Engraftment Efficiency after Intra-Bone Marrow versus Intravenous Transplantation of Bone Marrow Cells in a Canine Nonmyeloablative Dog Leukocyte Antigen-Identical Transplantation Model.

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Lange, Sandra; Steder, Anne; Killian, Doreen; Knuebel, Gudrun; Sekora, Anett; Vogel, Heike; Lindner, Iris; Dunkelmann, Simone; Prall, Friedrich; Murua Escobar, Hugo; Freund, Mathias; Junghanss, Christian

2017-02-01

An intra-bone marrow (IBM) hematopoietic stem cell transplantation (HSCT) is assumed to optimize the homing process and therefore to improve engraftment as well as hematopoietic recovery compared with conventional i.v. HSCT. This study investigated the feasibility and efficacy of IBM HSCT after nonmyeloablative conditioning in an allogeneic canine HSCT model. Two study cohorts received IBM HSCT of either density gradient (IBM-I, n = 7) or buffy coat (IBM-II, n = 6) enriched bone marrow cells. An historical i.v. HSCT cohort served as control. Before allogeneic HSCT experiments were performed, we investigated the feasibility of IBM HSCT by using technetium-99m marked autologous grafts. Scintigraphic analyses confirmed that most IBM-injected autologous cells remained at the injection sites, independent of the applied volume. In addition, cell migration to other bones occurred. The enrichment process led to different allogeneic graft volumes (IBM-I, 2 × 5 mL; IBM-II, 2 × 25 mL) and significantly lower counts of total nucleated cells in IBM-I grafts compared with IBM-II grafts (1.6 × 10 8 /kg versus 3.8 × 10 8 /kg). After allogeneic HSCT, dogs of the IBM-I group showed a delayed engraftment with lower levels of donor chimerism when compared with IBM-II or to i.v. HSCT. Dogs of the IBM-II group tended to reveal slightly faster early leukocyte engraftment kinetics than intravenously transplanted animals. However, thrombocytopenia was significantly prolonged in both IBM groups when compared with i.v. HSCT. In conclusion, IBM HSCT is feasible in a nonmyeloablative HSCT setting but failed to significantly improve engraftment kinetics and hematopoietic recovery in comparison with conventional i.v. HSCT. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

The Prognostic Significance of Elevated Serum Ferritin Levels Prior to Transplantation in Patients With Lymphoma Who Underwent Autologous Hematopoietic Stem Cell Transplantation (autoHSCT): Role of Iron Overload.

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Sivgin, Serdar; Karamustafaoglu, Mehmet Fatih; Yildizhan, Esra; Zararsiz, Gokmen; Kaynar, Leylagul; Eser, Bulent; Cetin, Mustafa; Unal, Ali

2016-08-01

Hematopoietic stem cell transplantation is a common and preferred treatment of lymphomas in many centers. Our goal was to determine the association between pretransplant iron overload and survival in patients who underwent autologous hematopoietic stem cell transplantation (autoHSCT). A total of 165 patients with lymphoma, who underwent autoHSCT between the years of 2007 and 2014, were included in this study. Ferritin levels were used to determine iron status; the cut-off value was 500 ng/mL. The relationship between iron overload and survival was assessed by statistical analysis. The median ferritin level in the normal ferritin (ferritin < 500) group was 118 ng/mL (range, 9-494 ng/mL) and in the high-ferritin group (ferritin ≥ 500), it was 908 ng/mL (range, 503-4549 ng/mL). A total of 64 (38.8%) patients died during follow-up. Of these patients that died, 52 (81.25%) were in the high-ferritin group, and 12 (18.75%) were in the normal ferritin group (P ≤ .001). Twelve (14.1%) of 85 patients died in the normal ferritin group, and 52 (65.0%) of 80 patients died in the high-ferritin group. The overall mortality was significantly higher in the high-ferritin group (P < .001). The median overall survival was 42 months (range, 25-56 months) in the normal-ferritin group and20 months (range, 5-46) in the high-ferritin group. The difference between the groups was statistically significant (P < .001). The median disease-free survival was 39 months (range, 16-56) in the normal ferritin group and 10 months (range, 3-29) in the high-ferritin group. The difference between the groups was statistically significant (P < .001). Elevated serum ferritin levels might predict poorer survival in autoHSCT recipients. Copyright © 2016 Elsevier Inc. All rights reserved.

Perceptions of Hematopoietic Stem Cell Transplantation and Coping Predict Emotional Distress During the Acute Phase After Transplantation.

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Baliousis, Michael; Rennoldson, Michael; Dawson, David L; Mills, Jayne; das Nair, Roshan

2017-01-01

To test whether a widely used model of adjustment to illness, the self-regulatory model, explains the patterns of distress during acute hematopoietic stem cell transplantation (HSCT). According to the model, perceptions of HSCT, coping, and coping appraisals are associated with distress.
. Longitudinal, correlational.
. The Centre for Clinical Haematology at Nottingham City Hospital and the Department of Haematology at Royal Hallamshire Hospital in Sheffield, both in the United Kingdom.
. 45 patients receiving mostly autologous transplantations for a hematologic malignancy.
. Patients were assessed at baseline, on transplantation day, and two and four weeks after transplantation using three questionnaires. Psychological distress, including depression, anxiety, stress, and overall distress (DASS-21); use of different coping styles (Brief COPE); and perceptions of HSCT and coping appraisals (Brief IPQ).
. As suggested by the self-regulatory model, greater distress was associated with negative perceptions of HSCT, controlling for the effects of confounding variables. Mixed support was found for the model's predictions about the impact of coping styles on distress. Use of active and avoidant coping styles was associated with more distress during the acute phase after HSCT.
. Negative perceptions of HSCT and coping contribute to psychological distress during the acute phase after HSCT and suggest the basis for intervention.
. Eliciting and discussing patients' negative perceptions of HSCT beforehand and supporting helpful coping may be important ways to reduce distress during HSCT.

