source (donor to site (recipient. Due to trauma from accidents by speedy vehicles, falling down from height or gunshot injury particularly in human being, acquired or developmental diseases like rickets, congenital defects like abnormal bone development, wearing out because of age and overuse; lead to bone loss and to replace the loss we need the bone grafting. Osteogenesis, osteoinduction, osteoconduction, mechanical supports are the four basic mechanisms of bone graft. Bone graft can be harvested from the iliac crest, proximal tibia, proximal humerus, proximal femur, ribs and sternum. An ideal bone graft material is biologically inert, source of osteogenic, act as a mechanical support, readily available, easily adaptable in terms of size, shape, length and replaced by the host bone. Except blood, bone is grafted with greater frequency. Bone graft indicated for variety of orthopedic abnormalities, comminuted fractures, delayed unions, non-unions, arthrodesis and osteomyelitis. Bone graft can be harvested from the iliac crest, proximal tibia, proximal humerus, proximal femur, ribs and sternum. By adopting different procedure of graft preservation its antigenicity can be minimized. The concept of bone banking for obtaining bone grafts and implants is very useful for clinical application. Absolute stability require for successful incorporation. Ideal bone graft must possess osteogenic, osteoinductive and osteocon-ductive properties. Cancellous bone graft is superior to cortical bone graft. Usually autologous cancellous bone graft are used as fresh grafts where as allografts are employed as an alloimplant. None of the available type of bone grafts possesses all these properties therefore, a single type of graft cannot be recomm-ended for all types of orthopedic abnormalities. Bone grafts and implants can be selected as per clinical problems, the equipments available and preference of

  3. Immunological Basis of Bone Marrow Failure after Allogeneic Hematopoietic Stem Cell Transplantation

    Science.gov (United States)

    Masouridi-Levrat, Stavroula; Simonetta, Federico; Chalandon, Yves

    2016-01-01

    Bone marrow failure (BMF) syndromes are severe complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this paper, we distinguish two different entities, the graft failure (GF) and the poor graft function (PGF), and we review the current understanding of the interactions between the immune and hematopoietic compartments in these conditions. We first discuss how GF occurs as the result of classical alloreactive immune responses mediated by residual host cellular and humoral immunity persisting after conditioning and prevented by host and donor regulatory T cells. We next summarize the current knowledge about the contribution of inflammatory mediators to the development of PGF. In situations of chronic inflammation complicating allo-HSCT, such as graft-versus-host disease or infections, PGF seems to be essentially the result of a sustained impairment of hematopoietic stem cells (HSC) self-renewal and proliferation caused by inflammatory mediators, such as interferon-γ (IFN-γ) and tumor necrosis factor-α, and of induction of apoptosis through the Fas/Fas ligand pathway. Interestingly, the production of inflammatory molecules leads to a non-MHC restricted, bystander inhibition of hematopoiesis, therefore, representing a promising target for immunological interventions. Finally, we discuss immune-mediated impairment of bone marrow microenvironment as a potential mechanism hampering hematopoietic recovery. Better understanding of immunological mechanisms responsible for BMF syndromes after allo-HSCT may lead to the development of more efficient immunotherapeutic interventions. PMID:27695456

  4. Cytomegalovirus shapes long-term immune reconstitution after allogeneic stem cell transplantation

    Science.gov (United States)

    Itzykson, Raphael; Robin, Marie; Moins-Teisserenc, Helene; Delord, Marc; Busson, Marc; Xhaard, Aliénor; de Fontebrune, Flore Sicre; de Latour, Régis Peffault; Toubert, Antoine; Socié, Gérard

    2015-01-01

    Immune reconstitution after allogeneic stem cell transplantation is a dynamic and complex process depending on the recipient and donor characteristics, on the modalities of transplantation, and on the occurrence of graft-versus-host disease. Multivariate methods widely used for gene expression profiling can simultaneously analyze the patterns of a great number of biological variables on a heterogeneous set of patients. Here we use these methods on flow cytometry assessment of up to 25 lymphocyte populations to analyze the global pattern of long-term immune reconstitution after transplantation. Immune patterns were most distinct from healthy controls at six months, and had not yet fully recovered as long as two years after transplant. The two principal determinants of variability were linked to the balance of B and CD8+ T cells and of natural killer and B cells, respectively. Recipient’s cytomegalovirus serostatus, cytomegalovirus replication, and chronic graft-versus-host disease were the main factors shaping the immune pattern one year after transplant. We identified a complex signature of under- and over-representation of immune populations dictated by recipient’s cytomegalovirus seropositivity. Finally, we identified dimensions of variance in immune patterns as significant predictors of long-term non-relapse mortality, independently of chronic graft-versus-host disease. PMID:25261095

  5. Lentivectors encoding immunosuppressive proteins genetically engineer pancreatic beta-cells to correct diabetes in allogeneic mice.

    Science.gov (United States)

    Kojaoghlanian, T; Joseph, A; Follenzi, A; Zheng, J H; Leiser, M; Fleischer, N; Horwitz, M S; DiLorenzo, T P; Goldstein, H

    2009-03-01

    The effectiveness of genetic engineering with lentivectors to protect transplanted cells from allogeneic rejection was examined using, as a model, type 1 diabetes treatment with beta-cell transplantation, whose widespread use has been limited by the requirement for sustained immunosuppressive treatment to prevent graft rejection. We examined whether lentivectors expressing select immunosuppressive proteins encoded by the adenoviral genome early region 3 (AdE3) would protect transplanted beta-cells from an alloimmune attack. The insulin-producing beta-cell line beta TC-tet (C3HeB/FeJ-derived) was transduced with lentiviruses encoding the AdE3 proteins gp19K and RID alpha/beta. The efficiency of lentiviral transduction of beta TC-tet cells exceeded 85%. Lentivector expression of gp19K decreased surface class I major histocompatibility complex expression by over 90%, whereas RID alpha/beta expression inhibited cytokine-induced Fas upregulation by over 75%. beta TC-tet cells transduced with gp19K and RID alpha/beta lentivectors, but not with a control lentivector, provided prolonged correction of hyperglycemia after transplantation into diabetic BALB/c severe combined immunodeficient mice reconstituted with allogeneic immune effector cells or into diabetic allogeneic BALB/c mice. Thus, genetic engineering of beta-cells using gp19K- and RID alpha/beta-expressing lentiviral vectors may provide an alternative that has the potential to eliminate or reduce treatment with the potent immunosuppressive agents necessary at present for prolonged engraftment with transplanted islets.

  6. Electron beam irradiation to the allogeneic, xenogenic and synthetic bone materials

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Soung Min; Park, Min Woo; Jeong, Hyun Oh [School of Dentistry Seoul National University, Seoul (Korea, Republic of); and others

    2013-07-01

    For the development of the biocompatible bony regeneration materials, allogenic, xenogenic and synthetic bone were irradiated by electron beam to change the basic components and structures. For the efficient electron beam irradiating condition of these allogenic, xenogenic and artificial bone substitutes, the optimal electron beam energy and their individual dose were established, to maximize the bony regeneration capacity. Commercial products of four allogenic bones, such as Accell (ISOTIS OrthogBiologics Co., USA), Allotis (Korea Bone Bank Co., Korea), Oragraft (LifeNet Co., USA), and Orthoblast (Integra Orthobiologics Inc., USA), six xenogenic bones, such as BBP (OscoTec Co., Korea), Bio-cera (OscoTec Co., Korea), Bio-oss (Geistlich Pharma AG, Switzerland), Indu-cera (OscoTec Co., Korea), OCS-B (Nibec Co., Korea), and OCS-H (Nibec Co., Korea), and six synthetic bones, such as BMP (Couellmedi Co., Korea), BoneMedik (Meta Biomed Co., Korea), Bone plus (Megagen Co., Korea), MBCP (Biomatlante Co., France), Osteon (Genoss Co., Korea), and Osteogen (Impladent LTD., USA), were used. We used 1.0 and 2.0 MeV superconduction accelerator, and/or microtrone with different individual 60, 120 kGy irradiation dose. Different dose irradiated specimens were divided 6 portions each, so total 360 groups were prepared. 4 portions were analyzed each by elementary analysis using FE-SEM (Field Emission Scanning Microscopy) and another 2 portions were grafted to the calvarial defect of Sprague-Dawley rat, following histologic, immunohistochemical analysis and TEM study were processed at the 8th and 16th weeks, in vivo. This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MEST)

  7. Modeling Human Graft-Versus-Host Disease in Immunocompromised Mice.

    Science.gov (United States)

    Norelli, Margherita; Camisa, Barbara; Bondanza, Attilio

    2016-01-01

    Hematopoietic stem cell transplantation (HSCT) from an allogeneic donor is an effective form of cancer immunotherapy, especially for acute leukemias. HSCT is however frequently complicated by the occurrence of graft-versus-host disease (GVHD). Immunocompromised mice infused with human T cells often develop a clinical syndrome resembling human GVHD (xenogeneic or X-GVHD). Herein, we describe a method for inducing X-GVHD in a highly reproducible manner. Given the human nature of immune effectors, this xenogeneic model can be routinely adopted for screening the efficacy of new treatments for GVHD.

  8. Monitoring of Pathogen-Specific T-Cell Immune Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation

    Science.gov (United States)

    Fuji, Shigeo; Kapp, Markus; Einsele, Hermann

    2013-01-01

    The clinical outcome after allogeneic hematopoietic stem cell transplantation (HSCT) has been significantly improved during the last decades with regard to the reduction in organ failure, infection, and severe acute graft-versus-host disease. However, severe complications due to infectious diseases are still one of the major causes of morbidity and mortality after allogeneic HSCT, in particular in patients receiving haploidentical HSCT or cord blood transplant due to a slow and often incomplete immune reconstitution. In order to improve the immune control of pathogens without an increased risk of alloreactivity, adoptive immunotherapy using highly enriched pathogen-specific T cells offers a promising approach. In order to identify patients who are at high risk for infectious diseases, several monitoring assays have been developed with potential for the guidance of immunosuppressive drugs and adoptive immunotherapy in clinical practice. In this article, we aim to give a comprehensive overview regarding current developments of T-cell monitoring techniques focusing on T cells against viruses and fungi. In particular, we will focus on rather simple, fast, non-labor-intensive, cellular assays which could be integrated in routine clinical screening approaches. PMID:24062744

  9. Lung function after allogeneic bone marrow transplantation for leukaemia or lymphoma.

    Science.gov (United States)

    Nysom, K; Holm, K; Hesse, B; Ulrik, C S; Jacobsen, N; Bisgaard, H; Hertz, H

    1996-05-01

    Longitudinal data were analysed on the lung function of 25 of 29 survivors of childhood leukaemia or lymphoma, who had been conditioned with cyclophosphamide and total body irradiation before allogeneic bone marrow transplantation, to test whether children are particularly vulnerable to pulmonary damage after transplantation. None developed chronic graft-versus-host disease. Transfer factor and lung volumes were reduced immediately after bone marrow transplantation, but increased during the following years. However, at the last follow up, 4-13 years (median 8) after transplantation, patients had significantly reduced transfer factor, total lung capacity, and forced vital capacity (-1.0, -1.2, and -0.8 SD score, respectively), and increased ratio of forced expiratory volume in one second to forced vital capacity (+0.9 SD score). None of the patients had pulmonary symptoms, and changes were unrelated to their age at bone marrow transplantation. In conclusion, patients had subclinical restrictive pulmonary disease at a median of eight years after total body irradiation and allogeneic bone marrow transplantation.

  10. CD4+CD25+FOXP3+ Regulatory T Cells In Allogeneic Hematopoietic Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Young-Ho Lee

    2011-06-01

    Full Text Available CD4+CD25+FOXP3+ regulatory T cells (Treg require activation through the T cell receptor for function. CD4+CD25+FOXP3+ regulatory T cells are believed to be key players of the immune tolerance network and control the induction and effector phase of the immune system. Although these cells require antigen-specific activation, they are generally able to suppress bystander T cell responses once activated. This raises the possibility that antigen-specific Treg may be useful therapeutically by localizing generalized suppressive activity to tissues expressing select target antigens. Treg can exert a potent suppressive effect on immune effector cells reactive to host antigens and prevent graft versus host disease (GVHD in allogeneic bone marrow transplantation (BMT. Here, we observed that co-transfer of CD4+CD25+FOXP3+ T cells derived from donor type along with the donor bone marrow cells could control GVHD-like reactions by suppressing effectors cells of host responding to the donor hematopoietic compartment, and resulted in prevention of autoimmunity and rejection. We further demonstrate that CD4+CD25+FOXP3+ regulatory T cells can control immune-based morbidity after allogeneic BMT by suppressing the development of granulocytes cells and increasing the level of B cell expression.

  11. [Adenovirus infections in children: experience in the field of the allogeneic stem cell transplantation].

    Science.gov (United States)

    Le Henaff, G; Corradini, N; Gras, C; Méchinaud, F

    2007-07-01

    Adenovirus (Adv) infections are frequent in pediatric patients, sometimes serious, above all in immunocompromised children. We report the cases of 2 children who presented an Adv infection after allogeneic stem cell transplantation (SCT). Case n(o) 1 concerns a boy who received SCT at the age of 6 years. He had a hemorragic cystitis, which resolved after antiviral treatment and successful engraftment. Case n(o) 2 concerns a boy who received SCT at the age of 2. He shortly presented a disseminated infection, and died in spite of antiviral treatment and re-infusion of an autologous transplant. T-cell depletion (mainly carried out in vivo at present) is the major risk factor of Adv infection after allogeneic SCT. It is important to be recognized, in order to proceed to a routine screening among transplanted patients. Moreover, the detection of viral genoma by molecular biology is a predictive factor of disseminated disease development, with mortality rates higher than 50%. Early treatment is thus crucial. Immunotherapy is to be developed, by tapering of immunosuppression, or by manipulating grafts and donor lymphocyte infusions, in order to improve Adv specific responses. The possibility of a prophylaxis is still to be investigated.

  12. Change of serum alpha-1 microglobulin and beta-2 microglobulin following allogeneic bone marrow transplantation.

    Science.gov (United States)

    Ashida, T; Tsubaki, K; Urase, F; Ishikawa, H; Tsuji, K; Hazu, S; Ezumi, M; Horiuchi, A

    1994-10-01

    By serially measuring serum levels of alpha-1 microglobulin and beta-2 microglobulin following allogeneic bone marrow transplantation (BMT), we tried to define their relationship to renal dysfunction, acute graft-versus-host disease (GVHD) and infection as complications of the transplantation. The study involved a total of 25 patients with leukemia, myelodysplastic syndrome and aplastic anemia who received BMT in this department; one patient received re-transplantation, thus bringing the total number of transplants to 26. Twenty-four patients received BMT from HLA-identical siblings while two others received BMT from unrelated donors. Alpha-1 microglobulin was within normal limits in all patients before BMT; among various complications such as nephrotoxicity, acute GVHD and infection which took place after transplantation, a raised alpha-1 microglobulin level was found only in nephrotoxicity; however, the increase was not significant compared with the pre-transplantation level. The pre-transplantation beta-2 microglobulin level was higher than normal in some patients; it was significantly increased in all of the above complications compared with the pretransplantation level (1.57 +/- 0.57 mg/l). A significant correlation was found between the serum creatinine level and the beta-2 microglobulin level (r = 0.849) in patients with renal dysfunction. In some patients, however, the beta-2 microglobulin level increased earlier than the serum creatinine level, and this finding was considered useful for the early diagnosis of renal dysfunction following allogeneic BMT.

  13. Association between thymic function and allogeneic hematopoietic stem cell transplantation outcome: results of a pediatric study.

    Science.gov (United States)

    Saglio, Francesco; Cena, Silvia; Berger, Massimo; Quarello, Paola; Boccasavia, Viola; Ferrando, Federica; Pittana, Laura; Bruno, Benedetto; Fagioli, Franca

    2015-06-01

    Robust T cell function recovery has been shown to be crucial in determining allogeneic hematopoietic stem cell transplantation (HSCT) outcome, and there is growing evidence that the thymus plays a central role in regulating this process. We performed a long-term analysis of the role of thymic activity recovery in a population of pediatric patients undergoing allogeneic HSCT by signal joint T cell receptor excision circle (sjTREC) quantification. In this study, characterized by a long-term follow-up (median, 72 months), we found patients with higher levels of sjTRECs before transplantation had a statistically significant reduced risk of death compared with patients with lower values (relative risk, .31; 95% confidence interval, .30 to .32; P = .02), showing this different outcome was mainly related to a reduction of relapse incidence (14% versus 43%, P = .02). Unlike previous reports, we observed no correlation between sjTREC levels and lymphocyte recovery. Moreover, we confirmed that only graft-versus-host disease influenced thymic activity after transplantation. In conclusion, our results suggest an association between pretransplantation thymic activity and the long-term outcome of pediatric patients undergoing HSCT, mainly through a reduction of relapse opportunities.

  14. Cognitive function in the acute course of allogeneic hematopoietic stem cell transplantation for hematological malignancies.

    Science.gov (United States)

    Schulz-Kindermann, F; Mehnert, A; Scherwath, A; Schirmer, L; Schleimer, B; Zander, A R; Koch, U

    2007-06-01

    The aim of the study was to assess cognitive performance in patients with hematological malignancies before, and 3 months after, allogeneic hematopoietic stem cell transplant (HSCT). A consecutive sample of 39 patients was assessed before admission with a comprehensive neuropsychological test battery and health-related quality-of-life (HRQoL) questionnaires; 19 of these patients were retested around 100 days post HSCT. Test results were compared with normative data and revealed minimal differences at both time points in the level of group-means. One parameter - simple reaction time - was significantly worse (prolonged) at second measurement after HSCT. According to the definition of an impairment score (more than three impaired functions), 26% of patients were classified as impaired before as well as after HSCT. Neuropsychological test results did not vary systematically according to medical variables such as extent of pretreatment, graft-versus-host-disease (GvHD) and kind of conditioning protocol. As a dimension of HRQoL, self-rated cognitive function was in the normal range before and after HSCT. Significant correlations between HRQoL and neuropsychological parameters were related to symptom scales. This study showed impairments of neuropsychological performance for a subgroup of patients before and after allogeneic HSCT. Systematic effects of conditioning, medical variables or self-rated HRQoL could not be observed.

  15. Therapy of relapsed leukemia after allogeneic hematopoietic cell transplantation with T cells specific for minor histocompatibility antigens.

    Science.gov (United States)

    Warren, Edus H; Fujii, Nobuharu; Akatsuka, Yoshiki; Chaney, Colette N; Mito, Jeffrey K; Loeb, Keith R; Gooley, Ted A; Brown, Michele L; Koo, Kevin K W; Rosinski, Kellie V; Ogawa, Seishi; Matsubara, Aiko; Appelbaum, Frederick R; Riddell, Stanley R

    2010-05-13

    The adoptive transfer of donor T cells that recognize recipient minor histocompatibility antigens (mHAgs) is a potential strategy for preventing or treating leukemic relapse after allogeneic hematopoietic cell transplantation (HCT). A total of 7 patients with recurrent leukemia after major histocompatibility complex (MHC)-matched allogeneic HCT were treated with infusions of donor-derived, ex vivo-expanded CD8(+) cytotoxic T lymphocyte (CTL) clones specific for tissue-restricted recipient mHAgs. The safety of T-cell therapy, in vivo persistence of transferred CTLs, and disease response were assessed. Molecular characterization of the mHAgs recognized by CTL clones administered to 3 patients was performed to provide insight into the antileukemic activity and safety of T-cell therapy. Pulmonary toxicity of CTL infusion was seen in 3 patients, was severe in 1 patient, and correlated with the level of expression of the mHAg-encoding genes in lung tissue. Adoptively transferred CTLs persisted in the blood up to 21 days after infusion, and 5 patients achieved complete but transient remissions after therapy. The results of these studies illustrate the potential to selectively enhance graft-versus-leukemia activity by the adoptive transfer of mHAg-specific T-cell clones and the challenges for the broad application of this approach in allogeneic HCT. This study has been registered at http://clinicaltrials.gov as NCT00107354.

  16. Solid organ transplantation after allogeneic hematopoietic stem cell transplantation: a retrospective, multicenter study of the EBMT

    DEFF Research Database (Denmark)

    Koenecke, C; Hertenstein, B; Schetelig, J

    2010-01-01

    To analyze the outcome of solid organ transplantation (SOT) in patients who had undergone allogeneic hematopoietic stem cell transplantation (HSCT), a questionnaire survey was carried out within 107 European Group of Blood and Marrow Transplantation centers. This study covered HSCT between 1984...... and 2007 in Europe. Forty-five SOT in 40 patients were reported. Fifteen liver, 15 renal, 13 lung, 1 heart and 1 skin transplantations were performed in 28 centers. Overall survival (OS) of patients after SOT was 78% at 5 years (95% confidence interval [CI], 64% to 92%). OS at 5 years was 100% for renal......, 71% (95% CI, 46% to 96%) for liver and 63% (95% CI, 23% to 100%) for lung transplant recipients. The 2-year-incidence of SOT failure was 20% (95% CI, 4% to 36%) in patients with graft-versus-host disease (GvHD) and 7% (95% CI, 0% to 21%) in patients without GvHD before SOT. The relapse incidence...

  17. Regulatory T-Cell Therapy for Graft-versus-host Disease

    OpenAIRE

    Heinrichs, Jessica; Bastian, David; Veerapathran, Anandharaman; Anasetti, Claudio; Betts, Brain; Yu, Xue-Zhong

    2016-01-01

    Graft-versus-host disease (GVHD) is a significant cause of non-relapse mortality after allogeneic hematopoietic cell transplantation (allo-HCT). Existing strategies to prevent and treat GVHD are incomplete, where a significant portion of allo-HCT recipients developed this complication. Despite this, one such therapy has emerged involving the use of regulatory T cells (Tregs) to control GVHD. The use of natural Tregs (nTregs) yielded positive pre-clinical results and are actively under investi...

  18. Bone grafts in dentistry

    Directory of Open Access Journals (Sweden)

    Prasanna Kumar

    2013-01-01

    Full Text Available Bone grafts are used as a filler and scaffold to facilitate bone formation and promote wound healing. These grafts are bioresorbable and have no antigen-antibody reaction. These bone grafts act as a mineral reservoir which induces new bone formation.

  19. 静脉用丙种球蛋白对HLA预致敏小鼠异基因皮肤移植的影响%Effects of IVIG on allogenic skin graft in an HLA-A2 pre-sensitized mouse model

    Institute of Scientific and Technical Information of China (English)

    何瑶; 陈瑜君; 黄文生; 熊理守; 陈白莉

    2010-01-01

    目的:探讨IVIG对存在HLA预致敏的异基因皮肤移植的作用及其可能机制。方法自人HLA-A2.1转基因小鼠(C57BL/6-TgN[HLA-2.1])脾脏获取人HLA-A2抗原,分别于第0天、第3及第4周以腹腔注射人HLA-A2抗原的方式对野生型小鼠(C57BL/6)进行预致敏。第7周时连续5天分别以人IVIG、人血清白蛋白、甘氨酸及磷酸盐缓冲液( PBS)给予上述HLA-A2预致敏小鼠腹腔注射进行脱敏处理。第10周时以转HLA-A2.1基因小鼠为供体,野生型小鼠为受体行皮肤移植建立异基因皮肤移植的小鼠模型,以研究人IVIG对人HLA.A2抗原预致敏的小鼠异基因皮肤移植的影响。结果受体小鼠血清中HLA-A2 IgG变化:HLA-A2致敏后小鼠血清中HLA-A2 IgG水平较基线水平显著升高。腹腔注射人IVIG脱敏后,于第9周时可见小鼠血清中HLA-A2 IgG显著降低( P<0.01),与人血清白蛋白、甘氨酸及PBS注射组相比差异有统计学意义( P <0.01)。异基因皮肤移植后各种受体小鼠血清中HLA-A2 IgG水平迅速升高致极高水平( P <0.01),并持续于高水平。小鼠异基因皮肤移植情况:受体小鼠移植皮肤存活时间均约为术后7d,各组间差异无统计学意义( P>0.05)。结论单独使用IVIG对HLA-A2预致敏小鼠进行脱敏处理不能防止皮肤移植术后抗I类HLA抗体的产生,亦不能有效延长移植皮肤存活时间,提示移植后仍需联用其它有效免疫抑制剂以防止术后排斥反应的发生。%Objective To investigate the effect of IVIG on pre-existing anti-HLA-A2 Ab levels and graft skin survival.Methods C57BL/6 wild type mice were sensitized to HLA-A2 by intraperitoneal injec-tion (IP) of HLA-A2 TgN mouse spleen cells (C57BL/6-TgN [HLA-2.1]1Enge SC) expressing human HLA-A2 at day 0, week 3 and 4.Sensitized mice were respectively treated with human IVIG , albumin, gly-cine, or PBS for 5 days during week 7.Skin transplantation

  20. Polymorphisms in CCR6 are associated with chronic graft-versus-host disease and invasive fungal disease in matched-related hematopoietic stem cell transplantation

    NARCIS (Netherlands)

    Broen, K.C.J.; Waart, A.B. van der; Greupink-Draaisma, A.L.; Metzig, J.; Feuth, T.; Schaap, N.P.M.; Blijlevens, N.M.A.; Velden, W.J. van der; Dolstra, H.

    2011-01-01

    Graft-versus-host disease (GVHD) and fungal infections are frequent complications after allogeneic hematopoietic stem cell transplantation (HSCT). Single nucleotide polymorphisms (SNPs) in genes of the immune system can influence the inflammatory cascade and T cell-driven alloimmune reactions after

  1. Programming of donor T cells using allogeneic δ-like ligand 4-positive dendritic cells to reduce GVHD in mice.

    Science.gov (United States)

    Mochizuki, Kazuhiro; Meng, Lijun; Mochizuki, Izumi; Tong, Qing; He, Shan; Liu, Yongnian; Purushe, Janaki; Fung, Henry; Zaidi, M Raza; Zhang, Yanyun; Reshef, Ran; Blazar, Bruce R; Yagita, Hideo; Mineishi, Shin; Zhang, Yi

    2016-06-23

    Alloreactive T cells play a critical role in eliminating hematopoietic malignant cells but are also the mediators of graft-versus-host disease (GVHD), a major complication that subverts the success of allogeneic hematopoietic stem cell transplantation (HSCT). However, induction of alloreactive T cells does not necessarily lead to GVHD. Here we report the development of a cellular programming approach to render alloreactive T cells incapable of causing severe GVHD in both major histocompatibility complex (MHC)-mismatched and MHC-identical but minor histocompatibility antigen-mismatched mouse models. We established a novel platform that produced δ-like ligand 4-positive dendritic cells (Dll4(hi)DCs) from murine bone marrow using Flt3 ligand and Toll-like receptor agonists. Upon allogeneic Dll4(hi)DC stimulation, CD4(+) naïve T cells underwent effector differentiation and produced high levels of interferon γ (IFN-γ) and interleukin-17 in vitro, depending on Dll4 activation of Notch signaling. Following transfer, allogeneic Dll4(hi)DC-induced T cells were unable to mediate severe GVHD but preserved antileukemic activity, significantly improving the survival of leukemic mice undergoing allogeneic HSCT. This effect of Dll4(hi)DC-induced T cells was associated with their impaired expansion in GVHD target tissues. IFN-γ was important for Dll4(hi)DC programming to reduce GVHD toxicities of alloreactive T cells. Absence of T-cell IFN-γ led to improved survival and expansion of Dll4(hi)DC-induced CD4(+) T cells in transplant recipients and caused lethal GVHD. Our findings demonstrate that Dll4(hi)DC programming can overcome GVHD toxicity of donor T cells and produce leukemia-reactive T cells for effective immunotherapy.

  2. T Cell Receptor Excision Circle (TREC) Monitoring after Allogeneic Stem Cell Transplantation; a Predictive Marker for Complications and Clinical Outcome

    Science.gov (United States)

    Gaballa, Ahmed; Sundin, Mikael; Stikvoort, Arwen; Abumaree, Muhamed; Uzunel, Mehmet; Sairafi, Darius; Uhlin, Michael

    2016-01-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is a well-established treatment modality for a variety of malignant diseases as well as for inborn errors of the metabolism or immune system. Regardless of disease origin, good clinical effects are dependent on proper immune reconstitution. T cells are responsible for both the beneficial graft-versus-leukemia (GVL) effect against malignant cells and protection against infections. The immune recovery of T cells relies initially on peripheral expansion of mature cells from the graft and later on the differentiation and maturation from donor-derived hematopoietic stem cells. The formation of new T cells occurs in the thymus and as a byproduct, T cell receptor excision circles (TRECs) are released upon rearrangement of the T cell receptor. Detection of TRECs by PCR is a reliable method for estimating the amount of newly formed T cells in the circulation and, indirectly, for estimating thymic function. Here, we discuss the role of TREC analysis in the prediction of clinical outcome after allogeneic HSCT. Due to the pivotal role of T cell reconstitution we propose that TREC analysis should be included as a key indicator in the post-HSCT follow-up. PMID:27727179

  3. Olecranon bone graft: revisited.

    Science.gov (United States)

    Mersa, Berkan; Ozcelik, Ismail Bulent; Kabakas, Fatih; Sacak, Bulent; Aydin, Atakan

    2010-09-01

    Autogenous bone grafts are frequently in use in the field of reconstructive upper extremity surgery. Cancellous bone grafts are applied to traumatic osseous defects, nonunions, defects after the resection of benign bone tumors, arthrodesis, and osteotomy procedures. Cancellous bone grafts do not only have benefits such as rapid revascularization, but they also have mechanical advantages. Despite the proximity to the primary surgical field, cancellous olecranon grafts have not gained the popularity they deserve in the field of reconstructive hand surgery. In this study, the properties, advantages, and technical details of harvesting cancellous olecranon grafts are discussed.

  4. Pathogenic mechanisms of Acute Graft versus Host Disease

    Directory of Open Access Journals (Sweden)

    Ferrara James L.M.

    2002-01-01

    Full Text Available Graft-versus-host-disease (GVHD is the major complication of allogeneic Bone Marrow Transplant (BMT. Older BMT recipients are a greater risk for acute GVHD after allogeneic BMT, but the causes of this association are poorly understood. Using well-characterized murine BMT models we have explored the mechanisms of increased GVHD in older mice. GVHD mortality and morbidity, and pathologic and biochemical indices were all worse in old recipients. Donor T cell responses were significantly increased in old recipients both in vivo and in vitro when stimulated by antigen-presenting cells (APCs from old mice. In a haploidential GVHD model, CD4+ donor T cells mediated more severe GVHD in old mice. We confirmed the role of aged APCs in GVHD using bone marrow chimera recipient created with either old or young bone marrow. APCs from these mice also stimulated greater responses from allogeneic cells in vitro. In a separate set of experiments we evaluated whether alloantigen expression on host target epithelium is essential for tissue damage induced by GVHD. Using bone marrow chimeras recipients in which either MHC II or MHC I alloantigen was expressed only on APCs, we found that acute GVHD does not require alloantigen expression on host target epithelium and that neutralization of tumor necrosis factor-alpha and interleukin-1 prevents acute GVHD. These results pertain to CD4-mediated GVHD and to a lesser extent in CD8-mediated GVHD, and confirm the central role of most APCs as well as inflammatory cytokines.

  5. Long-term outcomes of the use of allogeneic, radiation-sterilised bone blocks in reconstruction of the atrophied alveolar ridge in the maxilla and mandible.

    Science.gov (United States)

    Krasny, Marta; Krasny, Kornel; Fiedor, Piotr; Zadurska, Małgorzata; Kamiński, Artur

    2015-12-01

    Increasingly dental surgeons face the challenge of reconstruction of the height and/or thickness of the alveolar ridge as more and more patients wish to have permanent restoration of their dental defects based on intraosseous implants. Evaluation of human allogeneic bone tissue grafts in reconstruction of atrophied alveolar ridge as a pre-implantation procedure. The material comprised 21 patients aged 19-63, treated between 2009 and 2012 by the same surgeon. Restoration of bone tissue defects was performed with allogeneic, frozen, radiation-sterilised, corticocancellous blocks. The study included 26 grafting procedures with 7 procedures consisting in reconstruction of the alveolar ridge in the mandible and 19 in the maxilla. In all the cases the atrophied alveolar ridge was successfully reconstructed, which allowed placement of intraosseous implants in compliance with the initial treatment plan. After the treatment was completed the patients reported for follow-up annually. The average time of follow-up amounted to 39 months (28-50 months). None of the implants was lost during the follow-up period. There was one case of gingival recession causing aesthetics deterioration of the prosthetic restoration. In three cases the connector became unscrewed partially, which was corrected at the same visit. Frozen, radiation-sterilised, allogeneic bone blocks constitute good and durable bone-replacement material allowing effective and long-lasting reconstruction of the atrophied alveolar ridge to support durable, implant-based, prosthetic restoration.

  6. 不同时段应用他克莫司纳米微球缓释颗粒促进同种异体神经移植再生的实验研究%Effects of controlled release of FK506 by P (DLLA-co-TMC) microspheres at different intervals on regeneration after allogenic nerve graft in a rodent model

    Institute of Scientific and Technical Information of China (English)

    柯于海; 张振伟; 冯登殿; 廖坚文; 李征; 庄加川

    2010-01-01

    目的 探讨不同时间段使用他克莫司(FK506)纳米微球在同种异体移植后促进神经的再生作用.方法 采用单乳化-溶剂挥发法(O/W)制备FK506纳米微球,同种异体移植大鼠胫神经.A组术后立即局部应用FK506纳米微球,B组24 h给药,C组3 d后给药,D组不给药;于术后第4、8和12周行移植神经大体观察、组织学检查及有髓纤维图像分析、小腿三头肌湿重测定、荧光素逆行标记神经元、双侧胫神经电生理比较.结果 FK506纳米微球降解快、吸收好.A、B组神经再生效果相似,都明显要比C、D组好,差异有统计学意义;C、D组之间差异也有统计学意义.结论 FK506纳米微球释药速度符合神经损伤后再生规律,局部应用有良好的促进神经再生作用,而且早期(24 h内)给药效果更加明显.%Objective To study the effect of the application of P(DLLA-co-TMC)/FK506 microspheres at different intervals on peripheral nerve regeneration after tibial nerve allograft. Methods P (DLLA-coTMC)/FK506 microspheres were fabricated using an oil-in-water single emulsion and solvent evaporation method.Tibial nerve allograft model was created in mice which were divided into group A, B, C and D. In groups A, B and C were P( DLLA-co-TMC)/FK506 microspheres were administered locally on the day of surgery, 24 hours postoperatively, and 3 days postoperatively, respectively. Group D was left untreated. On postoperative weeks 4,8 and 12, gross observation of the graft, histomorphometric image analysis, triceps surae wet weight,retrograde tracing and fluorescence microscopy of motor neurons, and electrophysiological examination of bilateral tibial nerves were carried out. Results P (DLLA-co-TMC)/FK506 microspheres degraded fast and were well absorbed. There was a statistically significant improvement in neuroregeneration in groups A and B comparing to that in groups C and D. There was also significant difference between groups C and D. Conclusion The

  7. Acute graft versus host disease

    Directory of Open Access Journals (Sweden)

    Vogelsang Georgia B

    2007-09-01

    Full Text Available Abstract Acute graft-versus-host disease (GVHD occurs after allogeneic hematopoietic stem cell transplant and is a reaction of donor immune cells against host tissues. Activated donor T cells damage host epithelial cells after an inflammatory cascade that begins with the preparative regimen. About 35%–50% of hematopoietic stem cell transplant (HSCT recipients will develop acute GVHD. The exact risk is dependent on the stem cell source, age of the patient, conditioning, and GVHD prophylaxis used. Given the number of transplants performed, we can expect about 5500 patients/year to develop acute GVHD. Patients can have involvement of three organs: skin (rash/dermatitis, liver (hepatitis/jaundice, and gastrointestinal tract (abdominal pain/diarrhea. One or more organs may be involved. GVHD is a clinical diagnosis that may be supported with appropriate biopsies. The reason to pursue a tissue biopsy is to help differentiate from other diagnoses which may mimic GVHD, such as viral infection (hepatitis, colitis or drug reaction (causing skin rash. Acute GVHD is staged and graded (grade 0-IV by the number and extent of organ involvement. Patients with grade III/IV acute GVHD tend to have a poor outcome. Generally the patient is treated by optimizing their immunosuppression and adding methylprednisolone. About 50% of patients will have a solid response to methylprednisolone. If patients progress after 3 days or are not improved after 7 days, they will get salvage (second-line immunosuppressive therapy for which there is currently no standard-of-care. Well-organized clinical trials are imperative to better define second-line therapies for this disease. Additional management issues are attention to wound infections in skin GVHD and fluid/nutrition management in gastrointestinal GVHD. About 50% of patients with acute GVHD will eventually have manifestations of chronic GVHD.

  8. Successful repigmentation of vitiligo after allogeneic bone marrow transplantation for Hodgkin′s lymphoma by autologous noncultured melanocyte-keratinocyte transplantation

    Directory of Open Access Journals (Sweden)

    Huijuan Tang

    2015-01-01

    Full Text Available The treatment of vitiligo is derisory since the pathogenesis of vitiligo is not clear at present. Most conservative treatments are difficult to approach satisfactory therapy. So transplantation is the only way left when the disease becomes insensitive to those conservative treatments. Here we describe an 18-year-old patient who developed vitiligo, which was triggered by graft-versus-host disease after a allogeneic bone marrow transplantation for the treatment of Hodgkin′s lymphoma from his sister. In the following treatment to vitiligo, the patient successfully performed the transplantation of autologous uncultured melanocyte on the premise of poor reaction to other conservative methods. We infer that transplantation can be a treatment of the vitiligo after allogeneic bone marrow transplantation.

  9. Surgical technique for allogeneic uterus transplantation in macaques

    OpenAIRE

    Hideaki Obara; Iori Kisu; Yojiro Kato; Yohei Yamada; Kentaro Matsubara; Katsura Emoto; Masataka Adachi; Yusuke Matoba; Kiyoko Umene; Yuya Nogami; Kouji Banno; Hideaki Tsuchiya; Iori Itagaki; Ikuo Kawamoto; Takahiro Nakagawa

    2016-01-01

    No study has reported an animal model of uterus transplantation (UTx) using cynomolgus macaques. We aimed to establish a surgical technique of allogeneic UTx assuming the recovery of a uterus from a deceased donor in cynomolgus macaques. Four allogeneic UTxs were performed in female cynomolgus macaques. Donor surgeries comprised en bloc recovery of organs with iliac vessels on both sides, and/or abdominal aorta/vena cava after sufficient perfusion from one femoral artery or external iliac art...

  10. Dual character of interaction between lymphocytes and allogeneic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Petrov, R.V.; Dozmorov, I.M.; Kochetkova, M.O.; Nikolaeva, I.S.

    1986-10-01

    The mechanisms of stimulation of colony formation by small doses of allogeneic lymphocytes were studied in mice. When interaction of lymphocytes with allogeneic stem cells was studied, bone marrow cells of mice were injected into lethally irradiated recipients in the control, and mixtures of bone marrow cells with varied numbers of lymphocytes were injected in the experiment. Dependence of the inactivation indices on the number of lymphocytes injected, based on the results of counting macro- and microcolonies in the spleen, is shown.

  11. Advances in conditioning regimens for older adults undergoing allogeneic stem cell transplantation to treat hematologic malignancies.

    Science.gov (United States)

    William, Basem M; de Lima, Marcos

    2013-06-01

    Allogeneic stem cell transplantation (SCT) is a potentially curative treatment for patients with hematological malignancies. These diseases, however, have their peak incidence in the sixth to eighth decades of life. Historically, elderly patients have been considered unsuitable candidates for SCT because of high treatment-related mortality (TRM). Over the past 15 years, the use of reduced-intensity conditioning (RIC) regimens before SCT has allowed patients in the sixth and seventh decades of life to be routinely transplanted. Despite major differences among transplant centers in the intensity and composition of the conditioning regimen and immunosuppression, choice of graft source, postgraft immunomodulation, and supportive care, there has been a dramatic decrease in TRM, allowing safer delivery of SCT. Major obstacles to SCT in elderly patients include donor availability, graft-versus-host disease, delayed immune recovery, multiple comorbidities, and chemo refractoriness. Here we review the current results of SCT in elderly patients, focusing on the role of RIC, and using myeloid diseases as the model for discussion.

  12. Immunotherapy in allogeneic hematopoietic stem cell transplantation--not just a case for effector cells.

    Science.gov (United States)

    Troeger, A; Meisel, R; Moritz, T; Dilloo, D

    2005-03-01

    The concept that in allogeneic hematopoietic stem cell transplantation (alloHSCT) the immune system plays a prominent role in the control of leukemic disease is supported by the clinical observation that immunological effector mechanisms contribute to the elimination of leukemic blasts. The failure to induce prolonged remission after alloHSCT has led to resurgent interest in complementing concepts of immune modulation to improve the antileukemic reponse. While the general focus has been placed on manipulation of cytotoxic effector cell populations, we will explore the dual role of leukemia cells as both antigen-presenting and target cells and describe various vaccination strategies to facilitate a protective antileukemic immune response in this setting. In addition, we will introduce mesenchymal stem cells (MSC) as another cell population recently recognized for their immunomodulatory properties. The potential benefits and hazards of MSC-cotransplantation in alloHSCT with regard to the graft versus leukemia (GvL) and the graft versus host (GvH) response will be discussed.

  13. Allogeneic haematopoietic stem cell transplantation as therapy for chronic granulomatous disease--single centre experience.

    Science.gov (United States)

    Goździk, Jolanta; Pituch-Noworolska, Anna; Skoczeń, Szymon; Czogała, Wojciech; Wędrychowicz, Anna; Baran, Jarosław; Krasowska-Kwiecień, Aleksandra; Wiecha, Oktawiusz; Zembala, Marek

    2011-06-01

    Chronic granulomatous disease (CGD) is phagocytic cell metabolic disorder resulting in recurrent infections and granuloma formation. This paper reports the favourable outcome of allogeneic transplantation in six high-risk CGD patients. The following donors were used: HLA-matched, related (two) and unrelated (three), and HLA-mismatched, unrelated (one). One patient was transplanted twice using the same sibling donor because of graft rejection at 6 months after reduced-intensity conditioning transplant (fludarabine and melphalan). Myeloablative conditioning regimen consisted of busulphan and cyclophosphamide. Stem cell source was unmanipulated bone marrow containing: 5.2 (2.6-6.5) × 10(8) nucleated cells, 3.8 (2.0-8.0) × 10(6) CD34+ cells and 45 (27-64) × 10(6) CD3+ cells per kilogramme. Graft-versus-host disease prophylaxis consisted of cyclosporine A and, for unrelated donors, short course of methotrexate and anti-T-lymphocyte globulin. Mean neutrophile and platelet engraftments were observed at day 22 (20-23) and day 20 (16-29), respectively. Pre-existing infections and inflammatory granulomas resolved. With the follow-up of 4-35 months (mean, 20 months), all patients are alive and well with full donor chimerism and normalized superoxide production.