IMMUNITY TO INFECTIONS AFTER HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATION

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Franco Aversa

2016-10-01

Full Text Available The advantage of using a Human Leukocyte Antigen (HLA-mismatched related donor is that almost every patient who does not have a HLA-identical donor or who urgently needs hematopoietic stem cell transplantation (HSCT has at least one family member with whom shares one haplotype (haploidentical and who is promptly available as a donor. The major challenge of haplo-HSCT is intense bi-directional alloreactivity leading to high incidences of graft rejection and graft-versus-host disease (GVHD. Advances in graft processing and in pharmacologic prophylaxis of GVHD have reduced these risks and have made haplo-HSCT a viable alternative for patients lacking a matched donor. Indeed, the haplo-HSCT  has spread to centers worldwide even though some centers have preferred an approach based on T cell depletion of G-CSF-mobilized peripheral blood progenitor cells (PBPCs, others have focused on new strategies for GvHD prevention, such as G-CSF priming of bone marrow and robust post-transplant immune suppression or post-transplant cyclophosphamide (PTCY. Today, the graft can be a megadose of T-cell depleted PBPCs or standard dose of unmanipulated bone marrow and/or PBPCs.  Although haplo-HSCT modalities are based mainly on high intensity conditioning regimens, recently introduced reduced intensity regimens (RIC   showed promise in decreasing early transplant-related mortality (TRM, and extending the opportunity of HSCT to an elderly population with more comorbidities. Infections are still mostly responsible for toxicity and non-relapse mortality due to prolonged immunosuppression related, or not, to GVHD. Future challenges lie in determining the safest preparative conditioning regimen, minimizing GvHD and promoting rapid and more robust immune reconstitution.

Barriers to Mental Health Service Use among Hematopoietic Stem Cell Transplant Survivors

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Mosher, Catherine E.; DuHamel, Katherine N.; Rini, Christine M.; Li, Yuelin; Isola, Luis; Labay, Larissa; Rowley, Scott; Papadopoulos, Esperanza; Moskowitz, Craig; Scigliano, Eileen; Grosskreutz, Celia; Redd, William H.

2009-01-01

Summary This study examined barriers to mental health service use and their demographic, medical, and psychosocial correlates among hematopoietic stem cell transplant (HSCT) survivors. A sample of 253 HSCT survivors who were 1- to 3-years post-transplant completed measures of demographic, physical, psychological, and social characteristics as well as a newly modified measure of barriers to mental health service use. Only 50% of distressed HSCT survivors had received mental health services. An...

NK Cells and Other Innate Lymphoid Cells in Hematopoietic Stem Cell Transplantation.

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Vacca, Paola; Montaldo, Elisa; Croxatto, Daniele; Moretta, Francesca; Bertaina, Alice; Vitale, Chiara; Locatelli, Franco; Mingari, Maria Cristina; Moretta, Lorenzo

2016-01-01

Natural killer (NK) cells play a major role in the T-cell depleted haploidentical hematopoietic stem cell transplantation (haplo-HSCT) to cure high-risk leukemias. NK cells belong to the expanding family of innate lymphoid cells (ILCs). At variance with NK cells, the other ILC populations (ILC1/2/3) are non-cytolytic, while they secrete different patterns of cytokines. ILCs provide host defenses against viruses, bacteria, and parasites, drive lymphoid organogenesis, and contribute to tissue remodeling. In haplo-HSCT patients, the extensive T-cell depletion is required to prevent graft-versus-host disease (GvHD) but increases risks of developing a wide range of life-threatening infections. However, these patients may rely on innate defenses that are reconstituted more rapidly than the adaptive ones. In this context, ILCs may represent important players in the early phases following transplantation. They may contribute to tissue homeostasis/remodeling and lymphoid tissue reconstitution. While the reconstitution of NK cell repertoire and its role in haplo-HSCT have been largely investigated, little information is available on ILCs. Of note, CD34(+) cells isolated from different sources of HSC may differentiate in vitro toward various ILC subsets. Moreover, cytokines released from leukemia blasts (e.g., IL-1β) may alter the proportions of NK cells and ILC3, suggesting the possibility that leukemia may skew the ILC repertoire. Further studies are required to define the timing of ILC development and their potential protective role after HSCT.

NK cells and other innate lymphoid cells in haematopoietic stem cell transplantation

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Paola eVacca

2016-05-01

Full Text Available Natural Killer (NK cells play a major role in the T-cell depleted haploidentical haematopoietic stem cell transplantation (haplo-HSCT to cure high-risk leukemias. NK cells belong to the expanding family of innate lymphoid cells (ILC. At variance with NK cells, the other ILC populations (ILC1/2/3 are non-cytolytic, while they secrete different patterns of cytokines. ILC provide host defences against viruses, bacteria and parasites, drive lymphoid organogenesis, and contribute to tissue remodelling. In haplo-HSCT patients, the extensive T-cell depletion is required to prevent graft-versus-host disease (GvHD but increases risks of developing a wide range of life-threatening infections. However, these patients may rely on innate defences that are reconstituted more rapidly than the adaptive ones. In this context, ILC may represent important players in the early phases following transplantation. They may contribute to tissue homeostasis/remodelling and lymphoid tissue reconstitution. While the reconstitution of NK cell repertoire and its role in haplo-HSCT have been largely investigated, little information is available on ILC. Of note, CD34+ cells isolated from different sources of HSC, may differentiate in vitro towards various ILC subsets. Moreover, cytokines released from leukemia blasts (e.g. IL-1β may alter the proportions of NK cells and ILC3, suggesting the possibility that leukemia may skew the ILC repertoire. Further studies are required to define the timing of ILC development and their potential protective role after HSCT.

Outcome of children with acute leukemia given HLA-haploidentical HSCT after αβ T-cell and B-cell depletion.

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Locatelli, Franco; Merli, Pietro; Pagliara, Daria; Li Pira, Giuseppina; Falco, Michela; Pende, Daniela; Rondelli, Roberto; Lucarelli, Barbarella; Brescia, Letizia Pomponia; Masetti, Riccardo; Milano, Giuseppe Maria; Bertaina, Valentina; Algeri, Mattia; Pinto, Rita Maria; Strocchio, Luisa; Meazza, Raffaella; Grapulin, Lavinia; Handgretinger, Rupert; Moretta, Alessandro; Bertaina, Alice; Moretta, Lorenzo

2017-08-03

Allogeneic hematopoietic stem cell transplantation (HSCT) from an HLA-haploidentical relative (haplo-HSCT) is a suitable option for children with acute leukemia (AL) either relapsed or at high-risk of treatment failure. We developed a novel method of graft manipulation based on negative depletion of αβ T and B cells and conducted a prospective trial evaluating the outcome of children with AL transplanted with this approach. Eighty AL children, transplanted between September 2011 and September 2014, were enrolled in the trial. All children were given a fully myeloablative preparative regimen. Anti-T-lymphocyte globulin from day -5 to -3 was used for preventing graft rejection and graft-versus-host disease (GVHD); no patient received any posttransplantation GVHD prophylaxis. Two children experienced primary graft failure. The cumulative incidence of skin-only, grade 1-2 acute GVHD was 30%; no patient developed extensive chronic GVHD. Four patients died, the cumulative incidence of nonrelapse mortality being 5%, whereas 19 relapsed, resulting in a 24% cumulative incidence of relapse. With a median follow-up of 46 months for surviving patients, the 5-year probability of chronic GVHD-free, relapse-free survival (GRFS) is 71%. Total body irradiation-containing preparative regimen was the only variable favorably influencing relapse incidence and GRFS. The outcomes of these 80 patients are comparable to those of 41 and 51 children given transplantation from an HLA-identical sibling or a 10/10 allelic-matched unrelated donor in the same period. These data indicate that haplo-HSCT after αβ T- and B-cell depletion represents a competitive alternative for children with AL in need of urgent allograft. This trial was registered at www.clinicaltrials.gov as #NCT01810120. © 2017 by The American Society of Hematology.

Allogeneic CD19-CAR-T cell infusion after allogeneic hematopoietic stem cell transplantation in B cell malignancies.

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Liu, Jun; Zhong, Jiang F; Zhang, Xi; Zhang, Cheng

2017-01-31

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered the cornerstone in treatment of hematological malignancies. However, relapse of the hematological disease after allo-HSCT remains a challenge and is associated with poor long-term survival. Chimeric antigen receptor redirected T cells (CAR-T cells) can lead to disease remission in patients with relapsed/refractory hematological malignancies. However, the therapeutic window for infusion of CAR-T cells post allo-HSCT and its efficacy are debatable. In this review, we first discuss the use of CAR-T cells for relapsed cases after allo-HSCT. We then review the toxicities and the occurrence of graft-versus-host disease in relapsed patients who received CAR-T cells post allo-HSCT. Finally, we review clinical trial registrations and the therapeutic time window for infusion of CAR-T cells post allo-HSCT. The treatment of allogeneic CAR-T cells is beneficial for patients with relapsed B cell malignancies after allo-HSCT with low toxicities and complications. However, multicenter clinical trials with larger sample sizes should be performed to select the optimal therapeutic window and confirm its efficacy.

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...

Transplantation? Peripheral Stem Cell/Bone Marrow/Cord Blood

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Itır Sirinoglu Demiriz

2012-01-01

Full Text Available The introduction of peripheral stem cell (PSC and cord blood (CB as an alternative to bone marrow (BM recently has caused important changes on hematopoietic stem cell transplantation (HSCT practice. According to the CIBMTR data, there has been a significant decrease in the use of bone marrow and increase in the use of PSC and CB as the stem cell source for HSCT performed during 1997–2006 period for patients under the age of 20. On the other hand, the stem cell source in 70% of the HSCT procedures performed for patients over the age of 20 was PSC and the second most preferred stem cell source was bone marrow. CB usage is very limited for the adult population. Primary disease, stage, age, time and urgency of transplantation, HLA match between the patient and the donor, stem cell quantity, and the experience of the transplantation center are some of the associated factors for the selection of the appropriate stem cell source. Unfortunately, there is no prospective randomized study aimed to facilitate the selection of the correct source between CB, PSC, and BM. In this paper, we would like to emphasize the data on stem cell selection in light of the current knowledge for patient populations according to their age and primary disease.

Ocular findings after allogeneic hematopoietic stem cell transplantation.

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Tabbara, Khalid F; Al-Ghamdi, Ahmad; Al-Mohareb, Fahad; Ayas, Mouhab; Chaudhri, Naeem; Al-Sharif, Fahad; Al-Zahrani, Hazzaa; Mohammed, Said Y; Nassar, Amr; Aljurf, Mahmoud

2009-09-01

To study the incidence, causes, and outcome of major ocular complications in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Retrospective, noncomparative, observational clinical study. The study included a total of 620 patients who underwent allogeneic HSCT in the period from 1997 to 2007 at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. Allogeneic HSCT. Patients with ocular complications were referred to the ophthalmology division for complete ophthalmologic examination, including visual acuity, tonometry, Schirmer test, biomicroscopy, and dilated ophthalmoscopy. Laboratory investigations were performed whenever indicated. The incidence and causes of major ocular complications after allogeneic HSCT were determined. Visual acuity at 1 year after allogeneic HSCT was recorded. Major ocular complications occurred in 80 (13%) of 620 patients who underwent allogeneic HSCT. There were 36 male patients (45%) and 44 female patients (55%) with a mean age of 29 years and an age range of 9 to 65 years. Prophylaxis for graft-versus-host disease (GVHD) consisted of cyclosporine and methotrexate in 69 patients, and cyclosporine, methotrexate and corticosteroids, or mycophenolate mofetil in 11 patients. The most frequently encountered ocular complications were chronic GVHD, dry eye syndrome without GVHD, corneal ulcers, cataract, glaucoma, cytomegalovirus retinitis, fungal endophthalmitis, and acquisition of allergic conjunctivitis from atopic donors. There was no correlation between the pattern of ocular complications and the transplanted stem cell source. Best-corrected visual acuity (BCVA) at 1 year after transplantation was less than 20/200 in 13 patients (16%), less than 20/50 in 17 patients (21%), and better than 20/50 in 50 patients (63%). Ocular complications are common in patients undergoing allogeneic HSCT. Early recognition and prompt treatment are important. The author(s) have no proprietary or commercial

Lessons Learned from Talking with Parents about the Role of Hematopoietic Stem Cell Transplantation in the Treatment of Children with Sickle Cell Disease

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Friedrich, Paola; Steinfield, Elizabeth; Kim, Francis; Hays, Mary Margaret; Lehmann, Leslie; Sprinz, Philippa

2015-01-01

Background: Hematopoietic stem cell transplantation (HSCT) is currently the only cure for sickle cell disease (SCD), but only a fraction of eligible children proceed to transplantation. We aimed to understand parental awareness and perceptions as a contributor. Purpose: To discuss HSCT with parents of children with SCD and assess their awareness…

Immune Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation

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Ogonek, Justyna; Kralj Juric, Mateja; Ghimire, Sakhila; Varanasi, Pavankumar Reddy; Holler, Ernst; Greinix, Hildegard; Weissinger, Eva