  14. DNA Damage and Repair in Epithelium after Allogeneic Hematopoietic Stem Cell Transplantation

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    Maria Themeli

    2012-11-01

    Full Text Available Allogeneic hematopoietic stem cell transplantation (allo-HSCT in humans, following hematoablative treatment, results in biological chimeras. In this case, the transplanted hematopoietic, immune cells and their derivatives can be considered the donor genotype, while the other tissues are the recipient genotype. The first sequel, which has been recognized in the development of chimerical organisms after allo-HSCT, is the graft versus host (GvH reaction, in which the new developed immune cells from the graft recognize the host’s epithelial cells as foreign and mount an inflammatory response to kill them. There is now accumulating evidence that this chronic inflammatory tissue stress may contribute to clinical consequences in the transplant recipient. It has been recently reported that host epithelial tissue acquire genomic alterations and display a mutator phenotype that may be linked to the occurrence of a GvH reaction. The current review discusses existing data on this recently discovered phenomenon and focuses on the possible pathogenesis, clinical significance and therapeutic implications.

  15. Present and future of allogeneic natural killer cell therapy

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    Okjae eLim

    2015-06-01

    Full Text Available Natural killer (NK cells are innate lymphocytes that are capable of eliminating tumor cells and are therefore used for cancer therapy. Although many early investigators used autologous NK cells, including lymphokine-activated killer cells, the clinical efficacies were not satisfactory. Meanwhile, human leukocyte antigen (HLA-haploidentical hematopoietic stem cell transplantation revealed the anti-tumor effect of allogeneic NK cells, and HLA-haploidentical, killer cell immunoglobulin-like receptor (KIR ligand-mismatched allogeneic NK cells are currently used for many protocols requiring NK cells. Moreover, allogeneic NK cells from non-HLA-related healthy donors have been recently used in cancer therapy. The use of allogeneic NK cells from non-HLA-related healthy donors allows the selection of donor NK cells with higher flexibility and to prepare expanded, cryopreserved NK cells for instant administration without delay for ex vivo expansion. In cancer therapy with allogeneic NK cells, optimal matching of donors and recipients is important to maximize the efficacy of the therapy. In this review, we summarize the present state of allogeneic NK cell therapy and its future directions.

  16. Pharmacokinetics, Pharmacodynamics and Pharmacogenomics of Immunosuppressants in Allogeneic Haematopoietic Cell Transplantation: Part I.

    Science.gov (United States)

    McCune, Jeannine S; Bemer, Meagan J

    2016-05-01

    Although immunosuppressive treatments and target concentration intervention (TCI) have significantly contributed to the success of allogeneic haematopoietic cell transplantation (alloHCT), there is currently no consensus on the best immunosuppressive strategies. Compared with solid organ transplantation, alloHCT is unique because of the potential for bidirectional reactions (i.e. host-versus-graft and graft-versus-host). Postgraft immunosuppression typically includes a calcineurin inhibitor (cyclosporine or tacrolimus) and a short course of methotrexate after high-dose myeloablative conditioning, or a calcineurin inhibitor and mycophenolate mofetil after reduced-intensity conditioning. There are evolving roles for the antithymyocyte globulins (ATGs) and sirolimus as postgraft immunosuppression. A review of the pharmacokinetics and TCI of the main postgraft immunosuppressants is presented in this two-part review. All immunosuppressants are characterized by large intra- and interindividual pharmacokinetic variability and by narrow therapeutic indices. It is essential to understand immunosuppressants' pharmacokinetic properties and how to use them for individualized treatment incorporating TCI to improve outcomes. TCI, which is mandatory for the calcineurin inhibitors and sirolimus, has become an integral part of postgraft immunosuppression. TCI is usually based on trough concentration monitoring, but other approaches include measurement of the area under the concentration-time curve (AUC) over the dosing interval or limited sampling schedules with maximum a posteriori Bayesian personalization approaches. Interpretation of pharmacodynamic results is hindered by the prevalence of studies enrolling only a small number of patients, variability in the allogeneic graft source and variability in postgraft immunosuppression. Given the curative potential of alloHCT, the pharmacodynamics of these immunosuppressants deserves to be explored in depth. Development of

  17. Allogeneic T cells induce rapid CD34+ cell differentiation into CD11c+CD86+ cells with direct and indirect antigen-presenting function

    Science.gov (United States)

    Abbasian, Javaneh; Mahmud, Dolores; Mahmud, Nadim; Chunduri, Sandeep; Araki, Hiroto; Reddy, Pavan; Hoffman, Ronald; Arpinati, Mario; Ferrara, James L. M.; Rondelli, Damiano

    2006-01-01

    Dendritic cells (DCs) derive from CD34+ cells or monocytes and stimulate alloimmune responses in transplantation. We hypothesized that the interaction between CD34+ cells and allogeneic T cells would influence the function of hematopoietic stem cells (HSCs). Cord blood (CB) CD34+ cells proliferated briskly in response to allogeneic, but not autologous, T cells when mixed with irradiated T cells for 6 days in vitro. This proliferation was significantly inhibited by an anti-HLA class II monoclonal antibody (mAb), by an anti-TNFα mAb, or by CTLA4-Ig. Allogeneic T cells induced the differentiation of CD34+ progenitors into cells with the morphology of dendritic monocytic precursors and characterized by the expression of HLA-DR, CD86, CD40, CD14, and CD11c, due to an endogenous release of TNFα. Cotransplantation of CD34+ cells with allogeneic T cells into nonobese diabetic-severe combined immunodeficiency (NOD/SCID) mice resulted in a greater engraftment of myeloid CD1c+ dendritic cells compared with cotransplantation with autologous T cells. In vitro, CD34+ cell-derived antigen-presenting cells (APCs) were functionally capable of both direct and indirect presentation of alloantigens. Based on these findings, we hypothesize that in HSC transplantation the initial cross talk between allogeneic T cells and CD34+ cells may result in the increased generation of APCs that can present host alloantigens and possibly contribute to the development of graft-versus-host disease. (Blood. 2006;108:203-208) PMID:16478883

  18. Modified conditioning regimen busulfan-cyclophosphamide followed by allogeneic stem cell transplantation in patients with multiple myeloma

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xiao-hui; LU Dao-pei; HUANG Xiao-jun; LIU Kai-yan; XU Lan-ping; LIU Dai-hong; CHEN Huan; CHEN Yu-hong; WANG Jing-zhi; HAN Wei

    2007-01-01

    Background Allogeneic stem cell transplantation is a potential curative approach in patients with multiple myeloma.The very high transplant related mortality associated with standard allogeneic stem cell transplantation is currently the major limitation to wider use of this potentially curative treatment modality. The challenge for clinical investigators is to reduce the incidence of post-transplant complications for patients receiving autologous hematopoietic stem cell transplantion for multiple myeloma. In this study the toxicity and efficacy of modified myeloablative conditioning regimen followed by allogeneic stem cell transplantation was investigated in patients with multiple myeloma.Methods The conditioning regimen consisted of hydroxyurea, cytarabine, busulfan, cyclophosphamide, and semustine.Ten patients underwent allogeneic transplantation among them hydroxyurea (40 mg/kg) was administered twice on day -10 and cytarabine (2 g/m2) was given on day -9, busulfan was administered orally in four divided doses daily for 3 days (days -8 to -6). The dose of busulfan was 12 mg/kg in the protocol followed by cyclophosphamide intravenously over 1hour on days -5 and -4 (1.8 g/m2), and with semustine (Me-CCNU) 250 mg/m2 on day -3.Results Chimerism data were available on all patients and all patients achieved full donor chimerism without graft failure. Six patients had not acute graft-versus-host disease (GVHD, 36.4%; 95% CI:13.9%-38.6%). Two patients (18.2%) developed grade Ⅰ acute GVHD (95% CI:10.9%-35.9%) and grade Ⅱ acute GVHD occurred in one patient (9.1%;95% CI: 8.4%-32.3%). Severe grade Iva GVHD was seen in one patient, who died from acute GVHD. The incidence of chronic GVHD was 22.2% (95% CI: 11.7%-36.7%), among them one died of severe grade IV GVHD and one developed multiorgan failure on day +170; the treatment-related mortality was 22.0% (95% CI: 10.3%-34.1%). The overall 4-year survival rate was 67.8% (95% CI: 16.3%-46.7%). The estimated 4-year

  19. Meniscal allograft transplantation. Part 1: systematic review of graft biology, graft shrinkage, graft extrusion, graft sizing, and graft fixation.

    Science.gov (United States)

    Samitier, Gonzalo; Alentorn-Geli, Eduard; Taylor, Dean C; Rill, Brian; Lock, Terrence; Moutzouros, Vasilius; Kolowich, Patricia

    2015-01-01

    To provide a systematic review of the literature regarding five topics in meniscal allograft transplantation: graft biology, shrinkage, extrusion, sizing, and fixation. A systematic literature search was conducted using the PubMed (MEDLINE), ScienceDirect, and EBSCO-CINAHL databases. Articles were classified only in one topic, but information contained could be reported into other topics. Information was classified according to type of study (animal, in vitro human, and in vivo human) and level of evidence (for in vivo human studies). Sixty-two studies were finally included: 30 biology, 3 graft shrinkage, 11 graft extrusion, 17 graft size, and 6 graft fixation (some studies were categorized in more than one topic). These studies corresponded to 22 animal studies, 22 in vitro human studies, and 23 in vivo human studies (7 level II, 10 level III, and 6 level IV). The principal conclusions were as follows: (a) Donor cells decrease after MAT and grafts are repopulated with host cells form synovium; (b) graft preservation alters collagen network (deep freezing) and causes cell apoptosis with loss of viable cells (cryopreservation); (c) graft shrinkage occurs mainly in lyophilized and gamma-irradiated grafts (less with cryopreservation); (d) graft extrusion is common but has no clinical/functional implications; (e) overall, MRI is not superior to plain radiograph for graft sizing; (f) graft width size matching is more important than length size matching; (g) height appears to be the most important factor influencing meniscal size; (h) bone fixation better restores contact mechanics than suture fixation, but there are no differences for pullout strength or functional results; and (i) suture fixation has more risk of graft extrusion compared to bone fixation. Systematic review of level II-IV studies, Level IV.

  20. Long-term graft function of cryostored alginate encapsulated rat islets

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    Schneider Stephan

    2011-09-01

    Full Text Available Abstract Microencapsulation of pancreatic islets before transplantation is a promising approach to enable graft function in an immunocompetent recipient without immunosuppression. However, the insufficient availability of allogenic islet tissue is a major problem. One concept to overcome these shortcomings is the cryopreservation of encapsulated allogenic islets. Recently, we reported a gentle cryopreservation protocol for rat islets encapsulated in an alginate-based microcapsule system. Here, we report for the first time long-term transplantation data of these cryopreserved microencapsulated islets. We detected a stable graft function for more than 12 month (experiments still continuing after transplantation of 2500 cryopreserved microencapsulated CD rat islets in streptozotocin-diabetic Wistar rats. Moreover, the glucose clearance rate during an IPGTT was well preserved up to 56 weeks after transplantation. In addition, hyperglycemic blood glucose levels after removal of rat islet grafts 12 and 56 weeks after transplantation confirmed the efficacy of the encapsulated islets. Finally, the retrieved encapsulated rat islets responded well with a 7-fold increase of insulin secretion to a glucose stimulus (12 and 56 weeks. In conclusion, our study demonstrates for the first time that cryopreservation of encapsulated rat islets is possible without substantial losses on graft function for a very long time.

  1. The consequence of biologic graft processing on blood interface biocompatibility and mechanics.

    Science.gov (United States)

    Van de Walle, Aurore B; Uzarski, Joseph S; McFetridge, Peter S

    2015-09-01

    Processing ex vivo derived tissues to reduce immunogenicity is an effective approach to create biologically complex materials for vascular reconstruction. Due to the sensitivity of small diameter vascular grafts to occlusive events, the effect of graft processing on critical parameters for graft patency, such as peripheral cell adhesion and wall mechanics, requires detailed analysis. Isolated human umbilical vein sections were used as model allogenic vascular scaffolds that were processed with either: 1. sodium dodecyl sulfate (SDS), 2. ethanol/acetone (EtAc), or 3. glutaraldehyde (Glu). Changes in material mechanics were assessed via uniaxial tensile testing. Peripheral cell adhesion to the opaque grafting material was evaluated using an innovative flow chamber that allows direct observation of the blood-graft interface under physiological shear conditions. All treatments modified the grafts tensile strain and stiffness properties, with physiological modulus values decreasing from Glu 240±12 kPa to SDS 210±6 kPa and EtAc 140±3 kPa, Papplied to the umbilical vein scaffold were shown to modify structural mechanics and cell adhesion properties, with the EtAc treatment reducing thrombotic events relative to SDS treated samples. This approach allows time and cost effective prescreening of clinically relevant grafting materials to assess initial cell reactivity.

  2. Undifferentiated spondyloarthritis following allogeneic stem cell transplantation

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    Espinoza Luis R

    2010-06-01

    Full Text Available Abstract Background Stem cell transplant has been utilized in the treatment of malignancies and rheumatic disease. Rheumatic disease may be transferred from the donor with active disease or may be developed in a recipient de novo as a late complication of SCT. Case Presentation We here report the rare case of a 26-year old male patient, who has been diagnosed with undifferentiated spondyloarthropathy after unique circumstance. The patient suffered from intermittent inflammatory back pain and peripheral joint swelling for several years and did not find relief through multiple emergency room visits at different medical facilities. After a thorough history and physical exam, it was noted that our patient had developed signs of axial disease along with dactylitis and overall that he had been insidiously developing an undifferentiated spondyloarthopathy after allogeneic stem cell transplantation. Conclusion Our observation supports the hypothesis that de novo rheumatic disease can develop after stem cell transplant for a variety of reasons. Thus, larger studies and awareness of this association are needed to delineate the exact underlying mechanism(s.

  3. The efficacy of continuous fascia iliaca compartment block for pain management in burn patients undergoing skin grafting procedures.

    Science.gov (United States)

    Cuignet, Olivier; Pirson, Jean; Boughrouph, Jenna; Duville, Diane

    2004-04-01

    Postoperative pain from split skin donor sites is often more intense than the pain at the grafted site. In this prospective, randomized, double-blind study we assessed the efficacy of a continuous fascia iliaca compartment block (FICB) in reducing the pain at the thigh donor site. Twenty patients, with a total burn surface area of 16% +/- 13% (mean +/- SD) were randomized 1:1 to receive either ropivacaine 0.2% or saline 0.9%. All patients received a general anesthesic followed by preincision continuous FICB with 40 mL of the randomized solution, then an infusion of 10 mL/h of either ropivacaine or saline until the first dressing change (72 h later). Postoperative analgesia consisted of propacetamol 2g/6h, IV patient-controlled analgesia of morphine chlorhydrate (2 mg/mL), and morphine hydrochlorate 0.5 mg/kg PO once 60 min before first dressing change. The visual analog scale (VAS) scores were compared using the Mann-Whitney U-test preoperatively, 24 and 48 h postoperatively, and during the first dressing change. The cumulative morphine consumption was compared with repeated-measures analysis of variance followed by Scheffé's method if indicated. Patients with continuous FICB had significantly reduced postoperative morphine consumption at all time points (23 +/- 20 versus 88 +/- 29 mg after 72 h, study versus control groups, respectively; P < 0.05). In both groups, VAS scores remained low but were only significantly lower for patients with continuous FICB during the first dressing change (3 [1] versus 7 [3]; median [interquartile range]; P < 0.05). We conclude that continuous FICB is an efficient method for diminishing pain at the thigh donor site. (250 words) Postoperative pain at the split skin donor sites is often more intense than the pain at the grafted site. This prospective, randomized, double-blind study assessed the efficacy of a continuous fascia iliaca compartment block in reducing the pain at the thigh donor site.

  4. MHC Universal Cells Survive in an Allogeneic Environment after Incompatible Transplantation

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    Constança Figueiredo

    2013-01-01

    Full Text Available Cell, tissue, and organ transplants are commonly performed for the treatment of different diseases. However, major histocompatibility complex (MHC diversity often prevents complete donor-recipient matching, resulting in graft rejection. This study evaluates in a preclinical model the capacity of MHC class I-silenced cells to engraft and grow upon allogeneic transplantation. Short hairpin RNA targeting β2-microglobulin (RN_shβ2m was delivered into fibroblasts derived from LEW/Ztm (RT1l (RT1-Al rats using a lentiviral-based vector. MHC class I (RT1-A- expressing and -silenced cells were injected subcutaneously in LEW rats (RT1l and MHC-congenic LEW.1W rats (RT1u, respectively. Cell engraftment and the status of the immune response were monitored for eight weeks after transplantation. In contrast to RT1-A-expressing cells, RT1-A-silenced fibroblasts became engrafted and were still detectable eight weeks after allogeneic transplantation. Plasma levels of proinflammatory cytokines IL-1α, IL-1β, IL-6, TNF-α, and IFN-γ were significantly higher in animals transplanted with RT1-A-expressing cells than in those receiving RT1-A-silenced cells. Furthermore, alloantigen-specific T-cell proliferation rates derived from rats receiving RT1-A-expressing cells were higher than those in rats transplanted with RT1-A-silenced cells. These data suggest that silencing MHC class I expression might overcome the histocompatibility barrier, potentially opening up new avenues in the field of cell transplantation and regenerative medicine.

  5. MHC Universal Cells Survive in an Allogeneic Environment after Incompatible Transplantation

    Science.gov (United States)

    Figueiredo, Constança; Wedekind, Dirk; Müller, Thomas; Vahlsing, Stefanie; Horn, Peter A.; Seltsam, Axel; Blasczyk, Rainer

    2013-01-01

    Cell, tissue, and organ transplants are commonly performed for the treatment of different diseases. However, major histocompatibility complex (MHC) diversity often prevents complete donor-recipient matching, resulting in graft rejection. This study evaluates in a preclinical model the capacity of MHC class I-silenced cells to engraft and grow upon allogeneic transplantation. Short hairpin RNA targeting β2-microglobulin (RN_shβ2m) was delivered into fibroblasts derived from LEW/Ztm (RT1l) (RT1-Al) rats using a lentiviral-based vector. MHC class I (RT1-A-) expressing and -silenced cells were injected subcutaneously in LEW rats (RT1l) and MHC-congenic LEW.1W rats (RT1u), respectively. Cell engraftment and the status of the immune response were monitored for eight weeks after transplantation. In contrast to RT1-A-expressing cells, RT1-A-silenced fibroblasts became engrafted and were still detectable eight weeks after allogeneic transplantation. Plasma levels of proinflammatory cytokines IL-1α, IL-1β, IL-6, TNF-α, and IFN-γ were significantly higher in animals transplanted with RT1-A-expressing cells than in those receiving RT1-A-silenced cells. Furthermore, alloantigen-specific T-cell proliferation rates derived from rats receiving RT1-A-expressing cells were higher than those in rats transplanted with RT1-A-silenced cells. These data suggest that silencing MHC class I expression might overcome the histocompatibility barrier, potentially opening up new avenues in the field of cell transplantation and regenerative medicine. PMID:24350288

  6. Cryptozoospermia with normal testicular function after allogeneic stem cell transplantation: a case report.

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    Tauchmanovà, L; Alviggi, C; Foresta, C; Strina, I; Garolla, A; Colao, A; Lombardi, G; De Placido, G; Rotoli, B; Selleri, C

    2007-02-01

    One of the most frequent consequences of allogeneic haemopoietic stem cell transplantation (allo-SCT) in both males and females is gonadal insufficiency. We report the case of a 27-year-old myelodysplastic male who developed azoospermia after allogeneic transplantation of haemopoietic stem cells from his HLA-identical sister. Post-transplant azoospermia was alternated with intermittent severe oligospermia. The patient had a normal endocrine pattern and evidence of mild chronic graft-versus-host disease (cGVHD). Normal intratesticular spermatogenesis was revealed by bilateral fine needle aspiration (FNA) cytology. Inflammation was evident at semen analysis, but no infection was detected by microbiological examination and sperm culture. These findings, together with the re-appearance of sperm cells at semen analysis after a low-dose immunosuppressive treatment, suggested the presence of cGVHD of the urogenital tract, causing a reversible obstruction of the spermatic tract and cryptozoospermia. This is the first case report documenting a severe impairment of sperm count because of a reversible obstruction of the seminal tract, likely caused by cGVHD, in a long-term survivor of allo-SCT with normal endocrine pattern. An important practical consequence of this case report is the fact that azoospermia was cured using low-dose immunosuppressive therapy, and this allowed us to avoid expensive stimulatory treatments with gonadotrophins, which remain, however, ineffective if the obstruction of spermatic tracts is not removed. A spontaneous uncomplicated pregnancy occurred in the partner of the patient 3 months after the corticosteroid treatment withdrawal.

  7. Plerixafor (a CXCR4 antagonist following myeloablative allogeneic hematopoietic stem cell transplantation enhances hematopoietic recovery

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    Michael M. B. Green

    2016-08-01

    Full Text Available Abstract Background The binding of CXCR4 with its ligand (stromal-derived factor-1 maintains hematopoietic stem/progenitor cells (HSPCs in a quiescent state. We hypothesized that blocking CXCR4/SDF-1 interaction after hematopoietic stem cell transplantation (HSCT promotes hematopoiesis by inducing HSC proliferation. Methods We conducted a phase I/II trial of plerixafor on hematopoietic cell recovery following myeloablative allogeneic HSCT. Patients with hematologic malignancies receiving myeloablative conditioning were enrolled. Plerixafor 240 μg/kg was administered subcutaneously every other day beginning day +2 until day +21 or until neutrophil recovery. The primary efficacy endpoints of the study were time to absolute neutrophil count >500/μl and platelet count >20,000/μl. The cumulative incidence of neutrophil and platelet engraftment of the study cohort was compared to that of a cohort of 95 allogeneic peripheral blood stem cell transplant recipients treated during the same period of time and who received similar conditioning and graft-versus-host disease prophylaxis. Results Thirty patients received plerixafor following peripheral blood stem cell (n = 28 (PBSC or bone marrow (n = 2 transplantation. Adverse events attributable to plerixafor were mild and indistinguishable from effects of conditioning. The kinetics of neutrophil and platelet engraftment, as demonstrated by cumulative incidence, from the 28 study subjects receiving PBSC showed faster neutrophil (p = 0.04 and platelet recovery >20 K (p = 0.04 compared to the controls. Conclusions Our study demonstrated that plerixafor can be given safely following myeloablative HSCT. It provides proof of principle that blocking CXCR4 after HSCT enhances hematopoietic recovery. Larger, confirmatory studies in other settings are warranted. Trial registration ClinicalTrials.gov NCT01280955

  8. Alpha-GalCer Administration after Allogeneic Bone Marrow Transplantation Improves Immune Reconstitution in Mice

    Institute of Scientific and Technical Information of China (English)

    Jing-hua Liu; Li-ping Dou; Li-xin Wang; Li-li Wang; Fan Zhou; Li Yu

    2011-01-01

    Objective To explore the effect of a-galactosyleramide (α-GalCer) on immune recovstitution un der acute graft-versus-host disease (aGVHD). Methods BALB/c mice were transplanted with allogeneic C57BL/6 bone marrow cells and spleno cytes (both 1 × 107) after receiving lethal total-body irradiation, a-GalCer (100 ug/kg) or vehicle (dimethylsulfoxide) was administered intraperitoneally immediately after transplantation. The effects of α-GalCer on immune reconstitution, proliferation of T cells and B cells, hematopoiesis, and thymic microenvironment were assessed.Results The α-GalCer group exhibited higher percentages of CD3+, CD4+, CD8+, B220+, CD40+,and CD86+ cells compared with the vehicle group. The number of colony forming unit per 1000 CD34+cells in the α-GalCer group was higher than in the vehicle group (P=0.0012). In vitro proliferation assays showed that the α-GalCer group had higher percentages of CD3+, CD4+, CD8+, and B220+ cells compared with the vehicle group. As for the results of in vivo proliferation assays, the numbers of CD3+, CD4+, CD8+,and B220+ cells were higher in the α-GalCer group than in the normal group, especially the number of B220+ cells (P=0.007). Significant difference was not found in thymocyte count between the α-GalCer group and the vehicle group, nor in the percentages of CD3+, CD4+, and CD8+ cells. Conclusion Administration of α-GalCer after allogeneic bone marrow transplantation may promote immune reconstitution in the presence of aGVHD.

  9. Site-specific rectocele repair with dermal graft augmentation: comparison of porcine dermal xenograft (Pelvicol) and human dermal allograft.

    Science.gov (United States)

    Biehl, Roger C; Moore, Robert D; Miklos, John R; Kohli, Neeraj; Anand, Indu S; Mattox, T Fleming

    2008-01-01

    This study is a retrospective chart review comparing 195 women who underwent rectocele repair with either a porcine dermal xenograft or human allogenic cadaveric dermal graft augmentation over a two year period. A site-specific defect repair was completed prior to augmentation with the graft. Examinations were performed preoperatively and postoperatively using the pelvic organ prolapse quantification system. Questionnaires were used to assess constipation and dyspareunia. De novo dyspareunia and cure rates for constipation and dyspareunia were not statistically different between the two groups. Site-specific fascial rectocele repairs with xenograft or allograft augmentation were found to have similar complication rates as well as objective and subjective cure rates.

  10. Busulfan and melphalan as conditioning regimen for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia in first complete remission

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    Nadjanara Dorna Bueno

    2011-06-01

    Full Text Available BACKGROUND: Allogeneic hematopoietic stem cell transplantation with HLA-identical donors has been established for the treatment of acute myeloid leukemia patients for over 30 years with a cure rate of 50% to 60%. OBJECTIVES: To analyze the overall survival of patients and identify factors that influence the outcomes of this type of transplant in patients in 1st complete remission who received a busulfan and melphalan combination as conditioning regimen. METHODS: Twenty-five consecutive patients with acute myeloid leukemia were enrolled between 2003 and 2008. The median age was 34 years old (Range: 16 - 57 years. All patients received cyclosporine and methotrexate for prophylaxis against graft-versus-host disease. Median neutrophil engraftment time was 16 days (Range: 7 - 22 days and 17 days (Range: 7 - 46 days for platelets. Sinusoidal obstructive syndrome was observed in three patients, seven had grade II acute graft-versus-host disease and one extensive chronic graft-versus-host disease. RESULTS: The overall survival by the Kaplan-Meier method was 48% after 36 months with a plateau at 36 months after transplantation. Intensive consolidation with high-dose arabinoside resulted in an improved survival (p-value = 0.0001, as did grade II acute graft-versus-host disease (p-value = 0.0377 and mild chronic graft-versus-host disease (p-value < 0.0001. Thirteen patients died, five due to infection within 100 days of transplant, two due to hemorrhages, one to infection and graftversus-host disease and three relapses followed by renal failure (one and infection (two. The cause of death could not be determined for two patients. CONCLUSION: The busulfan and melphalan conditioning regimen is as good as other conditioning regimens providing an excellent survival rate.

  11. Autophagy-dependent regulatory T cells are critical for the control of graft-versus-host disease

    Science.gov (United States)

    Le Texier, Laëtitia; Lineburg, Katie E.; Leveque-El Mouttie, Lucie; Nicholls, Jemma; Melino, Michelle; Nalkurthi, Blessy C.; Alexander, Kylie A.; Teal, Bianca; Blake, Stephen J.; Souza-Fonseca-Guimaraes, Fernando; Engwerda, Christian R.; Kuns, Rachel D.; Lane, Steven W.; Teh, Charis; Gray, Daniel; Clouston, Andrew D.; Nilsson, Susan K.; Blazar, Bruce R.; Hill, Geoffrey R.; MacDonald, Kelli P.A.

    2016-01-01

    Regulatory T cells (Tregs) play a crucial role in the maintenance of peripheral tolerance. Quantitative and/or qualitative defects in Tregs result in diseases such as autoimmunity, allergy, malignancy, and graft-versus-host disease (GVHD), a serious complication of allogeneic stem cell transplantation (SCT). We recently reported increased expression of autophagy-related genes (Atg) in association with enhanced survival of Tregs after SCT. Autophagy is a self-degradative process for cytosolic components that promotes cell homeostasis and survival. Here, we demonstrate that the disruption of autophagy within FoxP3+ Tregs (B6.Atg7fl/fl-FoxP3cre+) resulted in a profound loss of Tregs, particularly within the bone marrow (BM). This resulted in dysregulated effector T cell activation and expansion, and the development of enterocolitis and scleroderma in aged mice. We show that the BM compartment is highly enriched in TIGIT+ Tregs and that this subset is differentially depleted in the absence of autophagy. Moreover, following allogeneic SCT, recipients of grafts from B6.Atg7fl/fl-FoxP3cre+ donors exhibited reduced Treg reconstitution, exacerbated GVHD, and reduced survival compared with recipients of B6.WT-FoxP3cre+ grafts. Collectively, these data indicate that autophagy-dependent Tregs are critical for the maintenance of tolerance after SCT and that the promotion of autophagy represents an attractive immune-restorative therapeutic strategy after allogeneic SCT. PMID:27699243

  12. Kinetics of lymphocyte reconstitution after allogeneic bone marrow transplantation: markers of graft-versus-host disease.

    Science.gov (United States)

    Zinöcker, Severin; Sviland, Lisbet; Dressel, Ralf; Rolstad, Bent

    2011-07-01

    GVHD causes extensive morbidity and mortality in patients who receive alloHCT. Predictive and reliable markers for GVHD are currently lacking but required to improve the safety and accessibility of alloHCT. We present an experimental rat model of myeloablative total body irradiation and fully mismatched major and minor histoincompatible, T cell-depleted BMT, followed by delayed infusion of donor lymphocytes. This treatment, in contrast to marrow transplantation alone, resulted in severe aGVHD and 100% lethality within 2-6 weeks. We investigated the reconstitution kinetics and phenotypes of donor leukocyte subpopulations as well as the histopathology of selected organs that may correlate with GVHD, with the goal to find potential disease-related markers. We observed histological changes mainly confined to the skin, with degenerative changes in the basal layer. LNs and spleen showed deranged architecture with markedly increased accumulation of lymphocytes, whereas the gut, liver, and lungs appeared normal. Of the lymphocyte markers tested, donor-derived CD62L(+) T cells were markedly decreased in animals suffering from GVHD. Furthermore, we observed peripheral depletion of CD4(+)CD25(hi)FoxP3(+) T(reg), which was in contrast to controls. The relative frequency of these lymphocyte subpopulations in blood may therefore serve as accessible cellular markers of aGVHD. We propose that the animal model presented is instructive for the identification of clinically relevant markers of GVHD, which could improve disease diagnosis and management in alloHCT.

  13. Graft-derived anti-HPA-2b production after allogeneic bone-marrow transplantation

    DEFF Research Database (Denmark)

    Taaning, E; Jacobsen, N; Morling, N

    1994-01-01

    We report on a male who received a bone-marrow allograft from his HLA identical sister for acute myelogenous leukaemia. After transplantation, the patient suffered from refractoriness to the transfusions of HLA-matched platelets and a strong platelet-specific antibody, anti-HPA-2b, of IgG1 subcla...

  14. Graft-derived anti-HPA-2b production after allogeneic bone-marrow transplantation

    DEFF Research Database (Denmark)

    Taaning, E; Jacobsen, N; Morling, N

    1994-01-01

    We report on a male who received a bone-marrow allograft from his HLA identical sister for acute myelogenous leukaemia. After transplantation, the patient suffered from refractoriness to the transfusions of HLA-matched platelets and a strong platelet-specific antibody, anti-HPA-2b, of IgG1 subcla...

  15. MMSC-LIKE LIMBAL CELLS COTRANSPLANTATION PROMOTES LOCAL IMMUNOCORRECTION AND CORNEAL GRAFT TRANSPARENT RETENTION IN HIGH RISK KERATOPLASTY

    Directory of Open Access Journals (Sweden)

    S. A. Borzenok

    2014-01-01

    Full Text Available Aim was to evaluate clinical results of donor corneal graft survival in high-risk recipients in co-transplantation of preserved allogenic limbal grafts. Materials and methods. Two types of penetrative keratoplasties were carried out in patients with corneal graft opacities and high risk of rejection (n = 69. Co-transplantation of donor cornea and allogenic MMSC-like limbal cells in the form of limbal transplants was carried out in the 1st group (n = 36; in the 2nd group (n = 33 only the cornea was transplanted. Results. Observation of the patients during one year after surgery showed that the rate of transparent cornea engraftment increased in the 1st group (86,1 against 69,7% in the 2nd group. The density of endothelial cells was also higher in the 1st group (85,9 against 76,2% in the 2nd group. At the same time, progressive decreasing of pro-inflammatory cytokines (IL-6, IFNγ, TNFα and increasing of anti-inflammatory cytokines (IL-10, IL-1RA, TGFβ along with higher level of HLA-G5 were revealed in the recipients’ tear fluid in the 1st group in comparison to the 2nd group. Conclusion. Simultaneous transplantation of preserved limbal grafts with corneal graft in high-risk keratoplasty favors the transparent cornea engraftment, obviously, this is due to immunoregulatory activity of the MMSC-like limbal cells. 

  16. [Detection of mixed lymphoid chimerism after allogeneic bone marrow transplantation: demonstration by interphase cytogenetics in paraffin-embedded tissue].

    Science.gov (United States)

    Friedrich, T; Ott, G; Kalla, J; Helbig, W; Schwenke, H; Kubel, M; Pönisch, W; Feyer, P; Friedrich, A

    1994-01-01

    In bone marrow transplantation (BMT) the detection of residual host lymphoid or haematopoietic cells surviving conditioning therapy is because of its association to graft-versus-host disease, graft-versus-leukemia reaction, and relapse of leukemia a matter of great interest. We studied the occurrence of this mixed lymphoid chimerism (MC) in the formol-fixed lymphatic tissue of lymph nodes and spleen from 21 autopsies after allogeneic sex-mismatched BMT (5 females, 16 males, survival 5 to 1140 days after BMT). In situ hybridisation with biotinylated centromer-specific anti-X- and anti-Y-chromosome probes was performed on pepsin-digested paraffin sections. The number of double X-, single X-, and Y-chromosome bearing cells was analysed microscopically. Because of artefacts only 14 cases remained for valid investigation. MC was detected in 6 cases (5 out of 11 males 5 days to 840 days and 1 out of 3 females 76 days after BMT). MC occurred after whole body irradiation with 10 Gy (n = 5) and 7 Gy (n = 1). In 1 autopsy relapse of leukemia caused host cell infiltration. Cases with MC did not express histological signs of acute or chronic graft-versus-host disease, but 5 out of 8 with complete lymphoid chimerism did. The sensitivity of interphase cytogenetics on paraffin embedded tissue is low.

  17. Studies of allogeneic bone marrow and spleen cell transplantation in a murine model using ultraviolet-B light

    Energy Technology Data Exchange (ETDEWEB)

    Pamphilon, D.H.; Alnaqdy, A.A.; Godwin, V.; Preece, A.W.; Wallington, T.B. (South Western Regional Transfusion Centre, Bristol (United Kingdom))

    1991-05-01

    Ultraviolet irradiation inhibits alloreactive and mitogen-induced responses and might reduce both graft-versus-host and host-versus-graft reactions after bone marrow transplantation (BMT). We have studied proliferative responses to mitogens and reactivity in mixed lymphocyte culture after irradiation with ultraviolet (UV)-B light using splenocytes from Balb/c (H-2d) and CBA (H-2k) mice. Response to mitogens and in MLC was strongly inhibited by 20 J/m{sup 2} and abolished at 50 J/m{sup 2}. Clonogenic cell recovery (CFU-GM; CFU-S) after UV-B irradiation was also reduced. When bone marrow and spleen cells were transplanted from parent (Balb/c) animals into F1 hybrid (Balb/c X CBA) recipients, all animals died with features indicative of graft-versus-host disease (GVHD) in 34 days. If the grafts were first irradiated with 100 J/m{sup 2} of UV-B at a mean wavelength of 310 nm, then 76% survived to day 80 when they were killed and shown to have normal marrow cellularity. The remainder died in marrow aplasia or of GVHD. H-2 typing in a group of surviving recipients showed either donor hematopoiesis only (8 of 15), mixed allogeneic chimerism (5 of 15), or recipient type hematopoiesis (2 of 15). Higher doses (200 to 300 J/m{sup 2}) were detrimental to survival with 88% of recipients dying in marrow aplasia. Syngeneic BMT in Balb/c mice showed slower hematopoietic reconstitution when the grafts were first irradiated with 100 J/m{sup 2}. After BMT from Balb/c to CBA mice all recipients of unirradiated grafts died within 54 days. By contrast, after graft irradiation with 100 J/m{sup 2} survival of recipient animals to day 80 was 59%. If these grafts were treated with 50 J/m{sup 2} survival was only 26% with an increase in deaths due to GVHD. Hematopoiesis at day 80 in a group of survivors studied by Ig heavy chain allotyping indicated donor type hematopoiesis in 6 of 10 (50 J/m{sup 2}) and 2 of 9 (100 J/m{sup 2}).

  18. Treatment of splenic marginal zone lymphoma of the CNS with high-dose therapy and allogeneic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Busemann Christoph

    2012-10-01

    Full Text Available Abstract Therapy of indolent lymphomas with involvement of the central nervous system (CNS has not been standardized so far. A 42-year old male patient presented with neurological signs because of leukemic splenic marginal zone lymphoma (SMZL manifested in bone marrow, lymph nodes and CNS. Due to the aggressiveness of the disease and the young age of the patient, an intensive immunochemotherapy followed by high-dose therapy with busulfan, thiotepa and fludarabine and subsequent unrelated allogeneic stem cell transplantation (alloSCT was performed. The haemopoietic stem cells engrafted in time and the patient is doing well (ECOG 0 without evidence for active lymphoma three years after transplantation. Highly sensitive tests by specific quantitative real-time polymerase chain reaction for presence of lymphoma cells in blood and bone marrow indicated also a molecular remission. The reported case shows the feasibility of high-dose therapy and allogeneic stem cell transplantation in high-risk patients with CNS-involvement of indolent non-Hodgkin’s lymphoma. In addition, the case supports the hypothesis that the graft-versus lymphoma effect after alloSCT is also active within the CNS.

  19. Altered regulatory T cell homeostasis in patients with CD4+ lymphopenia following allogeneic hematopoietic stem cell transplantation

    Science.gov (United States)

    Matsuoka, Ken-ichi; Kim, Haesook T.; McDonough, Sean; Bascug, Gregory; Warshauer, Ben; Koreth, John; Cutler, Corey; Ho, Vincent T.; Alyea, Edwin P.; Antin, Joseph H.; Soiffer, Robert J.; Ritz, Jerome

    2010-01-01

    CD4+CD25+Foxp3+ Tregs have an indispensable role in the maintenance of tolerance after allogeneic HSC transplantation (HSCT). Patients with chronic graft-versus-host disease (GVHD) have fewer circulating Tregs, but the mechanisms that lead to this deficiency of Tregs after HSCT are not known. Here, we analyzed reconstitution of Tregs and conventional CD4+ T cells (Tcons) in patients who underwent allogeneic HSCT after myeloablative conditioning. Following transplant, thymic generation of naive Tregs was markedly impaired, and reconstituting Tregs had a predominantly activated/memory phenotype. In response to CD4+ lymphopenia after HSCT, Tregs underwent higher levels of proliferation than Tcons, but Tregs undergoing homeostatic proliferation also showed increased susceptibility to Fas-mediated apoptosis. Prospective monitoring of CD4+ T cell subsets revealed that Tregs rapidly expanded and achieved normal levels by 9 months after HSCT, but Treg levels subsequently declined in patients with prolonged CD4+ lymphopenia. This resulted in a relative deficiency of Tregs, which was associated with a high incidence of extensive chronic GVHD. These studies indicate that CD4+ lymphopenia is a critical factor in Treg homeostasis and that prolonged imbalance of Treg homeostasis after HSCT can result in loss of tolerance and significant clinical disease manifestations. PMID:20389017

  20. Seroprotective Titers against 2009 H1N1 Influenza A Virus after Vaccination in Allogeneic Hematopoietic Stem Cell Transplantation Recipients

    Science.gov (United States)

    Issa, Nicolas C.; Marty, Francisco M.; Gagne, Lisa S.; Koo, Sophia; Verrill, Kelly A.; Alyea, Edwin P.; Cutler, Corey S.; Koreth, John; Armand, Philippe; Ho, Vincent T.; Antin, Joseph H.; Soiffer, Robert J.; Baden, Lindsey R.

    2012-01-01

    Little data are available regarding the safety and immunologic response to pandemic H1N1 influenza vaccine in recipients of allogeneic hematopoietic stem cell transplantation (HSCT). We measured serum antibody titers against A/California/7/2009 H1N1 using a hemagglutination inhibition assay in 82 allogeneic HSCT recipients who received the 2009 H1N1 vaccine between November 2009 and January 2010 after it became available at our institution. The median time between HSCT and vaccination was 19 months (range, 2.5–94 months), and the median time from vaccination to specimen collection was 56 days (range, 14–140 days). Seroprotective antibody titers (hemagglutination inhibition titer ≥1:40) against 2009 H1N1 influenza A virus were detected in 51% of patients. The presence of chronic graft-versus-host disease and type of conditioning regimen did not affect the rate of detection of seroprotective titers after vaccination. Patients were more likely to have a seroprotective titer the farther away from HSCT they were (adjusted odds ratio, 1.79 per year; 95% confidence interval, 1.12–2.85). Rituximab administration in the year before vaccination was associated with a lack of seroprotective titer (adjusted odds ratio, 0.11; 95% confidence interval, 0.01–0.97). The vaccine was safe and well tolerated. Strategies are needed to improve the influenza vaccine response in this population, especially those receiving immunotherapy. PMID:20950701

  1. Delayed minimally invasive injection of allogenic bone marrow stromal cell sheets regenerates large bone defects in an ovine preclinical animal model.