2016-01-01

The timely reconstitution and regain of function of a donor-derived immune system is of utmost importance for the recovery and long-term survival of patients after allogeneic hematopoietic stem cell transplantation (HSCT). Of note, new developments such as umbilical cord blood or haploidentical grafts were associated with prolonged immunodeficiency due to delayed immune reconstitution, raising the need for better understanding and enhancing the process of immune reconstitution and finding strategies to further optimize these transplant procedures. Immune reconstitution post-HSCT occurs in several phases, innate immunity being the first to regain function. The slow T cell reconstitution is regarded as primarily responsible for deleterious infections with latent viruses or fungi, occurrence of graft-versus-host disease, and relapse. Here we aim to summarize the major steps of the adaptive immune reconstitution and will discuss the importance of immune balance in patients after HSCT. PMID:27909435

Curative or pre-emptive adenovirus-specific T cell transfer from matched unrelated or third party haploidentical donors after HSCT, including UCB transplantations: a successful phase I/II multicenter clinical trial

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Chongsheng Qian

2017-05-01

Full Text Available Abstract Background Allogeneic hematopoietic stem cell transplantation (HSCT, the most widely used potentially curable cellular immunotherapeutic approach in the treatment of hematological malignancies, is limited by life-threatening complications: graft versus host disease (GVHD and infections especially viral infections refractory to antiviral drugs. Adoptive transfer of virus-specific T cells is becoming an alternative treatment for infections following HSCT. We report here the results of a phase I/II multicenter study which includes a series of adenovirus-specific T cell (ADV-VST infusion either from the HSCT donor or from a third party haploidentical donor for patients transplanted with umbilical cord blood (UCB. Methods Fourteen patients were eligible and 11 patients received infusions of ADV-VST generated by interferon (IFN-γ-based immunomagnetic isolation from a leukapheresis from their original donor (42.9% or a third party haploidentical donor (57.1%. One patient resolved ADV infection before infusion, and ADV-VST could not reach release or infusion criteria for two patients. Two patients received cellular immunotherapy alone without antiviral drugs as a pre-emptive treatment. Results One patient with adenovirus infection and ten with adenovirus disease were infused with ADV-VST (mean 5.83 ± 8.23 × 103 CD3+IFN-γ+ cells/kg up to 9 months after transplantation. The 11 patients showed in vivo expansion of specific T cells up to 60 days post-infusion, associated with adenovirus load clearance in ten of the patients (91%. Neither de novo GVHD nor side effects were observed during the first month post-infusion, but GVHD reactivations occurred in three patients, irrespective of the type of leukapheresis donor. For two of these patients, GVHD reactivation was controlled by immunosuppressive treatment. Four patients died during follow-up, one due to refractory ADV disease. Conclusions Adoptive transfer of rapidly isolated ADV

The clinical application of mesenchymal stromal cells in hematopoietic stem cell transplantation

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Ke Zhao

2016-05-01

Full Text Available Abstract Mesenchymal stromal cells (MSCs are multipotent stem cells well known for repairing tissue, supporting hematopoiesis, and modulating immune and inflammation response. These outstanding properties make MSCs as an attractive candidate for cellular therapy in immune-based disorders, especially hematopoietic stem cell transplantation (HSCT. In this review, we outline the progress of MSCs in preventing and treating engraftment failure (EF, graft-versus-host disease (GVHD following HSCT and critically discuss unsolved issues in clinical applications.

Skin Cancer Risk in Hematopoietic Stem-Cell Transplant Recipients Compared With Background Population and Renal Transplant Recipients

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Omland, Silje Haukali; Gniadecki, Robert; Hædersdal, Merete

2016-01-01

IMPORTANCE: While a high risk of nonmelanoma skin cancer is well recognized in solid-organ transplant recipients, the risk of skin cancer in hematopoietic stem-cell transplant (HSCT) recipients has not been extensively studied. OBJECTIVE: To determine the risk of cutaneous cancer in HSCT recipients...... autologous) from 1999 through 2014, 4789 RTRs from 1976 through 2014, and 10 age- and sex-matched nontransplanted individuals for each of the groups from the background population. Person-years at risk were calculated from the time of study inclusion until first cutaneous cancer. To compare the risk of skin...... cancer between transplant recipients and background population, we used a stratified proportional hazard regression model for hazard ratio (HR) estimations. By use of the cumulative incidence, we estimated 5- and 10-year risks of skin cancers. All RTR and HSCT recipients were treated and followed up...

What Unrelated Hematopoietic Stem Cell Transplantation in Thalassemia Taught us about Transplant Immunogenetics

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La Nasa, Giorgio; Vacca, Adriana; Littera, Roberto; Piras, Eugenia; Orru, Sandro; Greco, Marianna; Carcassi, Carlo; Caocci, Giovanni

2016-01-01

Although the past few decades have shown an improvement in the survival and complication-free survival rates in patients with beta-thalassemia major and gene therapy is already at an advanced stage of experimentation, hematopoietic stem cell transplantation (HSCT) continues to be the only effective and realistic approach to the cure of this chronic non-malignant disease. Historically, human leukocyte antigen (HLA)-matched siblings have been the preferred source of donor cells owing to superior outcomes compared with HSCT from other sources. Nowadays, the availability of an international network of voluntary stem cell donor registries and cord blood banks has significantly increased the odds of finding a suitable HLA matched donor. Stringent immunogenetic criteria for donor selection have made it possible to achieve overall survival (OS) and thalassemia-free survival (TFS) rates comparable to those of sibling transplants. However, acute and chronic graft-versus-host disease (GVHD) remains the most important complication in unrelated HSCT in thalassemia, leading to significant rates of morbidity and mortality for a chronic non-malignant disease. A careful immunogenetic assessment of donors and recipients makes it possible to individualize appropriate strategies for its prevention and management. This review provides an overview of recent insights about immunogenetic factors involved in GVHD, which seem to have a potential role in the outcome of transplantation for thalassemia. PMID:27872728

WHAT UNRELATED HEMATOPOIETIC STEM CELL TRANSPLANTATION IN THALASSEMIA TAUGHT US ABOUT TRANSPLANT IMMUNOGENETICS.