    Science.gov (United States)

    Berner, Arne; Henkel, Jan; Woodruff, Maria A; Steck, Roland; Nerlich, Michael; Schuetz, Michael A; Hutmacher, Dietmar W

    2015-05-01

    Cell-based tissue engineering approaches are promising strategies in the field of regenerative medicine. However, the mode of cell delivery is still a concern and needs to be significantly improved. Scaffolds and/or matrices loaded with cells are often transplanted into a bone defect immediately after the defect has been created. At this point, the nutrient and oxygen supply is low and the inflammatory cascade is incited, thus creating a highly unfavorable microenvironment for transplanted cells to survive and participate in the regeneration process. We therefore developed a unique treatment concept using the delayed injection of allogenic bone marrow stromal cell (BMSC) sheets to regenerate a critical-sized tibial defect in sheep to study the effect of the cells' regeneration potential when introduced at a postinflammatory stage. Minimally invasive percutaneous injection of allogenic BMSCs into biodegradable composite scaffolds 4 weeks after the defect surgery led to significantly improved bone regeneration compared with preseeded scaffold/cell constructs and scaffold-only groups. Biomechanical testing and microcomputed tomography showed comparable results to the clinical reference standard (i.e., an autologous bone graft). To our knowledge, we are the first to show in a validated preclinical large animal model that delayed allogenic cell transplantation can provide applicable clinical treatment alternatives for challenging bone defects in the future. ©AlphaMed Press.

  2. Skin graft - slideshow

    Science.gov (United States)

    ... ency/presentations/100100.htm Skin graft - series—Normal anatomy To use the sharing features on this page, ... 2017 Updated by: Debra G. Wechter, MD, FACS, general surgery practice specializing in breast cancer, Virginia Mason ...

  3. High-dose total body irradiation and myeloablative conditioning before allogeneic hematopoietic cell transplantation: time to rethink?

    Science.gov (United States)

    Mohty, Mohamad; Malard, Florent; Savani, Bipin N

    2015-04-01

    Over the last decade, the care of patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) has significantly improved, leading to a decrease in deaths related to allo-HCT as well as improved long-term survival. However, for many patients, long-term survivorship is associated with a substantial burden of chronic morbidities. Indeed, malignant and nonmalignant late complications after allo-HCT are numerous and usually multifactorial, with all organs and tissues a potential target. In many cases, these long-term side effects are associated with the use of high-dose total body irradiation, myeloablative conditioning regimens, and the onset of chronic graft-versus-host disease. It appears to be essential to change the natural history of these late effects. This requires the introduction of improved conditioning regimens and the development of lifelong monitoring controls, patient counseling, and preventative treatment measures. This approach will allow us to pursue our efforts to improve patient outcome.

  4. Photoreceptor Differentiation following Transplantation of Allogeneic Retinal Progenitor Cells to the Dystrophic Rhodopsin Pro347Leu Transgenic Pig

    DEFF Research Database (Denmark)

    Klassen, H; Kiilgaard, Jens Folke; Warfvinge, K;

    2012-01-01

    Purpose. Transplantation of stem, progenitor, or precursor cells has resulted in photoreceptor replacement and evidence of functional efficacy in rodent models of retinal degeneration. Ongoing work has been directed toward the replication of these results in a large animal model, namely, the pig....... Methods. Retinal progenitor cells were derived from the neural retina of GFP-transgenic pigs and transplanted to the subretinal space of rhodopsin Pro347Leu-transgenic allorecipients, in the early stage of the degeneration and the absence of immune suppression. Results. Results confirm the survival...... of allogeneic porcine RPCs without immune suppression in the setting of photoreceptor dystrophy. The expression of multiple photoreceptor markers by grafted cells included the rod outer segment-specific marker ROM-1. Further evidence of photoreceptor differentiation included the presence of numerous...

  5. Prognostic significance of interleukin-7 receptor-α gene polymorphisms in allogeneic stem-cell transplantation: a confirmatory study

    DEFF Research Database (Denmark)

    Shamim, Zaiba; Ryder, Lars P; Christensen, Ib J;

    2011-01-01

    allogeneic stem-cell transplantation (SCT) identified donor genotype GG at rs1494555 as a risk factor for treatment-related mortality (TRM) after SCT. METHODS: In this validation study, 116 British and French SCT patients and their donors were investigated by sequence-specific primer polymerase chain......BACKGROUND: Interleukin-7 (IL-7) is a hematopoietic cytokine essential for T-cell development in the thymus and for the maintenance of peripheral T cells. A previous study of single nucleotide polymorphisms in the exons of IL-7 receptor a-chain (IL-7Ra) in a Danish cohort of patients undergoing...... reaction. RESULTS: Both donor rs1494555GG genotype and the tightly coupled rs1494558TT genotype were significantly associated with grade 3 to 4 acute graft versus host disease. Although both genotypes tended to be associated with increased TRM, this did not translate into altered overall survival...

  6. A Trial of Alemtuzumab Adjunctive Therapy in Allogeneic Hematopoietic Cell Transplantation with Minimal Conditioning for Severe Combined Immunodeficiency

    Science.gov (United States)

    Dvorak, Christopher C.; Horn, Biljana N.; Puck, Jennifer M.; Adams, Stuart; Veys, Paul; Czechowicz, Agnieszka; Cowan, Morton J.

    2014-01-01

    For infants with severe combined immunodeficiency (SCID) the ideal conditioning regimen before allogeneic hematopoietic cell transplantation (HCT) would omit cytotoxic chemotherapy to minimize short- and long-term complications. We performed a prospective pilot trial with alemtuzumab monotherapy to overcome NK-cell mediated immunologic barriers to engraftment. We enrolled 4 patients who received CD34-selected haploidentical cells, two of whom failed to engraft donor T cells. The 2 patients who engrafted had delayed T cell reconstitution, despite rapid clearance of circulating alemtuzumab. Although well-tolerated, alemtuzumab failed to overcome immunologic barriers to donor engraftment. Furthermore, alemtuzumab may slow T cell development in patients with SCID in the setting of a T-cell depleted graft. PMID:24977928

  7. A trial of alemtuzumab adjunctive therapy in allogeneic hematopoietic cell transplantation with minimal conditioning for severe combined immunodeficiency.

    Science.gov (United States)

    Dvorak, Christopher C; Horn, Biljana N; Puck, Jennifer M; Adams, Stuart; Veys, Paul; Czechowicz, Agnieszka; Cowan, Morton J

    2014-09-01

    For infants with SCID the ideal conditioning regimen before allogeneic HCT would omit cytotoxic chemotherapy to minimize short- and long-term complications. We performed a prospective pilot trial with alemtuzumab monotherapy to overcome NK-cell mediated immunologic barriers to engraftment. We enrolled four patients who received CD34-selected haploidentical cells, two of whom failed to engraft donor T cells. The two patients who engrafted had delayed T-cell reconstitution, despite rapid clearance of circulating alemtuzumab. Although well-tolerated, alemtuzumab failed to overcome immunologic barriers to donor engraftment. Furthermore, alemtuzumab may slow T-cell development in patients with SCID in the setting of a T-cell depleted graft.

  8. Mass Cytometry and Topological Data Analysis Reveal Immune Parameters Associated with Complications after Allogeneic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Tadepally Lakshmikanth

    2017-08-01

    Full Text Available Human immune systems are variable, and immune responses are often unpredictable. Systems-level analyses offer increased power to sort patients on the basis of coordinated changes across immune cells and proteins. Allogeneic stem cell transplantation is a well-established form of immunotherapy whereby a donor immune system induces a graft-versus-leukemia response. This fails when the donor immune system regenerates improperly, leaving the patient susceptible to infections and leukemia relapse. We present a systems-level analysis by mass cytometry and serum profiling in 26 patients sampled 1, 2, 3, 6, and 12 months after transplantation. Using a combination of machine learning and topological data analyses, we show that global immune signatures associated with clinical outcome can be revealed, even when patients are few and heterogeneous. This high-resolution systems immune monitoring approach holds the potential for improving the development and evaluation of immunotherapies in the future.

  9. Cyclin-dependent kinase 5 activity is required for allogeneic T-cell responses after hematopoietic cell transplantation in mice

    Science.gov (United States)

    Pareek, Tej K.; Eid, Saada; Ganguly, Sudipto; Tyler, Megan; Huang, Alex Y.; Letterio, John J.

    2017-01-01

    Molecular intermediates in T-cell activation pathways are crucial targets for the therapy and prevention of graft-versus-host disease (GVHD) following allogeneic hematopoietic cell transplantation (allo-HCT). We recently identified an essential role for cyclin-dependent kinase 5 (Cdk5) in T-cell activation and effector function, but the contribution of Cdk5 activity to the development of GVHD has not been explored. Using an established, preclinical, murine, GVHD model, we reveal that Cdk5 activity is increased in key target organs early after allo-HCT. We then generated chimeric mice (Cdk5+/+C or Cdk5−/−C) using hematopoietic progenitors from either embryonic day 16.5 Cdk5+/+ or Cdk5−/− embryos to enable analyses of the role of Cdk5 in GVHD, as germ line Cdk5 gene deletion is embryonically lethal. The immunophenotype of adult Cdk5−/−C mice is identical to control Cdk5+/+C mice. However, transplantation of donor Cdk5−/−C bone marrow and T cells dramatically reduced the severity of systemic and target organ GVHD. This phenotype is attributed to decreased T-cell migration to secondary lymphoid organs (SLOs), reduced in vivo proliferation within these organs, and fewer cytokine-producing donor T cells during GVHD development. Moreover, these defects in Cdk5−/− T-cell function are associated with altered CCR7 signaling following ligation by CCL19, a receptor:ligand interaction critical for T-cell migration into SLOs. Although Cdk5 activity in donor T cells contributed to graft-versus-tumor effects, pharmacologic inhibition of Cdk5 preserved leukemia-free survival. Collectively, our data implicate Cdk5 in allogeneic T-cell responses after HCT and as an important new target for therapeutic intervention. PMID:28064242

  10. Longitudinal Changes in Body Mass and Composition in Survivors of Childhood Hematologic Malignancies After Allogeneic Hematopoietic Stem-Cell Transplantation

    Science.gov (United States)

    Inaba, Hiroto; Yang, Jie; Kaste, Sue C.; Hartford, Christine M.; Motosue, Megan S.; Chemaitilly, Wassim; Triplett, Brandon M.; Shook, David R.; Pui, Ching-Hon; Leung, Wing

    2012-01-01

    Purpose To measure longitudinal changes in body mass and composition in survivors of childhood hematologic malignancies after allogeneic hematopoietic stem-cell transplantation (HSCT). Patients and Methods Body mass index (BMI) was analyzed in 179 survivors by category (underweight, healthy-weight, overweight, and obese) and by z score. Fat and lean body mass measured by dual-energy x-ray absorptiometry was analyzed as z scores. Results Over a median 6.6 years of follow-up, BMI z scores diminished significantly (0.32 pre-HSCT v −0.60 at 10 years post-HSCT; P < .001). Mean z scores for fat mass stayed within population norms, but those for lean mass remained below normal levels and diminished significantly over time (P = .018). Pre-HSCT BMI category and/or z score were strongly predictive of post-HSCT BMI (P < .001) and of fat and lean mass z scores (both P < .001). Survivors with extensive chronic graft-versus-host disease were more likely than others to have low BMI (P = .004) and low lean mass (P < .001) post-HSCT. Older age at HSCT (P = .015) and T-cell–depleted graft (P = .018) were predictive of lower post-HSCT BMI. Female patients had higher body fat (P = .002) and lower lean mass (P = .013) z scores than male patients, and black patients had higher fat mass z scores than white patients (P = .026). Conclusion BMI declines significantly after allogeneic HSCT for childhood hematologic malignancies, reflecting primarily a substantial decrease in lean mass but not fat mass. Monitoring and preservation of BMI and lean mass are vital, especially in those with the identified risk factors. PMID:23032628

  11. Intravenous transplantation of allogeneic bone marrow mesenchymal stem cells and its directional migration to the necrotic femoral head

    Directory of Open Access Journals (Sweden)

    Zhang-hua Li, Wen Liao, Xi-long Cui, Qiang Zhao, Ming Liu, You-hao Chen, Tian-shu Liu, Nong-le Liu, Fang Wang, Yang Yi, Ning-sheng Shao

    2011-01-01

    Full Text Available In this study, we investigated the feasibility and safety of intravenous transplantation of allogeneic bone marrow mesenchymal stem cells (MSCs for femoral head repair, and observed the migration and distribution of MSCs in hosts. MSCs were labeled with green fluorescent protein (GFP in vitro and injected into nude mice via vena caudalis, and the distribution of MSCs was dynamically monitored at 0, 6, 24, 48, 72 and 96 h after transplantation. Two weeks after the establishment of a rabbit model of femoral head necrosis, GFP labeled MSCs were injected into these rabbits via ear vein, immunological rejection and graft versus host disease were observed and necrotic and normal femoral heads, bone marrows, lungs, and livers were harvested at 2, 4 and 6 w after transplantation. The sections of these tissues were observed under fluorescent microscope. More than 70 % MSCs were successfully labeled with GFP at 72 h after labeling. MSCs were uniformly distributed in multiple organs and tissues including brain, lungs, heart, kidneys, intestine and bilateral hip joints of nude mice. In rabbits, at 6 w after intravenous transplantation, GFP labeled MSCs were noted in the lungs, liver, bone marrow and normal and necrotic femoral heads of rabbits, and the number of MSCs in bone marrow was higher than that in the, femoral head, liver and lungs. Furthermore, the number of MSCs peaked at 6 w after transplantation. Moreover, no immunological rejection and graft versus host disease were found after transplantation in rabbits. Our results revealed intravenously implanted MSCs could migrate into the femoral head of hosts, and especially migrate directionally and survive in the necrotic femoral heads. Thus, it is feasible and safe to treat femoral head necrosis by intravenous transplantation of allogeneic MSCs.

  12. Experimental bladder regeneration using a poly-l-lactide/silk fibroin scaffold seeded with nanoparticle-labeled allogenic bone marrow stromal cells.

    Science.gov (United States)

    Yudintceva, Natalia M; Nashchekina, Yulia A; Blinova, Miralda I; Orlova, Nadezhda V; Muraviov, Alexandr N; Vinogradova, Tatiana I; Sheykhov, Magomed G; Shapkova, Elena Y; Emeljannikov, Dmitriy V; Yablonskii, Petr K; Samusenko, Igor A; Mikhrina, Anastasiya L; Pakhomov, Artem V; Shevtsov, Maxim A

    In the present study, a poly-l-lactide/silk fibroin (PL-SF) bilayer scaffold seeded with allogenic bone marrow stromal cells (BMSCs) was investigated as a potential approach for bladder tissue engineering in a model of partial bladder wall cystectomy in rabbits. The inner porous layer of the scaffold produced from silk fibroin was designed to promote cell proliferation and the outer layer produced from poly-l-lactic acid to serve as a waterproof barrier. To compare the feasibility and efficacy of BMSC application in the reconstruction of bladder defects, 12 adult male rabbits were divided into experimental and control groups (six animals each) that received a scaffold seeded with BMSCs or an acellular one, respectively. For BMSC tracking in the graft in in vivo studies using magnetic resonance imaging, cells were labeled with superparamagnetic iron oxide nanoparticles. In vitro studies demonstrated high intracellular incorporation of nanoparticles and the absence of a toxic influence on BMSC viability and proliferation. Following implantation of the graft with BMSCs into the bladder, we observed integration of the scaffold with surrounding bladder tissues (as detected by magnetic resonance imaging). During the follow-up period of 12 weeks, labeled BMSCs resided in the implanted scaffold. The functional activity of the reconstructed bladder was confirmed by electromyography. Subsequent histological assay demonstrated enhanced biointegrative properties of the PL-SF scaffold with cells in comparison to the control graft, as related to complete regeneration of the smooth muscle and urothelium tissues in the implant. Confocal microscopy studies confirmed the presence of the superparamagnetic iron oxide nanoparticle-labeled BMSCs in newly formed bladder layers, thus indicating the role of stem cells in bladder regeneration. The results of this study demonstrate that application of a PL-SF scaffold seeded with allogenic BMSCs can enhance biointegration of the graft in

  13. Maxillary sinus augmentation using sinus membrane elevation without grafts - A Systematic Review

    Directory of Open Access Journals (Sweden)

    Rakshith Hegde

    2016-01-01

    Full Text Available Implants have a predictable outcome and are the foremost treatment modality for prosthetic rehabilitation of edentulous patients. Due to loss of bone after extraction and pneumatization of maxillary sinus, there is insufficient bone volume for implant placement. The direct maxillary sinus lift procedure has been performed with different grafting materials (autogenous bone grafts, alloplasts, allografts, and xenografts and without grafting material, having new bone formation around the implant. There is no evidence to prove the need for grafting material in all direct sinus lift procedures, hence the need for this review. Previous meta-analysis showed that survival rates of implants placed in grafted maxillary sinuses had similar survival rates whether autogenous, allogenous, or alloplastic grafts were used. This paper aims to review scientific data on the direct sinus elevation technique without use of any grafting material, volume of new bone formed, and also mechanism behind this technique. Articles were searched from 1997 to October 2014 in PubMed, Google Scholar, and Cochrane CENTRAL. The study eligibility criteria were (1 direct sinus lift procedure without any graft material during implant placement and (2 human or animal studies with a minimum follow-up of 6 months or more. Two authors independently scrutinized the literature and if any controversy was raised, third author's opinion was sought to arrive at a mutual consensus for including the study in the review. Due to the heterogeneity across all studies in all study designs, the data were not pooled and a meta-analysis was not performed. Taking into consideration all factors reviewed in this regard along with the outcomes, the direct sinus lift technique without grafting can be suggested as a viable treatment option keeping in mind the limitations involved. The average bone gain was seen across all studies ranging from 2.37 to 10 mm and with an implant survival rate ranging from 79

  14. Allogeneic hematopoietic stem cell transplantation: transfusion issues

    Directory of Open Access Journals (Sweden)

    Akkök ÇA

    2016-05-01

    Full Text Available Çiğdem Akalın Akkök,1,21Department of Immunology and Transfusion Medicine, Oslo University Hospital, Ullevaal, Oslo, Norway; 2Department of Clinical Immunology and Transfusion Medicine, Lund University Hospital, Lund, Sweden Abstract: Allogeneic hematopoietic stem cell transplantation (AHSCT is an intention-to-cure treatment strategy in several malignancies and nonmalignancies. The number of patients receiving AHSCT is increasing due to new indications, and more elderly patients with comorbidities are included in the protocols. Survival of the patients undergoing AHSCT has improved owing to better patient care, including optimization of transfusion support, which has a major contribution. However, transfusion can also be hazardous. Increasing awareness about transfusion and finding the balance between avoiding unnecessary transfusions and transfusing the correct component when needed are the key issues. Myeloablative conditioning results in pancytopenia, and the patients are prone to infections, anemia, and bleeding both before and after transplantation. Until red cell and platelet engraftment, the patients are usually transfusion dependent needing red cell and/or platelet components. Physicians dealing with AHSCT patients should be well informed about the attributes of the blood components they order. Knowledge about transfusion indications, triggers, and how to prevent and manage eventual transfusion complications is also required. The clinical picture can be challenging, and transplantation/treatment-related toxicity/complications can sometimes be difficult to distinguish from a transfusion complication, especially if the latter one took place, for instance, several days or weeks ago. ABO compatibility between the patient and the donor is not a prerequisite when choosing human leukocyte antigen-matched hematopoietic stem cell donor. Consequently, ABO incompatibility exists in ~40% of the cases and brings some immunohematological issues

  15. Isolation and culture of adult Sertoli cells and their effects on the function of co-cultured allogeneic islets in vitro

    Institute of Scientific and Technical Information of China (English)

    TENG Yan; XUE Wu-jun; DING Xiao-ming; FENG Xin-shun; XIANG He-li; JIANG Ya-zhuo; TIAN Pu-xun

    2005-01-01

    Background Globally, 180 million people suffer from diabetes mellitus. Islet transplantation is believed to be an almost ideal therapy for insulin-dependent patients. How to maintain the viability and the function of isolated human islets is a challenge in clinical practice. Sertoli cells are considered ‘nurse cells'in the seminiferous tubules and have been used in cell graft protocols for neurodegenerative diseases and diabetes in many studies. Many researchers have used immature murine testes as the primarily source of Sertoli cells in islet transplantation because they are easily purified. Mature human Sertoli cells have been seldom investigated. In the present study, we developed a method for the isolation and culture of Sertoli cells derived from adult human testes, and investigated their effects on the function of allogeneic islets when they were cultured together in vitro. Methods Adult Sertoli cells were prepared successfully by two-step enzyme digestion with trypsin, collagenase and hyaluronidase. They were identified by morphological characteristics and their activity was determined by MTT colorimetry over a 28-day culture time in vitro. A glucose-stimulated insulin secretion test was performed to detect the effects of Sertoli cells on allogeneic islets' function when they were co-cultured for 21 days in vitro. Results In cultured cells, mature human Sertoli cells accounted for more than 90% of total cells. The activity of Sertoli cells reached 95% and they remained highly cytoactive for a long time in vitro (P>0.05). Compared with the islets cultured alone, the co-cultured islets with allogeneic Sertoli cells maintained higher sensitivity to glucose stimulation for the duration of the experiment (P<0.01). Conclusions A method of isolation and culture of Sertoli cells from adult testes has been established. Sertoli cells could enhance allogeneic islets' function when they were co-cultured in vitro. They could be a helper cell in islet transplantation.

  16. Chronic graft-versus-host disease complicated by nephrotic syndrome.

    Science.gov (United States)

    Wang, Hsin-Hui; Yang, An-Hang; Yang, Ling-Yu; Hung, Giun-Yi; Chang, Jei-Wen; Wang, Chun-Kai; Lee, Tzong-Yann; Tang, Ren-Bin

    2011-09-01

    Chronic graft-versus-host disease (cGVHD) is one of the most frequent and serious complications of allogeneic hematopoietic stem cell transplantation (HSCT). Nephrotic syndrome (NS) is an uncommon and underrecognized manifestation of cGVHD. We report a patient who developed NS 18 months after allogeneic bone marrow transplantation. The onset of NS was accompanied by active manifestations of cGVHD, and immunosuppressants had not been tapered recently. Renal biopsy revealed membranous nephropathy. The patient failed to improve with three combined immunosuppressants (prednisolone, cyclosporine, and mycophenolate mofetil), but achieved partial remission after intravenous immunoglobulin (IVIG) infusion. Twenty-four months after the diagnosis of NS, the patient was still in hematological remission, with normal serum creatinine level, urinary protein loss of 0.7-1.9 g/day and mild oral mucositis. Our report suggests that NS can be a cGVHD-related immune disorder in HSCT patients. Monitoring of renal parameters, especially proteinuria, is important in cGVHD patients. Our case indicated that post-transplant NS, occurring without history of tapering or following immunosuppressant withdrawal, presents a more severe activity of cGVHD and a relatively severe clinical course. IVIG may modify and control the refractory GVHD-related NS, and can be one of the choices of treatment. Copyright © 2011. Published by Elsevier B.V.

  17. Chronic graft-versus-host disease complicated by nephrotic syndrome

    Directory of Open Access Journals (Sweden)

    Hsin-Hui Wang

    2011-09-01

    Full Text Available Chronic graft-versus-host disease (cGVHD is one of the most frequent and serious complications of allogeneic hematopoietic stem cell transplantation (HSCT. Nephrotic syndrome (NS is an uncommon and underrecognized manifestation of cGVHD. We report a patient who developed NS 18 months after allogeneic bone marrow transplantation. The onset of NS was accompanied by active manifestations of cGVHD, and immunosuppressants had not been tapered recently. Renal biopsy revealed membranous nephropathy. The patient failed to improve with three combined immunosuppressants (prednisolone, cyclosporine, and mycophenolate mofetil, but achieved partial remission after intravenous immunoglobulin (IVIG infusion. Twenty-four months after the diagnosis of NS, the patient was still in hematological remission, with normal serum creatinine level, urinary protein loss of 0.7–1.9 g/day and mild oral mucositis. Our report suggests that NS can be a cGVHD-related immune disorder in HSCT patients. Monitoring of renal parameters, especially proteinuria, is important in cGVHD patients. Our case indicated that post-transplant NS, occurring without history of tapering or following immunosuppressant withdrawal, presents a more severe activity of cGVHD and a relatively severe clinical course. IVIG may modify and control the refractory GVHD-related NS, and can be one of the choices of treatment.

  18. Increased rejection of murine allogeneic bone marrow in presensitized recipients

    NARCIS (Netherlands)

    vanOs, R; deWitte, T; Dillingh, JH; Mauch, PM; Down, JD

    1997-01-01

    The role of presensitizing murine recipients with donor spleen cells prior to T cell-depleted or -repleted H-2 compatible allogeneic bone marrow transplantation (BMT) was investigated at two different doses of total body irradiation (TBI). Recipients that were presensitized with 2 x 10(7) irradiated

  19. First report on fertility after allogeneic uterus transplantation.

    Science.gov (United States)

    Díaz-García, César; Akhi, Shamima N; Wallin, Ann; Pellicer, Antonio; Brännström, Mats

    2010-11-01

    Uterus transplantation may become the first available treatment for uterine factor infertility, which is due to the absence or malfunction of the uterus. Here we describe for the first time pregnancy after allogeneic uterus transplantation, as a proof of concept of uterine function in a transplanted uterus in a standardized animal model (rat) under immunosuppression.

  20. Toll-like receptor polymorphisms in allogeneic hematopoietic cell transplantation

    DEFF Research Database (Denmark)

    Kornblit, Brian; Enevold, Christian; Wang, Tao;

    2014-01-01

    To assess the impact of the genetic variation in toll-like receptors (TLRs) on outcome after allogeneic myeloablative conditioning hematopoietic cell transplantation (HCT), we investigated 29 single nucleotide polymorphisms across 10 TLRs in 816 patients and donors. Only donor genotype of TLR8 rs...

  1. Sinusitis in patients undergoing allogeneic bone marrow transplantation - a review.

    Science.gov (United States)

    Drozd-Sokolowska, Joanna Ewa; Sokolowski, Jacek; Wiktor-Jedrzejczak, Wieslaw; Niemczyk, Kazimierz

    Sinusitis is a common morbidity in general population, however little is known about its occurrence in severely immunocompromised patients undergoing allogeneic hematopoietic stem cell transplantation. The aim of the study was to analyze the literature concerning sinusitis in patients undergoing allogeneic bone marrow transplantation. An electronic database search was performed with the objective of identifying all original trials examining sinusitis in allogeneic hematopoietic stem cell transplant recipients. The search was limited to English-language publications. Twenty five studies, published between 1985 and 2015 were identified, none of them being a randomized clinical trial. They reported on 31-955 patients, discussing different issues i.e. value of pretransplant sinonasal evaluation and its impact on post-transplant morbidity and mortality, treatment, risk factors analysis. Results from analyzed studies yielded inconsistent results. Nevertheless, some recommendations for good practice could be made. First, it seems advisable to screen all patients undergoing allogeneic hematopoietic stem cell transplantation with Computed Tomography (CT) prior to procedure. Second, patients with symptoms of sinusitis should be treated before hematopoietic stem cell transplantation (HSCT), preferably with conservative medical approach. Third, patients who have undergone hematopoietic stem cell transplantation should be monitored closely for sinusitis, especially in the early period after transplantation. Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  2. Maintenance Therapy with Decitabine after Allogeneic Stem Cell Transplantation for Acute Myelogenous Leukemia and Myelodysplastic Syndrome.

    Science.gov (United States)

    Pusic, Iskra; Choi, Jaebok; Fiala, Mark A; Gao, Feng; Holt, Matthew; Cashen, Amanda F; Vij, Ravi; Abboud, Camille N; Stockerl-Goldstein, Keith E; Jacoby, Meghan A; Uy, Geoffrey L; Westervelt, Peter; DiPersio, John F

    2015-10-01

    Decitabine is a hypomethylating agent that irreversibly inhibits DNA methyltransferase I, inducing leukemic differentiation and re-expression of epigenetically silenced putative tumor antigens. We assessed safety and efficacy of decitabine maintenance after allogeneic transplantation for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Decitabine maintenance may help eradicate minimal residual disease, decrease the incidence of graft-versus-host disease (GVHD), and facilitate a graft-versus-leukemia effect by enhancing the effect of T regulatory lymphocytes. Patients with AML/MDS in complete remission (CR) after allotransplantation started decitabine between day +50 and +100. We investigated 4 decitabine doses in cohorts of 4 patients: 5, 7.5, 10, and 15 mg/m(2)/day × 5 days every 6 weeks, for a maximum 8 cycles. The maximum tolerated dose (MTD) was defined as the maximum dose at which ≤ 25% of people experience dose-limiting toxicities during the first cycle of treatment. Twenty-four patients were enrolled and 22 were evaluable. All 4 dose levels were completed and no MTD was reached. Overall, decitabine maintenance was well tolerated. Grade 3 and 4 hematological toxicities were experienced by 75% of patients, including all patients treated at the highest dose level. Nine patients completed all 8 cycles and 8 of them remain in CR. Nine patients died from relapse (n = 4), infectious complications (n = 3), and GVHD (n = 2). Most occurrences of acute GVHD were mild and resolved without interruption of treatment; 1 patient died of acute gut GVHD. Decitabine maintenance did not clearly impact the rate of chronic GVHD. Although there was a trend of increased FOXP3 expression, results were not statistically significant. In conclusion, decitabine maintenance is associated with acceptable toxicities when given in the post-allotransplantation setting. Although the MTD was not reached, the dose of 10 mg/m(2) for 5 days every 6 weeks appeared to be the

  3. Allogeneic hematopoietic cell transplant for acute myeloid leukemia: Current state in 2013 and future directions.

    Science.gov (United States)

    Kanate, Abraham S; Pasquini, Marcelo C; Hari, Parameswaran N; Hamadani, Mehdi

    2014-04-26

    Acute myeloid leukemia (AML) represents a heterogeneous group of high-grade myeloid neoplasms of the elderly with variable outcomes. Though remission-induction is an important first step in the management of AML, additional treatment strategies are essential to ensure long-term disease-free survival. Recent pivotal advances in understanding the genetics and molecular biology of AML have allowed for a risk-adapted approach in its management based on relapse-risk. Allogeneic hematopoietic cell transplantation (allo-HCT) represents an effective therapeutic strategy in AML providing the possibility of cure with potent graft-versus-leukemia reactions, with a demonstrable survival advantage in younger patients with intermediate- or poor-risk cytogenetics. Herein we review the published data regarding the role of allo-HCT in adults with AML. We searched MEDLINE/PubMed and EMBASE/Ovid. In addition, we searched reference lists of relevant articles, conference proceedings and ongoing trial databases. We discuss the role of allo-HCT in AML patients stratified by cytogenetic- and molecular-risk in first complete remission, as well as allo-HCT as an option in relapsed/refractory AML. Besides the conventional sibling and unrelated donor allografts, we review the available data and recent advances for alternative donor sources such as haploidentical grafts and umbilical cord blood. We also discuss conditioning regimens, including reduced intensity conditioning which has broadened the applicability of allo-HCT. Finally we explore recent advances and future possibilities and directions of allo-HCT in AML. Practical therapeutic recommendations have been made where possible based on available data and expert opinion.

  4. Risk factors for bronchiolitis obliterans syndrome in allogeneic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    MO Xiao-dong; XU Lan-ping; LIU Dai-hong; ZHANG Xiao-hui; CHEN Huan; CHEN Yu-hong; HAN Wei

    2013-01-01

    Background The occurrence of bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (alIo-HSCT) is rare but severe.We examine the role of pre-HSCT chemotherapeutic exposure,pre-HSCT comorbidities,and transplant-related complications in the development of BOS after allo-HSCT.Methods A nested case-control study was designed.Cases with BOS and controls matched for the year of alIo-HSCT and length of the follow-up were identified from a cohort of 1646 patients who underwent alIo-HSCT for treatment of hematologic malignancies between 2006 and 2011.Antithymocyte globulin was used in the partial matched related and unrelated matched donor HSCT,or patients with severe aplastic anemia.Results Thirty-six patients suffered from BOS; the mean age at the time of presentation was (32.7±12.4) years,and the mean time to presentation was (474±350) days post-HSCT.A pre-HSCT cyclophosphamide dose of >3.2 g/m2 (OR=8.74,P=0.025),chronic graft-versus-host disease (moderate to severe) (OR=12.02,P=0.000),and conditioning regimens without antithymocyte globulin (OR=2.79,P=0.031) were independently associated with BOS.Conclusions We found that higher pre-HSCT cyclophosphamide exposure,a conditioning regimen without antithymocyte globulin,and moderate to severe chronic graft-versus-host disease are significantly and independently associated with BOS.Based on these results,we can identify patients who are at a higher risk of developing BOS after alIo-HSCT,select a more appropriate therapeutic strategy,and improve the outcome of HSCT recipients.

  5. Optimizing outcomes following allogeneic hematopoietic progenitor cell transplantation in AML: the role of hypomethylating agents.

    Science.gov (United States)

    Martino, Massimo; Fedele, Roberta; Moscato, Tiziana; Ronco, Francesca

    2013-07-01

    Aberrant DNA methylation is a key pathological mechanism in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), and provides rationale for the clinical development of hypomethylating agents (HMAs) for the treatment of these diseases. One HMA, azacitidine (Vidaza®, Celgene Corp.), has demonstrated improved survival versus conventional care regimens in patients with intermediate-2/high-risk MDS and AML (20-30% blasts) and has a favorable tolerability profile. Emerging evidence indicates that azacitidine can have an immunomodulatory effect by, for example, increasing functional regulatory T-cell (Treg) numbers and killer-cell-immunoglobulin-like receptor expression. Allogeneic hematopoietic progenitor cell transplantation (allo HPCT) is the only potentially curative treatment approach in patients with advanced MDS or AML. Unfortunately, allo HPCT in these settings is limited because most patients are ineligible due to age/comorbidities, or are at a high risk of treatment failure due to disease relapse. Recent studies have shown that azacitidine after allo HPCT increases Treg numbers while inducing a cytotoxic CD8+ T-cell response, suggesting a potential mechanism for augmenting the graft-versus-leukemia (GvL) effect without increasing graft-versushost- disease (GVHD). In patients at a high risk of relapse following allo HPCT, pre-emptive azacitidine may help prevent/delay relapse. For patients who have relapsed following allo HPCT, azacitidine may be a salvage therapy option, either as monotherapy or in combination with donor lymphocyte infusions (DLI). In this mini-review, we discuss these emerging clinical data for HMAs in the post-allo HPCT regimens and highlight the possible future role of azacitidine in this setting.

  6. 异体骨垫在腰椎结核椎间融合术中的临床应用%Clinical application of allogeneic bone pad in intervertebral fusion of lumbar spine tuberculosis

    Institute of Scientific and Technical Information of China (English)

    范相成; 关玉成; 贾勇; 邵向明

    2012-01-01

    [目的]评价异体骨垫在腰椎结核椎间融合中的临床应用效果.[方法]2005年6月~2009年11月,采用异体骨垫对腰椎单节段结核病灶清除后进行植骨融合41例.[结果]所有病例全部治愈,未发生结核复发,椎间融合率100%.[结论]采用异体骨垫对腰椎单节段结核病灶清除后进行植骨融合,方法简单,效果可靠,值得临床应用.%[Objective] To clinically evaluate the application effect of allogeneic bone pad in interveitebral fusion of lumbar spine tuberculosis. [Methods] Forty -one cases of bone graft fusion were performed with allogeneic bone pad after clearance of tuberculose focus at single lumbar segment from June 2005 to November 2009. [ Results] All patients were cured without recurrence of tuberculosis and the ratio of interveitebral fusion were 100%. [Conclusion] For its reliability and simplicity, bone graft fusion with allogeneic bone pad is worthy of clinical application after clearance of tuberculose focus at single lumbar segment

  7. Minor histocompatibility antigens--targets of graft versus leukemia responses.

    Science.gov (United States)

    Riddell, Stanley R; Murata, M; Bryant, S; Warren, E H

    2002-08-01

    Immune-mediated elimination of tumor cells by donor T cells recognizing recipient minor H antigens contributes to the curative potential of allogeneic HCT. The importance of the allogeneic response to a successful outcome is clearly illustrated by the results of stem cell transplant for malignancy after nonmyeloablative conditioning. Remarkably little is understood about the molecular nature of minor H antigens and this has impeded efforts to determine the role of specific disparities in graft versus tumor reactions or to manipulate T cell responses to augment antitumor activity without exacerbating GVHD. The isolation of minor H antigen-specific CD8+ and CD4+ T cell clones from recipients of allogeneic HCT has provided the reagents to characterize their expression on leukemic progenitors and to identify the genes encoding these antigens. Using cDNA expression cloning, genetic polymorphisms in the human IFI-75, Uty, KIAA0020, and UGT2B17 genes have been identified to encode new minor H antigens presented by HLA A3, B8, A2, and A29 respectively. Two of these genes are preferentially expressed in hematopoietic cells including leukemic progenitors suggesting it may be possible to augment T cell responses to promote a selective graft versus leukemia effect. A third gene, UGT2B17 is highly expressed in liver and GI tract and may be a target for GVHD in these organs. The studies to identify the molecular nature of minor H antigens have provided insights into the complexities of the graft versus host response associated with allogeneic HCT, but the challenge for the future will be to develop strategies that can selectively induce durable graft versus tumor effects without GVHD. A critical issue in developing specific immunotherapy to augment GVL responses is to determine which minor H antigens are expressed on leukemic stem cells. Studies using transplantation of human AML into SCID mice have identified a putative leukemic stem cell which is contained in the CD34+ CD38

  8. Low Counts of Plasmacytoid Dendritic Cells after Engraftment Are Associated with High Early Mortality after Allogeneic Stem Cell Transplantation.

    Science.gov (United States)

    Gonçalves, Matheus Vescovi; Yamamoto, Mihoko; Kimura, Eliza Yurico Sugano; Colturato, Vergílio Antônio Rensi; de Souza, Mair Pedro; Mauad, Marcos; Ikoma, Maura Valerio; Novis, Yana; Rocha, Vanderson; Ginani, Valeria Cortez; Wanderley de Oliveira Felix, Olga Margareth; Seber, Adriana; Kerbauy, Fabio Rodrigues; Hamerschlak, Nelson; Orfao, Alberto; Rodrigues, Celso Arrais

    2015-07-01

    Dendritic cells (DCs) are antigen-presenting cells that drive immune responses and tolerance and are divided in different subsets: myeloid DCs (mDCs: lineage-; HLA-DR+, 11c+), plasmacytoid dendritic cells (pDCs: HLA-DR+, CD123+), and monocyte-derived DCs (moDC: lineage-, 11c+, 16+). After hematopoietic stem cell transplantation (HSCT), low DC counts in the recipients' peripheral blood (PB) have been associated with worse outcomes, but the relevance of DC graft content remains unclear, and there are few data in the setting of unrelated donor HSCT. We evaluated the DC graft content and monitored DC recovery in PB from 111 HSCT recipients (median age, 17 years; range 1 to 74), who received bone marrow (46%), umbilical cord blood (32%), or PB (22%) from unrelated (81%) or related donors (19%). In 86 patients with sustained allogeneic recovery, patients with higher counts of all DC subsets (pDC, mDC, and moDC) 3 weeks after engraftment had lower incidence of nonrelapse mortality (NMR) and acute graft-versus-host disease (aGVHD) and better survival. pDC counts were associated with more striking results: patients with higher pDC counts had much lower incidences of NRM (3% versus 47%, P < .0001), lower incidence of aGVHD (24% versus 67%, P < .0001), and better overall survival (92% versus 45%, P < .0001). In contrast, higher pDC counts in the graft was associated with an increased risk of aGVHD (55% versus 26%, P = .02). Our results indicate that DC counts are closely correlated with HSCT outcomes and warrant further prospective evaluation and possible early therapeutic interventions to ameliorate severe aGVHD and decrease mortality.

  9. Treosulfan, Fludarabine and 2 Gy Total Body Irradiation Followed by Allogeneic Hematopoietic Cell Transplantation in Patients with MDS and AML

    Science.gov (United States)

    Gyurkocza, Boglarka; Gutman, Jonathan; Nemecek, Eneida R.; Bar, Merav; Milano, Filippo; Ramakrishnan, Aravind; Scott, Bart; Fang, Min; Wood, Brent; Pagel, John M.; Baumgart, Joachim; Delaney, Colleen; Maziarz, Richard T.; Sandmaier, Brenda M.; Estey, Elihu H.; Appelbaum, Frederick R.; Storer, Barry E.; Deeg, H. Joachim

    2014-01-01

    Allogeneic hematopoietic cell transplantation (HCT) offers curative therapy for many patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). However, post-HCT relapse remains a major problem, particularly in patients with high-risk cytogenetics. In this prospective phase II trial we assessed the efficacy and toxicity of treosulfan, fludarabine and 2 Gy total body irradiation (TBI) as conditioning for allogeneic HCT in patients with MDS or AML. Ninety-six patients with MDS (n=36; 15 RMCD; 10 RAEB-1; 10 RAEB-2; 1 CMML-1) or AML (n=60; 35 CR1; 18 CR2; 3 advanced CR; 4 refractory relapse) were enrolled; median age was 51 (range: 1–60) years. Twelve patients had undergone a prior HCT with high intensity conditioning. Patients received intravenous (IV) treosulfan, 14 g/m2/day on days −6 to −4, IV fludarabine, 30 mg/m2/day on days −6 to −2, and 2 Gy TBI on day 0, followed by infusion of hematopoietic cells from related (n=27) or unrelated (n=69) donors. Graft-vs.-host disease prophylaxis consisted of tacrolimus and methotrexate. With a median follow-up of 30 months, the 2-year overall survival (OS), relapse incidence and non-relapse mortality were 73%, 27% and 8%, respectively. The incidences of grades II–IV (III–IV) acute and chronic graft-versus-host disease were 59% (10%) and 47%, respectively. Two-year OS was not significantly different between MDS patients with poor risk and good/intermediate risk cytogenetics (69% and 85%, respectively), or between AML patients with unfavorable and favorable/intermediate risk cytogenetics (64% and 76%, respectively). In AML patients, minimal residual disease (MRD; n=10) at the time of HCT predicted higher relapse incidence (70% vs. 18%) and lower OS (41% vs. 79%) at 2 years, when compared to patients without MRD. In conclusion, treosulfan, fludarabine and low-dose TBI provided effective conditioning for allogeneic HCT in patients with MDS or AML, and resulted in low relapse incidence, regardless

  10. Management of endocrino-metabolic dysfunctions after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Vantyghem, Marie-Christine; Cornillon, Jérôme; Decanter, Christine; Defrance, Frédérique; Karrouz, Wassila; Leroy, Clara; Le Mapihan, Kristell; Couturier, Marie-Anne; De Berranger, Eva; Hermet, Eric; Maillard, Natacha; Marcais, Ambroise; Francois, Sylvie; Tabrizi, Reza; Yakoub-Agha, Ibrahim

    2014-10-29

    Allogeneic hematopoietic stem cell transplantation is mainly indicated in bone marrow dysfunction related to blood diseases, but also in some rare diseases (adrenoleucodystrophy, mitochondrial neurogastrointestinal encephalomyopathy or MNGIE...). After decades, this treatment has proven to be efficient at the cost of numerous early and delayed side effects such as infection, graft-versus-host disease, cardiovascular complications and secondary malignancies. These complications are mainly related to the conditioning, which requires a powerful chemotherapy associated to total body irradiation (myelo-ablation) or immunosuppression (non myelo-ablation). Among side effects, the endocrine complications may be classified as 1) hormonal endocrine deficiencies (particularly gonado- and somatotropic) related to delayed consequences of chemo- and above all radiotherapy, with their consequences on growth, puberty, bone and fertility); 2) auto-immune diseases, particularly dysthyroidism; 3) secondary tumors involving either endocrine glands (thyroid carcinoma) or dependent on hormonal status (breast cancer, meningioma), favored by immune dysregulation and radiotherapy; 4) metabolic complications, especially steroid-induced diabetes and dyslipidemia with their increased cardio-vascular risk. These complications are intricate. Moreover, hormone replacement therapy can modulate the cardio-vascular or the tumoral risk of patients, already increased by radiotherapy and chemotherapy, especially steroids and anthracyclins... Therefore, patients and families should be informed of these side effects and of the importance of a long-term follow-up requiring a multidisciplinary approach.

  11. CMV reactivation after allogeneic HCT and relapse risk: evidence for early protection in acute myeloid leukemia.

    Science.gov (United States)

    Green, Margaret L; Leisenring, Wendy M; Xie, Hu; Walter, Roland B; Mielcarek, Marco; Sandmaier, Brenda M; Riddell, Stanley R; Boeckh, Michael

    2013-08-15

    The association between cytomegalovirus (CMV) reactivation and relapse was evaluated in a large cohort of patients with acute myeloid leukemia (AML) (n = 761), acute lymphoblastic leukemia (ALL) (n = 322), chronic myeloid leukemia (CML) (n = 646), lymphoma (n = 254), and myelodysplastic syndrome (MDS) (n = 371) who underwent allogeneic hematopoietic cell transplantation (HCT) between 1995 and 2005. In multivariable models, CMV pp65 antigenemia was associated with a decreased risk of relapse by day 100 among patients with AML (hazard ratio [HR] = 0.56; 95% confidence interval [CI], 0.3-0.9) but not in patients with ALL, lymphoma, CML, or MDS. The effect appeared to be independent of CMV viral load, acute graft-versus-host disease, or ganciclovir-associated neutropenia. At 1 year after HCT, early CMV reactivation was associated with reduced risk of relapse in all patients, but this did not reach significance for any disease subgroup. Furthermore, CMV reactivation was associated with increased nonrelapse mortality (HR = 1.31; 95% CI, 1.1-1.6) and no difference in overall mortality (HR = 1.05; 95% CI, 0.9-1.3). This report demonstrates a modest reduction in early relapse risk after HCT associated with CMV reactivation in a large cohort of patients without a benefit in overall survival.

  12. Menstrual patterns, fertility and main pregnancy outcomes after allogeneic haematopoietic stem cell transplantation.

    Science.gov (United States)

    Chiodi, Sandra; Spinelli, Simonetta; Bruzzi, Paolo; Anserini, Paola; Di Grazia, Carmen; Bacigalupo, Andrea

    2016-08-01

    Two-hundred and sixty-nine females aged ≤42 and undergoing an allogeneic stem cell transplant were retrospectively studied to assess the effect of age, conditioning regimen and chronic graft-versus-host disease (cGVHD) on resumption of stable menstrual cyclicity. Overall, a stable menstrual cyclicity was observed in 22% of cases. The cumulative probability of menses resumption was significantly age and conditioning regimen related. A statistically significant inverse correlation between cGVHD severity and menses resumption was observed only in univariate analysis. In patients with residual ovarian function, infertility was found in 43% and early menopause in 45%. An increased incidence of prematurity and low birth weight (LBW) was observed among the single spontaneous pregnancies. Follicle-stimulating hormone (FSH) and 17 beta-oestradiol levels were found to be inadequate to detect both early signs of menses resumption and menstrual stability. Our study confirms the crucial role of full dose total body irradiation (TBI) and age on menses recovery and fertility after haematopoietic stem cell transplantation (HSCT). The impact of severe cGVHD remains unclear.

  13. Longitudinal analysis of antibody response to immunization in paediatric survivors after allogeneic haematopoietic stem cell transplantation

    Science.gov (United States)

    Inaba, Hiroto; Hartford, Christine M.; Pei, Deqing; Posner, Meredith J.; Yang, Jie; Hayden, Randall T.; Srinivasan, Ashok; Triplett, Brandon M.; McCulllers, Jon A.; Pui, Ching-Hon; Leung, Wing

    2011-01-01

    Summary The long-term antibody responses to re-immunization in recipients of allogeneic haematopoietic stem cell transplantation (allo-HSCT) have not been well studied. We prospectively and longitudinally evaluated the antibody responses to 8 vaccine antigens (diphtheria, tetanus, pertussis, measles, mumps, rubella, hepatitis B, and poliovirus) and assessed the factors associated with negative titres in 210 allo-HSCT recipients at St. Jude Children’s Research Hospital. Antibody responses lasting for more than 5 years after immunization were observed in most patients for tetanus (95.7%), rubella (92.3%), poliovirus (97.9%), and, in diphtheria-tetanus-acellular pertussis (DTaP) recipients, diphtheria (100%). However, responses to pertussis (25.0%), measles (66.7%), mumps (61.5%), hepatitis B (72.9%), and diphtheria in tetanus-diphtheria (Td) recipients (48.6%) were less favourable, with either only transient antibody responses or persistently negative titres. Factors associated with vaccine failure were older age at immunization; lower CD3, CD4 or CD19 counts; higher IgM concentrations; positive recipient cytomegalovirus serology; negative titres before immunization; acute or chronic graft-versus-host disease; and radiation during preconditioning. These response patterns and clinical factors can be used to formulate re-immunization and monitoring strategies. Patients at risk for vaccine failure should have long-term follow-up; those with loss of antibody response or no seroconversion should receive booster immunizations. PMID:22017512

  14. Allogeneic Hematopoietic Cell Transplantation for Advanced Polycythemia Vera and Essential Thrombocythemia

    Science.gov (United States)

    Ballen, Karen K.; Woolfrey, Ann E.; Zhu, Xiaochun; Ahn, Kwang Woo; Wirk, Baldeep; Arora, Mukta; George, Biju; Savani, Bipin N.; Bolwell, Brian; Porter, David L.; Copelan, Ed; Hale, Gregory; Schouten, Harry C.; Lewis, Ian; Cahn, Jean Yves; Halter, Joerg; Cortes, Jorge; Kalaycio, Matt E.; Antin, Joseph; Aljurf, Mahmoud D.; Carabasi, Matthew H.; Hamadani, Mehdi; McCarthy, Philip; Pavletic, Steven; Gupta, Vikas; Deeg, H. Joachim; Maziarz, Richard T.; Horowitz, Mary M.; Saber, Wael

    2012-01-01

    Allogeneic hematopoietic cell transplantation (HCT) is curative for selected patients with advanced essential thrombocythemia (ET) or polycythemia vera (PV). From 1990 to 2007, 75 patients with ET (median age 49 years) and 42 patients with PV (median age 53 years) underwent transplantations at the Fred Hutchinson Cancer Research Center (FHCRC; n = 43) or at other Center for International Blood and Marrow Transplant Research (CIBMTR) centers (n = 74). Thirty-eight percent of the patients had splenomegaly and 28% had a prior splenectomy. Most patients (69%for ET and 67%for PV) received a myeloablative (MA) conditioning regimen. Cumulative incidence of neutrophil engraftment at 28 days was 88% for ET patients and 90% for PV patients. Acute graft-versus- host disease (aGVHD) grades II to IV occurred in 57% and 50% of ET and PV patients, respectively. The 1-year treatment-related mortality (TRM) was 27% for ET and 22% for PV. The 5-year cumulative incidence of relapse was 13% for ET and 30% for PV. Five-year survival/progression-free survival (PFS) was 55%/47%and 71%/48% for ET and PV, respectively. Patients without splenomegaly had faster neutrophil and platelet engraftment, but there were no differences in TRM, survival, or PFS. Presence of myelofibrosis (MF) did not affect engraftment or TRM. Over 45% of the patients who undergo transplantations for ET and PV experience long-term PFS. PMID:22449610

  15. Allogeneic stem cell transplant for adults with myelodysplastic syndromes: relevance of pre-transplant disease status.

    Science.gov (United States)

    Busca, Alessandro; Pecoraro, Clara; Giaccone, Luisa; Bruno, Benedetto; Allione, Bernardino; Corsetti, Maria Teresa; Pini, Massimo; Marmont, Filippo; Audisio, Ernesta; D'Ardia, Stefano; Frairia, Chiara; Castiglione, Anna; Ciccone, Giovannino; Levis, Alessandro; Vitolo, Umberto; Falda, Michele

    2014-04-01

    The aim of the present study was to investigate the outcome of 94 adult patients with myelodysplasia (MDS) who received an allogeneic stem cell transplant between January 1995 and September 2010 in two Italian hematology centers. At the time of transplant, 53 patients (56%) had relapsed/refractory disease. The cumulative incidence of grades II-IV acute graft-versus-host disease (GVHD) and chronic GVHD was 33% (95% confidence interval [CI] 21-45%) and 78% (95% CI 66-90%), respectively. The cumulative incidence of transplant-related mortality (TRM) at 100 days was 13% (95% CI 6-21%). The 2-year progression free survival (PFS) and overall survival (OS) were 41% (95% CI 31-51%) and 49% (95% CI 38-59%), respectively. On multivariate analysis, advanced disease stage at transplant was the major independent variable associated with an inferior 2-year PFS (HR 3.66, 95% CI 1.98-6.76) and OS (HR 3.68, 95% CI 1.95-6.93). Use of an alternative donor was an independent variable associated with TRM (HR 3.18, 95% CI 1.31-7.72). In conclusion, our data suggest that disease status at the time of transplant is the major predictor for improved PFS and OS, and treatments required to reach this goal may have value in leading to an improved outcome.

  16. Bone marrow B cell precursor number after allogeneic stem cell transplantation and GVHD development.

    Science.gov (United States)

    Fedoriw, Yuri; Samulski, T Danielle; Deal, Allison M; Dunphy, Cherie H; Sharf, Andrew; Shea, Thomas C; Serody, Jonathan S; Sarantopoulos, Stefanie

    2012-06-01

    Patients without chronic graft-versus-host disease (cGVHD) have robust B cell reconstitution and are able to maintain B cell homeostasis after allogeneic hematopoietic stem cell transplantation (HSCT). To determine whether B lymphopoiesis differs before cGVHD develops, we examined bone marrow (BM) biopsies for terminal deoxynucleotidyl transferase (TdT) and PAX5 immunostaining early post-HSCT at day 30 when all patients have been shown to have high B cell activating factor (BAFF) levels. We found significantly greater numbers of BM B cell precursors in patients who did not develop cGVHD compared with those who developed cGVHD (median = 44 vs 2 cells/high powered field [hpf]; respectively; P < .001). Importantly, a significant increase in precursor B cells was maintained when patients receiving high-dose steroid therapy were excluded (median = 49 vs 20 cells/hpf; P = .017). Thus, we demonstrate the association of BM B cell production capacity in human GVHD development. Increased BM precursor B cell number may serve to predict good clinical outcome after HSCT. Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  17. Early human herpes virus type 6 reactivation in umbilical cord blood allogeneic stem cell transplantation.

    Science.gov (United States)

    Cirrone, Frank; Ippoliti, Cindy; Wang, Hanhan; Zhou, Xi Kathy; Gergis, Usama; Mayer, Sebastian; Shore, Tsiporah; van Besien, Koen

    2016-11-01

    Human herpes virus type 6 can reactivate in patients after allogeneic stem cell transplantation and has been associated with serious sequelae such as delayed engraftment and an increased risk of developing acute graft-versus-host disease (GVHD). This study investigated human herpes virus type 6 (HHV-6) reactivation within 60 days of transplantation in stem cell transplants utilizing single umbilical cord blood, double umbilical cord blood, or umbilical cord blood plus haploidentical stem cells. Of 92 patients, 60 (65%) had HHV-6 reactivation. Reactivation was not significantly influenced by any patient characteristics, disease characteristics, or by stem cell source (umbilical cord blood only versus haploidentical plus umbilical cord blood). We did not observe any impact of HHV-6 reactivation on neutrophil or platelet count recovery or on relapse-free survival. HHV-6 reactivation was associated with subsequent development of prerelapse acute GVHD (HR = 3.00; 95% CI, 1.4 to 6.4; p = 0.004).

  18. Reduced-intensity conditioning allogeneic hematopoietic-cell transplantation for older patients with acute myeloid leukemia.

    Science.gov (United States)

    Goyal, Gaurav; Gundabolu, Krishna; Vallabhajosyula, Saraschandra; Silberstein, Peter T; Bhatt, Vijaya Raj

    2016-06-01

    Elderly patients (>60 years) with acute myeloid leukemia have a poor prognosis with a chemotherapy-alone approach. Allogeneic hematopoietic-cell transplantation (HCT) can improve overall survival (OS). However, myeloablative regimens can have unacceptably high transplant-related mortality (TRM) in an unselected group of older patients. Reduced-intensity conditioning (RIC) or nonmyeloablative (NMA) conditioning regimens preserve the graft-versus-leukemia effects but reduce TRM. NMA regimens result in minimal cytopenia and may not require stem cell support for restoring hematopoiesis. RIC regimens, intermediate in intensity between NMA and myeloablative regimens, can cause prolonged myelosuppresion and usually require stem cell support. A few retrospective and prospective studies suggest a possibility of lower risk of relapse with myeloablative HCT in fit older patients with lower HCT comorbidity index; however, RIC and NMA HCTs have an important role in less-fit patients and those with significant comorbidities because of lower TRM. Whether early tapering of immunosuppression, monitoring of minimal residual disease, and post-transplant maintenance therapy can improve the outcomes of RIC and NMA HCT in elderly patients will require prospective trials.

  19. Relapse risk in patients with malignant diseases given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning.

    Science.gov (United States)

    Kahl, Christoph; Storer, Barry E; Sandmaier, Brenda M; Mielcarek, Marco; Maris, Michael B; Blume, Karl G; Niederwieser, Dietger; Chauncey, Thomas R; Forman, Stephen J; Agura, Edward; Leis, Jose F; Bruno, Benedetto; Langston, Amelia; Pulsipher, Michael A; McSweeney, Peter A; Wade, James C; Epner, Elliot; Bo Petersen, Finn; Bethge, Wolfgang A; Maloney, David G; Storb, Rainer

    2007-10-01

    Allogeneic hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning for hematologic malignancies depends on graft-versus-tumor effects for eradication of cancer. Here, we estimated relapse risks according to disease characteristics. Between 1997 and 2006, 834 consecutive patients (median age, 55 years; range, 5-74 years) received related (n = 498) or unrelated (n = 336) HCT after 2 Gy total body irradiation alone (n = 171) or combined with fludarabine (90 mg/m(2); n = 663). Relapse rates per patient year (PY) at risk, corrected for follow-up and competing nonrelapse mortality, were calculated for 29 different diseases and stages. The overall relapse rate per PY was 0.36. Patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) in remission (CR), low-grade or mantle cell non-Hodgkin lymphoma (NHL) (CR + partial remission [PR]), and high-grade NHL-CR had the lowest rates (0.00-0.24; low risk). In contrast, patients with advanced myeloid and lymphoid malignancies had rates of more than 0.52 (high risk). Patients with lymphoproliferative diseases not in CR (except Hodgkin lymphoma and high-grade NHL) and myeloid malignancies in CR had rates of 0.26-0.37 (standard risk). In conclusion, patients with low-grade lymphoproliferative disorders experienced the lowest relapse rates, whereas patients with advanced myeloid and lymphoid malignancies had high relapse rates after nonmyeloablative HCT. The latter might benefit from cytoreductive treatment before HCT.

  20. Nephrotic syndrome after allogeneic hematopoietic stem cell transplantation: etiology and pathogenesis.

    Science.gov (United States)

    Luo, Xiao-dan; Liu, Qi-fa; Zhang, Yu; Sun, Jing; Wang, Guo-bao; Fan, Zhi-ping; Yi, Zheng-shan; Ling, Yi-wen; Wei, Yong-qiang; Liu, Xiao-li; Xu, Bing

    2011-02-15

    In this study we investigated the etiology and pathogenesis of nephrotic syndrome (NS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 257 patients with hematopoietic malignancies who survived more than 2 months post allo-HSCT. Associations of NS with the conditioning regimen, graft versus host disease (GVHD), and other variables were analyzed. Pathologic features of the kidney, regulatory T cells (Tregs), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) were studied. NS was identified in 9 patients. The number of Tregs at day+30, 60, 90, and 180 was lower in NS patients than non-NS patients (P=0.001, 0.001, 0.007, 0.003). Serum levels of IFN-γ and TNF-α were higher in NS patients (P=0.032, 0.001, respectively). NS post allo-HSCT was associated with the occurrence of chronic GVHD (P=0.02). NS post-HSCT is an immune disorder that may involve immune complex deposition, Th1 cytokines, and Tregs.

  1. Patients with Multiple Myeloma Develop SOX2-Specific Autoantibodies after Allogeneic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Sebastian Kobold

    2011-01-01

    Full Text Available The occurrence of SOX2-specific autoantibodies seems to be associated with an improved prognosis in patients with monoclonal gammopathy of undetermined significance (MGUS. However, it is unclear if SOX2-specific antibodies also develop in established multiple myeloma (MM. Screening 1094 peripheral blood (PB sera from 196 MM patients and 100 PB sera from healthy donors, we detected SOX2-specific autoantibodies in 7.7% and 2.0% of patients and donors, respectively. We identified SOX2211–230 as an immunodominant antibody-epitope within the full protein sequence. SOX2 antigen was expressed in most healthy tissues and its expression did not correlate with the number of BM-resident plasma cells. Accordingly, anti-SOX2 immunity was not related to SOX2 expression levels or tumor burden in the patients’ BM. The only clinical factor predicting the development of anti-SOX2 immunity was application of allogeneic stem cell transplantation (alloSCT. Anti-SOX2 antibodies occurred more frequently in patients who had received alloSCT (n=74. Moreover, most SOX2-seropositive patients had only developed antibodies after alloSCT. This finding indicates that alloSCT is able to break tolerance towards this commonly expressed antigen. The questions whether SOX2-specific autoantibodies merely represent an epiphenomenon, are related to graft-versus-host effects or participate in the immune control of myeloma needs to be answered in prospective studies.

  2. Acute cutaneous graft-versus-host disease resembling type II (atypical adult) pityriasis rubra pilaris.

    Science.gov (United States)

    Surjana, Devita; Robertson, Ivan; Kennedy, Glen; James, Daniel; Weedon, David

    2015-02-01

    We present a case of cutaneous acute graft-versus-host disease (aGVHD) with confluent erythematous perifollicular hyperkeratosis and ichthyosiform scale in the clinical pattern of type II (atypical adult) pityriasis rubra pilaris (PRP), which developed 26 days after allogeneic peripheral blood stem cell transplant. Skin histology confirmed features of both aGVHD and PRP. The skin lesions were refractory to oral prednisolone and cyclosporine and only partially responsive to a combination of i.v. methylprednisolone, oral tacrolimus, oral mycophenolate mofetil, and infusions of anti-thymocyte globulin and the tumour necrosis factor-α inhibitor, etanercept. © 2013 The Australasian College of Dermatologists.

  3. [Chickenpox, burns and grafts].

    Science.gov (United States)

    Rojas Zegers, J; Fidel Avendaño, L

    1979-01-01

    An outbreak of chickenpox that occurred at the Burns Repair Surgery Unit, Department of Children's Surgery, Hospital R. del Río, between June and November, 1975, is reported. 27 cases of burned children were studied, including analysis of correlations of the stages and outcome of the disease (varicela), the trauma (burns) and the graft (repair surgery). As a result, the authors emphasize the following findings: 1. Burns and their repair are not aggravating factors for varicella. In a small number of cases the exanthema looked more confluent in the graft surgical areas and in the first degree burns healing spontaneously. 2. Usually there was an uneventful outcome of graft repair surgery on a varicella patient, either during the incubation period, the acme or the convalescence. 3. The fact that the outmost intensity of secondary viremia of varicella occurs before the onset of exanthemia, that is, during the late incubation period, is confirmed.

  4. Alveolar bone grafting

    Directory of Open Access Journals (Sweden)

    Lilja Jan

    2009-10-01

    Full Text Available In patients with cleft lip and palate, bone grafting in the mixed dentition in the residual alveolar cleft has become a well-established procedure. The main advantages can be summarised as follows: stabilisation of the maxillary arch; facilitation of eruption of the canine and sometimes facilitation of the lateral incisor eruption; providing bony support to the teeth adjacent to the cleft; raising the alar base of the nose; facilitation of closure of an oro-nasal fistula; making it possible to insert a titanium fixture in the grafted site and to obtain favourable periodontal conditions of the teeth within and adjacent to the cleft. The timing of the ABG surgery take into consideration not only eruption of the canine but also that of the lateral incisor, if present. The best time for bone grafting surgery is when a thin shell of bone still covers the soon erupting lateral incisor or canine tooth close to the cleft.

  5. Arteriovenous shunt graft ulceration with sinus and graft epithelialization

    Directory of Open Access Journals (Sweden)

    Pooja Singhal

    2015-03-01

    Full Text Available Arteriovenous fistula and grafts are used as access sites for patients with chronic kidney disease and are prone for complications. Stent grafts are used to treat access site complications. We report a rare and unusual finding of epithelialization of the sinus tract and the lumen of a polytetrafluoroethylene graft, following ulceration of the overlying skin.

  6. Post-thaw viability of cryopreserved hematopoietic progenitor cell grafts: does it matter?

    Science.gov (United States)

    Vrhovac, Radovan; Perić, Zinaida; Jurenec, Silvana; Kardum-Skelin, Ika; Jelić-Puskarić, Biljana; Jaksić, Branimir

    2010-03-01

    Cell viability in peripheral blood progenitor cell (PBPC) grafts and its influence on the clinical course following transplantation was evaluated in 81 consecutive transplantations (72 autologous, 9 allogeneic) performed in patients with hematological diseases. Viability of cells in PBPC grafts immediately upon collection was 98.6 +/- 3.5%, after addition of dimethyl sulfoxide (DMSO) 73.3 +/- 21.8%, and post-thaw 65.2 +/- 16.1%. It did not differ significantly between patients with different diagnoses, gender, age, type of priming used, dose of G-CSF administered or number of CD34+ cells collected. However grafts stored for more than 60 days showed lower post-thaw viability compared to the ones thawed in the 60 days following cryopreservation (56.61 +/- 15.2% vs. 67.6 +/- 15.5%, p = 0.04). Post-thaw graft viability did not influence engraftment time, but there was a predisposition towards infectious complications in the post-transplant period in patients receiving grafts with lower percentage of viable cells. They developed febrile neutropenia more often (72.2% vs. 50% of patients, p = 0.05) and had more febrile days (2.4 +/- 2.6 vs. 1.5 +/- 2.3, p = 0.05) following transplantation. We have demonstrated that PBPC grafts are capable of long term engraftment regardless of the graft storage time or percentage of viable cells post-thaw, which confirms the robustness of CD34+ cells during the freeze/thaw procedures carried out in daily clinical practice. Granulocyte concentration in PBPC grafts could have an influence on infectious complications following transplantation and needs to be further investigated on a larger number of patients.

  7. Insights into the mechanism of FTY720 and compatibility with regulatory T cells for the inhibition of graft-versus-host disease (GVHD)

    OpenAIRE

    Taylor, Patricia A.; Ehrhardt, Michael J.; Lees, Christopher J.; Tolar, Jakub; Weigel, Brenda J; Panoskaltsis-Mortari, Angela; Serody, Jonathan S.; Brinkmann, Volker; Blazar, Bruce R.

    2007-01-01

    The immunomodulator FTY720 (FTY) has been shown to be beneficial in experimental models of organ transplantation and autoimmunity. We show that FTY significantly inhibited but did not prevent graft-versus-host disease (GVHD) in lethally irradiated or nonirradiated allogeneic recipients. Although most studies implicate prevention of lymphocyte egress from lymphoid organs as the primary mechanism of action, our data indicate that FTY effects on the host are more likely to be responsible for GVH...

  8. Sternal Repair with Bone Grafts Engineered from Amniotic Mesenchymal Stem Cells

    Science.gov (United States)

    Steigman, Shaun A.; Ahmed, Azra; Shanti, Rabie M.; Tuan, Rocky S.; Valim, Clarissa; Fauza, Dario O.

    2013-01-01

    Background We aimed at determining whether osseous grafts engineered from amniotic mesenchymal stem cells (aMSCs) could be employed in postnatal sternal repair. Methods Leporine aMSCs were isolated, identified, transfected with green fluorescent protein (GFP), expanded, and seeded onto biodegradable electrospun nanofibrous scaffolds (n=6). Constructs were dynamically maintained in an osteogenic medium and equally divided into two groups with respect to time in vitro, namely 14.6 or 33.9 weeks. They were then used to repair full thickness sternal defects spanning 2–3 intercostal spaces in allogeneic kits (n=6). Grafts were submitted to multiple analyses 2 months thereafter. Results Chest roentgenograms showed defect closure in all animals, confirmed at necropsy. Graft density as assessed by micro-CT scans increased significantly in vivo, yet there were no differences in mineralization by extracellular calcium measurements pre- and post-implantation. There was a borderline increase in alkaline phosphatase activity in vivo, suggesting ongoing graft remodeling. Histologically, implants contained GFP-positive cells and few mononuclear infiltrates. There were no differences between the two construct groups in any comparison. Conclusions Engineered osseous grafts derived from amniotic mesenchymal stem cells may become a viable alternative for sternal repair. The amniotic fluid can be a practical cell source for engineered chest wall reconstruction. PMID:19524727

  9. Assessing the Influence of Different Comorbidities Indexes on the Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in a Developing Country.

    Directory of Open Access Journals (Sweden)

    Gustavo Machado Teixeira

    Full Text Available Although the application of Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI has enabled better prediction of transplant-related mortality (TRM in allogeneic hematopoietic stem cell transplants (AHSCT, data from developing countries are scarce. This study prospectively evaluated the HCT-CI and the Adult Comorbidity Evaluation (ACE-27, in its original and in a modified version, as predictors of post-transplant complications in adults undergoing a first related or unrelated AHSCT in Brazil. Both bone marrow (BM and peripheral blood stem cells (PBSC as graft sources were included. We analyzed the cumulative incidence of granulocyte and platelet recovery, sinusoidal obstructive syndrome, acute and chronic graft-versus-host disease, relapse and transplant-related mortality, and rates of event-free survival and overall survival. Ninety-nine patients were assessed. Median age was 38 years (18-65 years; HCT-CI ≥ 3 accounted for only 8% of cases; hematologic malignancies comprised 75.8% of the indications for AHSCT. There was no association between the HCT-CI or the original or modified ACE-27 with TRM or any other studied outcomes after AHSCT. These results show that, in the population studied, none of the comorbidity indexes seem to be associated with AHSCT outcomes. A significantly low frequency of high-risk (HCT-CI ≥ 3 in this Brazilian population might justify these results.

  10. Primary renal graft thrombosis

    NARCIS (Netherlands)

    Bakir, N; Sluiter, WJ; Ploeg, RJ; van Son, WJ; Tegzess, Adam

    1996-01-01

    Background. Renal allograft thrombosis is a serious complication of kidney transplantation that ultimately leads to graft loss. Its association with acute and hyperacute rejection is well documented; however, in a large proportion of patients the precise cause remains obscure. The exact incidence an

  11. Ready-made allogeneic ABO-specific serum eye drops

    DEFF Research Database (Denmark)

    Harritshøj, Lene Holm; Nielsen, Connie; Ullum, Henrik

    2014-01-01

    , registered and stored at -30°C in the blood bank. Upon request, frozen ABO-identical serum drops in lots of 14 bottles could be provided immediately. Safety and efficacy were evaluated in 34 patients with severe ocular surface disease refractory to conventional medical therapy. Patients were treated six...... serum treatment. CONCLUSION: Ready-made ABO-identical allogeneic serum eye drops were straightforwardly produced, quality-assured and registered as a safe standard blood product for the treatment of certain cases of severe dry eye disease. Therapeutic efficacy was comparable to previous reports......PURPOSE: To overcome problems and delays of the preparation of autologous serum eye drops, a production line of ABO-specific allogeneic serum eye drops from male blood donors was set up in a blood bank. Feasibility, clinical routine, safety and efficacy were evaluated in a cohort of patients...

  12. Leukemia in donor cells after allogeneic hematopoietic stem cell transplant

    OpenAIRE

    2002-01-01

    The development of leukemia in donor cells after allogeneic hematopoietic stem cell transplant is an extremely rare event. We report here the case of a patient who developed myelodysplastic syndrome/acute myeloid leukemia, in cells of donor origin 3.5 years after related donor HSCT for refractory chronic lymphocytic leukemia and therapy-induced myelodysplastic syndrome. The origin of the leukemia was determined by analysis of minisatillite polymorphism tested on CD34(+) cells.

  13. Financial burden in recipients of allogeneic hematopoietic cell transplantation.

    Science.gov (United States)

    Khera, Nandita; Chang, Yu-hui; Hashmi, Shahrukh; Slack, James; Beebe, Timothy; Roy, Vivek; Noel, Pierre; Fauble, Veena; Sproat, Lisa; Tilburt, Jon; Leis, Jose F; Mikhael, Joseph

    2014-09-01

    Although allogeneic hematopoietic cell transplantation (HCT) is an expensive treatment for hematological disorders, little is known about the financial consequences for the patients who undergo this procedure. We analyzed factors associated with its financial burden and its impact on health behaviors of allogeneic HCT recipients. A questionnaire was retrospectively mailed to 482 patients who underwent allogeneic HCT from January 2006 to June 2012 at the Mayo Clinic, to collect information regarding current financial concerns, household income, employment, insurance, out-of-pocket expenses, and health and functional status. A multivariable logistic regression analysis identified factors associated with financial burden and treatment nonadherence. Of the 268 respondents (56% response rate), 73% reported that their sickness had hurt them financially. All patients for whom the insurance information was available (missing, n = 13) were insured. Forty-seven percent of respondents experienced financial burden, such as household income decreased by >50%, selling/mortgaging home, or withdrawing money from retirement accounts. Three percent declared bankruptcy. Younger age and poor current mental and physical functioning increased the likelihood of financial burden. Thirty-five percent of patients reported deleterious health behaviors because of financial constraints. These patients were likely to be younger, have lower education, and with a longer time since HCT. Being employed decreased the likelihood of experiencing financial burden and treatment nonadherence due to concern about costs. A significant proportion of allogeneic HCT survivors experience financial hardship despite insurance coverage. Future research should investigate potential interventions to help at-risk patients and prevent adverse financial outcomes after this life-saving procedure. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  14. The role of dendritic cells in graft-versus-tumor effect

    Directory of Open Access Journals (Sweden)

    Pavan eReddy

    2014-02-01

    Full Text Available Dendritic cells (DCs are the most potent antigen presenting cells (APCs. DCs play a pivotal role in determining the character and magnitude of immune responses to tumors. Host and donor hematopoietic derived DCs play a critical role in the development of graft-versus host disease (GVHD following allogeneic hematopoietic cell transplantation (allo-HCT. GVHD is tightly linked with the graft-versus-tumor (GVT effect. Although both host and donor DCs are important regulators of GVHD, the role of DCs in GVT is poorly understood. GVT is caused by donor T cells that attack recipient tumor cells. The donor T cells recognize alloantigens and tumor specific antigens (TSAs are mediating GVHD. The process of presentation of these antigens, especially TSAs remains unknown. Recent data suggested that DC may be essential role for inducing GVT. The mechanisms that DCs possess may include direct presentation, cross-presentation, cross-dressing. . The role they play in GVT will be reviewed.

  15. Inverse modeling approach to allogenic karst system characterization.

    Science.gov (United States)

    Dörfliger, N; Fleury, P; Ladouche, B

    2009-01-01

    Allogenic karst systems function in a particular way that is influenced by the type of water infiltrating through river water losses, by karstification processes, and by water quality. Management of this system requires a good knowledge of its structure and functioning, for which a new methodology based on an inverse modeling approach appears to be well suited. This approach requires both spring and river inflow discharge measurements and a continuous record of chemical parameters in the river and at the spring. The inverse model calculates unit hydrographs and the impulse responses of fluxes from rainfall hydraulic head at the spring or rainfall flux data, the purpose of which is hydrograph separation. Hydrograph reconstruction is done using rainfall and river inflow data as model input and enables definition at each time step of the ratio of each component. Using chemical data, representing event and pre-event water, as input, it is possible to determine the origin of spring water (either fast flow through the epikarstic zone or slow flow through the saturated zone). This study made it possible to improve a conceptual model of allogenic karst system functioning. The methodology is used to study the Bas-Agly and the Cent Font karst systems, two allogenic karst systems in Southern France.

  16. Altered Allogeneic Immune Responses in Middle-Aged Mice

    Institute of Scientific and Technical Information of China (English)

    Yimin Sun; Hanhan Li; Alan N. Langnas; Yong Zhao

    2004-01-01

    It is well known that leukocyte composition, T cell phenotypes and immune function change in aged mice and humans. However, limited and conflicting results on the age-related immune changes in middle-aged mice were reported. Identification of the characteristics of allogeneic immune responses in aging mice may offer important information for transplantation immunology. The major age-related changes in the immune cell phenotypes and function of 12 months old mice include: 1) the significantly decreased CD4+ cell population in the peripheral blood, the major peripheral CD4+ cells is CD45RBlowCD62Llow memory phenotype; 2) the in vitro responses to alloantigens and Con A of splenocytes markedly reduced; 3) the in vivo secondary humoral immune responses to alloantigens significantly declined; 4) the age-related alteration in the thymus mainly occurred in CD4/CD8 double positive (DP) stage; and 5) increased CD80+ and MHC class Ⅱ+ cell population in spleens. Thus, the major age-related immune changes in 12 months old mice occurred in CD4+ T cells in the periphery and DP stage in the thymus, which may subsequently lead to the decreased allogeneic immune responses and the different sensitivity to immunosuppressive drugs and treatments. Further studies on the characteristics of allogeneic immunity in aging individuals may help to determine the appropriated treatment for transplant aging individuals. Cellular & Molecular Immunology. 2004; 1(6) :440-446.

  17. Repair of osteochondral defects with allogeneic tissue engineered cartilage implants.

    Science.gov (United States)

    Schreiber, R E; Ilten-Kirby, B M; Dunkelman, N S; Symons, K T; Rekettye, L M; Willoughby, J; Ratcliffe, A

    1999-10-01

    The objective of this study was to evaluate the effect of allogeneic tissue engineered cartilage implants on healing of osteochondral defects. Rabbit chondrocytes were cultured in monolayer, then seeded onto biodegradable, three-dimensional polyglycolic acid meshes. Cartilage constructs were cultured hydrodynamically to yield tissue with relatively more (mature) or less (immature) hyalinelike cartilage, as compared with adult rabbit articular cartilage. Osteochondral defects in the patellar grooves of both stifle joints either were left untreated or implanted with allogeneic tissue engineered cartilage. Histologic samples from in and around the defect sites were examined 3, 6, 9, and 12, and 24 months after surgery. By 9 months after surgery, defects sites treated with cartilage implants contained significantly greater amounts of hyalinelike cartilage with high levels of proteoglycan, and had a smooth, nonfibrillated articular surface as compared to untreated defects. In contrast, the repair tissue formed in untreated defects had fibrillated articular surfaces, significant amounts of fibrocartilage, and negligible proteoglycan. These differences between treated and untreated defects persisted through 24 months after surgery. The results of this study suggest that the treatment of osteochondral lesions with allogenic tissue engineered cartilage implants may lead to superior repair tissue than that found in untreated osteochondral lesions.

  18. Allogeneic leukocytes in cardiac surgery: Good or bad?

    Directory of Open Access Journals (Sweden)

    Anneke Brand

    2011-09-01

    Full Text Available Worldwide, cardiac surgery is a common procedure requiring a large quantity of allogeneic blood products, which are associated with postoperative complications. Leukocytes present in blood products may play a role in these complications, which are referred to as transfusion-related immunomodulation (TRIM. Several randomized controlled trials (RCTs in different settings investigated the effects of allogeneic leukocytes in red blood cells (RBCs. Cardiac surgery studies reported a reduction in postoperative infections and mortality in patients that received leukocyte-reduced RBCs compared with leukocyte-containing RBCs; this was mainly due to more deaths due to infections and multiple organ dysfunction syndrome (MODS in the group that received leukocyte-containing RBCs. Patients with postoperative complications had higher concentrations of inflammatory mediators. These findings suggest that leukocyte-containing transfusion during cardiac surgery induces a second insult to the systemic inflammatory response. In the present review we discuss the possible role of blood transfusions in cardiac surgery. Especially, we focus on the possible role of allogeneic leukocytes associated with postoperative complications after cardiac surgery.

  19. Altered Allogeneic Immune Responses in Middle-Aged Mice

    Institute of Scientific and Technical Information of China (English)

    YiminSun; HanhanLi; AlanN.Langnas

    2004-01-01

    It is well known that leukocyte composition, T cell phenotypes and immune function change in aged mice and humans. However, limited and conflicting results on the age-related immune changes in middle-aged mice were reported. Identification of the characteristics of allogeneic immune responses in aging mice may offer important information for transplantation immunology. The major age-related changes in the immune cell phenotypes and function of 12 months old mice include: 1) the significantly decreased CD4+ cell population in the peripheral blood, the major peripheral CD4+ cells is CD45RBlowCD62Llow memory phenotype; 2) the in vitro responses to alloantigens and Con A of splenocytes markedly reduced; 3) the in vivo secondary humoral immune responses to alloantigens significantly declined; 4) the age-related alteration in the thymus mainly occurred in CD4/CD8 double positive (DP) stage; and 5) increased CD80+ and MHC class II+ cell population in spleens. Thus, the major age-related immune changes in 12 months old mice occurred in CD4+ T cells in the periphery and DP stage in the thymus, which may subsequently lead to the decreased allogeneic immune responses and the different sensitivity to immunosuppressive drugs and treatments. Further studies on the characteristics of allogeneic immunity in aging individuals may help to determine the appropriated treatment for transplant aging individuals. Cellular & Molecular Immunology. 2004;1(6):440-446.

  20. Allogeneic Mesenchymal Stem Cell Treatment Induces Specific Alloantibodies in Horses

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    Sean D. Owens

    2016-01-01

    Full Text Available Background. It is unknown whether horses that receive allogeneic mesenchymal stem cells (MSCs injections develop specific humoral immune response. Our goal was to develop and validate a flow cytometric MSC crossmatch procedure and to determine if horses that received allogeneic MSCs in a clinical setting developed measurable antibodies following MSC administration. Methods. Serum was collected from a total of 19 horses enrolled in 3 different research projects. Horses in the 3 studies all received unmatched allogeneic MSCs. Bone marrow (BM or adipose tissue derived MSCs (ad-MSCs were administered via intravenous, intra-arterial, intratendon, or intraocular routes. Anti-MSCs and anti-bovine serum albumin antibodies were detected via flow cytometry and ELISA, respectively. Results. Overall, anti-MSC antibodies were detected in 37% of the horses. The majority of horses (89% were positive for anti-bovine serum albumin (BSA antibodies prior to and after MSC injection. Finally, there was no correlation between the amount of anti-BSA antibody and the development of anti-MSC antibodies. Conclusion. Anti allo-MSC antibody development was common; however, the significance of these antibodies is unknown. There was no correlation between either the presence or absence of antibodies and the percent antibody binding to MSCs and any adverse reaction to a MSC injection.

  1. [Grafting of carotid arteries].

    Science.gov (United States)

    Belov, Iu V; Stepanenko, A B; Gens, A P; Bazylev, V V; Seleznev, M N; Savichev, D D

    2005-01-01

    Over 5-years, 167 reconstructive surgeries for stenosis of internal carotid arteries (ICA) were performed in 124 patients. Mean age of the patients was 63.5 years. One hundred and twenty-nine carotid endarterectomies (CEAE) in 86 patients and 38 reconstructive operations of ICA in 38 patients were performed. There were no lethal outcomes in short- and long-term postoperative period. In short-term period after prosthesis of ICA restenosis was revealed in 3% patients, after eversion CEAE in 3% patients the embolism was seen, after standard CEAE restenosis were diagnosed in 8% patients and thrombosis -- in 3%. In long-term period after grafting of ICA the strokes were seen in 3%, stenosis -- in 6% patients, after eversion endarterectomy -- in 0 and 3% patients, and after standard CEAE -- in 3 and 24% patients, respectively. It is concluded that grafting of ICA is adequate surgical method of reconstruction and stroke prevention in specific variants of carotid atherosclerosis.

  2. Buccal Mucosal Graft Urethroplasty

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    Angela M. Arlen

    2010-01-01

    Full Text Available At our institution, the majority of buccal mucosal graft urethroplasties are performed using a two-team approach with an otolaryngologic surgeon. We report our two-surgeon experience with buccal mucosal grafting for reconstruction of all anterior urethral strictures. Twenty-four men underwent autologous buccal mucosal graft urethroplasty between October 2001 and September 2008 for recurrent urethral stricture disease. Twenty-two underwent a single-stage repair and two underwent a two-stage repair. Medical charts were retrospectively reviewed for demographics, comorbidities, etiology, location and length of stricture, and prior interventions in order to identify predictors of buccal urethroplasty success, defined as no evidence of stricture recurrence. All patients underwent retrograde urethrogram and cystoscopy. Operative and anesthesia times were evaluated. We determined an overall success rate of 83.3% (20 of 24 cases. Mean anesthesia time for single-stage urethroplasty was 155 min and mean operative time was 123 min. One of the two two-stage urethroplasties experienced stricture recurrence (50%. The single-stage buccal graft success rate was 86.4% (19 of 22 cases. Two of the four who developed recurrent stricture disease that required intervention had undergone a previous mesh urethroplasty. Complications developed in four of 24 patients (16.6%, including superficial wound infection (one, superficial wound dehiscence (two, and abscess/fistula formation requiring reoperation (one. The buccal mucosa is an ideal tissue for both single- and two-stage substitution urethroplasty for patients with recurrent stricture disease. Our two-surgeon technique minimizes anesthesia and operative times, and contributes to the overall high success rate and relatively low complication rate.