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Giorgio La Nasa

2016-10-01

Full Text Available Abstract Although the past few decades have shown an improvement in the survival and complication-free survival rates in patients with beta-thalassemia major and gene therapy is already at an advanced stage of experimentation, hematopoietic stem cell transplantation (HSCT continues to be the only effective and realistic approach to the cure of this chronic non-malignant disease. Historically, human leukocyte antigen (HLA-matched siblings have been the preferred source of donor cells owing to superior outcomes compared with HSCT from other sources. Nowadays, the availability of an international network of voluntary stem cell donor registries and cordon blood banks has significantly increased the odds of finding a suitable HLA matched donor. Stringent immunogenetic criteria for donor selection have made it possible to achieve overall survival (OS and thalassemia-free survival (TFS rates comparable to those of sibling transplants. However, acute and chronic graft-versus-host disease (GVHD remains the most important complication in unrelated HSCT in thalassemia, leading to considerable rates of morbidity and mortality for a chronic non-malignant disease. A careful immunogenetic assessment of donors and recipients makes it possible to individuate appropriate strategies for its prevention and management. This review provides an overview on recent insights about immunogenetic factors involved in GVHD, which seem to have a potential role in the outcome of transplantation for thalassemia.

Allogeneic Stem Cell Transplantation: A Historical and Scientific Overview.

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Singh, Anurag K; McGuirk, Joseph P

2016-11-15

The field of hematopoietic stem cell transplant (HSCT) has made ground-breaking progress in the treatment of many malignant and nonmalignant conditions. It has also pioneered the concepts of stem cell therapy and immunotherapy as a tool against cancer. The success of transplant for hematologic malignancies derives both from the ability to treat patients with intensive chemoradiotherapy and from potent graft-versus-leukemia (GVL) effects mediated by donor immunity. Additionally, HSCT has been a curative therapy for several nonmalignant hematologic disorders through the provision of donor-derived hematopoiesis and immunity. Preclinical and clinical research in the field has contributed to an advanced understanding of histocompatibility, graft-versus-host disease (GVHD), GVL effect, and immune reconstitution after transplant. Improved donor selection, tailored conditioning regimens, and better supportive care have helped reduce transplant-related morbidity and mortality and expanded access. The development of unrelated donor registries and increased utilization of cord blood and partially matched related donor transplants have ensured a donor for essentially everyone who needs a transplant. However, significant barriers still remain in the form of disease relapse, GVHD infectious complications, and regimen-related toxicities. Recent developments in the field of cellular therapy are expected to further improve the efficacy of transplant. In this review, we discuss the current science of HSCT from a historical perspective, highlighting major discoveries. We also speculate on future directions in this field. Cancer Res; 76(22); 6445-51. ©2016 AACR. ©2016 American Association for Cancer Research.

Development of tumor-reactive T cells after nonmyeloablative allogeneic hematopoietic stem cell transplant for chronic lymphocytic leukemia.

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Nishida, Tetsuya; Hudecek, Michael; Kostic, Ana; Bleakley, Marie; Warren, Edus H; Maloney, David; Storb, Rainer; Riddell, Stanley R

2009-07-15

Allogeneic nonmyeloablative hematopoietic stem cell transplant (NM-HSCT) can result in durable remission of chronic lymphocytic leukemia (CLL). It is thought that the efficacy of NM-HSCT is mediated by recognition of tumor cells by T cells in the donor stem cell graft. We evaluated the development of CTLs specific for CLL after NM-HSCT to determine if their presence correlated with antitumor efficacy. Peripheral blood mononuclear cells obtained from 12 transplant recipients at intervals after NM-HSCT were stimulated in vitro with CLL cells. Polyclonal T-cell lines and CD8(+) T-cell clones were derived from these cultures and evaluated for lysis of donor and recipient target cells including CLL. The presence and specificity of responses was correlated with clinical outcomes. Eight of the 12 patients achieved remission or a major antitumor response and all 8 developed CD8(+) and CD4(+) T cells specific for antigens expressed by CLL. A clonal analysis of the CD8(+) T-cell response identified T cells specific for multiple minor histocompatibility (H) antigens expressed on CLL in six of the responding patients. A significant fraction of the CD8(+) T-cell response in some patients was also directed against nonshared tumor-specific antigens. By contrast, CLL-reactive T cells were not detected in the four patients who had persistent CLL after NM-HSCT, despite the development of graft-versus-host disease. The development of a diverse T-cell response specific for minor H and tumor-associated antigens expressed by CLL predicts an effective graft-versus-leukemia response after NM-HSCT.

Hematopoietic Stem Cell Transplantation Activity Worldwide in 2012 and a SWOT Analysis of the Worldwide Network for Blood and Marrow Transplantation Group (WBMT) including the global survey

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Niederwieser, Dietger; Baldomero, Helen; Szer, Jeff; Gratwohl, Michael; Aljurf, Mahmoud; Atsuta, Yoshiko; Bouzas, Luis Fernando; Confer, Dennis; Greinix, Hildegard; Horowitz, Mary; Iida, Minako; Lipton, Jeff; Mohty, Mohamad; Novitzky, Nicolas; Nunez, José; Passweg, Jakob; Pasquini, Marcelo C.; Kodera, Yoshihisa; Apperley, Jane; Seber, Adriana; Gratwohl, Alois

2016-01-01

Data on 68,146 hematopoietic stem cell transplants (HSCT) (53% autologous and 47% allogeneic) gathered by 1566 teams from 77 countries and reported through their regional transplant organizations were analyzed by main indication, donor type and stem cell source for the year 2012. With transplant rates ranging from 0.1 to 1001 per 10 million inhabitants, more HSCT were registered from unrelated 16,433 than related 15,493 donors. Grafts were collected from peripheral blood (66%), bone marrow (24%; mainly non-malignant disorders) and cord blood (10%). Compared to 2006, an increase of 46% total (57% allogeneic and 38% autologous) was observed. Growth was due to an increase in reporting teams (18%) and median transplant activity/team (from 38 to 48 HSCT/team). An increase of 67% was noted in mismatched/haploidentical family HSCT. A SWOT analysis revealed the global perspective of WBMT to be its major strength and identified potential to be the key professional body for patients and authorities. The limited data collection remains its major weakness and threat. In conclusion, global HSCT grows over the years without plateauing (allogeneic>autologous) and at different rates in the four WHO regions. Major increases were observed in allogeneic, haploidentical HSCT and, to a lesser extent, in cord blood. PMID:26901703

Autologous CLL cell vaccination early after transplant induces leukemia-specific T cells.