  3. Impact of stem cell source on allogeneic stem cell transplantation outcome in hematological malignancies

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    Stamatović Dragana

    2011-01-01

    Full Text Available Background/Aim. Peripheral blood (PB is used more frequently as a source of stem cells (SCs for allogeneic transplantation. However, the influence of cell source on the clinical outcome of SC transplantation is not yet well established. The aim of this study was to compare the results of PBSC transplantation (PBSCT with bone marrow transplantation (BMT on the basis of engraftment, frequency and severity of immediate (mucositis, acute Graft versus Host Disease - aGvHD and delayed (chronic GvHD - cGvHD complications, as well as transplant-related mortality (TRM, transfusion needs, relapses and overall survival (OS. Methods. We analyzed 158 patients, women/men ratio 64/94 median age 29 (range 9-57, who underwent allogeneic SC transplantation between 1989 and 2009. All included patients had diseases as follows: acute myeloid leukemia (AML - 39, acute lymphoblastic leukemia (ALL - 47, chronic myeloid leukemia (CML - 32, myelodysplastic syndrome (MDS - 10, Hodgkin’s lymphoma (HL - 2, multiple myeloma (MM - 3, granulocytic sarcoma (GrSa - 3, severe aplastic anemia (sAA - 22. The patients underwent transplantations were divided into two groups: BMT group (74 patients and PBSCT group (84 patients. Each recipient had HLA identical sibling donor. SCs from bone marrow were collected by multiple aspirations of iliac bone and from PB by one “Large Volume Leukapheresis” (after recombinant human granulocyte colony stimulating factor, rHuG-CSF application (5-12 μg/kgbm, 5 days. Conditioning regimens were applied according to primary disease, GvHD prophylaxis consisted of combination of a cyclosporine A and methotrexate. Results. Engraftment, according to the count of polymorphonuclear and platelets, were significantly (p < 0.001 faster in the PBSCT vs BMT group. The needs for transfusion support were significantly (p < 0.01 higher in the BMT group. Those patients had more frequently oropharingeal mucositis grade 3/4 (33.3% vs 10.0%, p < 0.05. There were

  4. IL-35 mitigates murine acute graft-versus-host disease with retention of graft-versus-leukemia effects.

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    Liu, Y; Wu, Y; Wang, Y; Cai, Y; Hu, B; Bao, G; Fang, H; Zhao, L; Ma, S; Cheng, Q; Song, Y; Liu, Y; Zhu, Z; Chang, H; Yu, X; Sun, A; Zhang, Y; Vignali, D A A; Wu, D; Liu, H

    2015-04-01

    IL-35 is a newly discovered inhibitory cytokine secreted by regulatory T cells (Tregs) and may have therapeutic potential in several inflammatory disorders. Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation and caused by donor T cells and inflammatory cytokines. The role of IL-35 in aGVHD is still unknown. Here we demonstrate that IL-35 overexpression suppresses CD4(+) effector T-cell activation, leading to a reduction in alloreactive T-cell responses and aGVHD severity. It also leads to the expansion of CD4(+)Foxp3(+) Tregs in the aGVHD target organs. Furthermore, IL-35 overexpression results in a selective decrease in the frequency of Th1 cells and an increase of IL-10-producing CD4(+) T cells in aGVHD target tissues. Serum levels of TNF-α, IFN-γ, IL-6, IL-22 and IL-23 decrease and IL-10 increases in response to IL-35. Most importantly, IL-35 preserves graft-versus-leukemia effect. Finally, aGVHD grade 2-4 patients have decreased serum IL-35 levels comparing with time-matched patients with aGVHD grade 0-1. Our findings indicate that IL-35 has an important role in reducing aGVHD through promoting the expansion of Tregs and repressing Th1 responses, and should be investigated as the therapeutic strategy for aGVHD.

  5. Single-centre experience of allogeneic haemopoietic stem cell transplant in paediatric patients in Cape Town, South Africa

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    A van Eyssen

    2017-03-01

    Full Text Available Background. Allogeneic haemopoietic stem cell transplant (Allo-HSCT is a specialised and costly intervention, associated with significant morbidity and mortality. It is used to treat a broad range of paediatric conditions. South Africa (SA is an upper middle-income country with limitations on healthcare spending. The role of paediatric Allo-HSCT in this setting is reviewed. Objectives. To review paediatric patients who underwent Allo-HSCT at the Groote Schuur Hospital/University of Cape Town Private Academic Hospital transplant unit in Cape Town, South Africa, and received post-transplant care at Red Cross War Memorial Children’s Hospital, over the period January 2006 - December 2014 in respect of indications for the transplant, donor sources, conditioning regimens, treatment-related morbidity and overall survival (OS. Methods. A retrospective analysis of patient records was performed and a database was created in Microsoft Access. Descriptive analyses of relevant demographic, clinical and laboratory data were performed. Summary statistics of demographic and clinical parameters were derived with Excel. OS was calculated from the date of transplant to the date of an event (death or last follow-up using the Kaplan-Meier method in Statistica. Results. A total of 48 children received Allo-HSCT: 24 for haematological malignancies, 20 for non-oncological haematological conditions, 3 for immune disorders and 1 for adrenoleukodystrophy. There were 28 boys (median age 7.5 years and 20 girls (8.5 years. There were 31 sibling matched peripheral-blood stem cell (PBSC transplants and 1 maternal haploidentical PBSC transplant. Stem cells were mobilised from bone marrow into peripheral blood by administering granulocyte-colony stimulating factor to donors. PBSCs were harvested by apheresis. Eight patients received 10/10 HLA-matched grafts from unrelated donors. Six were PBSC grafts and 2 were bone marrow grafts. Three of the unrelated PBSC grafts were from

  6. Phase IV open-label study of the efficacy and safety of deferasirox after allogeneic stem cell transplantation.

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    Vallejo, Carlos; Batlle, Montserrat; Vázquez, Lourdes; Solano, Carlos; Sampol, Antonia; Duarte, Rafael; Hernández, Dolores; López, Javier; Rovira, Montserrat; Jiménez, Santiago; Valcárcel, David; Belloch, Vicente; Jiménez, Mónica; Jarque, Isidro

    2014-10-01

    This is the first prospective study of deferasirox in adult allogeneic hematopoietic stem cell transplant recipients with transfusional iron overload in hematologic malignancies. Patients at least six months post transplant were treated with deferasirox at a starting dose of 10 mg/kg/day for 52 weeks or until serum ferritin was less than 400 ng/mL on two consecutive occasions. Thirty patients were enrolled and 22 completed the study. A significant reduction from baseline in median serum ferritin and in liver iron concentration at 52 weeks was observed in the overall population: from 1440 to 755.5 ng/mL (P=0.002) and from 14.5 to 4.6 mg Fe/g dw (P=0.0007), respectively. Reduction in serum ferritin in patients who did not discontinue deferasirox therapy was significantly greater than that found in those who prematurely discontinued the treatment (from 1541 to 581 ng/mL vs. from 1416 to 1486 ng/mL; P=0.008). Drug-related adverse events, reported in 17 patients (56.7%), were mostly mild to moderate in severity. There were no drug-related serious adverse events. Twelve patients (40.0%) showed an increase of over 33% in serum creatinine compared to baseline and greater than the upper limit of normal on two consecutive visits. Two patients (6.7%) with active graft-versus-host disease showed an increase in alanine aminotransferase exceeding 10 times upper limit of normal; both resolved. In this prospective study, deferasirox provided a significant reduction in serum ferritin and liver iron concentration over one year of treatment in allogeneic hematopoietic stem cell transplant recipients with iron overload. In addition, the majority of adverse events related to deferasirox were mild or moderate in severity. (clinicaltrials.gov identifier:01335035).

  7. Recombinant IL-7/HGFβ hybrid cytokine enhances T cell recovery in mice following allogeneic bone marrow transplantation.

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    Laijun Lai

    Full Text Available T cell immunodeficiency is a major complication of bone marrow (BM transplantation (BMT. Therefore, approaches to enhance T cell reconstitution after BMT are required. We have purified a hybrid cytokine, consisting of IL-7 and the β-chain of hepatocyte growth factor (HGFβ (IL-7/HGFβ, from a unique long-term BM culture system. We have cloned and expressed the IL-7/HGFβ gene in which the IL-7 and HGFβ genes are connected by a flexible linker to generate rIL-7/HGFβ protein. Here, we show that rIL-7/HGFβ treatment enhances thymopoiesis after allogeneic BMT. Although rIL-7 treatment also enhances the number of thymocytes, rIL-7/HGFβ hybrid cytokine was more effective than was rIL-7 and the mechanisms by which rIL-7 and rIL-7/HGFβ increase the numbers of thymocytes are different. rIL-7 enhances the survival of double negative (DN, CD4 and CD8 single positive (SP thymocytes. In contrast, rIL-7/HGFβ enhances the proliferation of the DN, SP thymocytes, as well as the survival of CD4 and CD8 double positive (DP thymocytes. rIL-7/HGFβ treatment also increases the numbers of early thymocyte progenitors (ETPs and thymic epithelial cells (TECs. The enhanced thymic reconstitution in the rIL-7/HGFβ-treated allogeneic BMT recipients results in increased number and functional activities of peripheral T cells. Graft-versus-host-disease (GVHD is not induced in the rIL-7/HGFβ-treated BMT mice. Therefore, rIL-7/HGFβ may offer a new tool for the prevention and/or treatment of T cell immunodeficiency following BMT.

  8. Outcome of allogeneic hematopoietic stem cell transplantation for childhood acute lymphoblastic leukemia in second complete remission: a single institution study

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    Eun-Jung Lee

    2012-03-01

    Full Text Available Purpose : The survival rate for childhood acute lymphoblastic leukemia (ALL has improved significantly. However, overall prognosis for the 20 to 25% of patients who relapse is poor, and allogeneic hematopoietic stem cell transplantation (HSCT offers the best chance for cure. In this study, we identified significant prognostic variables by analyzing the outcomes of allogeneic HSCT in ALL patients in second complete remission (CR. Methods : Fifty-three ALL patients (42 men, 79% who received HSCT in second CR from August 1991 to February 2009 were included (26 sibling donor HSCTs, 49%; 42 bone marrow transplantations, 79%. Study endpoints included cumulative incidence of acute and chronic graft-versus-host disease (GVHD, relapse, 1-year transplant-related mortality (TRM, disease-free survival (DFS, and overall survival (OS. Results : Cumulative incidences of acute GVHD (grade 2 or above and chronic GVHD were 45.3% and 28.5%, respectively. The estimated 5-year DFS and OS for the cohort was 45.2¡?#?.8%; and 48.3¡?#?%,; respectively. Only donor type, i.e., sibling versus unrelated, showed significant correlation with DFS in multivariate analysis (P=0.010. The rates of relapse and 1 year TRM were 28.9¡?#?.4%; and 26.4¡?#?.1%;, respectively, and unrelated donor HSCT (P=0.002 and HLA mismatch (P =0.022 were significantly correlated with increased TRM in univariate analysis. Conclusion : In this single institution study spanning more than 17 years, sibling donor HSCT was the only factor predicting a favorable result in multivariate analysis, possibly due to increased TRM resulting from unrelated donor HSCT.

  9. Allogeneic mesenchymal precursor cells (MPCs) combined with an osteoconductive scaffold to promote lumbar interbody spine fusion in an ovine model.

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    Wheeler, Donna L; Fredericks, Douglas C; Dryer, Randall F; Bae, Hyun W

    2016-03-01

    MPC- and AG-treated groups. Approximately 6% residual graft material remained in the MPC-treated fusion sites at 16 weeks. Adult allogeneic MPCs delivered using an osteoconductive scaffold were both safe and efficacious in this ovine spine interbody fusion model. These results support the use ofallogeneic MPCs as an alternative to AG for lumbar interbody spinal fusion procedures. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Combination of CTLA4-FasL gene transfer and allogeneic bone marrow transplantation led to durable macrochimerism and donor-specific tolerance in mouse model

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    FENG Yougang; WANG Guangming; HAO Jie; LI Ailing; YUAN Guohong; LI Chong; ZENG Fuqing; XIE Shusheng

    2005-01-01

    Mixed hemopoietic chimerism is capable of inducing donor specific tolerance, thus eliminating the chronic immunosuppressive therapy following organ transplantation. As yet no safe and effective tolerance protocol is available for clinical implementation. Here we describe an alternative nonmyeloablative based strategy of using a single injection of recombination adenovirus vector encoding CTLA4-FasL fusing gene and donor bone marrow cells to promote durable mixed macrochimerism (>20% on 140 d). Chimeras exhibited robust donor-specific tolerance, as evidenced by acceptance of fully allogeneic skin grafts (the mean survival time (MST)>200 d) and rejection of third- party skin grafts in a normal manner (MST<10 d). In this model, the frequencies of helper T lymphocyte precursor (HTLp) and cytotoxic T lymphocyte precursor (CTLp) were greatly reduced on day 14 after transplantation, suggesting that CTLA4-FasL led to rapid systemic peripheral tolerance to facilitate the bone marrow engraftment, while both HTLp and CTLp remained at low level only in recipient mice with mixed chimerism on day 140 after transplantation, demonstrating that long-term skin grafts tolerance was associated with stable mixed chimerism, and central deletion of donor specific T cell may be the main mechanism for tolerance maintenance.

  11. Clinicopathological analysis of allogeneic hematopoietic stem cell transplantation-related membranous glomerulonephritis.

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    Hiramatsu, Rikako; Ubara, Yoshifumi; Sawa, Naoki; Hasegawa, Eiko; Kawada, Masahiro; Imafuku, Aya; Sumida, Keiichi; Mise, Koki; Yamanouchi, Masayuki; Ueno, Toshiharu; Sekine, Akinari; Hayami, Noriko; Suwabe, Tatsuya; Hoshino, Junichi; Takaichi, Kenmei; Ohashi, Kenichi; Fujii, Takeshi; Wake, Atsushi; Taniguchi, Shuichi

    2016-04-01

    Allogeneic hematopoietic stem cell transplantation (HSCT)-related membranous glomerulonephritis (MGN) is poorly understood. A total of 830 patients who underwent HSCT at Toranomon Hospital from 2000 to 2012 were evaluated retrospectively, including 621 patients receiving umbilical cord blood transplantation (UCBT) and 208 patients receiving unrelated bone marrow transplantation. MGN was diagnosed in 5 patients after UCBT (versus none after bone marrow transplantation) and occurred concomitantly with chronic graft-versus-host disease after cessation of immunosuppression. Light microscopy did not show any definite spikes or bubbling of the glomerular basement membrane (GBM) in all 5 patients. In 1 patient (case 5), endocapillary proliferative lesions with fibrin-like deposits were noted in addition to MGN findings. Immunofluorescence demonstrated granular deposits of immunoglobulin G (IgG; IgG1 and IgG4) along the GBM with negativity for C3, C4, and C1q in 4 patients (cases 1-4), whereas case 5 showed positivity for IgG (IgG1, IgG2, IgG3, and IgG4) as well as for C3, C4, and C1q. Electron microscopy revealed electron-dense deposits in the subepithelial space of the GBM in cases 1-4. In case 5, electron-dense deposits were present in the mesangium and the subendothelial space of the GBM, as well as in the subepithelial space. After treatment with immunosuppressants (prednisolone and/or cyclosporin) or angiotensin-converting enzyme inhibitors, complete remission with disappearance of proteinuria was achieved 12.2 months in all 5 patients, but nephrotic-range proteinuria relapsed in 2 patients during follow-up. Serum anti-PLA2R autoantibody was negative in 3 patients. HSCT-related MGN only occurred after UCBT. We believe that there were 2 morphologic patterns: early MGN and membranoproliferative pattern glomerulonephritis.

  12. Allogeneic haematopoietic stem cell transplantation as a promising treatment for natural killer-cell neoplasms.

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    Murashige, Naoko; Kami, Masahiro; Kishi, Yukiko; Kim, Sung-Won; Takeuchi, Masami; Matsue, Kosei; Kanda, Yoshinobu; Hirokawa, Makoto; Kawabata, Yoshinari; Matsumura, Tomoko; Kusumi, Eiji; Hirabayashi, Noriyuki; Nagafuji, Koji; Suzuki, Ritsuro; Takeuchi, Kengo; Oshimi, Kazuo

    2005-08-01

    The efficacy of allogeneic haematopoietic stem-cell transplantation (allo-HSCT) for natural killer (NK)-cell neoplasms is unknown. We investigated the results of allo-HSCT for NK-cell neoplasms between 1990 and 2003 through questionnaires. After reclassification by a haematopathologist, of 345 patients who underwent allo-HSCT for malignant lymphoma, 28 had NK-cell neoplasms (World Health Organization classification): extranodal NK/T-cell lymphoma (n=22), blastic NK-cell lymphoma (n=3), and aggressive NK-cell leukaemia (n=3). Twelve were chemosensitive and 16 chemorefractory. Twenty-two had matched-related donors. Stem-cell source was bone marrow in eight and mobilised peripheral blood in 20. Conditioning regimens were myeloablative (n=23) and non-myeloablative (n=5). Grade 2-4 acute graft-versus-host disease (GVHD) and chronic GVHD developed in 12 and 8 respectively. Eight died of disease progression, three of infection, two of acute GVHD, one of veno-occlusive disease, one of interstitial pneumonitis, and one of thrombotic microangiopathy. Two-year progression-free and overall survivals were 34% and 40% respectively (median follow-up, 34 months). All patients who did not relapse/progress within 10 months achieved progression-free survival (PFS) during the follow-up. In multivariate analysis, stem cell source (BM versus peripheral blood; relative risk 3.03), age (>or=40 years vs. <40 years; relative risk 2.85), and diagnoses (extranodal NK/T-cell lymphoma versus others; relative risk 3.94) significantly affected PFS. Allo-HSCT is a promising treatment for NK-cell neoplasms.

  13. Safety of posaconazole and sirolimus coadministration in allogeneic hematopoietic stem cell transplants.

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    Kubiak, David W; Koo, Sophia; Hammond, Sarah P; Armand, Philippe; Baden, Lindsey R; Antin, Joseph H; Marty, Francisco M

    2012-09-01

    Sirolimus is used in allogeneic hematopoietic stem cell transplants (HSCTs) for prevention and treatment of graft-versus-host disease (GVHD). Posaconazole is used in this population for invasive fungal disease (IFD) prophylaxis and treatment. As posaconazole strongly inhibits CYP3A4, concurrent administration of sirolimus, a CYP3A4 substrate, and posaconazole has been reported to increase sirolimus drug exposure substantially. Coadministration of posaconazole and sirolimus is contraindicated by the manufacturer of posaconazole. We identified 15 patients who underwent HSCTs at our institution receiving a steady-state dose of sirolimus who subsequently started posaconazole therapy from January 2006 to March 2009. We recorded baseline characteristics, drug administration details, and potential adverse effects related to either drug. All patients underwent HSCTs for treatment of hematologic malignancy. All patients were initially prescribed sirolimus for GVHD prophylaxis and continued therapy after developing GVHD. Twelve patients (80%) received posaconazole for IFD prophylaxis in the setting of GVHD and 3 (20%) for IFD treatment. Patients received sirolimus and posaconazole concurrently for a median of 78 days (interquartile range [IQR] 25-177; range, 6-503). The median daily dose of sirolimus (2 mg/day) before initiation of posaconazole was reduced 50% to a median daily dose of 1 mg/day at steady state. Six patients experienced sirolimus trough levels greater than 12 ng/mL during coadministration, but only 1 patient experienced an adverse event potentially associated with sirolimus exposure during the first month of coadministration. This patient's sirolimus dose was empirically reduced by only 30% on posaconazole initiation. Concurrent sirolimus and posaconazole use seems to be well tolerated with a 33% to 50% empiric sirolimus dose reduction and close monitoring of serum sirolimus trough levels at the time of posaconazole initiation.

  14. Allogeneic hematopoietic cell transplantation for acute myeloid leukemia in older adults.

    Science.gov (United States)

    Sorror, Mohamed L; Estey, Elihu

    2014-12-01

    Acute myeloid leukemia (AML) is primarily a disease of the elderly and the numbers of these patients are increasing. Patients ≥60 years of age continue to have poor prognosis. Preliminary results suggest benefit from reduced-intensity allogeneic hematopoietic cell transplantation (HCT) in selected patients 60-80 years of age. However, although patients in this age range comprise >50% of those with AML, they currently constitute only 17% of those offered HCT. In the absence of prospective randomized studies comparing HCT and chemotherapy, the decision to recommend HCT rests on retrospective analyses of the risks of relapse and nonrelapse mortality after each approach. There is strong evidence that pre-HCT comorbidities can predict HCT-related morbidity and mortality. Age alone does not appear predictive and, particularly if the risk of relapse with chemotherapy is high, should not be the sole basis for deciding against HCT. Use of geriatric assessment tools, inflammatory biomarkers, and genetic polymorphism data may further aid in predicting nonrelapse mortality after HCT. Disease status and pretreatment cytogenetics with FLT3-TID, NPM-1, and CEBP-α status are the main factors predicting relapse and these are likely to be supplemented by incorporation of other molecular markers and the level of minimal residual disease after chemotherapy. HLA-matched related and unrelated donor grafts seem preferable to those from other donor sources. Donor age is of no clear significance. Models combining comorbidities with AML risk factors are useful in risk assessment before HCT. In this chapter, we integrated information on AML-specific, HCT-specific, and patient-specific risk factors into a risk-adapted approach to guide decisions about HCT versus no HCT.

  15. Clinical and serological characterization of autoimmune hemolytic anemia after allogeneic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Yang Zhen; Wu Bangzhao; Zhou Youning; Wang Wenjuan; Chen Suning; Sun Aining; Wu Depei

    2014-01-01

    Background Autoimmune hemolytic anemia (AIHA) is an uncommon complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) which has only been reported in a few cases.We here aimed to explore its mechanism.Methods We retrospectively analyzed 296 patients who underwent allo-HSCT in our center from July 2010 to July 2012.Clinical manifestations were carefully reviewed and the response to currently available treatment approaches were evaluated.The survival and risk factors of AIHA patients after allo-HSCT were further analyzed.Results Twelve patients were diagnosed with AIHA at a median time of 100 days (15-720 days) after allo-HSCT.The incidence of AIHA after allo-HSCT was 4.1%.IgG antibody were detected in ten patients and IgM antibody in two patients.The two cold antibody AIHA patients had a better response to steroid corticoid only treatment and the ten warm antibody AIHA patients responded to corticosteroid treatment and adjustment of immunosuppressant therapy.Rituximab was shown to be effective for AIHA patients who failed conventional therapy.Survival analysis showed that the combination of AIHA in allo-HSCT patients hinted at poor survival.Cytomegalovirus (CMV) infection,graft-versus-host disease (GVHD) and histocompatibility leukocyte antigen (HLA) mismatch seemed to increase the risk of developing AIHA.Conclusions Patients who develop AIHA after allo-HSCT have poor survival compared to non-AIHA patients.Possible risk factors of AIHA are CMV infection,GVHD,and HLA mismatch.Rituximab is likely to be the effective treatment choice for the refractory patients.

  16. Impact of cyclophosphamide dose of conditioning on the outcome of allogeneic hematopoietic stem cell transplantation for aplastic anemia from human leukocyte antigen-identical sibling.

    Science.gov (United States)

    Mori, Takehiko; Koh, Hideo; Onishi, Yasushi; Kako, Shinichi; Onizuka, Makoto; Kanamori, Heiwa; Ozawa, Yukiyasu; Kato, Chiaki; Iida, Hiroatsu; Suzuki, Ritsuro; Ichinohe, Tatsuo; Kanda, Yoshinobu; Maeda, Tetsuo; Nakao, Shinji; Yamazaki, Hirohito

    2016-04-01

    The standard conditioning regimen in allogeneic hematopoietic stem cell transplantation (HSCT) for aplastic anemia from a human leukocyte antigen (HLA)-identical sibling has been high-dose cyclophosphamide (CY 200 mg/kg). In the present study, results for 203 patients with aplastic anemia aged 16 years or older who underwent allogeneic HSCT from HLA-identical siblings were retrospectively analyzed using the registry database of Japan Society for Hematopoietic Cell Transplantation. Conditioning regimens were defined as a (1) high-dose CY (200 mg/kg or greater)-based (n = 117); (2) reduced-dose CY (100 mg/kg or greater, but less than 200 mg/kg)-based (n = 38); and (3) low-dose CY (less than 100 mg/kg)-based (n = 48) regimen. Patient age and the proportion of patients receiving fludarabine were significantly higher in the reduced- and low-dose CY groups than the high-dose CY group. Engraftment was comparable among the groups. Five-year overall survival (OS) tended to be higher in the low-dose CY group [93.0 % (95 % CI 85.1-100.0 %)] than the high-dose CY [84.2 % (95 % CI 77.1-91.3 %)] or reduced-dose CY groups [83.8 % (95 % CI 71.8-95.8 %); P = 0.214]. Age-adjusted OS was higher in the low-dose CY group than the high- and reduced-dose CY groups with borderline significance (P = 0.067). These results suggest that CY dose can safely be reduced without increasing graft rejection by adding fludarabine in allogeneic HSCT for aplastic anemia from an HLA-identical sibling.

  17. Interactions of allogeneic human mononuclear cells in the two-way mixed leucocyte culture (MLC): influence of cell numbers, subpopulations and cyclosporin

    Science.gov (United States)

    Sato, T; Deiwick, A; Raddatz, G; Koyama, K; Schlitt, H J

    1999-01-01

    With organ allografts considerable numbers of donor-type mononuclear cells are transferred to the recipient, leading to bilateral immunological interactions between donor and recipient lymphocytes. To study such bilateral immune reactions in detail, human two-way MLC were performed. In this model proliferation kinetics, patterns of activation, and survival of the two populations were analysed, and the relevance of initial cell subset composition, relative cell numbers, and the effect of immunosuppression on this co-culture were evaluated. It could be demonstrated that with an initial 50:50 ratio of two populations of allogeneic cells one population dominated after 21 days of co-culture in 78 out of 80 combinations (97%) tested; the other population decreased markedly after an initially stable phase of 6–7 days. With unequal starting conditions the larger population dominated when resting cells were used, but small populations of preactivated cells or separated CD8+ cells could also dominate. Depletion of CD16+ natural killer (NK) cells and of CD2− cells (B cell and monocytes) had no effect on domination. Addition of cyclosporin delayed or blocked the domination process while addition of IL-2 accelerated it. Disappearance of one population was associated with detection of apoptotic cells. The findings indicate that co-cultures of allogeneic mononuclear cells are generally not stable for more than 1 week, but lead to active elimination of one population. CD8+ cells and particularly preactivated cells seem to play the most important role in that process, while NK cells are of less importance. Cyclosporin can prolong survival of allogeneic cells in co-culture. These observations suggest that under the conditions of clinical organ transplantation even small amounts of immunocompetent donor cells transferred by the graft may persist for some time and may, thereby, have the chance to exert immunomodulatory functions. PMID:9933457

  18. Tendon Reattachment to Bone in an Ovine Tendon Defect Model of Retraction Using Allogenic and Xenogenic Demineralised Bone Matrix Incorporated with Mesenchymal Stem Cells

    Science.gov (United States)

    2016-01-01

    Background Tendon-bone healing following rotator cuff repairs is mainly impaired by poor tissue quality. Demineralised bone matrix promotes healing of the tendon-bone interface but its role in the treatment of tendon tears with retraction has not been investigated. We hypothesized that cortical demineralised bone matrix used with minimally manipulated mesenchymal stem cells will result in improved function and restoration of the tendon-bone interface with no difference between xenogenic and allogenic scaffolds. Materials and Methods In an ovine model, the patellar tendon was detached from the tibial tuberosity and a complete distal tendon transverse defect measuring 1 cm was created. Suture anchors were used to reattach the tendon and xenogenic demineralised bone matrix + minimally manipulated mesenchymal stem cells (n = 5), or allogenic demineralised bone matrix + minimally manipulated mesenchymal stem cells (n = 5) were used to bridge the defect. Graft incorporation into the tendon and its effect on regeneration of the enthesis was assessed using histomorphometry. Force plate analysis was used to assess functional recovery. Results Compared to the xenograft, the allograft was associated with significantly higher functional weight bearing at 6 (P = 0.047), 9 (P = 0.028), and 12 weeks (P = 0.009). In the allogenic group this was accompanied by greater remodeling of the demineralised bone matrix into tendon-like tissue in the region of the defect (p = 0.015), and a more direct type of enthesis characterized by significantly more fibrocartilage (p = 0.039). No failures of tendon-bone healing were noted in either group. Conclusion Demineralised bone matrix used with minimally manipulated mesenchymal stem cells promotes healing of the tendon-bone interface in an ovine model of acute tendon retraction, with superior mechanical and histological results associated with use of an allograft. PMID:27606597

  19. Apoptotic signaling through Fas and TNF receptors ameliorates GVHD in mobilized peripheral blood grafts.

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    Mizrahi, K; Yaniv, I; Ash, S; Stein, J; Askenasy, N

    2014-05-01

    Mobilized peripheral blood (mPB) is a prevalent source of hematopoietic progenitors for transplantation; however, allogeneic and haploidentical transplants are often accompanied by severe GVHD. Following the observation that murine GVHD is ameliorated by pretransplant donor cell exposure to Fas-ligand (FasL) without host-specific sensitization, we assessed the susceptibility of mPB cells to spontaneous and receptor-induced apoptosis as a possible approach to GVHD prophylaxis. Short incubation for 4 h resulted in spontaneous apoptosis of 50% of the T and B lymphocytes and 60% myeloid cells. Although expression of Fas and TNF-R1 was proportionate to fractional apoptosis, cell death was dominated by spontaneous apoptosis. Functional assays revealed that the death receptors modulated mPB graft composition as compared with incubation in medium, without detectable quantitative variations. Removal of dead cells increased the frequency of mPB myeloid progenitors (P<0.001 vs medium), and recipients of mPB exposed to death ligands displayed reduced GVHD (P<0.01 vs medium) and improved survival following lipopolysacharide stimulation. mPB grafts exposed to the apoptotic challenge retained SCID reconstituting potential and graft versus tumor activity. These data emphasize that short-term exposure of mPB grafts to an apoptotic challenge is effective in reduction of GVHD effector activity.

  20. Magnetic resonance imaging of mouse islet grafts labeled with novel chitosan-coated superparamagnetic iron oxide nanoparticles.

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    Jyuhn-Huarng Juang

    Full Text Available OBJECT: To better understand the fate of islet isografts and allografts, we utilized a magnetic resonance (MR imaging technique to monitor mouse islets labeled with a novel MR contrast agent, chitosan-coated superparamagnetic iron oxide (CSPIO nanoparticles. MATERIALS AND METHODS: After being incubated with and without CSPIO (10 µg/ml, C57BL/6 mouse islets were examined under transmission electron microscope (TEM and their insulin secretion was measured. Cytotoxicity was examined in α (αTC1 and β (NIT-1 and βTC cell lines as well as islets. C57BL/6 mice were used as donors and inbred C57BL/6 and Balb/c mice were used as recipients of islet transplantation. Three hundred islets were transplanted under the left kidney capsule of each mouse and then MR was performed in the recipients periodically. At the end of study, the islet graft was removed for histology and TEM studies. RESULTS: After incubation of mouse islets with CSPIO (10 µg/mL, TEM showed CSPIO in endocytotic vesicles of α- and β-cells at 8 h. Incubation with CSPIO did not affect insulin secretion from islets and death rates of αTC1, NIT-1 and βTC cell lines as well as islets. After syngeneic and allogeneic transplantation, grafts of CSPIO-labeled islets were visualized on MR scans as persistent hypointense areas. At 8 weeks after syngeneic transplantation and 31 days after allogeneic transplantation, histology of CSPIO-labeled islet grafts showed colocalized insulin and iron staining in the same areas but the size of allografts decreased with time. TEM with elementary iron mapping demonstrated CSPIO distributed in the cytoplasm of islet cells, which maintained intact ultrastructure. CONCLUSION: Our results indicate that after syngeneic and allogeneic transplantation, islets labeled with CSPIO nanoparticles can be effectively and safely imaged by MR.

  1. A comparison between allogeneic stem cell transplantation from unmanipulated haploidentical and unrelated donors in acute leukemia

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    Simona Piemontese

    2017-01-01

    Full Text Available Abstract Background In the absence of a HLA-matched related or matched unrelated donor, allogeneic stem cell transplantation (allo-SCT from mismatched unrelated donors or haploidentical donors are potential alternatives for patients with acute leukemia with an indication to allo-SCT. The objective of this study was to compare the outcome of allo-SCT from T cell-replete haploidentical (Haplo versus matched (MUD 10/10 or mismatched unrelated donor at a single HLA-locus (MMUD 9/10 for patients with acute leukemia in remission. Methods Two hundred sixty-five adult patients with de novo acute leukemia in first or second remission that received a Haplo-SCT between January 2007 and December 2013 were compared with 2490 patients receiving a MUD 10/10 and 813 receiving a MMUD 9/10. Propensity score weighted analysis was conducted in order to control for disease risk imbalances between the groups. Results The weighted 3-year non-relapse mortality and relapse incidence were 29 and 30% for Haplo, 21 and 29% for MUD 10/10, and 29 and 25% for MMUD 9/10, respectively. The weighted 3-year leukemia-free survival (LFS and overall survival (OS were 41 and 46% for Haplo, 50 and 56% for MUD 10/10, and 46 and 48% for MMUD 9/10, respectively. Using weighted Cox model, both LFS and OS were significantly higher in transplants from MUD 10/10 compared from those in Haplo but not different between transplants from MMUD 9/10 and Haplo. The type of donor was not significantly associated with neither acute nor chronic graft-versus-host disease. Conclusions Patients with acute leukemia in remission have better outcomes if transplanted from a MUD 10/10. We did not find any significant difference in outcome between transplants from MMUD 9/10 and Haplo, suggesting that both can be equally used in the absence of a 10/10 MUD. Key point 1 Better outcomes using fully (10/10 matched unrelated donor for allo-SCT in acute leukemia in remission. Key point 2 Similar outcomes after allo

  2. Grafting the alar rim: application as anatomical graft.

    Science.gov (United States)

    Gruber, Ronald P; Fox, Paige; Peled, Anne; Belek, Kyle A

    2014-12-01

    Alar rim contour and alar rim grafts have become essential components of rhinoplasty. Ideally, grafts of the nose should be anatomical in shape. So doing might make grafts of the alar rim more robust. The authors considered doing that by applying the graft as a continuous extension of the lateral crus. Twelve patients (two men and 10 women) constituted the study group (seven primary and five secondary cases). Of those, there were five concave rims, two concave rims with rim retraction, two boxy tips, and three cephalically oriented lateral crura. Surgical technique included the following: (1) an open approach was used; (2) a marginal incision that ignored the caudal margin of the lateral crus (the incision went straight posteriorly to a point 5 to 6 mm from the rim margin) was used; (3) a triangular graft was made to cover the exposed vestibular skin; (4) it was secured end to end to the caudal border of the lateral crus; and (5) the poster end was allowed to sit in a small subcutaneous pocket. Follow-up was 11 to 19 months. All 12 patients exhibited good rims as judged by a blinded panel. Rim retraction was not fully corrected in one patient, but no further treatment was required. One patient did require a secondary small rim graft for residual rim concavity. The concept of grafting the alar rim is strongly supported by the authors' results. The modifications the authors applied by designing the graft to be anatomical in shape has been a technical help.

  3. RENAL ALLOGENEIC TRANSPLANTATION IN PATIENT WITH HAEMOPHILIA B

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    N. V. Purlo

    2014-01-01

    Full Text Available We report the case of successful renal allogeneic transplantation and treatment in a 56-year-old patient with haemophilia B at Hematology Research Center. He has received replacement therapy by factor IX since 2010. The transplant is marked with good renal function during 13 post-transplant months without episodes of rejection or bleeding complications. The complicated surgical interventions are possible in patients with haemophilia В аnd end-stage chronic renal failure in the presence of replacement therapy of IX factor for the purpose of achievement of optimum hemostasis.

  4. Donor lymphocyte infusion after allogeneic stem cell transplantation.

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    Castagna, Luca; Sarina, Barbara; Bramanti, Stefania; Perseghin, Paolo; Mariotti, Jacopo; Morabito, Lucio

    2016-06-01

    Allogeneic stem cell transplantation (allo-SCT) is considered the cornerstone in the treatment of several malignant and not malignant hematological diseases. However, relapse of hematological disease after allo-SCT is considered the most challenging point in the field. The risk can be reduced through optimal patients, donor and disease selection before allo-SCT, but harnessing donor immune system is an appealing way to treat or avoid disease relapse. Donor lymphocyte infusion (DLI) is a simple and effective therapy after allo-SCT. In this paper, the efficacy of DLI will be analyzed in different hematological diseases, focusing also on their therapeutic or pre-emptive use.

  5. Integration of a CD19 CAR into the TCR Alpha Chain Locus Streamlines Production of Allogeneic Gene-Edited CAR T Cells.

    Science.gov (United States)

    MacLeod, Daniel T; Antony, Jeyaraj; Martin, Aaron J; Moser, Rachel J; Hekele, Armin; Wetzel, Keith J; Brown, Audrey E; Triggiano, Melissa A; Hux, Jo Ann; Pham, Christina D; Bartsevich, Victor V; Turner, Caitlin A; Lape, Janel; Kirkland, Samantha; Beard, Clayton W; Smith, Jeff; Hirsch, Matthew L; Nicholson, Michael G; Jantz, Derek; McCreedy, Bruce

    2017-04-05

    Adoptive cellular therapy using chimeric antigen receptor (CAR) T cell therapies have produced significant objective responses in patients with CD19(+) hematological malignancies, including durable complete responses. Although the majority of clinical trials to date have used autologous patient cells as the starting material to generate CAR T cells, this strategy poses significant manufacturing challenges and, for some patients, may not be feasible because of their advanced disease state or difficulty with manufacturing suitable numbers of CAR T cells. Alternatively, T cells from a healthy donor can be used to produce an allogeneic CAR T therapy, provided the cells are rendered incapable of eliciting graft versus host disease (GvHD). One approach to the production of these cells is gene editing to eliminate expression of the endogenous T cell receptor (TCR). Here we report a streamlined strategy for generating allogeneic CAR T cells by targeting the insertion of a CAR transgene directly into the native TCR locus using an engineered homing endonuclease and an AAV donor template. We demonstrate that anti-CD19 CAR T cells produced in this manner do not express the endogenous TCR, exhibit potent effector functions in vitro, and mediate clearance of CD19(+) tumors in an in vivo mouse model. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  6. ACTIVATION OF T. GONDII INFECTION AFTER ALLOGENEIC TRANSPLANTATION OF HEMATOPOIETIC STEM CELLS: DEPENDENCE ON TIME OF TRANSPLANTATION AND SEROLOGICAL STATUS OF THE PATIENTS

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    A. B. Chukhlovin

    2014-01-01

    Full Text Available The article focuses on aspects of T. gondii reactivation/reinfection in patients undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT. We have observed 297 patients who received conditioning therapy and allogeneic grafts due to different oncohematological or lymphoproliferative diseases (1 to 60 years old, at a mediane of 19 years. Conditioning regimens were either myeloablative (35%, or non-myeloablative (65%. DNA diagnostics of T. gondii was performed on a regular basis at 0 to 6 months post-HSCT. IgG and IgM antibodies against T. gondii were determined in 78 patients before HSCT, as well as in their donors. T. gondii DNA post-transplant proved to be positive in 13% of blood specimens, 9% of cerebrospinal liquor samples, 11% of bronchoalveolar cell lavages, and in 5% of urine sediments. In adolescent patients (10 to 14 years old, an increased prevalence of T. gondii was found in patients who received myeloablative treatment (p = 0.01. When assessing posttransplant dynamics of T. gondii, we have revealed distinct increase in the pathogen excretion within 1st month after HSCT (p = 0.03. Finally, initial presence of IgG antibodies against T. gondii in the patients was associated with lower incidence of the pathogen reactivation post-transplant.

  7. Provision of cellular blood components to CMV-seronegative patients undergoing allogeneic stem cell transplantation in the UK: survey of UK transplant centres.

    Science.gov (United States)

    Morton, S; Peniket, A; Malladi, R; Murphy, M F

    2017-09-15

    To identify current UK practice with regards to provision of blood components for cytomegalovirus (CMV)-seronegative, potential, allogeneic stem cell recipients of seronegative grafts. Infection with CMV remains a major cause of morbidity and mortality after allogeneic stem cell transplantation (aSCT). CMV transmission has been a risk associated with the transfusion of blood components from previously exposed donors, but leucocyte reduction has been demonstrated to minimise this risk. In 2012, the UK Advisory Committee for the Safety of Tissues and Organs (SaBTO) recommended that CMV-unselected components could be safely transfused without increased risk of CMV transmission. We surveyed UK aSCT centres to establish current practice. Fifteen adult and seven paediatric centres (75%) responded; 22·7% continue to provide components from CMV-seronegative donors. Reasons cited include the continued perceived risk of CMV transmission by blood transfusion, its associated morbidity and concerns regarding potential for ambiguous CMV serostatus in seronegative potential transplant recipients due to passive antibody transfer from CMV-seropositive blood donors, leading to erroneous donor/recipient CMV matching at transplant. The survey demonstrated a surprisingly high rate (22.7%) of centres continuing to provide blood components from CMV-seronegative donors despite SaBTO guidance. © 2017 British Blood Transfusion Society.

  8. Suction blister grafting - Modifications for easy harvesting and grafting

    Directory of Open Access Journals (Sweden)

    2012-01-01

    Full Text Available Suction blister grafting is a simple modality of treatment of patients with resistant and stable vitiligo. But raising the blisters may be time consuming and transferring to the recipient site may be difficult as the graft is ultrathin. By doing some modifications we can make the technique simpler and easier. We can decrease the blister induction time by intradermal injection of saline, exposure to Wood′s lamp, intrablister injection of saline. By these methods we can decrease the blister induction time from 2-3 hrs to 45-90 minutes. After harvesting the graft, it can be transferred to the recipient area by taking the graft on a sterile glass slide, on the gloved finger, rolling the graft over a sterile syringe and then spreading on the recipient area, or taking on the sterile wrapper of paraffin dressing and then placing over the recipient area.

  9. Cytoreductive treatment with clofarabine/ara-C combined with reduced-intensity conditioning and allogeneic stem cell transplantation in patients with high-risk, relapsed, or refractory acute myeloid leukemia and advanced myelodysplastic syndrome.