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Burkhardt, Ute E; Hainz, Ursula; Stevenson, Kristen; Goldstein, Natalie R; Pasek, Mildred; Naito, Masayasu; Wu, Di; Ho, Vincent T; Alonso, Anselmo; Hammond, Naa Norkor; Wong, Jessica; Sievers, Quinlan L; Brusic, Ana; McDonough, Sean M; Zeng, Wanyong; Perrin, Ann; Brown, Jennifer R; Canning, Christine M; Koreth, John; Cutler, Corey; Armand, Philippe; Neuberg, Donna; Lee, Jeng-Shin; Antin, Joseph H; Mulligan, Richard C; Sasada, Tetsuro; Ritz, Jerome; Soiffer, Robert J; Dranoff, Glenn; Alyea, Edwin P; Wu, Catherine J

2013-09-01

Patients with advanced hematologic malignancies remain at risk for relapse following reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-HSCT). We conducted a prospective clinical trial to test whether vaccination with whole leukemia cells early after transplantation facilitates the expansion of leukemia-reactive T cells and thereby enhances antitumor immunity. We enrolled 22 patients with advanced chronic lymphocytic leukemia (CLL), 18 of whom received up to 6 vaccines initiated between days 30 and 45 after transplantation. Each vaccine consisted of irradiated autologous tumor cells admixed with GM-CSF-secreting bystander cells. Serial patient PBMC samples following transplantation were collected, and the impact of vaccination on T cell activity was evaluated. At a median follow-up of 2.9 (range, 1-4) years, the estimated 2-year progression-free and overall survival rates of vaccinated subjects were 82% (95% CI, 54%-94%) and 88% (95% CI, 59%-97%), respectively. Although vaccination only had a modest impact on recovering T cell numbers, CD8+ T cells from vaccinated patients consistently reacted against autologous tumor, but not alloantigen-bearing recipient cells with increased secretion of the effector cytokine IFN-γ, unlike T cells from nonvaccinated CLL patients undergoing allo-HSCT. Further analysis confirmed that 17% (range, 13%-33%) of CD8+ T cell clones isolated from 4 vaccinated patients by limiting dilution of bulk tumor-reactive T cells solely reacted against CLL-associated antigens. Our studies suggest that autologous tumor cell vaccination is an effective strategy to advance long-term leukemia control following allo-HSCT. Clinicaltrials.gov NCT00442130. NCI (5R21CA115043-2), NHLBI (5R01HL103532-03), and Leukemia and Lymphoma Society Translational Research Program.

Second neoplasms in adult patients submitted to haematopoietic stem cell transplantation.

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Torrent, Anna; Ferrá, Christelle; Morgades, Mireia; Jiménez, María-José; Sancho, Juan-Manuel; Vives, Susana; Batlle, Montserrat; Moreno, Miriam; Xicoy, Blanca; Oriol, Albert; Ibarra, Gladys; Ribera, Josep-Maria

2018-06-08

Patients submitted to haematopoietic stem cell transplantation (HSCT) are at increased risk of late complications, such as second neoplasm (SN). The incidence and risk factors of SN in patients receiving HSCT at a single centre were analysed. The follow-up of adult patients who received a first HSCT (autologous [auto-HSCT] or allogeneic [allo-HSCT]) between January 2000 and December 2015 was reviewed. We collected their demographic characteristics, the primary disease and type of HSCT, and analysed the cumulative incidence of SN and their risk factors. Of 699 transplanted patients (auto-HSCT, n=451; allo-HSCT, n=248), 42 (6%) developed SN (17 haematological and 25 solid), 31 post-auto-HSCT and 11 post-allo-HSCT. Haematologic SN were more frequent after auto-HSCT than after allo-HSCT. The median time between HSCT and SN was 4.09 years [range 0.07-13.15], with no differences between auto-HSCT and allo-HSCT. The cumulative incidence of SN was 5% (95% CI 3-6) at 5 years, 7% (95% CI 5-10) at 10 years and 11% (95% CI 8-15) at 15 years, without differences according to the type of HSCT. Only the age over 40 years correlated with an increased risk of SN. In this series, the incidence of post-HSCT SN was similar to that previously described. Patients submitted to an auto-HSCT showed a higher frequency of haematologic SN. A higher incidence of SN was detected in patients older than 40 at the time of HSCT. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Clinico-serologic co-relation in bi-directional ABO incompatible hemopoietic stem cell transplantation

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Sabita Basu

2015-01-01

Full Text Available Background: The ABO blood group system is of prime significance in red cell transfusion and organ transplantation. However, ABO compatibility is not critical in allogenic hemopoietic stem cell transplantation (HSCT and approximately 40-50% of hemopoietic stem cell transplants are ABO incompatible. This incompatibility may be major, minor or bi-directional. Though there are descriptions of transfusion practice and protocols in ABO incompatible HSCT, there are considerable variations and transfusion support in these patients can be very challenging. Aims: The immunohematologic observations in two cases of bi-directional ABO incompatible HSCT have been described, and clinico-serologic correlation has been attempted. Materials and Methods: In both cases, peripheral blood stem cell harvests were obtained using the Cobe spectra cell separator. Immunohematologic assessments in the donor and recipient were done as a part of pre HSCT evaluation. Both the standard tube technique and column agglutination method (Ortho Biovue Micro Bead System was used. Antibody screen was done by column agglutination method using three cell panel (Surgiscreen cells. Isoagglutinin titration was done by the master dilution method and standard validated techniques were used. Results: The pattern of laboratory findings in the two cases was different and so were the clinical outcomes. Although there was early engraftment in the first case, the second case developed pure red cell aplasia and this was well-reflected in the immunohematologic assessments. Conclusion: Immunohematologic assessment correlated well with the clinical picture and could be used to predict clinical outcome and onset of complications in ABO incompatible HSCT.

Quality of life concerns and depression among hematopoietic stem cell transplant survivors.

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Mosher, Catherine E; DuHamel, Katherine N; Rini, Christine; Corner, Geoffrey; Lam, Joanne; Redd, William H

2011-09-01

This study examined quality of life, transplant-related concerns, and depressive symptoms and their demographic and medical correlates at 1 to 3 years following hematopoietic stem cell transplantation (HSCT). HSCT survivors (N=406) completed telephone-administered questionnaires that assessed demographic variables, functional status, quality of life, transplant-related concerns, and depressive symptoms. The most prevalent concerns among HSCT survivors included physical symptoms (e.g., fatigue and pain), maintaining current health status and employment, changes in appearance, and lack of sexual interest and satisfaction. In addition, almost one-third (32%) of survivors age 40 years and younger reported concern about their ability to have children. Unemployed survivors and those with lower incomes and worse functional status were more likely to experience poorer quality of life in multiple domains. Fifteen percent of the sample reported moderate to severe depressive symptoms, and these symptoms were higher among allogeneic transplant recipients and those with lower functional status. Results suggest that interventions are needed to address physical symptoms, coping with an uncertain future, infertility, and sexual issues during the early phase of HSCT survivorship.