    Science.gov (United States)

    Buchholz, Stefanie; Dammann, Elke; Stadler, Michael; Krauter, Juergen; Beutel, Gernot; Trummer, Arne; Eder, Matthias; Ganser, Arnold

    2012-01-01

    The combination of cytoreductive chemotherapy with reduced-intensity conditioning (RIC) is a highly effective antileukemic therapy. Purpose of this retrospective analysis was to evaluate the antileukemic efficacy and toxicity of clofarabine-based chemotherapy followed by RIC and allogeneic stem cell transplantation (SCT) for high-risk, relapsed, or refractory acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). From May 2007 until October 2009, a total of 27 patients underwent allogeneic SCT after treatment with clofarabine and ara-C for 5d and RIC (4Gy TBI/cyclophosphamide/ATG). Prophylaxis of graft-versus-host disease (GvHD) consisted of cyclosporine and mycophenolate mofetil. Unmanipulated G-CSF mobilized PBSC (n=26) or bone marrow cells (n=1) were transplanted from unrelated (n=21) or matched related (n=6) donors. Non-hematological toxicities of this regimen mainly affected liver and skin and were all reversible. Seven patients relapsed within a median time of 5.7 months. The overall survival (OS) and relapse-free survival rates were 56% and 52% at 2 yr, respectively. In this cohort of patients, cytoreduction with clofarabine/ara-C (ClAraC) followed by RIC allogeneic SCT was well tolerated and showed good antileukemic efficacy even in patients with high-risk AML or MDS, with engraftment and GvHD-incidence comparable to other RIC regimens.

  10. Transfusion in CMV seronegative T-depleted allogeneic stem cell transplant recipients with CMV-unselected blood components results in zero CMV transmissions in the era of universal leukocyte reduction: a U.K. dual centre experience.

    Science.gov (United States)

    Hall, S; Danby, R; Osman, H; Peniket, A; Rocha, V; Craddock, C; Murphy, M; Chaganti, S

    2015-12-01

    To establish rates of cytomegalovirus (CMV) transmission with use of CMV-unselected (CMV-U), leukocyte-reduced blood components transfused to CMV-seronegative patient/CMV-seronegative donor (CMV neg/neg) allogeneic stem cell transplantation (SCT) recipients including those receiving T-depleted grafts. CMV infection remains a major cause of morbidity following SCT. CMV-seronegative SCT recipients are particularly at risk of transfusion transmitted CMV (TT-CMV) and until recently they have received blood components from CMV-seronegative donors with significant resource implications. Although leukocyte reduction of blood components is reported to minimise risk of TT-CMV, its efficacy in high-risk situations, such as in T-depleted transplant recipients, is unknown. We retrospectively analysed the incidence of TT-CMV in CMV neg/neg allogeneic SCT recipients transfused with CMV-U, leukocyte-reduced blood components in two transplantation centres in the UK. Patients were monitored for CMV infection by weekly CMV polymerase chain reaction testing. Leukocyte reduction of blood components was in accordance with current UK standards. Among 76 patients, including 59 receiving in vivo T-depletion, no episodes of CMV infection were detected. Patients were transfused with 1442 CMV-unselected, leukocyte-reduced components, equating to 1862 donor exposures. Our findings confirm the safety of leukocyte reduction as a strategy in preventing TT-CMV in high-risk allogeneic SCT recipients. © 2015 British Blood Transfusion Society.

  11. Polyether/Polyester Graft Copolymers

    Science.gov (United States)

    Bell, Vernon L., Jr.; Wakelyn, N.; Stoakley, D. M.; Proctor, K. M.

    1986-01-01

    Higher solvent resistance achieved along with lower melting temperature. New technique provides method of preparing copolymers with polypivalolactone segments grafted onto poly (2,6-dimethyl-phenylene oxide) backbone. Process makes strong materials with improved solvent resistance and crystalline, thermally-reversible crosslinks. Resulting graft copolymers easier to fabricate into useful articles, including thin films, sheets, fibers, foams, laminates, and moldings.

  12. Graft selection in cerebral revascularization.

    Science.gov (United States)

    Baaj, Ali A; Agazzi, Siviero; van Loveren, Harry

    2009-05-01

    Cerebral revascularization constitutes an important treatment modality in the management of complex aneurysms, carotid occlusion, tumor, and moyamoya disease. Graft selection is a critical step in the planning of revascularization surgery, and depends on an understanding of graft and regional hemodynamics, accessibility, and patency rates. The goal of this review is to highlight some of these properties.

  13. Interleukin-10 spot-forming cells as a novel biomarker of chronic graft-versus-host disease

    Science.gov (United States)

    Hirayama, Masahiro; Azuma, Eiichi; Nakagawa-Nakazawa, Atsuko; Kumamoto, Tadashi; Iwamoto, Shotaro; Amano, Keishiro; Tamaki, Shigehisa; Usui, Eiji; Komada, Yoshihiro

    2013-01-01

    Although there are National Institutes of Health consensus criteria for the global assessment of chronic graft-versus-host disease, no validated biomarkers have been established for this disease. Furthermore, whereas the role of T cells, B cells, and dendritic cells in chronic graft-versus-host disease has been established, the contribution of monocytes has not been clearly addressed. Using an enzyme-linked immunospot assay, we measured the spot-forming cells for interferon-γ, interleukin-4, interleukin-10, and interleukin-17 in unstimulated peripheral blood of patients following allogeneic hematopoietic stem cell transplantation. Other immunological examinations, including skin biopsy, were also done. Fifty-seven patients were enrolled. Interleukin-10 spot-forming cells were evaluable for therapeutic monitoring in 16 patients with chronic graft-versus-host disease. The number of interleukin-10 spot-forming cells in patients with active chronic graft-versus-host disease was significantly higher than the number in those with no or inactive chronic graft-versus-host disease. Interleukin-10 was predominantly produced by monocytes. CD29 expression on monocytes in patients with active chronic graft-versus-host disease was elevated. The level of plasma fibronectin, a ligand of CD29, correlated with the number of interleukin-10 spot-forming cells. Immunohistochemical analysis of the skin in active chronic graft-versus-host disease showed that infiltrating CD29+ monocytes might produce interleukin-10. A novel biomarker, interleukin-10 spot-forming cells, shows promise as both a diagnostic and prognostic indicator for chronic graft-versus-host disease, and may allow for early intervention prior to the onset of the disease. Measurement of interleukin-10 spot-forming cells would be helpful in clinical trials and in patients' management. PMID:22733028

  14. Impact of Pretransplantation 18F-fluorodeoxy Glucose—Positron Emission Tomography Status on Outcomes after Allogeneic Hematopoietic Cell Transplantation for Non-Hodgkin Lymphoma

    Science.gov (United States)

    Bachanova, Veronika; Burns, Linda J.; Ahn, Kwang Woo; Laport, Ginna G.; Akpek, Görgün; Kharfan-Dabaja, Mohamed A.; Nishihori, Taiga; Agura, Edward; Armand, Philippe; Jaglowski, Samantha M.; Cairo, Mitchell S.; Cashen, Amanda F.; Cohen, Jonathon B.; D'Souza, Anita; Freytes, César O.; Gale, Robert Peter; Ganguly, Siddhartha; Ghosh, Nilanjan; Holmberg, Leona A.; Inward, David J.; Kanate, Abraham S.; Lazarus, Hillard M.; Malone, Adriana K.; Munker, Reinhold; Mussetti, Alberto; Norkin, Maxim; Prestidge, Tim D.; Rowe, Jacob M.; Satwani, Prakash; Siddiqi, Tanya; Stiff, Patrick J.; William, Basem M.; Wirk, Baldeep; Maloney, David G.; Smith, Sonali M.; Sureda, Anna M.; Carreras, Jeanette; Hamadani, Mehdi

    2015-01-01

    Assessment with 18F-fluorodeoxy glucose (FDG)—positron emission tomography (PET) before hematopoietic cell transplantation (HCT) for lymphoma may be prognostic for outcomes. Patients with chemotherapy-sensitive non—Hodgkin lymphoma (NHL) undergoing allogeneic HCT reported to the Center of International Blood and Marrow Transplantation Registry between 2007 and 2012 were included. Pre-HCT PET status (positive versus negative) was determined by the reporting transplantation centers. We analyzed 336 patients; median age was 55 years and 60% were males. Follicular lymphoma (n = 104) was more common than large cell (n = 85), mantle cell (n = 69), and mature natural killer or T cell lymphoma (n = 78); two thirds of the cohort received reduced-intensity conditioning; one half had unrelated donor grafts. Patients underwent PET scanning a median of 1 month (range, .07 to 2.83 months) before HCT; 159 were PET positive and 177 were PET negative. At 3 years, relapse/progression, progression-free survival (PFS), and overall survival (OS) in PET-positive versus PET-negative groups were 40% versus 26%; P = .007; 43% versus 47%; P = .47; and 58% versus 60%; P = .73, respectively. On multivariate analysis, a positive pretransplantation PET was associated with an increased risk of relapse/progression (risk ratio [RR], 1.86; P = .001) but was not associated with worse OS (RR, 1.29, 95% confidence interval [CI], .96 to 1.7; P = .08), PFS (RR, 1.32; 95% CI, .95 to 1.84; P = .10), or nonrelapse mortality (RR, .75; 95% CI, .48 to 1.18; P = .22). PET status conferred no influence on graft-versus-host disease. A positive PET scan before HCT is associated with increased relapse risk but should not be interpreted as a barrier to a successful allograft. PET status does not appear to predict survival after allogeneic HCT for NHL. PMID:25983043

  15. Radiation grafting on natural films

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    Lacroix, M.; Khan, R.; Senna, M.; Sharmin, N.; Salmieri, S.; Safrany, A.

    2014-01-01

    Different methods of polymer grafting using gamma irradiation are reported in the present study for the preparation of newly functionalized biodegradable films, and some important properties related to their mechanical and barrier properties are described. Biodegradable films composed of zein and poly(vinyl alcohol) (PVA) were gamma-irradiated in presence of different ratios of acrylic acid (AAc) monomer for compatibilization purpose. Resulting grafted films (zein/PVA-g-AAc) had their puncture strength (PS=37-40 N mm-1) and puncture deformation (PD=6.5-9.8 mm) improved for 30% and 50% PVA in blend, with 5% AAc under 20 kGy. Methylcellulose (MC)-based films were irradiated in the presence of 2-hydroxyethyl methacrylate (HEMA) or silane, in order to determine the effect of monomer grafting on the mechanical properties of films. It was found that grafted films (MC-g-HEMA and MC-g-silane) using 35% monomer performed higher mechanical properties with PS values of 282-296 N mm-1 and PD of 5.0-5.5 mm under 10 kGy. Compatibilized polycaprolactone (PCL)/chitosan composites were developed via grafting silane in chitosan films. Resulting trilayer grafted composite film (PCL/chitosan-g-silane/PCL) presented superior tensile strength (TS=22 MPa) via possible improvement of interfacial adhesion (PCL/chitosan) when using 25% silane under 10 kGy. Finally, MC-based films containing crystalline nanocellulose (CNC) as a filling agent were prepared and irradiated in presence of trimethylolpropane trimethacrylate (TMPTMA) as a grafted plasticizer. Grafted films (MC-g-TMPTMA) presented superior mechanical properties with a TS of 47.9 MPa and a tensile modulus (TM) of 1792 MPa, possibly due to high yield formation of radicals to promote TMPTMA grafting during irradiation. The addition of CNC led to an additional improvement of the barrier properties, with a significant 25% reduction of water vapor permeability (WVP) of grafted films.

  16. Distinguishing allogenic from autogenic causes of bed elevation change in late Quaternary alluvial stratigraphic records

    Science.gov (United States)

    Daniels, J. Michael

    2008-10-01

    Allogenic and autogenic mechanisms both cause changes in the bed elevation of rivers and thereby influence the characteristics of alluvial stratigraphic records (ASRs). Allogenic forcing mechanisms can be grouped into five categories whose relative influence varies with timescale: climate, tectonism, base level, land use/land cover and direct human modification of channels. Late Quaternary ASRs are influenced by the greatest range of allogenic forcing variables with climate among the most important. Autogenic mechanisms of bed elevation change are ubiquitous throughout fluvial systems and are always time-transgressive. Autogenic bed elevation change propagates through drainage networks at predictable rates and results in a time-space envelope within which its effects are capable of operating. ASRs that can be correlated over geographical areas large enough and time intervals small enough to exist outside this envelope most likely result from allogenic forcing. This formulation represents a quantitative and geographic set of threshold criteria for distinguishing between autogenic and allogenic mechanisms. Over late Quaternary timescales (10 2 to 10 5 years) in tectonically stable regions climate change is the dominant allogenic mechanism and, therefore, the first-order control on the morphology, sedimentology, pedologic characteristics and chronology of alluvial stratigraphic records that meet or exceed the threshold criteria for demonstrating allogenic causality.

  17. Application of allogeneic bone marrow cells in view of residual alloreactivity: sirolimus but not cyclosporine evolves tolerogenic properties.

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    Kai Timrott

    Full Text Available Application of bone marrow cells (BMC is a promising strategy for tolerance induction, but usually requires strong depletion of the host immune system. This study evaluates the ability of immunosuppressants to evolve tolerogenic properties of BMC in view of residual alloreactivity.The rat model used a major histocompatibility complex (MHC class II disparate bone marrow transplantation (BMT setting (LEW.1AR1 (RT1auu → LEW.1AR2 (RT1aau. Heart grafts (LEW.1WR1 (RT1uua were disparate for the complete MHC to recipients and for MHC class I to BMC donors. Limited conditioning was performed by total body irradiation of 6 Gy. Cyclosporine (CsA or Sirolimus (Srl were administered for 14 or 28 days. Transplantation of heart grafts (HTx was performed at day 16 or at day 100 after BMT. Chimerism and changes in the T cell pool were detected by flow cytometry.Mixed chimeras accepted HTx indefinitely, although the composition of the regenerated T cell pool was not changed to a basically donor MHC class II haplotype. Non-chimeric animals rejected HTx spontaneously. BMC recipients, who received HTx during T cell recovery at day 16, accepted HTx only after pre-treatment with Srl, although chimerism was lost. CsA pre-treatment led to accelerated HTx rejection as did isolated application of BMC.Srl evolves tolerogenic properties of allogeneic BMC to achieve indefinite acceptance of partly MHC disparate HTx despite residual alloreactivity and in particular loss of chimerism.

  18. Allogeneic Hematopoietic Stem Cell Transplantation in the Treatment of Human C1q Deficiency: The Karolinska Experience.

    Science.gov (United States)

    Olsson, Richard F; Hagelberg, Stefan; Schiller, Bodil; Ringdén, Olle; Truedsson, Lennart; Åhlin, Anders

    2016-06-01

    Human C1q deficiency is associated with systemic lupus erythematosus (SLE) and increased susceptibility to severe bacterial infections. These patients require extensive medical therapy and some develop treatment-resistant disease. Because C1q is produced by monocytes, it has been speculated that allogeneic hematopoietic stem cell transplantation (allo-HSCT) may cure this disorder. We have so far treated 5 patients with C1q deficiency. In 3 cases, SLE symptoms remained relatively mild after the start of medical therapy, but 2 patients developed treatment-resistant SLE, and we decided to pursue treatment with allo-HSCT. For this purpose, we chose a conditioning regimen composed of treosulfan (14 g/m) and fludarabine (30 mg/m) started on day -6 and given for 3 and 5 consecutive days, respectively. Thymoglobulin was given at a cumulative dose of 8 mg/kg, and graft-versus-host disease prophylaxis was composed of cyclosporine and methotrexate. A 9-year-old boy and a 12-year-old girl with refractory SLE restored C1q production after allo-HSCT. This resulted in normal functional properties of the classical complement pathway followed by reduced severity of SLE symptoms. The boy developed posttransplant lymphoproliferative disease, which resolved after treatment with rituximab and donor lymphocyte infusion. Unfortunately, donor lymphocyte infusion induced severe cortisone-resistant gastrointestinal graft-versus-host disease, and the patient died from multiple organ failure 4 months after transplantation. The girl is doing well 33 months after transplantation, and clinically, all signs of SLE have resolved. Allo-HSCT can cure SLE in human C1q deficiency and should be considered early in subjects resistant to medical therapy.

  19. Haploidentical Natural Killer Cells Infused before Allogeneic Stem Cell Transplantation for Myeloid Malignancies: A Phase I Trial.

    Science.gov (United States)

    Lee, Dean A; Denman, Cecele J; Rondon, Gabriela; Woodworth, Glenda; Chen, Julianne; Fisher, Tobi; Kaur, Indreshpal; Fernandez-Vina, Marcelo; Cao, Kai; Ciurea, Stefan; Shpall, Elizabeth J; Champlin, Richard E

    2016-07-01

    Allogeneic stem cell transplantation is an effective treatment for high-risk myeloid malignancies, but relapse remains the major post-transplantation cause of treatment failure. Alloreactive natural killer (NK) cells mediate a potent antileukemic effect and may also enhance engraftment and reduce graft-versus-host disease (GVHD). Haploidentical transplantations provide a setting in which NK cell alloreactivity can be manipulated, but they are associated with high rates of GVHD. We performed a phase I study infusing escalating doses of NK cells from an HLA haploidentical-related donor-selected for alloreactivity when possible-as a component of the preparative regimen for allotransplantation from a separate HLA-identical donor. The goal of infusing third-party alloreactive NK cells was to augment the antileukemic effect of the transplantation without worsening GVHD and, thus, improve the overall outcome of hematopoietic transplantation. Twenty-one patients with high-risk acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelogenous leukemia refractory or beyond first remission received a preparative regimen with busulfan and fludarabine followed by infusion of apheresis-derived, antibody-selected, and IL-2-activated NK cells. Doses were initially based on total nucleated cell (TNC) content and later based on CD56(+) cells to reduce variability. CD56(+) content ranged from .02 to 8.32 × 10(6)/kg. IL-2, .5 × 10(6) units/m(2) subcutaneously was administered daily for 5 days in the final cohort (n = 10). CD3(+) cells in the NK cell product were required to be transplantation-related causes, and 11 patients died of relapse. Despite the small sample size, survival was highly associated with CD56(+) cells delivered (P = .022) and development of ≥ grade 3 GVHD (P = .006). There were nonsignificant trends toward higher survival rates in those receiving NK cells from KIR ligand-mismatched donors and KIR-B haplotype donors. There was no

  20. Graft stability after endothelial keratoplasty

    Directory of Open Access Journals (Sweden)

    Jovanović Vesna

    2015-01-01

    Full Text Available Bacground/Aim. Techniques for replacing the corneal endothelium have been improved. The host-graft interface is the key to graft adhesion and visual recovery. The aim of this study was to establish graft stability after Descemet stripping with endothelial keratoplasty (DSEK, compare it to the graft stability after endothelial keratoplasty with the intact posterior corneal layers (nDSEK in the rabbit cornea, and to investigate the nature of wound healing. Methods. Adult white rabbits (n = 20 were divided in two experimental groups: ten rabbits underwent monocular DSEK, and ten rabbits underwent endothelial keratoplasty without Descemet stripping (nDSEK. On the second postoperative day a horizontal dislocation of the graft was tried using the Lindstrom roller in each animal. Corneas were processed for the light microscopy study. Results. Rolling the Lindstrom instrument over the corneal surface did not cause horizontal dislocation in any of the operated eyes. In the DSEK group light microscopy revealed the lack of inflammation and fibrosis at the clearly distinctive donor-recipient interface (DRI. Retrocorneal membrane was found in two eyes. In nDSEK group, the host Descemet` s membrane (DM was intact without endothelial cells, with good graft apposition, without inflammation, fibrosis, or retrocorneal membrane. Conclusion. This study suggests that there is no difference in graft stability in DSEK compared to nDSEK in rabbit corneas. Wounds healed at DRI by hypocellular scarring only in both experimental groups.

  1. Disease severity and mortality can be independently regulated in a mouse model of experimental graft versus host disease.

    Directory of Open Access Journals (Sweden)

    Rômulo G Galvani

    Full Text Available Graft versus host disease (GVHD is the major limitation of allogeneic hematopoietic stem cell transplantation (HSCT presenting high mortality and morbidity rates. However, the exact cause of death is not completely understood and does not correlate with specific clinical and histological parameters of disease. Here we show, by using a semi-allogeneic mouse model of GVHD, that mortality and morbidity can be experimentally separated. We injected bone marrow-derived dendritic cells (BMDC from NOD2/CARD15-deficient donors into semi-allogeneic irradiated chimaeras and observed that recipients were protected from death. However, no protection was observed regarding clinical or pathological scores up to 20 days after transplantation. Protection from death was associated with decreased bacterial translocation, faster hematologic recovery and epithelial integrity maintenance despite mononuclear infiltration at day 20 post-GVHD induction with no skew towards different T helper phenotypes. The protected mice recovered from aGVHD and progressively reached scores compatible with healthy animals. Altogether, our data indicate that severity and mortality can be separate events providing a model to study transplant-related mortality.

  2. Titanium implant insertion into dog alveolar ridges augmented by allogenic material

    DEFF Research Database (Denmark)

    Pinholt, E M; Haanaes, H R; Donath, K

    1994-01-01

    The purpose of this investigation was to evaluate whether titanium endosseous implants would osseointegrate in dog alveolar ridges augmented by allogenic material. In 8 dogs en bloc resection, including 2 pre-molars, was performed bilaterally in the maxilla and the mandible. After a healing period...... of 6 weeks allogenic, demineralized and lyophilized dentin or bone was implanted subperiosteally. Titanium implants were installed 5.5 months later in some of the regions. Light and fluorescence microscopic evaluation revealed fibrous encapsulation of the implanted allogenic material, no osteoinduction...... and only minimal osteoconduction, few multinuclear giant cells and a sparse inflammatory reaction. The titanium implants healed mainly by fibrous encapsulation....

  3. Antitumor immunomodulatory activity of allogenic bone marrow cells on TiNi scaffold

    Science.gov (United States)

    Kokorev, O. V.; Hodorenko, V. N.; Cherdyntseva, N. V.; Gunther, V. E.

    2016-08-01

    The present study was undertaken to evaluate the feasibility of modulation of anti-tumor response by allogenic bone marrow cell transplantation into porous TiNi-based scaffold. Transplantation of bone marrow cells into porous TiNi-based scaffold leads to antitumor (35%) and antimetastatic (55%) effects. The lifetime of tumor-bearing animals and implanted allogenic bone marrow cells in incubator of TiNi increases up to 60%. The possible mechanisms of the effect of allogenic cells on tumor process are the stimulation of endogenous effectors of antitumor immunity.

  4. The clinical impact of cytomegalovirus infection following allogeneic hematopoietic cell transplantation: Why the quest for meaningful prophylaxis still matters.

    Science.gov (United States)

    Chan, Shawna T; Logan, Aaron C

    2017-02-02

    Latent infection with human cytomegalovirus (CMV) is common. Functional immunity effectively contains such latent infections; however, CMV reactivation may cause significant complications in patients undergoing allogeneic hematopoietic cell transplantation (alloHCT). In spite of the universal implementation of post-transplant screening for CMV viremia and the institution of pre-emptive antiviral management, CMV disease still occurs in a small portion of patients. Moreover, interactions between CMV and the immune system have significant implications for the incidence of graft-versus-host disease, the recurrence of malignancy, and non-relapse mortality following alloHCT, even in the era of pre-emptive antiviral management. CMV serostatus thus remains an important consideration for patients undergoing alloHCT. We review the clinical impact of CMV in the setting of alloHCT, interactions between CMV serostatus, viral reactivation, and transplant outcomes, as well as current and evolving strategies for prevention and treatment of CMV-related complications that may have significant impact for alloHCT recipients.

  5. THE ROLE OF AUTOLOGOUS AND ALLOGENEIC STEM CELL TRANSPLANTATION IN FOLLICULAR LYMPHOMA IN THE NEW DRUGS ERA.

    Directory of Open Access Journals (Sweden)

    Francesco Maura

    2016-09-01

    Full Text Available Follicular lymphoma (FL is the second most common histotype of non-Hodgkin’s lymphoma and it is generally characterized by a heterogeneous clinical course. Despite recent therapeutic and diagnostic improvements, a significant fraction of FL patients still relapsed. In younger and/or fit FL relapsed patients bone marrow transplant (BMT has represented the main salvage therapy for many years. Thanks to the ability of high dose chemotherapy to overcome the lymphoma resistance and refractoriness, autologous stem cell transplantation (ASCT is able to achieve a high complete remission rate (CR and favourable outcome in terms of progression free survival (PFS and overall survival (OS. Allogeneic stem cell transplantation (alloSCT combines the high dose chemotherapy effect together with the immune reaction of the donor immune system against lymphoma, the so called ‘graft versus lymphoma’ (GVL effect. Considering the generally higher transplant related mortality (TRM, alloSCT is mostly indicated for FL relapsed after ASCT. During the last years there has been a great spread of novel effective and feasible drugs Although these and future novel drugs will probably change our current approach to FL, the OS post-BMT (ASCT and alloSCT has never been reproduced by any novel combination. In this scenario, it is important to correctly evaluate the disease status, the relapse risk and the comorbidity profile of the relapsed FL patients in order to provide the best salvage therapy and eventually transplant consolidation.

  6. Improving Safety of Preemptive Therapy with Oral Valganciclovir for Cytomegalovirus Infection after Allogeneic Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Corinna Barkam

    2012-01-01

    Full Text Available Valganciclovir (VGC, an oral prodrug of ganciclovir (GCV, has been shown to clear cytomegalovirus (CMV viremia in preemptive treatment of patients after allogeneic hematopoietic stem cell transplantation (alloHSCT, apparently without significant toxicity. Since VGC obviates hospitalization, it is increasingly being adopted, although not approved, in alloHSCT. When we retrospectively evaluated preemptive treatment with VGC versus GCV, foscarnet or cidofovir, in all 312 consecutive CMV viremias of 169 patients allotransplanted at our institution between 1996 and 2006, we found VGC more efficacious (79% than non-VGC therapies (69%. The advantage of outpatient VGC, however, was outbalanced by more profound neutropenias (including two cases of agranulocytosis, one with graft loss requiring subsequent prolonged rehospitalization. Thus, in a second, prospective cohort from 2007 to 2011 (all 202 consecutive CMV viremias of 118 yet older and sicker patients, we implemented twice weekly neutrophil monitoring during outpatient VGC treatment and avoided VGC maintenance therapy. While conserving efficacy (VGC 71%, non-VGC 72%, we could now demonstrate a reduced mean duration of hospitalization with VGC (9 days (0–66 compared to non-VGC (25 days (0–115, without any agranulocytosis episodes. We conclude that safe outpatient VGC therapy is possible in alloHSCT recipients, but requires frequent monitoring to prevent severe myelotoxicity.

  7. Graft nephrectomy: The SGPGI experience

    Directory of Open Access Journals (Sweden)

    Nand Kishore Arvind

    2002-01-01

    Full Text Available Background: Graft nephrectomy is often considered a hazardous procedure with high morbidity and occasional mortality, and this may pose a technical challenge. The aim of this study was to evaluate the indications, etiology and complications following graft nephrectomy. Materials and Methods: From 1988 to 2001, among total of 1,019 live related renal transplants carried at our center, 46 underwent graft nephrectomy. Patients were divided into 2 groups depending on timing of graft re-moval. The early group included 27 patients (within 2 months of transplantation while in late group (graft re-moval after 2 months of transplantation there were 19 patients. The 2 groups were compared in terms of indica-tion, etiology and complications. Results: In early group the indications for graft removal were acute rejection, thrombosis/infarction and hyper-acute rejection, while in late group the indications were pain, hematuria, fever, hypertension and infection along with chronic failure. Overall, the external iliac artery in-jury occurred in I and 4 patients in early and late group respectively. Major blood loss occurred in I and 6 pa-tients in early and late graft removal respectively. There were 2 deaths in early group due to ftdminant pneumoni-tis that progressed to sepsis and disseminated intravascu-lar coagulation. There were 9 major wound infections all in early group except in 2 patients of late group. Respira-tory infections occurred in 14 patients in early group and 1 in late group. In early group patients had CNS compli-cations in form of seizures, clinical depression and delusional psychosis in 12 patients. Conclusions: Our experience highlights the risk in-volved in graft nephrectomies. Severe acute rejection and thrombosis lead to early graft nephrectomies. Pain, hematuria, infection and hypertension in setting of chronic rejection are predominant causes for the delayed graft ne- phrectomies. Early graft nephrectomy, though technically easy, is

  8. Design of a Sapling Branch Grafting Robot

    Directory of Open Access Journals (Sweden)

    Qun Sun

    2014-01-01

    Full Text Available The automatic sapling grafting methods and grafting robot technologies are not comprehensively studied despite the fact that they are urgently required in practice. For this reason, a sapling grafting robot is developed to implement automatic grafting for saplings. The developed grafting robot includes clipping mechanism, moving mechanism, cutting mechanism, binding mechanism, and Arduino MCU based control system, which is capable of clipping, moving, positioning, cutting, grafting, and binding saplings. Experiments show that the stock cutting efficiency is 98.4%, the scion cutting efficiency is 98.9%, the grafting efficiency is 87.3%, and the binding efficiency is 68.9%.

  9. Chlamydia pneumoniae respiratory infection after allogeneic stem cell transplantation.

    Science.gov (United States)

    Geisler, William M; Corey, Lawrence

    2002-03-27

    Chlamydia pneumoniae is a common cause of upper and lower respiratory tract infections in immunocompetent patients; however, its role as a respiratory pathogen in immunocompromised hosts has been infrequently recognized. We describe C. pneumoniae lower respiratory tract infection in a 19-year-old male after allogeneic stem cell transplantation. The patient developed fever on day +14, and a subsequent computed tomography scan of the chest revealed a right lateral pleural-based opacity, which was then resected during thoracoscopy. Diagnosis was made by culture and staining of the resected tissue with C. pneumoniae-specific monoclonal antibodies, and azithromycin was administered. To the best of our knowledge, this is the first report of C. pneumoniae respiratory infection after stem cell or marrow transplantation. C. pneumoniae often coexists with other etiologic agents of pneumonia in immunocompromised patients. Considering the infrequency of infections from this organism in this clinical setting, one must still rule out other more likely respiratory pathogens.

  10. Sexual function 1-year after allogeneic hematopoietic stem cell transplantation

    DEFF Research Database (Denmark)

    Noerskov, K. H.; Schjødt, I.; Syrjala, K. L.

    2016-01-01

    Treatment with allogeneic hematopoietic stem cell transplantation (HSCT) is associated with short and long-term toxicities that can result in alterations in sexual functioning. The aims of this prospective evaluation were to determine: (1) associations between HSCT and increased sexual dysfunction......). Assessment included descriptive data, Sexual Functioning Questionnaire, Body Image Scale and Hospital Anxiety and Depression Scale. The results showed a significant decline in overall sexual function in both men and women (P=.... Forty-seven percent of men and 60% of women reported at least one physical sexual problem 1 year after HSCT. Patients with chronic GVHD trended toward reporting lower levels of sexual function. Finally, women with chronic GVHD scored lower than those without chronic GVHD on the sexual function problem...

  11. Allogeneic transplantation in the UK: an aggregation of marginal gains?

    Science.gov (United States)

    Thomson, Kirsty J; Peggs, Karl S

    2013-10-01

    A number of advances in clinical practice that are considered routine in modern allogeneic transplant programmes lack definitive supporting evidence, partly because they may offer modest incremental benefits that are difficult to demonstrate in a statistically robust manner given the relatively small cohorts of patients who undergo such procedures. Nevertheless, these marginal gains probably contribute therapeutically meaningful overall benefit, particularly when aggregated. We review the evidence for a number of these practices in terms of impact on transplant outcomes, with particular reference to the setting of T cell depletion as widely practiced in the United Kingdom, including high resolution tissue typing, surveillance for and therapy of infectious complications, chimerism-directed immune modulation and more sensitive monitoring for residual or progressive disease.

  12. Allogeneic cell therapy bioprocess economics and optimization: downstream processing decisions.

    Science.gov (United States)

    Hassan, Sally; Simaria, Ana S; Varadaraju, Hemanthram; Gupta, Siddharth; Warren, Kim; Farid, Suzanne S

    2015-01-01

    To develop a decisional tool to identify the most cost effective process flowsheets for allogeneic cell therapies across a range of production scales. A bioprocess economics and optimization tool was built to assess competing cell expansion and downstream processing (DSP) technologies. Tangential flow filtration was generally more cost-effective for the lower cells/lot achieved in planar technologies and fluidized bed centrifugation became the only feasible option for handling large bioreactor outputs. DSP bottlenecks were observed at large commercial lot sizes requiring multiple large bioreactors. The DSP contribution to the cost of goods/dose ranged between 20-55%, and 50-80% for planar and bioreactor flowsheets, respectively. This analysis can facilitate early decision-making during process development.

  13. Allogeneic Mesenchymal Stem Cell Transplantation in Dogs With Keratoconjunctivitis Sicca

    Science.gov (United States)

    Bittencourt, Maura K. W.; Barros, Michele A.; Martins, João Flávio P.; Vasconcellos, Jose Paulo C.; Morais, Bruna P.; Pompeia, Celine; Bittencourt, Matheus Domingues; Evangelho, Karine dos Santos; Kerkis, Irina; Wenceslau, Cristiane V.

    2016-01-01

    Keratoconjunctivitis sicca (KCS) is a dysfunction in tear production associated with clinical signs, which include conjunctival hyperemia, ocular discharge, discomfort, pain, and, eventually, corneal vascularization and pigmentation. Immunosuppressive drugs are routinely administrated for long periods to treat KCS but with side effects and limited results. Evaluation of the clinical benefits of intralacrimal transplantation of allogeneic mesenchymal stem cells (MSCs) in dogs with mild–moderate and severe KCS was done. A total of 24 eyes with KCS from 15 dogs of different breeds were enrolled in the present study. A single transplantation of MSCs (1 × 106) directly into lacrimal glands (dorsal and third eyelid) was performed. The Schirmer tear tests (STTs) and ocular surface improvements were used to assess short- and long-term effects of these cells. The STTs were carried out on day 0 (before MSCs transplantation) and on days 7, 14, 21, and 28, as well as 6 and 12 months after MSC transplantation. Our data demonstrate that allogeneic MSC transplantation in KCS dogs is safe since no adverse effects were observed immediately after transplantation and in short- and long-term follow-ups. A statistically significant increase in the STT and ocular surface improvements was found in all eyes studied. In all the eyes with mild–moderate KCS, STT values reverted to those of healthy eyes, while in eyes with severe KCS, although complete reversion was not found, there was improvement in tear production and in other clinical signs. Our study shows that a single dose of a low number of MSCs can be used to treat KCS in dogs. In contrast to immunosuppressive drug use, MSC transplantation has an effect over a long period (up to 12 months), even after a single administration, and does not require daily drug administration. PMID:28003932

  14. Pulpal regeneration following allogenic tooth transplantation into mouse maxilla.

    Science.gov (United States)

    Unno, Hideki; Suzuki, Hironobu; Nakakura-Ohshima, Kuniko; Jung, Han-Sung; Ohshima, Hayato

    2009-04-01

    Autogenic tooth transplantation is now a common procedure in dentistry for replacing a missing tooth. However, there are many difficulties in clinical application of allogenic tooth transplantation because of immunological rejection. This study aims to clarify pulpal regeneration following allogenic tooth transplantation into the mouse maxilla by immunohistochemistry for 5-bromo-2'-deoxyuridine (BrdU) and nestin, and by the histochemistry for tartrate-resistant acid phosphatase (TRAP). The upper right first molar (M1) of 2-week-old mice was extracted and allografted in the original socket in both the littermate and non-littermate after the extraction of M1. Tooth transplantation weakened the nestin-positive reactions in the pulp tissue that had shown immunoreactivity for nestin before operation. On postoperative Days 5-7, tertiary dentin formation commenced next to the preexisting dentin where nestin-positive odontoblast-like cells were arranged in all cases of the littermate group until Day 14, except for one case showing immunological rejection in the pulp chamber. In the non-littermate group, bone-like tissue formation occurred in the pulp chamber in addition to tertiary dentin formation until Day 14. The rate of tertiary dentin was 38%, and the rate of the mixed form of dentin and bone-like tissue formation was 23% (the remainder was immunological rejection). Interestingly, the periodontal tissue recovered even in the case of immunological rejection in which the pulp chamber was replaced by sparse connective tissue. These results suggest that the selection of littermate or non-littermate is decisive for the survival of odontoblast-lineage cells and that the immunological rejection does not influence the periodontal regeneration.

  15. Vascular graft infections with Mycoplasma

    DEFF Research Database (Denmark)

    Levi-Mazloum, Niels Donald; Skov Jensen, J; Prag, J;

    1995-01-01

    Vascular graft infection is one of the most serious complications in vascular surgery. It is associated with mortality rates ranging from 25% to 75% and with morbidity in the form of amputation in approximately 30% of patients. Staphylococcus aureus is the leading pathogen. With conventional...... laboratory techniques, the percentage of culture-negative yet grossly infected vascular grafts seems to be increasing and is not adequately explained by the prior use of antibiotics. We have recently reported the first case of aortic graft infection with Mycoplasma. We therefore suggest the hypothesis...... that the large number of culture-negative yet grossly infected vascular grafts may be due to Mycoplasma infection not detected with conventional laboratory technique....

  16. Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies

    Science.gov (United States)

    2009-10-14

    Immunologic Deficiency Syndromes; Chediak-Higashi Syndrome; Common Variable Immunodeficiency; Graft Versus Host Disease; X-Linked Lymphoproliferative Syndrome; Familial Erythrophagocytic Lymphohistiocytosis; Hemophagocytic Lymphohistiocytosis; X-linked Agammaglobulinemia; Wiskott-Aldrich Syndrome; Chronic Granulomatous Disease; X-linked Hyper IgM Syndrome; Severe Combined Immunodeficiency; Leukocyte Adhesion Deficiency Syndrome; Virus-Associated Hemophagocytic Syndrome

  17. Synthesis and characterization of polypyrrole grafted chitin

    Science.gov (United States)

    Ramaprasad, A. T.; Latha, D.; Rao, Vijayalakshmi

    2017-05-01

    Synthesis and characterization of chitin grafted with polypyrrole (PPy) is reported in this paper. Chitin is soaked in pyrrole solution of various concentrations for different time intervals and polymerized using ammonium peroxy disulphate (APS) as an initiator. Grafting percentage of polypyrrole onto chitin is calculated from weight of chitin before and after grafting. Grafting of polymer is further verified by dissolution studies. The grafted polymer samples are characterized by FTIR, UV-Vis absorption spectrum, XRD, DSC, TGA, AFM, SEM and conductivity studies.

  18. Evaluation of autogenous grafts used in vestibuloplasty.

    Science.gov (United States)

    Metin, M; Dolanmaz, D; Alkan, A

    2003-01-01

    Vestibuloplasty is indicated when prosthesis stability is poor due to mandibular or maxillary atrophy. The use of autogenous grafts to provide sufficient vestibular depth is widely accepted. In this retrospective study, the outcomes of vestibuloplasty performed on 41 patients using various types of autogenous grafts (full-thickness skin, dermal, reversed dermal, meshed skin and palatal mucosal) are presented. The best results were obtained with palatal mucosal grafts, but graft size is limited. Meshed skin grafts were shown to be the best alternative.

  19. Socially disadvantaged parents of children treated with allogeneic haematopoietic stem cell transplantation (HSCT)

    DEFF Research Database (Denmark)

    Larsen, Hanne Bækgaard; Heilmann, Carsten; Johansen, Christoffer

    2013-01-01

    PURPOSE: This study was undertaken to test a daily Family Navigator Nurse (FNN) conducted intervention program, to support parents during the distressful experience of their child's Allogeneic Haematopoietic Stem Cell Transplantation (HSCT). METHODS: A qualitative analysis of the supportive...

  20. Comparison of immune reconstitution after allogeneic vs. autologous stem cell transplantation in 182 pediatric recipients

    Directory of Open Access Journals (Sweden)

    V. Wiegering

    2017-03-01

    Conclusion: Children undergoing a HSCT show a different pattern of immune reconstitution in the allogeneic and autologous setting. This might influence the outcome and should affect the clinical handling of infectious prophylaxis and re-vaccinations.

  1. The risks of using allogeneic cell lines for vaccine production: the example of Bovine Neonatal Pancytopenia.

    Science.gov (United States)

    Benedictus, Lindert; Bell, Charlotte R

    2017-01-01

    Bovine neonatal pancytopenia (BNP) is a hemorrhagic disease that emerged in calves across Europe in 2007. Its occurrence is attributed to immunization of the calf's mother with a vaccine produced using an allogeneic cell line. Vaccine-induced alloantibodies specific for major-histocompatibility class I antigens are transferred from the mother to the calf via colostrum, leading to profound depletion of peripheral blood and bone marrow cells that is often fatal. Areas covered: Pubmed and Web of Science were used to search for literature relevant to BNP and the use of allogeneic vaccine cell lines. Following a review of the pathology and pathogenesis of this novel condition, we discuss potential risks associated with the use of allogeneic vaccine cell lines. Expert commentary: Although BNP is associated with a specific vaccine, it highlights safety concerns common to all vaccines produced using allogeneic cell lines. Measures to prevent similar vaccine-induced alloimmune-mediated adverse events in the future are discussed.

  2. Differential effect of conditioning regimens on cytokine responses during allogeneic stem cell transplantation

    DEFF Research Database (Denmark)

    Andersen, J; Heilmann, C; Jacobsen, N

    2006-01-01

    The purpose of this study was to characterize cytokine responses during conditioning in patients undergoing allogeneic stem cell transplantation (SCT) with the aim to identify which markers that may reliably reflect inflammatory activity during conditioning. We investigated inflammatory and anti-...

  3. Bone Grafting: Sourcing, Timing, Strategies, and Alternatives.

    Science.gov (United States)

    Egol, Kenneth A; Nauth, Aaron; Lee, Mark; Pape, Hans-Christoph; Watson, J Tracy; Borrelli, Joseph

    2015-12-01

    Acute fractures, nonunions, and nonunions with bone defects or osteomyelitis often need bone graft to facilitate union. There are several factors to consider when it is determined that a bone graft is needed. These factors include the source of the bone graft (autograft vs. allograft), proper timing for placement of the bone graft, strategies to avoid further complications (particularly in the setting of osteomyelitis), and with the development of a variety of bone graft substitutes, whether alternatives to autograft are available and appropriate for the task at hand. Autograft bone has commonly been referred to as the "gold standard" of bone grafts, against which the efficacy of other grafts has been measured. The best timing for when to place a bone graft or substitute is also somewhat controversial, particularly after an open fracture or a potentially contaminated bed. The treatment of infected nonunions, particularly those that require a graft to facilitate healing, can be quite challenging. Typically, the infection is completely eradicated before placement of a bone graft, but achieving a sterile bed and the timing of a bone graft require strategic thinking and planning. This review outlines the benefits of autografts, the most suitable sites for harvesting bone grafts, the timing of bone graft procedures, the potential risks and benefits of grafting in the face of infection, and the currently available bone graft extenders.