Critical care of the hematopoietic stem cell transplant recipient.

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Afessa, Bekele; Azoulay, Elie

2010-01-01

An estimated 50,000 to 60,000 patients undergo hematopoietic stem cell transplantation (HSCT) worldwide annually, of which 15.7% are admitted to the intensive care unit (ICU). The most common reason for ICU admission is respiratory failure and almost all develop single or multiorgan failure. Most HSCT recipients admitted to ICU receive invasive mechanical ventilation (MV). The overall short-term mortality rate of HSCT recipients admitted to ICU is 65%, and 86.4% for those receiving MV. Patient outcome has improved over time. Poor prognostic indicators include advanced age, poor functional status, active disease at transplant, allogeneic transplant, the severity of acute illness, and the development of multiorgan failure. ICU resource limitations often lead to triage decisions for admission. For HSCT recipients, the authors recommend (1) ICU admission for full support during their pre-engraftment period and when there is no evidence of disease recurrence; (2) no ICU admission for patients who refuse it and those who are bedridden with disease recurrence and without treatment options except palliation; (3) a trial ICU admission for patients with unknown status of disease recurrence with available treatment options.

Hematopoietic Stem Cell Transplantation Activity in Pediatric Cancer between 2008 and 2014 in the United States: A Center for International Blood and Marrow Transplant Research Report.

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Khandelwal, Pooja; Millard, Heather R; Thiel, Elizabeth; Abdel-Azim, Hisham; Abraham, Allistair A; Auletta, Jeffery J; Boulad, Farid; Brown, Valerie I; Camitta, Bruce M; Chan, Ka Wah; Chaudhury, Sonali; Cowan, Morton J; Angel-Diaz, Miguel; Gadalla, Shahinaz M; Gale, Robert Peter; Hale, Gregory; Kasow, Kimberly A; Keating, Amy K; Kitko, Carrie L; MacMillan, Margaret L; Olsson, Richard F; Page, Kristin M; Seber, Adriana; Smith, Angela R; Warwick, Anne B; Wirk, Baldeep; Mehta, Parinda A

2017-08-01

This Center for International Blood and Marrow Transplant Research report describes the use of hematopoietic stem cell transplantation (HSCT) in pediatric patients with cancer, 4408 undergoing allogeneic (allo) and3076 undergoing autologous (auto) HSCT in the United States between 2008 and 2014. In both settings, there was a greater proportion of boys (n = 4327; 57%), children reports of transplant practices in the United States. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Orthopaedic management of Hurler's disease after hematopoietic stem cell transplantation : A systematic review

NARCIS (Netherlands)

van der Linden, Marleen H.; Kruyt, Moyo C.; Sakkers, Ralph J. B.; de Koning, Tom J.; Oner, F. Cumhur; Castelein, Rene M.

The introduction of hematopoietic stem cell transplantation (HSCT) has significantly improved the life-span of Hurler patients (mucopolysaccharidosis type I-H, MPS I-H). Yet, the musculoskeletal manifestations seem largely unresponsive to HSCT. In order to facilitate evidence based management, the

Endobronchial Epstein-Barr Virus Associated Post-transplant Lymphoproliferative Disorder in Hematopoietic Stem Cell Transplantation

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S. Feuillet

2009-01-01

Full Text Available The Epstein-Barr virus (EBV associated Post-Transplant Lymphoproliferative Disorders (PTLD are increasingly recognized as a fatal complication of hematological stem cell transplantation (HSCT. Thoracic involvement, that may be isolated or part of a disseminated disease, usually encompasses pulmonary nodules or masses and mediastinal lymph node enlargement. The current case study presents 2 patients who underwent HSCT, one allogenic and the other autologous, who developed an exceptional endobronchial EBV related PTLD. The first patient had a fleshy white endobronchial mass resulting in a right upper lobe atelectasis and the second had an extensive necrotising mucosa from trachea to both basal bronchi without any significant change of lung parenchyma on the CT scan. In both cases, the diagnosis was made by bronchial biopsies. Physicians should be aware of an endobronchial pattern of EBV associated PTLD after HSCT to permit quick diagnosis and therapeutic intervention.

Prospective Study of a Cohort of Russian Nijmegen Breakage Syndrome Patients Demonstrating Predictive Value of Low Kappa-Deleting Recombination Excision Circle (KREC Numbers and Beneficial Effect of Hematopoietic Stem Cell Transplantation (HSCT

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Elena Deripapa

2017-07-01

Full Text Available BackgroundNijmegen breakage syndrome (NBS is a combined primary immunodeficiency with DNA repair defect, microcephaly, and other phenotypical features. It predominantly occurs in Slavic populations that have a high frequency of carriers with the causative NBN gene c.657_661del5 mutation. Due to the rarity of the disease in the rest of the world, studies of NBS patients are few. Here, we report a prospective study of a cohort of Russian NBS patients.Methods35 Russian NBS patients of ages 1–19 years, referred to our Center between years 2012 and 2016, were prospectively studied.ResultsDespite the fact that in 80% of the patients microcephaly was diagnosed at birth or shortly thereafter, the average delay of NBS diagnosis was 6.5 years. Though 80% of the patients had laboratory signs of immunodeficiency, only 51% of the patients experienced significant infections. Autoimmune complications including interstitial lymphocytic lung disease and skin granulomas were noted in 34%, malignancies—in 57% of the patients. T-cell excision circle (TREC/kappa-deleting recombination excision circle (KREC levels were low in the majority of patients studied. Lower KREC levels correlated with autoimmune and oncological complications. Fifteen patients underwent hematopoietic stem cell transplantation (HSCT, 10 of them were alive and well, with good graft function. Three patients in the HSCT group and five non-transplanted patients died; tumor progression being the main cause of death. The probability of the overall survival since NBS diagnosis was 0.76 in the HSCT group and 0.3 in the non-transplanted group.ConclusionBased on our findings of low TRECs in most NBS patients, independent of their age, TREC detection can be potentially useful for detection of NBS patients during neonatal screening. KREC concentration can be used as a prognostic marker of disease severity. HSCT is a viable treatment option in NBS and should be especially considered in patients with

CAR-T cells and allogeneic hematopoietic stem cell transplantation for relapsed/refractory B-cell acute lymphoblastic leukemia.