  4. Increased T cell glucose uptake reflects acute rejection in lung grafts

    Science.gov (United States)

    Chen, Delphine L.; Wang, Xingan; Yamamoto, Sumiharu; Carpenter, Danielle; Engle, Jacquelyn T.; Li, Wenjun; Lin, Xue; Kreisel, Daniel; Krupnick, Alexander S.; Huang, Howard J.; Gelman, Andrew E.

    2013-01-01

    Although T cells are required for acute lung rejection, other graft-infiltrating cells such as neutrophils accumulate in allografts and are also high glucose utilizers. Positron emission tomography (PET) with the glucose probe [18F]fluorodeoxyglucose ([18F]FDG) has been employed to image solid organ acute rejection, but the sources of glucose utilization remain undefined. Using a mouse model of orthotopic lung transplantation, we analyzed glucose probe uptake in the grafts of syngeneic and allogeneic recipients with or without immunosuppression treatment. Pulmonary microPET scans demonstrated significantly higher [18F]FDG uptake in rejecting allografts when compared to transplanted lungs of either immunosuppressed or syngeneic recipients. [18F]FDG uptake was also markedly attenuated following T cell depletion therapy in lung recipients with ongoing acute rejection. Flow-cytometric analysis using the fluorescent deoxyglucose analog 2-NBDG revealed that T cells, and in particular CD8+ T cells, were the largest glucose utilizers in acutely rejecting lung grafts followed by neutrophils and antigen presenting cells. These data indicate that imaging modalities tailored toward assessing T cell metabolism may be useful in identifying acute rejection in lung recipients PMID:23927673

  5. Early and late oral features of chronic graft-versus-host disease

    Directory of Open Access Journals (Sweden)

    Alessandra Oliveira Ferrari Gomes

    2014-01-01

    Full Text Available Background: Chronic graft-versus-host disease is a serious complication of allogeneic hematopoietic cell transplantation, and the mouth is one of the affected sites. Objective: The aim of this study was to evaluate the oral features of this disease after hematopoietic cell transplantation. Methods: This was a cross-sectional multicenter study that enrolled patients submitted to transplantation. Oral evaluations used the National Institutes of Health criteria, salivary flow rates, and the range of mouth opening. Pain and xerostomia were evaluated through a visual analogue scale. Patients were divided into two groups based on the transplantation time (up to one year and more than one year. Results: Of the 57 evaluated recipients, 44 had chronic graft-versus-host disease: ten (22.72% in the group with less than one year after transplantation, and 34 (77.27% in the group with more than one year after transplantation. Lichenoid/hyperkeratotic plaques, erythematous lesions, xerostomia, and hyposalivation were the most commonly reported oral features. Lichenoid/hyperkeratotic plaques were significantly more common in patients within the first year after the transplant. The labial mucosa was affected more in the first year. No significant changes occurred in the frequency of xerostomia, hyposalivation, and reduced mouth opening regarding time after transplantation. Conclusion: Oral chronic graft-versus-host disease lesions were identified early in the course of the disease. The changes observed in salivary gland function and in the range of mouth opening were not correlated with the time after transplantation.

  6. Comparative biomechanical and microstructural analysis of native versus peracetic acid-ethanol treated cancellous bone graft.

    Science.gov (United States)

    Rauh, Juliane; Despang, Florian; Baas, Jorgen; Liebers, Cornelia; Pruss, Axel; Gelinsky, Michael; Günther, Klaus-Peter; Stiehler, Maik

    2014-01-01

    Bone transplantation is frequently used for the treatment of large osseous defects. The availability of autologous bone grafts as the current biological gold standard is limited and there is a risk of donor site morbidity. Allogenic bone grafts are an appealing alternative, but disinfection should be considered to reduce transmission of infection disorders. Peracetic acid-ethanol (PE) treatment has been proven reliable and effective for disinfection of human bone allografts. The purpose of this study was to evaluate the effects of PE treatment on the biomechanical properties and microstructure of cancellous bone grafts (CBG). Forty-eight human CBG cylinders were either treated by PE or frozen at -20 °C and subjected to compression testing and histological and scanning electron microscopy (SEM) analysis. The levels of compressive strength, stiffness (Young's modulus), and fracture energy were significantly decreased upon PE treatment by 54%, 59%, and 36%, respectively. Furthermore, PE-treated CBG demonstrated a 42% increase in ultimate strain. SEM revealed a modified microstructure of CBG with an exposed collagen fiber network after PE treatment. We conclude that the observed reduced compressive strength and reduced stiffness may be beneficial during tissue remodeling thereby explaining the excellent clinical performance of PE-treated CBG.

  7. Comparative Biomechanical and Microstructural Analysis of Native versus Peracetic Acid-Ethanol Treated Cancellous Bone Graft

    Directory of Open Access Journals (Sweden)

    Juliane Rauh

    2014-01-01

    Full Text Available Bone transplantation is frequently used for the treatment of large osseous defects. The availability of autologous bone grafts as the current biological gold standard is limited and there is a risk of donor site morbidity. Allogenic bone grafts are an appealing alternative, but disinfection should be considered to reduce transmission of infection disorders. Peracetic acid-ethanol (PE treatment has been proven reliable and effective for disinfection of human bone allografts. The purpose of this study was to evaluate the effects of PE treatment on the biomechanical properties and microstructure of cancellous bone grafts (CBG. Forty-eight human CBG cylinders were either treated by PE or frozen at −20°C and subjected to compression testing and histological and scanning electron microscopy (SEM analysis. The levels of compressive strength, stiffness (Young’s modulus, and fracture energy were significantly decreased upon PE treatment by 54%, 59%, and 36%, respectively. Furthermore, PE-treated CBG demonstrated a 42% increase in ultimate strain. SEM revealed a modified microstructure of CBG with an exposed collagen fiber network after PE treatment. We conclude that the observed reduced compressive strength and reduced stiffness may be beneficial during tissue remodeling thereby explaining the excellent clinical performance of PE-treated CBG.

  8. Memory CD4+ T cells do not induce graft-versus-host disease.

    Science.gov (United States)

    Anderson, Britt E; McNiff, Jennifer; Yan, Jun; Doyle, Hester; Mamula, Mark; Shlomchik, Mark J; Shlomchik, Warren D

    2003-07-01

    Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality in allogeneic stem cell transplantation (alloSCT). Donor T cells that accompany stem cell grafts cause GVHD by attacking recipient tissues; therefore, all patients receive GVHD prophylaxis by depletion of T cells from the allograft or through immunosuppressant drugs. In addition to providing a graft-versus-leukemia effect, donor T cells are critical for reconstituting T cell-mediated immunity. Ideally, immunity to infectious agents would be transferred from donor to host without GVHD. Most donors have been exposed to common pathogens and have an increased precursor frequency of memory T cells against pathogenic antigens. We therefore asked whether memory CD62L-CD44+ CD4+ T cells would induce less GVHD than unfractionated or naive CD4+ T cells. Strikingly, we found that memory CD4 cells induced neither clinical nor histologic GVHD. This effect was not due to the increased number of CD4+CD25+ regulatory T cells found in the CD62L-CD44+ fraction because memory T cells depletion of these cells did not cause GVHD. Memory CD4 cells engrafted and responded to antigen both in vivo and in vitro. If these murine results are applicable to human alloSCT, selective administration of memory T cells could greatly improve post-transplant immune reconstitution.

  9. Combination of acellular nerve graft and schwann cells-like cells for rat sciatic nerve regeneration.

    Science.gov (United States)

    Gao, Songtao; Zheng, Yan; Cai, Qiqing; Deng, Zhansheng; Yao, Weitao; Wang, Jiaqiang; Wang, Xin; Zhang, Peng

    2014-01-01

    To investigate the effect of tissue engineering nerve on repair of rat sciatic nerve defect. Forty-five rats with defective sciatic nerve were randomly divided into three groups. Rats in group A were repaired by acellular nerve grafts only. Rats in group B were repaired by tissue engineering nerve. In group C, rats were repaired by autogenous nerve grafts. After six and twelve weeks, sciatic nerve functional index (SFI), neural electrophysiology (NEP), histological and transmission electron microscope observation, recovery ratio of wet weight of gastrocnemius muscle, regenerated myelinated nerve fibers number, nerve fiber diameter, and thickness of the myelin sheath were measured to assess the effect. After six and twelve weeks, the recovery ratio of SFI and wet weight of gastrocnemius muscle, NEP, and the result of regenerated myelinated nerve fibers in groups B and C were superior to that of group A (P 0.05). The tissue engineering nerve composed of acellular allogenic nerve scaffold and Schwann cells-like cells can effectively repair the nerve defect in rats and its effect was similar to that of the autogenous nerve grafts.

  10. Activated allogeneic NK cells preferentially kill poor prognosis B-cell chronic lymphocytic leukemia cells

    OpenAIRE

    2016-01-01

    Mutational status of TP53 together with expression of wild type (wt) IGHV represents the most widely accepted biomarkers, establishing a very poor prognosis in B-cell chronic lymphocytic leukemia (B-CLL) patients. Adoptive cell therapy using allogeneic HLA mismatched Natural Killer (NK) cells has emerged as an effective and safe alternative in the treatment of acute myeloid and lymphoid leukemias that do not respond to traditional therapies. We have described that allogeneic activated NK cell...

  11. The Role of Cortical Plasticity in Recovery of Function Following Allogeneic Hand Transplantation

    Science.gov (United States)

    2016-10-01

    AWARD NUMBER: W81XWH-13-1-0496 TITLE: The Role of Cortical Plasticity in Recovery of Function Following Allogeneic Hand Transplantation ...TITLE AND SUBTITLE The Role of Cortical Plasticity in Recovery of Function Following Allogeneic Hand Transplantation 5a. CONTRACT NUMBER W81XWH-13-1-0496...significant progress on data collection in our multi-day protocol. Our preliminary findings continue to indicate that: 1) Hand transplant recipients

  12. Autologous bone graft versus demineralized bone matrix in internal fixation of ununited long bones

    Directory of Open Access Journals (Sweden)

    Rubenbauer Bianka

    2009-12-01

    Full Text Available Abstract Background Non-unions are severe complications in orthopaedic trauma care and occur in 10% of all fractures. The golden standard for the treatment of ununited fractures includes open reduction and internal fixation (ORIF as well as augmentation with autologous-bone-grafting. However, there is morbidity associated with the bone-graft donor site and some patients offer limited quantity or quality of autologous-bone graft material. Since allogene bone-grafts are introduced on the market, this comparative study aims to evaluate healing characteristics of ununited bones treated with ORIF combined with either iliac-crest-autologous-bone-grafting (ICABG or demineralized-bone-matrix (DBM. Methods and results From 2000 to 2006 out of sixty-two consecutive patients with non-unions presenting at our Level I Trauma Center, twenty patients had ununited diaphyseal fractures of long bones and were treated by ORIF combined either by ICABG- (n = 10 or DBM-augmentation (n = 10. At the time of index-operation, patients of the DBM-group had a higher level of comorbidity (ASA-value: p = 0.014. Mean duration of follow-up was 56.6 months (ICABG-group and 41.2 months (DBM-group. All patients were clinically and radiographically assessed and adverse effects related to bone grafting were documented. The results showed that two non-unions augmented with ICABG failed osseous healing (20% whereas all non-unions grafted by DBM showed successful consolidation during the first year after the index operation (p = 0.146. No early complications were documented in both groups but two patients of the ICABG-group suffered long-term problems at the donor site (20% (p = 0.146. Pain intensity were comparable in both groups (p = 0.326. However, patients treated with DBM were more satisfied with the surgical procedure (p = 0.031. Conclusion With the use of DBM, the costs for augmentation of the non-union-site are more expensive compared to ICABG (calculated difference: 160

  13. Autologous bone graft versus demineralized bone matrix in internal fixation of ununited long bones.

    Science.gov (United States)

    Pieske, Oliver; Wittmann, Alexandra; Zaspel, Johannes; Löffler, Thomas; Rubenbauer, Bianka; Trentzsch, Heiko; Piltz, Stefan

    2009-12-15

    Non-unions are severe complications in orthopaedic trauma care and occur in 10% of all fractures. The golden standard for the treatment of ununited fractures includes open reduction and internal fixation (ORIF) as well as augmentation with autologous-bone-grafting. However, there is morbidity associated with the bone-graft donor site and some patients offer limited quantity or quality of autologous-bone graft material. Since allogene bone-grafts are introduced on the market, this comparative study aims to evaluate healing characteristics of ununited bones treated with ORIF combined with either iliac-crest-autologous-bone-grafting (ICABG) or demineralized-bone-matrix (DBM). From 2000 to 2006 out of sixty-two consecutive patients with non-unions presenting at our Level I Trauma Center, twenty patients had ununited diaphyseal fractures of long bones and were treated by ORIF combined either by ICABG- (n = 10) or DBM-augmentation (n = 10). At the time of index-operation, patients of the DBM-group had a higher level of comorbidity (ASA-value: p = 0.014). Mean duration of follow-up was 56.6 months (ICABG-group) and 41.2 months (DBM-group). All patients were clinically and radiographically assessed and adverse effects related to bone grafting were documented. The results showed that two non-unions augmented with ICABG failed osseous healing (20%) whereas all non-unions grafted by DBM showed successful consolidation during the first year after the index operation (p = 0.146). No early complications were documented in both groups but two patients of the ICABG-group suffered long-term problems at the donor site (20%) (p = 0.146). Pain intensity were comparable in both groups (p = 0.326). However, patients treated with DBM were more satisfied with the surgical procedure (p = 0.031). With the use of DBM, the costs for augmentation of the non-union-site are more expensive compared to ICABG (calculated difference: 160 euro/case). Nevertheless, this study demonstrated that the

  14. [Chemokine Receptor-5 and Graft-versus-Host Disease].

    Science.gov (United States)

    Yuan, Jing; Liu, Wei; Ren, Han-Yun

    2015-06-01

    Chemokine receptor-5 (CCR5) belongs to a G-protein coupled receptors superfamily. It is mainly expressed on a wide variety of immune cells. CCR5 can bind with its specific ligands, which plays very important roles in inflammatory cell growth, differentiation, activation, adhesion and migration. CCR5 was identified as a co-receptor for human immunodeficiency virus type-1 (HIV-1) to infect CD4+ T cells. In addition, CCR5 not only participates in the pathogenic mechanisms of many inflammation disease such as AIDS, auto-immune disease, and atherosclerosis, but also plays important roles in the development of acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Recent studies using murine models have demonstrated the critical role of CCR5 and its ligands which direct T-cell infiltration and recruitment into target tissues during acute GVHD. CCR5 has become the focus of intense interest and discussion, and this review will attempt to describe what is understood about the structure and function, internalization, signal transduction of CCR5, in order to investigate the relationship between CCR5 and acute GVHD.

  15. Pathways analysis of differential gene expression induced by engrafting doses of total body irradiation for allogeneic bone marrow transplantation in mice.

    Science.gov (United States)

    Chen, Xinjian; Wang, Yuanyuan; Li, Qiuxia; Tsai, Schickwann; Thomas, Alun; Shizuru, Judith A; Cao, Thai M

    2013-08-01

    A major challenge in allogeneic bone marrow (BM) transplantation is overcoming engraftment resistance to avoid the clinical problem of graft rejection. Identifying gene pathways that regulate BM engraftment may reveal molecular targets for overcoming engraftment barriers. Previously, we developed a mouse model of BM transplantation that utilizes recipient conditioning with non-myeloablative total body irradiation (TBI). We defined TBI doses that lead to graft rejection, that conversely are permissive for engraftment, and mouse strain variation with regards to the permissive TBI dose. We now report gene expression analysis, using Agilent Mouse 8x60K microarrays, in spleens of mice conditioned with varied TBI doses for correlation to the expected engraftment phenotype. The spleens of mice given engrafting doses of TBI, compared with non-engrafting TBI doses, demonstrated substantially broader gene expression changes, significant at the multiple testing-corrected P change ≥2. Functional analysis revealed significant enrichment for a down-regulated canonical pathway involving B-cell development. Genes enriched in this pathway suggest that suppressing donor antigen processing and presentation may be pivotal effects conferred by TBI to enable engraftment. Regardless of TBI dose and recipient mouse strain, pervasive genomic changes related to inflammation was observed and reflected by significant enrichment for canonical pathways and association with upstream regulators. These gene expression changes suggest that macrophage and complement pathways may be targeted to overcome engraftment barriers. These exploratory results highlight gene pathways that may be important in mediating BM engraftment resistance.

  16. Use of ubiquitous, highly heterozygous copy number variants and digital droplet polymerase chain reaction to monitor chimerism after allogeneic haematopoietic stem cell transplantation.

    Science.gov (United States)

    Whitlam, John B; Ling, Ling; Swain, Michael; Harrington, Tom; Mirochnik, Oksana; Brooks, Ian; Cronin, Sara; Challis, Jackie; Petrovic, Vida; Bruno, Damien L; Mechinaud, Francoise; Conyers, Rachel; Slater, Howard

    2017-01-29

    Chimerism analysis has an important role in the management of allogeneic hematopoietic stem cell transplantation. It informs response to disease relapse, graft rejection, and graft-versus-host disease. We have developed a method for chimerism analysis using ubiquitous copy number variation (CNV), which has the benefit of a "negative background" against which multiple independent informative markers are quantified using digital droplet polymerase chain reaction. A panel of up to 38 CNV markers with homozygous deletion frequencies of approximately 0.4-0.6 were used. Sensitivity, precision, reproducibility, and informativity were assessed. CNV chimerism results were compared against established fluorescence in situ hybridization, single nucleotide polymorphism, and short tandem repeat-based methods with excellent correlation. Using 30 ng of input DNA per well, the limit of detection was 0.05% chimerism and the limit of quantification was 0.5% chimerism. High informativity was seen with a median of four informative markers detectable per individual in 39 recipients and 43 donor genomes studied. The strength of this approach was exemplified in a multiple donor case involving four genomes (three related). The precision, sensitivity, and informativity of this approach recommend it for use in clinical practice.

  17. Second allogeneic stem cell transplant for aplastic anaemia: a retrospective study by the Severe Aplastic Anaemia Working Party of the European Society for Blood and Marrow Transplantation.

    Science.gov (United States)

    Cesaro, Simone; Peffault de Latour, Regis; Tridello, Gloria; Pillon, Marta; Carlson, Kristina; Fagioli, Franca; Jouet, Jean-Pierre; Koh, Mickey B C; Panizzolo, Irene Sara; Kyrcz-Krzemien, Slawomira; Maertens, Johan; Rambaldi, Alessandro; Strahm, Brigitte; Blaise, Didier; Maschan, Alexei; Marsh, Judith; Dufour, Carlo

    2015-11-01

    We analysed the outcome of a second allogeneic haematopoietic stem cell transplant (alloHSCT) in 162 patients reported to the European Society for Blood and Marrow Transplantation between 1998 and 2009. Donor origin was a sibling in 110 and an unrelated donor in 52 transplants, respectively. The stem cell source was bone marrow in 31% and peripheral blood in 69% of transplants. The same donor as for the first alloHSCT was used in 81% of transplants whereas a change in the choice of stem cell source was reported in 56% of patients, mainly from bone marrow to peripheral blood. Neutrophil and platelet engraftment occurred in 85% and 72% of patients, after a median time of 15 and 17 days, respectively. Grade II-IV acute graft-versus-host disease (GVHD) and chronic GVHD occurred in 21% and 37% of patients, respectively. Graft failure (GF) occurred in 42 patients (26%). After a median follow-up of 3·5 years, the 5-year overall survival (OS) was 60·7%. In multivariate analysis, the only factor significantly associated with a better outcome was a Karnofsky/Lansky score ≥80 (higher OS). We conclude that a second alloHSCT is feasible rescue option for GF in SAA, with a successful outcome in 60% of cases.

  18. Ceruloplasmin is a potential biomarker for aGvHD following allogeneic hematopoietic stem cell transplantation.

    Directory of Open Access Journals (Sweden)

    Meng Lv

    Full Text Available Acute graft-versus-host-disease (aGvHD is the major cause of non-relapse mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT. Recently, diagnostic biomarkers for aGvHD have been shown to play important roles in evaluating disease status and mortality risk after allo-HSCT. To identify plasma biomarkers for aGvHD with high sensitivity and specificity, a quantitative proteomic approach using 8-plex isobaric tags for relative and absolute quantitation (8-plex iTRAQ was employed to screen differentially expressed proteins in peripheral blood before and after the onset of aGvHD. Four target proteins, ceruloplasmin (CP, myeloperoxidase (MPO, complement factor H (CFH, and alpha-1-acid glycoprotein (AGP, were chosen for preliminary validation with enzyme linked immunosorbent assay (ELISA in 20 paired samples at both the time of diagnosis of aGvHD and the time of complete response. The most promising candidate, ceruloplasmin, was further validated at fixed time points after allo-HSCT and during aGvHD. The plasma ceruloplasmin levels were significantly increased during the period of aGvHD onset and were markedly decreased as aGvHD resolved. The plasma ceruloplasmin levels at different time points post-transplant in the aGvHD (+ group were significantly higher than those in the aGvHD (- group (p<0.001. The elevation of ceruloplasmin level in patients with active aGvHD was independent of infection status. Patients whose ceruloplasmin levels were elevated above 670 μg/ml at 7, 14 and 21 days after allo-HSCT had a remarkably increased probability of subsequently developing aGvHD. In conclusion, our results suggest that plasma ceruloplasmin is a potential plasma biomarker of aGvHD, and it also has prognostic value for risk-adapted prophylaxis during the consecutive time points monitored in the first month after allo-HSCT.

  19. Use of allogeneic platelet gel in the management of chemotherapy extravasation injuries: a case report

    Directory of Open Access Journals (Sweden)

    Di Costanzo G

    2015-02-01

    Full Text Available Gaetano Di Costanzo,1 Giovanna Loquercio,1 Gianpaolo Marcacci,2 Vincenzo Iervolino,1 Stefano Mori,3 Arnolfo Petruzziello,1 Pasquale Barra,1 Carmela Cacciapuoti1 1Transfusion Service, Department of Haematology, National Cancer Institute “G Pascale” Foundation, IRCCS, Naples, Italy; 2Hematology-Oncology and Stem Cell Transplantation Unit, National Cancer Institute “G Pascale” Foundation, IRCCS, Naples, Italy; 3Department of Surgery, Melanoma – Soft Tissues – Head and Neck – Skin Cancers, National Cancer Institute “G Pascale” Foundation, IRCCS, Naples, Italy Abstract: The allogeneic platelet (PLT gel offers to be a valid supportive measure in the management of chemotherapy extravasation injuries. We report a case of a 58-year-old patient with multiple myeloma enrolled for high-dose chemotherapy and autologous stem cell transplantation. As pretransplant therapy, the patient received induction therapy with bortezomib, adriblastina, and desametazone. A port was inserted in the vein on the back of the hand. After three cycles, the patient reported rapid development of redness, pain, and necrotic tissue in the left hand, and a diagnosis of extravasation was addressed. The patient presented a raw area on the back of the hand caused by cytotoxic/chemotherapeutic drug leakage because of the malposition of venous access devices. Skin ulcer was debrided, and the wound was reconstructed with a combination of local random rotational flap and abdomen skin graft. Two weeks later, a 20% skin flap necrosis was observed. In the context of wound healing, topical plasma-rich PLT gel is able to accelerate the regeneration and repair of tissue, so it was set out to assess PLT gel efficacy in this case. The PLT gel was applied topically once every 5 days, for a duration of 60 days on average. There were no adverse reactions observed during the topical therapy. Complete wound healing was observed after 12 PLT-rich plasma applications. No ulcer

  20. Quantitative chimerism kinetics in relapsed leukemia patients after allogeneic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    QIN Xiao-ying; WANG Jing-zhi; ZHANG Xiao-hui; LI Jin-lan; LI Ling-di; LIU Kai-yan; HUANG Xiao-jun; LI Guo-xuan; QIN Ya-zhen; WANG Yu; WANG Feng-rong; LIU Dai-hong; XU Lan-ping; CHEN Huan; HAN Wei

    2012-01-01

    Background Chimerism analysis is an important tool for the surveillance of post-transplant engraftment.It offers the possibility of identifying impending graft rejection and recurrence of underlying malignant or non-malignant disease.Here we investigated the quantitative chimerism kinetics of 21 relapsed leukemia patients after allogeneic hematopoietic stem cell transplantation (HSCT).Methods A panel of 29 selected sequence polymorphism (SP) markers was screened by real-time polymerase chain reaction (RT-PCR) to obtain the informative marker for every leukemia patient.Quantitative chimerism analysis of bone marrow (BM) samples of 21 relapsed patients and 20 patients in stable remission was performed longitudinally.The chimerisms of BM and peripheral blood (PB) samples of 14 patients at relapse were compared.Results Twenty-one patients experienced leukemia relapse at a median of 135 days (range,30-720 days) after transplantation.High recipient chimerism in BM was found in all patients at relapse,and increased recipient chimerism in BM samples was observed in 90% (19/21) of patients before relapse.With 0.5% recipient DNA as the cut-off,median time between the detection of increased recipient chimerism and relapse was 45 days (range,0-120 days),with 76% of patients showing increased recipient chimerism at least 1 month prior to relapse.Median percentage of recipient DNA in 20 stable remission patients was 0.28%,0.04%,0.05%,0.05%,0.08%,and 0.05% at 1,2,3,6,9,and 12 months,respectively,after transplantation.This was concordant with other specific fusion transcripts and fluorescent in situ hybridization examination.The recipient chimerisms in BM were significantly higher than those in PB at relapse (P=0.001).Conclusions This SP-based RT-PCR essay is a reliable method for chimerism analysis.Chimerism kinetics in BM can be used as a marker of impending leukemia relapse,especially when no other specific marker is available.Based on our findings

  1. Soluble Interleukin-7 receptor levels and risk of acute graft-versus-disease after allogeneic haematopoietic stem cell transplantation

    DEFF Research Database (Denmark)

    Kielsen, Katrine; Shamim, Zaiba; Thiant, Stephanie

    2017-01-01

    Interleukin-7 is a cytokine essential for T cell homeostasis. IL-7 binds to cellular IL-7 receptors in competition with a soluble form of the receptor (sIL-7Rα). We hypothesized that altered sIL-7Rα levels may cause adverse outcomes in patients undergoing HSCT. In parallel, we investigated...... the impact of the IL-7Rα SNP rs6897932, which has been associated with release of IL-7R. The sIL-7Rα levels decreased during HSCT (from 114ng/ml before to 48ng/ml at day +14 (PsIL-7Rα ratio at day +14 was significantly higher in patients...... developing grade II-IV aGVHD (OR=4.3, P=0.026). Furthermore, donor carriage of the rs6897932 T allele was associated with reduced sIL-7Rα levels, increased risk of grade II-IV aGVHD (OR=2.4, P=0.055) and increased transplant-related mortality (CC=4.5%, CT=21.4% and TT=27.3%, P=0.0037). In conclusion...

  2. Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts in Preventing GVHD in Children

    Science.gov (United States)

    2016-10-06

    Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Acute Biphenotypic Leukemia; Acute Leukemia of Ambiguous Lineage; Acute Myeloid Leukemia in Remission; Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Childhood Acute Lymphoblastic Leukemia in Remission; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; RAEB-1; RAEB-2; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

  3. Assessment of acute intestinal graft versus host disease by abdominal magnetic resonance imaging at 3 Tesla

    Energy Technology Data Exchange (ETDEWEB)

    Budjan, Johannes; Michaely, Henrik J.; Attenberger, Ulrike; Haneder, Stefan; Schoenberg, Stefan O. [Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim (Germany); Heidenreich, Daniela; Kreil, Sebastian; Nolte, Florian; Hofmann, Wolf-Karsten; Klein, Stefan A. [University Medical Center Mannheim, Department of Hematology and Oncology, Mannheim (Germany)

    2014-08-15

    After allogeneic stem cell transplantation (SCT), a reliable diagnosis of acute graft versus host disease (aGvHD) is essential for an early and successful treatment. It is the aim of this analysis to assess intestinal aGvHD by magnetic resonance imaging (MRI). Prior to allogeneic SCT, 64 consecutive patients underwent abdominal MRI examination on a 3 T MR system, including axial and coronal T2w sequences and a three-dimensional dynamic T1w, contrast enhanced sequence. After SCT, 20 patients with suspected aGvHD received a second MRI as well as an endoscopic examination. Nine patients suffered from histologically proven intestinal aGvHD. In eleven patients intestinal aGvHD was excluded. In all aGvHD patients typical MRI findings with long-segment bowel wall thickening - always involving the terminal ileum - with profound submucosal oedema, were detected. The bowel wall was significantly thickened in patients with intestinal aGvHD. Bowel contrast enhancement spared the submucosa while demonstrating strong mucosal hyperemia. In intestinal aGvHD, a characteristic MR-appearance can be detected. This MRI pattern might facilitate an early and non-invasive diagnosis of intestinal aGvHD. MRI might thus be used as a sensitive tool to rule out or support the clinical diagnosis of aGvHD. (orig.)

  4. The Role of Purine Metabolites as DAMPs in Acute Graft-versus-Host Disease

    Science.gov (United States)

    Apostolova, Petya; Zeiser, Robert

    2016-01-01

    Acute graft-versus-host disease (GvHD) causes high mortality in patients undergoing allogeneic hematopoietic cell transplantation. An early event in the classical pathogenesis of acute GvHD is tissue damage caused by the conditioning treatment or infection that consecutively leads to translocation of bacterial products [pathogen-associated molecular patterns (PAMPs)] into blood or lymphoid tissue, as well as danger-associated molecular patterns (DAMPs), mostly intracellular components that act as pro-inflammatory agents, once they are released into the extracellular space. A subtype of DAMPs is nucleotides, such as adenosine triphosphate released from dying cells that can activate the innate and adaptive immune system by binding to purinergic receptors. Binding to certain purinergic receptors leads to a pro-inflammatory microenvironment and promotes allogeneic T cell priming. After priming, T cells migrate to the acute GvHD target organs, mainly skin, liver, and the gastrointestinal tract and induce cell damage that further amplifies the release of intracellular components. This review summarizes the role of different purinergic receptors in particular P2X7 and P2Y2 as well as nucleotides in the pathogenesis of GvHD.

  5. The role of purine metabolites as DAMPs in acute graft-versus-host disease.

    Directory of Open Access Journals (Sweden)

    Petya Apostolova

    2016-10-01

    Full Text Available Acute graft-versus-host disease (GVHD causes high mortality in patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT. An early event in the classical pathogenesis of acute GVHD is tissue damage caused by the conditioning treatment or infection that consecutively leads to translocation of bacterial products (pathogen-associated molecular patterns, PAMPs into blood or lymphoid tissue, as well as danger-associated molecular patterns (DAMPs, mostly intracellular components which act as pro-inflammatory agents, once they are released into the extracellular space. A subtype of DAMPs are nucleotides such as adenosine triphosphate (ATP released from dying cells that can activate the innate and adaptive immune system by binding to purinergic receptors. Binding to certain purinergic receptors leads to a pro-inflammatory microenvironment and promotes allogeneic T cell priming. After priming, T cells migrate to the acute GVHD target organs, mainly skin, liver and the gastrointestinal tract and induce cell damage which further amplifies the release of intracellular components. This review summarizes the role of different purinergic receptors in particular P2X7 and P2Y2 as well as nucleotides in the pathogenesis of GVHD.

  6. Depletion of naïve lymphocytes with fas ligand ex vivo prevents graft-versus-host disease without impairing T cell support of engraftment or graft-versus-tumor activity.

    Science.gov (United States)

    Askenasy, Nadir; Mizrahi, Keren; Ash, Shifra; Askenasy, Enosh M; Yaniv, Isaac; Stein, Jerry

    2013-02-01

    Graft-versus-host disease (GVHD) can be prevented by Fas-mediated selective depletion of host-sensitized donor lymphocytes ex vivo. We tested the hypothesis that Fas-mediated depletion of lymphocytes in the absence of host-specific antigenic stimulation can alleviate GVHD. Brief exposure (24 hours) of unstimulated donor lymphocytes to Fas ligand (FasL) ex vivo results in balanced apoptosis of CD8(+) and CD4(+) subsets with preferential depletion of CD62L and CD69, increased T regulatory fractions, and sustained responses to stimulation. This procedure ameliorates weight loss and improves the clinical and histologic score of skin and gastrointestinal GVHD with and without concurrent transplantation of hematopoietic progenitors and irrespective of conditioning-induced tissue injury. Although FasL-resistant donor T cells are less potent effectors of GVHD, they facilitate hematopoietic progenitor engraftment when infused with or after the graft and retain the potential to elaborate graft-versus-tumor reactions. These findings in a preclinical model together with the known trophic effects of FasL on primitive hematopoietic progenitors suggest that brief ex vivo incubation of hematopoietic grafts with FasL may improve the outcome and safety of clinical T cell-replete allogeneic and haploidentical transplants.

  7. Treatment of osteochondral defects in the rabbit's knee joint by implantation of allogeneic mesenchymal stem cells in fibrin clots.

    Science.gov (United States)

    Berninger, Markus T; Wexel, Gabriele; Rummeny, Ernst J; Imhoff, Andreas B; Anton, Martina; Henning, Tobias D; Vogt, Stephan

    2013-05-21

    The treatment of osteochondral articular defects has been challenging physicians for many years. The better understanding of interactions of articular cartilage and subchondral bone in recent years led to increased attention to restoration of the entire osteochondral unit. In comparison to chondral lesions the regeneration of osteochondral defects is much more complex and a far greater surgical and therapeutic challenge. The damaged tissue does not only include the superficial cartilage layer but also the subchondral bone. For deep, osteochondral damage, as it occurs for example with osteochondrosis dissecans, the full thickness of the defect needs to be replaced to restore the joint surface (1). Eligible therapeutic procedures have to consider these two different tissues with their different intrinsic healing potential (2). In the last decades, several surgical treatment options have emerged and have already been clinically established (3-6). Autologous or allogeneic osteochondral transplants consist of articular cartilage and subchondral bone and allow the replacement of the entire osteochondral unit. The defects are filled with cylindrical osteochondral grafts that aim to provide a congruent hyaline cartilage covered surface (3,7,8). Disadvantages are the limited amount of available grafts, donor site morbidity (for autologous transplants) and the incongruence of the surface; thereby the application of this method is especially limited for large defects. New approaches in the field of tissue engineering opened up promising possibilities for regenerative osteochondral therapy. The implantation of autologous chondrocytes marked the first cell based biological approach for the treatment of full-thickness cartilage lesions and is now worldwide established with good clinical results even 10 to 20 years after implantation (9,10). However, to date, this technique is not suitable for the treatment of all types of lesions such as deep defects involving the subchondral

  8. Enlargement of the human spleen in graft-versus-host disease.

    Science.gov (United States)

    Dilly, S A; Sloane, J P

    1988-04-01

    The spleens of 49 patients who had undergone allogeneic bone marrow transplantation for leukemia were compared at autopsy to determine the pathological changes associated with graft-versus-host disease (GVHD). The only significant finding was an increase in weight of about 1.7 times that of spleens from patients without GVHD. This was not explained by differences in the patients' sex, length of survival after transplantation, presence of infection, or liver pathology. On histological examination, there was no detectable increase in congestion, siderosis, or numbers of lymphocytes, macrophages, antigen-presenting cells, blast cells, pyknotic cells, plasma cells, or hemopoietic cells to explain the increase in spleen weight. On the contrary, there was actually a reduction in CD8+ T lymphocytes. No proliferative phase of GVHD could be identified, possibly due to a lack of specimens examined less than 8 days after transplantation and to prophylactic measures undertaken to minimize GVHD. The pathogenesis of splenomegaly in human GVHD is unclear.

  9. New Insight for the Diagnosis of Gastrointestinal Acute Graft-versus-Host Disease

    Directory of Open Access Journals (Sweden)

    Florent Malard

    2014-01-01

    Full Text Available Allogeneic stem cell transplantation (allo-SCT is a curative therapy for different life-threatening malignant and nonmalignant hematologic disorders. Graft-versus-host disease (GVHD remains a major source of morbidity and mortality following allo-SCT, which limits the use of this treatment in a broader spectrum of patients. Early diagnostic of GVHD is essential to initiate treatment as soon as possible. Unfortunately, the diagnosis of GVHD may be difficult to establish, because of the nonspecific nature of the associated symptoms and of the numerous differential diagnosis. This is particularly true regarding gastrointestinal (GI acute GVHD. In the recent years many progress has been made in medical imaging test and endoscopic techniques. The interest of these different techniques in the diagnosis of GI acute GVHD has been evaluated in several studies. With this background we review the contributions, limitations, and future prospect of these techniques in the diagnosis of GI acute GVHD.

  10. A case of membranous nephropathy as a manifestation of graft-versus-host disease

    Directory of Open Access Journals (Sweden)

    Jae Hyun Han

    2013-03-01

    Full Text Available Nephrotic syndrome (NS rarely occurs after hematopoietic stem cell transplantation (HSCT as a late manifestation of graft-versus-host disease (GVHD. Herein, we report a case of HSCT-associated membranous nephropathy in a female patient with aplastic anemia. The patient received an allogeneic HSCT from her human leukocyte antigen-identical brother following myeloablative conditioning chemotherapy. NS occurred 21 months after HSCT without any concurrent features of chronic GVHD. The patient was treated with prednisolone and cyclosporine after renal biopsy confirmed membranous nephropathy, and achieved complete remission. Our report contradicts previous assumptions that concomitant chronic GVHD is responsible for the development of NS, suggesting that NS can develop as a new, independent manifestation of GVHD.

  11. ORAL CHRONIC GRAFT VERSUS HOST DISEASE IN AN IMMUNOCOMPETENT PATIENT: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Redwin Dhas Manchi

    2014-06-01

    Full Text Available Graft-versus-host disease (GVHD is a complication which occurs in an individual who has received allogenic transplant. This was first noticed in individuals who had undergone bone marrow transplantation. Since then it has been described in solid organ transplantation and even transfusion of blood and blood products. Transfusion-associated GVHD (TA-GVHD is acute or chronic in nature. Acute TA-GVHD is rare and usually runs a fulminant and fatal course. In its chronic form, oral cavity is frequently affected with wide variety of signs and symptoms resulting in significant short and long-term complications ranging from mucosal sensitivity and limited oral in take to secondary malignancy and early death. Herewith we report a case of oral cGVHD in an immuno competent patient who underwent transfusion of platelets from an unrelated donor

  12. [Research Progress on Notch Signal Pathway in Acute Graft-Versus-Host Disease -Review].

    Science.gov (United States)

    Guo, Dong-Mei; Li, Ban-Ban; Li, Chun-Pu; Teng, Qing-Liang

    2017-02-01

    The Notch signaling pathway is a highly conserved cell signaling system that plays an essential role in many biological processes. Notch signaling regulates multiple aspects of hematopoiesis, especially during T cell develop-ment. Recent data suggest that Notch also regulates mature T cell differentiation and function. The latest data show that Notch also plays an essential role in alloreactive T cells mediating acute graft-versus-host disease (aGVHD), the most severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Notch inhibition in donor-derived T cells or blockade of individual Notch ligands and receptors after transplantation can reduce GVHD severity and mortality in mouse models of allo-HSCT, without causing global immunosuppression. These findings indicate Notch in T cells as an attractive therapeutic target to control aGVHD. In this article, the pathophysiology of aGVHD, the Notch signal pathway and aGVHD are reviewed.

  13. Evolution of skin grafting for treatment of burns: Reverdin pinch grafting to Tanner mesh grafting and beyond.

    Science.gov (United States)

    Singh, Mansher; Nuutila, Kristo; Collins, K C; Huang, Anne

    2017-09-01

    Skin grafting is the current standard care in the treatment of full thickness burns. It was first described around 1500 BC but the vast majority of advancements have been achieved over the past 200 years. An extensive literature review was conducted on Pubmed, Medline and Google Scholar researching the evolution of skin grafting techniques. The authors concentrated on the major landmarks of skin grafting and also provide an overview of ongoing research efforts in this field. The major innovations of skin grafting include Reverdin pinch grafting, Ollier grafting, Thiersch grafting, Wolfe grafting, Padgett dermatome and modifications, Meek-wall microdermatome and Tanner mesh grafting. A brief description of the usage, advantages and limitations of each technique is included in the manuscript. Skin grafting technique have evolved significantly over past 200 years from Reverdin pinch grafting to modern day meshed skin grafts using powered dermatome. Increasing the expansion ratio and improving the cosmetic and functional outcome are the main focus of ongoing skin grafting research and emerging techniques (such as Integra(®), Recell(®), Xpansion(®)) are showing promise. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

  14. Intestinal dysbiosis and allogeneic hematopoietic progenitor cell transplantation

    OpenAIRE

    Raghunathan, Vikram M.; Sheng, Iris; Lim, Seah H.

    2016-01-01

    The intestinal microbiota is a diverse and dynamic ecosystem that is increasingly understood to play a vital role in human health. Hematopoietic stem cell transplant recipients undergo prolonged exposure to antimicrobials, chemotherapeutic agents, and immunosuppressants, resulting in profound shifts in the gut microbiome. A growing body of research has revealed the ways in which these microbiologic shifts shape immune modulation, affecting susceptibility to infections and graft-versus-host di...

  15. Long-term outcomes among older patients following nonmyeloablative conditioning and allogeneic hematopoietic cell transplantation for advanced hematologic malignancies

    DEFF Research Database (Denmark)

    Sorror, Mohamed L; Sandmaier, Brenda M; Storer, Barry E

    2011-01-01

    A minimally toxic nonmyeloablative regimen was developed for allogeneic hematopoietic cell transplantation (HCT) to treat patients with advanced hematologic malignancies who are older or have comorbid conditions....

  16. The changes of vaccinia related kinase 1 in grafted heart after rat heart transplantation

    Science.gov (United States)

    Qian, Shiguo; Yang, Xuechao; Wu, Kunpeng; Lv, Qiangsheng; Zhang, Yuanyuan; Dai, Jiahong; Chen, Cheng

    2014-01-01

    Objective To assess the expression and significance of vaccinia-related kinase 1 (VRK1) after rat heart transplantation. Materials and methods Lewis and Wistar rats weighing 250 to 300 g were used as donors and recipients. Allografts were from Wistar transplanted into Lewis, and isografts were transplanted from Lewis into Lewis. Grafts were harvested at 1, 3, 5, and 7 days after transplantation. We performed Western Blot of heart tissues after cardiac transplantation. To analyze VRK1 express between the isografts and allografts for immunohistochemical staining. At 5th day after heart transplantation use related cytokines VRK1 for immunohistochemical. We used double immunofluorescent staining on transverse cryosections of graft tissues by co-labeling with different markers, including those for VRK1, activate caspase-3, α-actinin, VCAM-1, CD4. Results Compared with rare expression in syngeneic Lewis rat hearts, VRK1 protein level in allogeneic hearts were detected at various survival times after heterotopic heart transplantation, which observably expressed on day 5 postoperative. In addition, we examined the expression of activate caspase-3 in allogeneic hearts, which has a similar expression with VRK1. Immunohistochemical and immunofluorescent method displayed that VRK1 was widely expressed in cytoplasm of cardiac tissue and activate caspase-3 was also expressed in cardiomyocytes. However, the VRK1 wasn’t express in inflammation. Conclusions The VRK1 expression has increased after heart transplantation in allograft and isograft, and VRK1 may play a significant role in myocardial apoptosis after heterotopic heart transplantation in rats. PMID:25589968

  17. IMMUNOBIOLOGY OF ACUTE GRAFT-VERSUS-HOST DISEASE

    Directory of Open Access Journals (Sweden)

    G. A. Efimov

    2015-01-01

    Full Text Available Transplantation of allogeneic hematopoietic stem cells is the only curative option for a number of diseases of hematopoietic system. It is intended to replace the hematopoietic system of the recipient withthe donor’s. However, when mature T cells contained in the graft enter the recipient organism, it may lead to a severe post-transplant complication, the “graft versus host” disease (GVHD. It occurs due to the fact that the donor immune system contains T cell clones specific to recipient alloantigens. These cell clones are activated upon encountering their antigens, thus causing systemic damage to healthy tissues. Development of the alloreactive clones is caused by genetic differences between donor and recipient. The most importantfactors determining successful transplantation concern the compatibility for the genes coding for Major Histocompatibility Complex (MHC, that are expressed in all nucleated cells and are responsible for antigen presentation to the immune cells. Currently established extensive donor banks allow for majority of patients to choose a compatible donor. However, this does not provide complete prevention of the GVHD development, because in addition to the MHC genes the donor and recipient may differ in so-called minor histocompatibility antigens. Minor antigens may be caused by genetic polymorphisms in all of the genome coding regions. Pre-transplantation conditioning of the patient, which is necessary for engraftment represent an additional factor contributing to the GVHDdevelopment, since as its side effect it leads to formation of a pro-inflammatory environment in the organism of recipient. Severe GVHD develops in approximately 40% of MHC-matched patients, while in cases of partial compatibility this proportion is even higher. GVHD causes mortality comparable to other causes of posttransplantdeath, such as viral infections or relapse of underlying disease. Thus, the development of severe GVHD is a

  18. 猪复合皮移植的实验研究%EXperimental study about the grafting of composite skin on swine

    Institute of Scientific and Technical Information of China (English)

    崔正军; 陈璧; 夏磊; 姜笃银; 汤朝武; 施新猷

    2000-01-01

    目的:为使复合皮移植的动物实验结果进一步接近临床,用小香猪作动物模型,探讨复合皮移植的术后效果和成活机制。方法:实验分3组,A组为移植异体普通乳猪真皮+成年小香猪自体表皮皮片;B组为移植异体成年小香猪真皮+成年小香猪自体表皮皮片;C组为移植成年小香猪自体表皮皮片。术后观察3组皮片的存活质量及组织学变化。结果:3组皮片早期成活情况均较好,A组和B组晚期收缩率及瘢痕程度均比C组低。A组和B组的组织学结构较完整,异体普通乳猪真皮的成活情况优于异体成年小香猪真皮。结论:异体真皮的存在能改进复合皮移植的质量,而且以含异体普通乳猪真皮组成的复合皮效果最佳。%Aim: Swine were used as animal models for composite skin to make their experimental results close to clinic, andto explore their survival mechanism and results after the operations. Methods:Three groups were designed:in group A, allogenicdermis of new-borne swine and autologous epidermis grafts were transplanted; but in group B, the allogenic dermis of adult swineand autologous epidermis graft; in group C, only the autologous epidermis graft. After the operations, the grafts were observed andtissue was obtained for histological study. Restults: The survival status in 3 groups were satisfied in early time. The contractiverate and scar forming in group A and group B were lower than those in group C. There was much integral histological structure ingroup A and group B than that in group C, and the survival status in allogenic dermis of new-borne swine was better than that inallogenic dermis of adult swine. C onclusion:Allogenic dermis can improve the composite skin's quality, furthermore, the com-posite skin having allogenic dermis of sucking swine has the best result.

  19. Vestibuloplasty: allograft versus mucosal graft.

    Science.gov (United States)

    Hashemi, H M; Parhiz, A; Ghafari, S

    2012-04-01

    The aim of the present study was to compare the application of alloderm and mucosal graft for vestibuloplasty. This randomized controlled trial with split mouth design was carried out on 20 edentulous patients. Patients underwent vestibuloplasty surgery with the Clark technique. Half of the prepared bed in each patient was covered with alloderm and the other half with mucosal graft. Vestibule depth (width of fixed tissue) and relapse in the two sides immediately after surgery, and 1, 3 and 6 months after surgery were measured and compared. Statistical analysis was carried out using the Kolmogorov-Smirnov, Student's paired t and Friedman tests. The width of the fixed tissue in the alloderm graft at 1, 3 and 6 month intervals was significantly lower than that in the autograft (Pvestibuloplasty. Copyright © 2011 International Association of Oral and Maxillofacial Surgeons. All rights reserved.

  20. Allogenic banking of dental pulp stem cells for innovative therapeutics.

    Science.gov (United States)

    Collart-Dutilleul, Pierre-Yves; Chaubron, Franck; De Vos, John; Cuisinier, Frédéric J

    2015-08-26

    Medical research in regenerative medicine and cell-based therapy has brought encouraging perspectives for the use of stem cells in clinical trials. Multiple types of stem cells, from progenitors to pluripotent stem cells, have been investigated. Among these, dental pulp stem cells (DPSCs) are mesenchymal multipotent cells coming from the dental pulp, which is the soft tissue within teeth. They represent an interesting adult stem cell source because they are recovered in large amount in dental pulps with non-invasive techniques compared to other adult stem cell sources. DPSCs can be obtained from discarded teeth, especially wisdom teeth extracted for orthodontic reasons. To shift from promising preclinical results to therapeutic applications to human, DPSCs must be prepared in clinical grade lots and transformed into advanced therapy medicinal products (ATMP). As the production of patient-specific stem cells is costly and time-consuming, allogenic biobanking of clinical grade human leukocyte antigen (HLA)-typed DPSC lines provides efficient innovative therapeutic products. DPSC biobanks represent industrial and therapeutic innovations by using discarded biological tissues (dental pulps) as a source of mesenchymal stem cells to produce and store, in good manufacturing practice (GMP) conditions, DPSC therapeutic batches. In this review, we discuss about the challenges to transfer biological samples from a donor to HLA-typed DPSC therapeutic lots, following regulations, GMP guidelines and ethical principles. We also present some clinical applications, for which there is no efficient therapeutics so far, but that DPSCs-based ATMP could potentially treat.

  1. Hypomethylating agents after allogeneic blood stem cell transplantation

    Science.gov (United States)

    Rautenberg, Christina; Haas, Rainer; Kobbe, Guido

    2016-01-01

    Allogeneic blood stem cell transplantation (allo-SCT) is a potentially curative treatment for patients with myeloid malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), but relapse remains the major cause of treatment failure. So far, therapeutic options for patients with AML or MDS who relapse after allo-SCT generally consisted of palliative care, low-dose or intensive chemotherapy as well as cellular therapies such as donor lymphocyte infusions (DLI) and second transplantation in selected cases. Nevertheless, the prognosis of patients with myeloid malignancies relapsing after allo-SCT remains dismal therefore asking for novel treatment strategies. Considering their well-balanced profile of good efficacy and moderate toxicity in the non-transplant setting, the hypomethylating agents (HMA) azacitidine (Aza) and decitabine (DAC) have also been tested either alone or in combination with DLI in the post-transplant period. This review summarizes the current knowledge about the use of these two HMA as pre-emptive, salvage or consolidation therapy mostly retrieved from retrospective studies but also from a few prospective trials. Within this review, we also comment on some practical issues such as optimal dose and schedule, the choice of HMA candidates and the role of additional cellular interventions. Finally, we also give an overview on the assumed mode of actions, ongoing research, clinical studies and potential combination partners aiming to improve this treatment approach. PMID:28066786

  2. Allogenic banking of dental pulp stem cells for innovative therapeutics

    Institute of Scientific and Technical Information of China (English)

    Pierre-Yves; Collart-Dutilleul; Franck; Chaubron; John; De; Vos; Frédéric; J; Cuisinier

    2015-01-01

    Medical research in regenerative medicine and cellbased therapy has brought encouraging perspectives for the use of stem cells in clinical trials. Multiple types of stem cells, from progenitors to pluripotent stem cells, have been investigated. Among these, dental pulp stem cells(DPSCs) are mesenchymal multipotent cells coming from the dental pulp, which is the soft tissue within teeth. They represent an interesting adult stem cell source because they are recovered in large amount in dental pulps with non-invasive techniques compared to other adult stem cell sources. DPSCs can be obtained from discarded teeth, especially wisdom teeth extracted for orthodontic reasons. To shift from promising preclinical results to therapeutic applications to human, DPSCs must be prepared in clinical grade lots and transformed into advanced therapy medicinal products(ATMP). As the production of patient-specific stem cells is costly and time-consuming, allogenic biobanking of clinical grade human leukocyte antigen(HLA)-typed DPSC lines provides efficient innovative therapeutic products. DPSC biobanks represent industrial and therapeutic innovations by using discarded biological tissues(dental pulps) as a source of mesenchymal stem cells to produce and store, in good manufacturing practice(GMP) conditions, DPSC therapeutic batches. In this review, we discuss about the challenges to transfer biological samples from a donor to HLA-typed DPSC therapeutic lots, following regulations, GMP guidelines and ethical principles. We also present some clinical applications, for which there is no efficient therapeutics so far, but that DPSCs-based ATMP could potentially treat.

  3. Prevention of primary vascular graft infection with silver-coated polyester graft in a porcine model

    DEFF Research Database (Denmark)

    Gao, H; Sandermann, J; Prag, J;

    2010-01-01

    To evaluate the efficacy of a silver-coated vascular polyester graft in the prevention of graft infection after inoculation with Staphylococcus aureus in a porcine model.......To evaluate the efficacy of a silver-coated vascular polyester graft in the prevention of graft infection after inoculation with Staphylococcus aureus in a porcine model....

  4. Recipient HLA-C Haplotypes and microRNA 148a/b Binding Sites Have No Impact on Allogeneic Hematopoietic Cell Transplantation Outcomes.

    Science.gov (United States)

    Hoff, Gretchen A; Fischer, Johannes C; Hsu, Katharine; Cooley, Sarah; Miller, Jeffrey S; Wang, Tao; Haagenson, Michael; Spellman, Stephen; Lee, Stephanie J; Uhrberg, Markus; Venstrom, Jeffrey M; Verneris, Michael R

    2017-01-01

    Natural killer cells are important in graft-versus-leukemia responses after hematopoietic cell transplantation (HCT). A variety of surface receptors dictates natural killer cell function, including killer cell immunoglobulin-like receptor recognition of HLA-C. Previous single-center studies show that HLA-C epitopes, designated C1 and C2, were associated with allogeneic HCT outcomes; specifically, recipients homozygous for the C1 epitope (C1/C1) experienced a survival benefit. Additionally, mismatching at HLA-C was beneficial in recipients possessing at least 1 C2 allele, whereas the opposite was true for homozygous C1 (C1/C1) recipients where HLA-C mismatching resulted in worse outcomes. In this analysis we aimed to validate these findings in a large multicenter study. We also set out to determine whether surface expression of recipient HLA-C, determined by polymorphism in a microRNA (miR-148a/b) binding site within the 3'-region of the HLA-C transcript, was associated with transplant outcomes. In this large registry cohort, we were unable to confirm the prior findings regarding recipient HLA-C epitope status and outcome. Additionally, HLA-C surface expression (ie, surface density), as predicted by the miR-148a/b binding single nucleotide polymorphism, was also not with associated transplant outcomes. Collectively, neither HLA-C surface expression, as determined by miR-148a/b, nor recipient HLA-C epitopes (C1, C2) are associated with allogeneic HCT outcomes.

  5. Reactivation of hepatitis B infection following allogeneic bone marrow transplantation in a hepatitis B-immune patient: case report and review of the literature.

    Science.gov (United States)

    Kempinska, Anna; Kwak, Eun J; Angel, Jonathan B

    2005-11-01

    Reactivation of hepatitis B virus (HBV) infection following allogeneic bone marrow transplantation is a rare phenomenon. Reverse seroconversion, defined as the clearance of antibody to hepatitis B surface antigen (HBsAb) and the appearance of hepatitis B surface antigen (HBsAg) in a patient with resolved HBV infection (i.e., a HBsAg-negative, HBsAb-positive, hepatitis B core antibody-positive patient) following receipt of a bone marrow transplant is described. A review of related cases in the literature was undertaken to identify clinical features associated with this phenomenon. We present a case of reactivation of HBV infection in a 47-year-old man after receipt of an allogeneic bone marrow transplant for acute myelogenous leukemia. Before undergoing bone marrow transplantation, the presence of HBsAb and hepatitis B core antibody and the absence of HBsAg indicated clearance of natural HBV infection. The donor was HBsAg and HBsAb negative. Twenty-nine months after bone marrow transplantation, the patient developed transaminitis and evidence of active HBV infection (the patient had test results positive for HBsAg, negative for HBsAb, and positive for HBV DNA). A total of 28 other cases of reverse seroconversion have been described in the literature, 11 of which provided adequate information to be summarized in detail together with the present case. Reactivation of HBV infection following bone marrow transplantation appears to occur almost exclusively in patients who have received marrow from an HBsAb-negative donor and have experienced graft-versus-host disease, the onset of which is associated with tapering of immunosuppressive therapy. Although HBV reverse seroconversion is an uncommon event, understanding the clinical features associated with the development of HBV reverse seroconversion may provide insight into how such a potentially fatal complication may be avoided.

  6. Supercritical carbon dioxide-processed resorbable polymer nanocomposites for bone graft substitute applications

    Science.gov (United States)

    Baker, Kevin C.

    Numerous clinical situations necessitate the use of bone graft materials to enhance bone formation. While autologous and allogenic materials are considered the gold standards in the setting of fracture healing and spine fusion, their disadvantages, which include donor site morbidity and finite supply have stimulated research and development of novel bone graft substitute materials. Among the most promising candidate materials are resorbable polymers, composed of lactic and/or glycolic acid. While the characteristics of these materials, such as predictable degradation kinetics and biocompatibility, make them an excellent choice for bone graft substitute applications, they lack mechanical strength when synthesized with the requisite porous morphology. As such, porous resorbable polymers are often reinforced with filler materials. In the presented work, we describe the use of supercritical carbon dioxide (scCO2) processing to create porous resorbable polymeric constructs reinforced by nanostructured, organically modified Montmorillonite clay (nanoclay). scCO2 processing simultaneously disperses the nanoclay throughout the polymeric matrix, while imparting a porous morphology to the construct conducive to facilitating cellular infiltration and neoangiogenesis, which are necessary components of bone growth. With the addition of as little as 2.5wt% of nanoclay, the compressive strength of the constructs nearly doubles putting them on par with human cortico-cancellous bone. Rheological measurements indicate that the dominant mode of reinforcement of the nanocomposite constructs is the restriction of polymer chain mobility. This restriction is a function of the positive interaction between polymer chains and the nanoclay. In vivo inflammation studies indicate biocompatibility of the constructs. Ectopic osteogenesis assays have determined that the scCO2-processed nanocomposites are capable of supporting growth-factor induced bone formation. scCO 2-processed resorbable

  7. Long-term survival and late effects among one-year survivors of second allogeneic hematopoietic cell transplantation for relapsed acute leukemia and myelodysplastic syndromes.

    Science.gov (United States)

    Duncan, Christine N; Majhail, Navneet S; Brazauskas, Ruta; Wang, Zhiwei; Cahn, Jean-Yves; Frangoul, Haydar A; Hayashi, Robert J; Hsu, Jack W; Kamble, Rammurti T; Kasow, Kimberly A; Khera, Nandita; Lazarus, Hillard M; Loren, Alison W; Marks, David I; Maziarz, Richard T; Mehta, Paulette; Myers, Kasiani C; Norkin, Maxim; Pidala, Joseph A; Porter, David L; Reddy, Vijay; Saber, Wael; Savani, Bipin N; Schouten, Harry C; Steinberg, Amir; Wall, Donna A; Warwick, Anne B; Wood, William A; Yu, Lolie C; Jacobsohn, David A; Sorror, Mohamed L

    2015-01-01

    We analyzed the outcomes of patients who survived disease-free for 1 year or more after a second allogeneic hematopoietic cell transplantation (HCT) for relapsed acute leukemia or myelodysplastic syndromes between 1980 and 2009. A total of 1285 patients received a second allogeneic transplant after disease relapse; among these, 325 were relapse free at 1 year after the second HCT. The median time from first to second HCT was 17 and 24 months for children and adults, respectively. A myeloablative preparative regimen was used in the second transplantation in 62% of children and 45% of adult patients. The overall 10-year conditional survival rates after second transplantation in this cohort of patients who had survived disease-free for at least 1 year was 55% in children and 39% in adults. Relapse was the leading cause of mortality (77% and 54% of deaths in children and adults, respectively). In multivariate analyses, only disease status before second HCT was significantly associated with higher risk for overall mortality (hazard ratio, 1.71 for patients with disease not in complete remission before second HCT, P < .01). Chronic graft-versus-host disease (GVHD) developed in 43% and 75% of children and adults after second transplantation. Chronic GVHD was the leading cause of nonrelapse mortality, followed by organ failure and infection. The cumulative incidence of developing at least 1 of the studied late effects within 10 years after second HCT was 63% in children and 55% in adults. The most frequent late effects in children were growth disturbance (10-year cumulative incidence, 22%) and cataracts (20%); in adults they were cataracts (20%) and avascular necrosis (13%). Among patients with acute leukemia and myelodysplastic syndromes who receive a second allogeneic HCT for relapse and survive disease free for at least 1 year, many can be expected to survive long term. However, they continue to be at risk for relapse and nonrelapse morbidity and mortality. Novel

  8. Allogeneic Transplantation of Müller-Derived Retinal Ganglion Cells Improves Retinal Function in a Feline Model of Ganglion Cell Depletion.

    Science.gov (United States)

    Becker, Silke; Eastlake, Karen; Jayaram, Hari; Jones, Megan F; Brown, Robert A; McLellan, Gillian J; Charteris, David G; Khaw, Peng T; Limb, G Astrid

    2016-02-01

    development of cell therapies to treat retinal disease. Using a feline model of retinal ganglion cell (RGC) depletion, cell grafting methods to improve RGC function have been developed. Using cellular scaffolds, allogeneic transplantation of Müller glia-derived RGC promoted cell attachment onto the retina and enhanced retinal function, as judged by improvement of the photopic negative and scotopic threshold responses of the electroretinogram. The results suggest that the improvement of RGC function observed may be ascribed to the neuroprotective ability of these cells and indicate that attachment of the transplanted cells onto the retina is required to promote effective neuroprotection.

  9. Grafting efficiency of synthetic polymers onto biomaterials: a comparative study of grafting-from versus grafting-to.

    Science.gov (United States)

    Hansson, Susanne; Trouillet, Vanessa; Tischer, Thomas; Goldmann, Anja S; Carlmark, Anna; Barner-Kowollik, Christopher; Malmström, Eva

    2013-01-14

    In the present study, the two grafting techniques grafting-from - by activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) - and grafting-to - by copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) - were systematically compared, employing cellulose as a substrate. In order to obtain a meaningful comparison, it is crucial that the graft lengths of the polymers that are grafted from and to the substrates are essentially identical. Herein, this was achieved by utilizing the free polymer formed in parallel to the grafting-from reaction as the polymer for the grafting-to reaction. Four graft lengths were investigated, and the molar masses of the four free polymers (21 ≤ M(n) ≤ 100 kDa; 1.07 ≤ Đ(M) ≤ 1.26), i.e. the polymers subsequently employed in the grafting-to reaction, were shown to be in the same range as the molar masses of the polymers grafted from the surface (23 ≤ M(n) ≤ 87 kDa; 1.08 ≤ Đ(M) ≤ 1.31). The molecular weights of the chains grafted from the surface were established after cleavage from the cellulose substrates via size exclusion chromatography (SEC). High-resolution Fourier transform infrared microscopy (FT-IRM) was employed as an efficient tool to study the spatial distribution of the polymer content on the grafted substrates. In addition, the functionalized substrates were analyzed by X-ray photoelectron spectroscopy (XPS), contact angle (CA) measurements, and field-emission scanning electron microscopy (FE-SEM). For cellulose substrates modified via the grafting-from approach, the content of polymer on the surfaces increased with increasing graft length, confirming the possibility to tailor not only the length of the polymer grafts but also the polymeric content on the surface. In comparison, for the grafting-to reaction, the grafted content could not be controlled by varying the length of the preformed polymer: the polymer content was essentially the same for the four graft lengths

  10. STUDY OF GRAFT SITES IN EPOXY GRAFT COPOLYMERS BY QUANTUM CHEMISTRY CALCULATIONS

    Institute of Scientific and Technical Information of China (English)

    Song Chen; Xiao-yu Li

    2009-01-01

    Exploration and characterization of grafting productions by experimental methods are often cumbersome or sometimes impossible. Therefore, quantum chemistry calculations were performed to characterize the graft sites of epoxy resin. According to the Gibbs free energy criterion of the second law of thermodynamic, the reported graft sites were confirmed, and more important, some unreported graft sites were found. In addition, method of increasing the number of graft sites was studied in this article.

  11. Polyether-polyester graft copolymer

    Science.gov (United States)

    Bell, Vernon L. (Inventor)

    1987-01-01

    Described is a polyether graft polymer having improved solvent resistance and crystalline thermally reversible crosslinks. The copolymer is prepared by a novel process of anionic copolymerization. These polymers exhibit good solvent resistance and are well suited for aircraft parts. Previous aromatic polyethers, also known as polyphenylene oxides, have certain deficiencies which detract from their usefulness. These commercial polymers are often soluble in common solvents including the halocarbon and aromatic hydrocarbon types of paint thinners and removers. This limitation prevents the use of these polyethers in structural articles requiring frequent painting. In addition, the most popular commercially available polyether is a very high melting plastic. This makes it considerably more difficult to fabricate finished parts from this material. These problems are solved by providing an aromatic polyether graft copolymer with improved solvent resistance and crystalline thermally reversible crosslinks. The graft copolymer is formed by converting the carboxyl groups of a carboxylated polyphenylene oxide polymer to ionic carbonyl groups in a suitable solvent, reacting pivalolactone with the dissolved polymer, and adding acid to the solution to produce the graft copolymer.

  12. The caudal septum replacement graft.

    Science.gov (United States)

    Foda, Hossam M T

    2008-01-01

    To describe a technique for reconstructing the lost tip support in cases involving caudal septal and premaxillary deficiencies. The study included 120 patients with aesthetic and functional nasal problems resulting from the loss of caudal septal and premaxillary support. An external rhinoplasty approach was performed to reconstruct the lost support using a cartilaginous caudal septum replacement graft and premaxillary augmentation with Mersilene mesh. The majority of cases (75%) involved revisions in patients who had previously undergone 1 or more nasal surgical procedures. A caudal septum replacement graft was combined with premaxillary augmentation in 93 patients (77.5%). The mean follow-up period was 3 years (range, 1-12 years). The technique succeeded in correcting the external nasal deformities in all patients and resulted in a significant improvement in breathing in 74 patients (86%) with preoperative nasal obstruction. There were no cases of infection, displacement, or extrusion. The caudal septum replacement graft proved to be very effective in restoring the lost tip support in patients with caudal septal deficiency. Combining the graft with premaxillary augmentation using Mersilene mesh helped increase support and stability over long-term follow-up.

  13. Prognostic Limitations of Donor T Cell Chimerism after Myeloablative Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes.

    Science.gov (United States)

    Wong, Eric; Mason, Kate; Collins, Jenny; Hockridge, Barbara; Boyd, Janis; Gorelik, Alexandra; Szer, Jeffrey; Ritchie, David S

    2017-02-06

    Donor T cell chimerism is associated with relapse outcomes after allogeneic stem cell transplantation (alloSCT) for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). However, measures of statistical association do not adequately assess the performance of a prognostic biomarker, which is best characterized by its sensitivity and specificity for the chosen outcome. We analyzed donor T cell chimerism results at day 100 (D100chim) after myeloablative alloSCT for AML or MDS in 103 patients and determined its sensitivity and specificity for relapse-free survival at 6 months (RFS6) and 12 months (RFS12) post-alloSCT. The area under the receiver operating characteristic curve for RFS6 was .68, demonstrating only modest utility as a predictive biomarker, although this was greater than RFS12 at .62. Using a D100chim threshold of 65%, the specificity for RFS6 was 96.6%; however, sensitivity was poor at 26.7%. This equated to a negative predictive value of 88.5% and positive predictive value of 57.1%. Changing the threshold for D100chim to 75% or 85% modestly improved the sensitivity of D100chim for RFS6; however, this was at the expense of specificity. D100chim is specific but lacks sensitivity as a prognostic biomarker of early RFS after myeloablative alloSCT for AML or MDS. Caution is required when using D100chim to guide treatment decisions including immunologic manipulation, which may expose patients to unwarranted graft-versus-host disease.

  14. An improved anti-leukemic effect achieved with donor progenitor cell infusion for relapse patients after allogeneic bone marrow transplantation

    Institute of Scientific and Technical Information of China (English)

    黄晓军; 郭乃榄; 任汉云; 张耀臣; 高志勇; 陆道培

    2003-01-01

    Objective To observe the antileukemic effect in relapse patients by infusion of donor immunocompetent cells with or without granulocyte colony-stimulating factor (G-CSF) mobilization.Methods Twenty patients with leukemia in relapse after allogeneic bone marrow transplantation (allo-BMT) were treated with chemotherapy followed by donor-derived lymphocytes (DDL) without G-CSF mobilization (Group A, n=11), or donor peripheral blood progenitor cells (PBPCs) with G-CSF mobilization (Group B, n=9).Results Five patients in Group A were in hematologic relapse. After DDL infusion, 3 of 5 patients had a temporary complete remission (CR) and relapsed after 3, 7 and 10 months, respectively. One achieved partial remission and died of interstitial pneumonia; and the other one showed no response. Another 6 patients in Group A were in cytogenetic relapse or central nerve system (CNS) leukemia, and all achieved CR and remained in disease free survival (DFS) for 10 to 98 months after DDL infusion. All 9 patients in group B were in hematologic relapse. Three patients with chronic myeloid leukemia (CML) had cytogenetic and molecular remission for 16, 35 and 51 months, respectively after PBPC infusion; and 5 patients with acute lymphoid leukemia (ALL) had CR and were still in CR for 10 to 18 months except 1 patient relapsed soon. And the other one with AML showed no response to the therapy.Conclusion Donor immunocompetent cells infusion is an effective therapy for relapsed leukemia after allo-BMT, especially for the patients with early (molecular and cytogenetic) or CNS relapse. Infusion of donor PBPC mobilized by G-CSF seems to have more potentiated graft-versus-leukemia (GVL) effect than DDL infusion.

  15. Immune reconstitution after allogeneic hematopoietic stem cell transplantation in children: a single institution study of 59 patients

    Directory of Open Access Journals (Sweden)

    Hyun O Kim

    2013-01-01

    Full Text Available &lt;b&gt;Purpose:&lt;/b&gt; Lymphocyte subset recovery is an important factor that determines the success of hematopoietic stem cell transplantation (HSCT. Temporal differences in the recovery of lymphocyte subsets and the factors influencing this recovery are important variables that affect a patient's posttransplant immune reconstitution, and therefore require investigation. &lt;b&gt;Methods:&lt;/b&gt; The time taken to achieve lymphocyte subset recovery and the factors influencing this recovery were investigated in 59 children who had undergone HSCT at the Department of Pediatrics, The Catholic University of Korea Seoul St. Mary's Hospital, and who had an uneventful follow-up period of at least 1 year. Analyses were carried out at 3 and 12 months post-transplant. An additional study was performed 1 month post-transplant to evaluate natural killer (NK cell recovery. The impact of preand post-transplant variables, including diagnosis of Epstein-Barr virus (EBV DNAemia posttransplant,on lymphocyte recovery was evaluated. &lt;b&gt;Results:&lt;/b&gt; The lymphocyte subsets recovered in the following order: NK cells, cytotoxic T cells, B cells,and helper T cells. At 1 month post-transplant, acute graft-versus-host disease was found to contribute significantly to the delay of CD16+/56+ cell recovery. Younger patients showed delayed recovery of both CD3+/CD8+ and CD19+ cells. EBV DNAemia had a deleterious impact on the recovery of both CD3+ and CD3+/CD4+ lymphocytes at 1 year post-transplant. &lt;b&gt;Conclusion:&lt;/b&gt; In our pediatric allogeneic HSCT cohort, helper T cells were the last subset to recover. Younger age and EBV DNAemia had a negative impact on the post-transplant recovery of T cells and B cells.

  16. Integrated meta-omic analyses of the gastrointestinal tract microbiome in patients undergoing allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Kaysen, Anne; Heintz-Buschart, Anna; Muller, Emilie E L; Narayanasamy, Shaman; Wampach, Linda; Laczny, Cédric C; Graf, Norbert; Simon, Arne; Franke, Katharina; Bittenbring, Jörg; Wilmes, Paul; Schneider, Jochen G

    2017-08-01

    In patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), treatment-induced changes to the gastrointestinal tract (GIT) microbiome have been linked to adverse outcomes, most notably graft-versus-host disease (GvHD). However, it is presently unknown whether this relationship is causal or consequential. Here, we performed an integrated meta-omic analysis to probe deeper into the GIT microbiome changes during allo-HSCT and its accompanying treatments. We used 16S and 18S rRNA gene amplicon sequencing to resolve archaea, bacteria, and eukaryotes within the GIT microbiomes of 16 patients undergoing allo-HSCT for the treatment of hematologic malignancies. These results revealed a major shift in the GIT microbiome after allo-HSCT including a marked reduction in bacterial diversity, accompanied by only limited changes in eukaryotes and archaea. An integrated analysis of metagenomic and metatranscriptomic data was performed on samples collected from a patient before and after allo-HSCT for acute myeloid leukemia. This patient developed severe GvHD, leading to death 9 months after allo-HSCT. In addition to drastically decreased bacterial diversity, the post-treatment microbiome showed a higher overall number and higher expression levels of antibiotic resistance genes (ARGs). One specific Escherichia coli strain causing a paravertebral abscess was linked to GIT dysbiosis, suggesting loss of intestinal barrier integrity. The apparent selection for bacteria expressing ARGs suggests that prophylactic antibiotic administration may adversely affect the overall treatment outcome. We therefore assert that such analyses including information about the selection of pathogenic bacteria expressing ARGs may assist clinicians in "personalizing" regimens for individual patients to improve overall outcomes. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Allogeneic hematopoietic cell transplantation for fanconi anemia in patients with pretransplantation cytogenetic abnormalities, myelodysplastic syndrome, or acute leukemia.

    Science.gov (United States)

    Ayas, Mouhab; Saber, Wael; Davies, Stella M; Harris, Richard E; Hale, Gregory A; Socie, Gerard; LeRademacher, Jennifer; Thakar, Monica; Deeg, H Joachim J; Al-Seraihy, Amal; Battiwalla, Minoo; Camitta, Bruce M; Olsson, Richard; Bajwa, Rajinder S; Bonfim, Carmem M; Pasquini, Ricardo; Macmillan, Margaret L; George, Biju; Copelan, Edward A; Wirk, Baldeep; Al Jefri, Abdullah; Fasth, Anders L; Guinan, Eva C; Horn, Biljana N; Lewis, Victor A; Slavin, Shimon; Stepensky, Polina; Bierings, Marc; Gale, Robert Peter

    2013-05-01

    Allogeneic hematopoietic cell transplantation (HCT) can cure bone marrow failure in patients with Fanconi anemia (FA). Data on outcomes in patients with pretransplantation cytogenetic abnormalities, myelodysplastic syndrome (MDS), or acute leukemia have not been separately analyzed. We analyzed data on 113 patients with FA with cytogenetic abnormalities (n = 54), MDS (n = 45), or acute leukemia (n = 14) who were reported to the Center for International Blood and Marrow Transplant Research from 1985 to 2007. Neutrophil recovery occurred in 78% and 85% of patients at days 28 and 100, respectively. Day 100 cumulative incidences of acute graft-versus-host disease grades B to D and C to D were 26% (95% CI, 19% to 35%) and 12% (95% CI, 7% to 19%), respectively. Survival probabilities at 1, 3, and 5 years were 64% (95% CI, 55% to 73%), 58% (95% CI, 48% to 67%), and 55% (95% CI, 45% to 64%), respectively. In univariate analysis, younger age was associated with superior 5-year survival (≤ v > 14 years: 69% [95% CI, 57% to 80%] v 39% [95% CI, 26% to 53%], respectively; P = .001). In transplantations from HLA-matched related donors (n = 82), younger patients (≤ v > 14 years: 78% [95% CI, 64% to 90%] v 34% [95% CI, 20% to 50%], respectively; P < .001) and patients with cytogenetic abnormalities only versus MDS/acute leukemia (67% [95% CI, 52% to 81%] v 43% [95% CI, 27% to 59%], respectively; P = .03) had superior 5-year survival. Our analysis indicates that long-term survival for patients with FA with cytogenetic abnormalities, MDS, or acute leukemia is achievable. Younger patients and recipients of HLA-matched related donor transplantations who have cytogenetic abnormalities only have the best survival.

  18. Bone marrow as stem cell source for allogeneic HLA-identical sibling transplantation following reduced-intensity preparative regimen.

    Science.gov (United States)

    Faucher, Catherine; Mohty, Mohamad; Vey, Norbert; Gaugler, Béatrice; Bilger, Karin; Moziconnacci, Marie-Joelle; Stoppa, Anne-Marie; Coso, Diane; Ladaique, Patrick; Chabannon, Christian; Reviron, Denis; Maraninchi, Dominique; Gastaut, Jean-Albert; Olive, Daniel; Blaise, Didier

    2003-10-01

    Reduced-intensity conditioning regimens (RIC) and peripheral blood stem cells (PBSC) are increasingly used for allogeneic stem cell transplantation (allo-BMT). RIC has been shown to allow engraftment with minimal early transplant-related mortality (TRM). However, in the context of RIC, the use of bone marrow (BM) as stem cell source is still little evaluated. In this report, we analyzed the outcome of 32 high-risk patients with hematological malignancies who received an HLA-identical sibling allo-BMT after RIC including fludarabine, busulfan, and anti-thymocyte globulin (ATG). Sustained neutrophil and platelet recovery occurred at a median of 13 days (range, 10-19) and 17 days (range, 0-45) respectively. Early and durable full donor chimerism could be established as soon as the first month after allo-BMT. Also, a sustained and early CD8(+) T-cell recovery was observed, but the CD4(+) T-cell compartment remained profoundly low. The cumulative incidences of grade II-IV acute GVHD and chronic GVHD were 26% (95% CI, 11-41%) and 31% (95% CI, 15-47%) respectively. The overall cumulative incidence of TRM was 28% (95% CI, 12-44%) occurring mainly in patients aged over 50. In this setting, GVHD showed a protective effect on disease progression or relapse with better progression-free survival for patients with GVHD as compared to patients without GVHD (p=0.03). Collectively, these results confirm that the use of BM grafts for RIC is feasible with durable donor engraftment and no detrimental GVHD.

  19. DAS181 Treatment of Severe Parainfluenza Virus 3 Pneumonia in Allogeneic Hematopoietic Stem Cell Transplant Recipients Requiring Mechanical Ventilation

    Directory of Open Access Journals (Sweden)

    B. Dhakal

    2016-01-01

    Full Text Available Parainfluenza virus (PIV may cause life-threatening pneumonia in allogeneic hematopoietic stem cell transplant (HSCT recipients. Currently, there are no proven effective therapies. We report the use of inhaled DAS181, a novel sialidase fusion protein, for treatment of PIV type 3 pneumonia in two allogeneic hematopoietic SCT recipients with respiratory failure.

  20. Eradication of tumour cells by successive injections of allogeneic immune and hyperimmune peritoneal cells in a murine lymphoma system

    NARCIS (Netherlands)

    Dullens, H.F.J.; Woutersen, R.A.; Weger, R.A. de; Otter, W. den

    2006-01-01

    Allogeneic C57BL immune and hyperimmune (vs SL2) peritoneal cells are used for eradication of DBA/2 derived SL2 lymphoma cells injected into the peritoneal cavity of DBA/2 mice. SL2 bearing DBA/2 mice are treated with 3, 5, or 8 successive i.p. injections of 2 × 106 allogeneic C57BL immune or hyper

  1. Allogeneic transplantation of the radial side of the hand in the rhesus monkey : technical, functional and immunological aspects.

    NARCIS (Netherlands)

    S.E.R. Hovius (Steven); H.P.J.D. Stevens (Jeroen)

    1991-01-01

    textabstractAs this is the era of transplantation it is inevitable that the field of allogeneic transplantation for the reconstruction of the upper extremity is explored also. This double-thesis deals with a number of aspects concerning allogeneic transplantation of the radial side of the hand in a

  2. The Genotype of the Donor for the (GT)n Polymorphism in the Promoter/Enhancer of FOXP3 Is Associated with the Development of Severe Acute GVHD but Does Not Affect the GVL Effect after Myeloablative HLA-Identical Allogeneic Stem Cell Transplantation

    Science.gov (United States)

    Buces, Elena; Pion, Marjorie; Sánchez-Hernández, Noemí; Martín-Antonio, Beatriz; Guillem, Vicent; Bosch-Vizcaya, Anna; Bento, Leyre; González-Rivera, Milagros; Balsalobre, Pascual; Kwon, Mi; Serrano, David; Gayoso, Jorge; de la Cámara, Rafael; Brunet, Salut; Rojas-Contreras, Rafael; Nieto, José B.; Martínez, Carmen; Gónzalez, Marcos; Espigado, Ildefonso; Vallejo, Juan C.; Sampol, Antonia; Jiménez-Velasco, Antonio; Urbano-Ispizua, Alvaro; Solano, Carlos; Gallardo, David; Díez-Martín, José L.; Buño, Ismael

    2015-01-01

    The FOXP3 gene encodes for a protein (Foxp3) involved in the development and functional activity of regulatory T cells (CD4+/CD25+/Foxp3+), which exert regulatory and suppressive roles over the immune system. After allogeneic stem cell transplantation, regulatory T cells are known to mitigate graft versus host disease while probably maintaining a graft versus leukemia effect. Short alleles (≤(GT)15) for the (GT)n polymorphism in the promoter/enhancer of FOXP3 are associated with a higher expression of FOXP3, and hypothetically with an increase of regulatory T cell activity. This polymorphism has been related to the development of auto- or alloimmune conditions including type 1 diabetes or graft rejection in renal transplant recipients. However, its impact in the allo-transplant setting has not been analyzed. In the present study, which includes 252 myeloablative HLA-identical allo-transplants, multivariate analysis revealed a lower incidence of grade III-IV acute graft versus host disease (GVHD) in patients transplanted from donors harboring short alleles (OR = 0.26, CI 0.08–0.82, p = 0.021); without affecting chronic GVHD or graft versus leukemia effect, since cumulative incidence of relapse, event free survival and overall survival rates are similar in both groups of patients. PMID:26473355

  3. The Genotype of the Donor for the (GTn Polymorphism in the Promoter/Enhancer of FOXP3 Is Associated with the Development of Severe Acute GVHD but Does Not Affect the GVL Effect after Myeloablative HLA-Identical Allogeneic Stem Cell Transplantation.

    Directory of Open Access Journals (Sweden)

    Víctor Noriega

    Full Text Available The FOXP3 gene encodes for a protein (Foxp3 involved in the development and functional activity of regulatory T cells (CD4+/CD25+/Foxp3+, which exert regulatory and suppressive roles over the immune system. After allogeneic stem cell transplantation, regulatory T cells are known to mitigate graft versus host disease while probably maintaining a graft versus leukemia effect. Short alleles (≤(GT15 for the (GTn polymorphism in the promoter/enhancer of FOXP3 are associated with a higher expression of FOXP3, and hypothetically with an increase of regulatory T cell activity. This polymorphism has been related to the development of auto- or alloimmune conditions including type 1 diabetes or graft rejection in renal transplant recipients. However, its impact in the allo-transplant setting has not been analyzed. In the present study, which includes 252 myeloablative HLA-identical allo-transplants, multivariate analysis revealed a lower incidence of grade III-IV acute graft versus host disease (GVHD in patients transplanted from donors harboring short alleles (OR = 0.26, CI 0.08-0.82, p = 0.021; without affecting chronic GVHD or graft versus leukemia effect, since cumulative incidence of relapse, event free survival and overall survival rates are similar in both groups of patients.

  4. The Genotype of the Donor for the (GT)n Polymorphism in the Promoter/Enhancer of FOXP3 Is Associated with the Development of Severe Acute GVHD but Does Not Affect the GVL Effect after Myeloablative HLA-Identical Allogeneic Stem Cell Transplantation.

    Science.gov (United States)

    Noriega, Víctor; Martínez-Laperche, Carolina; Buces, Elena; Pion, Marjorie; Sánchez-Hernández, Noemí; Martín-Antonio, Beatriz; Guillem, Vicent; Bosch-Vizcaya, Anna; Bento, Leyre; González-Rivera, Milagros; Balsalobre, Pascual; Kwon, Mi; Serrano, David; Gayoso, Jorge; de la Cámara, Rafael; Brunet, Salut; Rojas-Contreras, Rafael; Nieto, José B; Martínez, Carmen; Gónzalez, Marcos; Espigado, Ildefonso; Vallejo, Juan C; Sampol, Antonia; Jiménez-Velasco, Antonio; Urbano-Ispizua, Alvaro; Solano, Carlos; Gallardo, David; Díez-Martín, José L; Buño, Ismael

    2015-01-01

    The FOXP3 gene encodes for a protein (Foxp3) involved in the development and functional activity of regulatory T cells (CD4+/CD25+/Foxp3+), which exert regulatory and suppressive roles over the immune system. After allogeneic stem cell transplantation, regulatory T cells are known to mitigate graft versus host disease while probably maintaining a graft versus leukemia effect. Short alleles (≤(GT)15) for the (GT)n polymorphism in the promoter/enhancer of FOXP3 are associated with a higher expression of FOXP3, and hypothetically with an increase of regulatory T cell activity. This polymorphism has been related to the development of auto- or alloimmune conditions including type 1 diabetes or graft rejection in renal transplant recipients. However, its impact in the allo-transplant setting has not been analyzed. In the present study, which includes 252 myeloablative HLA-identical allo-transplants, multivariate analysis revea