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Liu, Jun; Zhang, Xi; Zhong, Jiang F; Zhang, Cheng

2017-10-01

Relapsed/refractory acute lymphoblastic leukemia (ALL) has a low remission rate after chemotherapy, a high relapse rate and poor long-term survival even when allogeneic hematopoietic stem cell transplantation (allo-HSCT) is performed. Chimeric antigen receptors redirected T cells (CAR-T cells) can enhance disease remission with a favorable outcome for relapsed/refractory ALL, though some cases quickly relapsed after CAR-T cell treatment. Thus, treatment with CAR-T cells followed by allo-HSCT may be the best way to treat relapsed/refractory ALL. In this review, we first discuss the different types of CAR-T cells. We then discuss the treatment of relapsed/refractory ALL using only CAR-T cells. Finally, we discuss the use of CAR-T cells, followed by allo-HSCT, for the treatment of relapsed/refractory ALL.

Impact of HSCT conditioning and glucocorticoid dose on exercise adherence and response

OpenAIRE

Wiskemann, Joachim; Herzog, Benedikt; Kuehl, Rea; Schmidt, Martina E.; Steindorf, Karen; Schwerdtfeger, Rainer; Dreger, Peter; Bohus, Martin

2017-01-01

Abstract: Purpose: Evidence from randomized controlled trials (RCT) that exercise interventions have beneficial effects in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) is growing. However, intensive chemotherapy conditioning and glucocorticoid (GC) treatment is always part of an allo-HSCT and possibly affect exercise adherence and training response. Therefore, we aimed to examine whether various conditioning protocols or different doses of GC treatment af...

Low Radiation Dose and Low Cell Dose Increase the Risk of Graft Rejection in a Canine Hematopoietic Stem Cell Transplantation Model.

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Lange, Sandra; Steder, Anne; Glass, Änne; Killian, Doreen; Wittmann, Susanne; Machka, Christoph; Werner, Juliane; Schäfer, Stephanie; Roolf, Catrin; Junghanss, Christian

2016-04-01

The canine hematopoietic stem cell transplantation (HSCT) model has become accepted in recent decades as a good preclinical model for the development of new transplantation strategies. Information on factors associated with outcome after allogeneic HSCT are a prerequisite for designing new risk-adapted transplantation protocols. Here we report a retrospective analysis aimed at identifying risk factors for allograft rejection in the canine HSCT model. A total of 75 dog leukocyte antigen-identical sibling HSCTs were performed since 2003 on 10 different protocols. Conditioning consisted of total body irradiation at 1.0 Gy (n = 20), 2.0 Gy (n = 40), or 4.5 Gy (n = 15). Bone marrow was infused either intravenously (n = 54) or intraosseously (n = 21). Cyclosporin A alone or different combinations of cyclosporine A, mycophenolate mofetil, and everolimus were used for immunosuppression. A median cell dose of 3.5 (range, 1.0 to 11.8) total nucleated cells (TNCs)/kg was infused. Cox analyses were used to assess the influence of age, weight, radiation dose, donor/recipient sex, type of immunosuppression, and cell dose (TNCs, CD34(+) cells) on allograft rejection. Initial engraftment occurred in all dogs. Forty-two dogs (56%) experienced graft rejection at median of 11 weeks (range, 6 to 56 weeks) after HSCT. Univariate analyses revealed radiation dose, type of immunosuppression, TNC dose, recipient weight, and recipient age as factors influencing long-term engraftment. In multivariate analysis, low radiation dose (P rejection. Peripheral blood mononuclear cell chimerism ≥30% (P = .008) and granulocyte chimerism ≥70% (P = .023) at 4 weeks after HSCT were independent predictors of stable engraftment. In summary, these data indicate that even in low-dose total body irradiation-based regimens, the irradiation dose is important for engraftment. The level of blood chimerism at 4 weeks post-HSCT was predictive of long-term engraftment in the canine HSCT

A human monoclonal antibody drug and target discovery platform for B-cell chronic lymphocytic leukemia based on allogeneic hematopoietic stem cell transplantation and phage display

OpenAIRE

Baskar, Sivasubramanian; Suschak, Jessica M.; Samija, Ivan; Srinivasan, Ramaprasad; Childs, Richard W.; Pavletic, Steven Z.; Bishop, Michael R.; Rader, Christoph

2009-01-01

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only potentially curative treatment available for patients with B-cell chronic lymphocytic leukemia (B-CLL). Here, we show that post-alloHSCT antibody repertoires can be mined for the discovery of fully human monoclonal antibodies to B-CLL cell-surface antigens. Sera collected from B-CLL patients at defined times after alloHSCT showed selective binding to primary B-CLL cells. Pre-alloHSCT sera, donor sera, and control sera w...

Gauchers disease--a reappraisal of hematopoietic stem cell transplantation.

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Ito, Sawa; Barrett, A John

2013-03-01

Hematopoietic stem cell transplantation (HSCT), first performed in 1984, was the first treatment approach for Gaucher's disease (GD) which had curative intent. The early successes in HSCT were soon eclipsed by the introduction of a highly effective enzyme replacement therapy (ERT), which has remained the single most widely used treatment. Experience with HSCT is limited to about 50 reported cases, mainly performed in the last century, with an overall survival around 85%. HSCT typically achieves complete correction of visceral and bony changes and can fully stabilize neurological features in otherwise progressive type II and III GD. ERT, in contrast, is completely safe and effective, but is limited by cost, incomplete resolution of visceral, hematological, and bony features in some patients, and lack of neurological correction in type II and III disease. In this review, we summarize and compare HSCT and ERT. With 20 years of experience of ERT, its limitations as well as its advantages are now well delineated. Meanwhile progress in HSCT over the last decade suggests that transplantation would today represent a very safe curative approach for GD offering one time complete correction of the disease, contrasting with the lifelong need for ERT with its associated expense and dependence on sophisticated drug manufacture. Additionally, unlike ERT, HSCT can be beneficial for neurological forms of GD. We conclude that the time has come to re-evaluate HSCT in selected patients with GD where ERT is less likely to fully eradicate symptoms of the disease.

Antimicrobial Resistance in Gram-Negative Rods Causing Bacteremia in Hematopoietic Stem Cell Transplant Recipients

DEFF Research Database (Denmark)

Averbuch, Diana; Tridello, Gloria; Hoek, Jennifer

2017-01-01

Background: This intercontinental study aimed to study gram-negative rod (GNR) resistance in hematopoietic stem cell transplantation (HSCT). Methods: GNR bacteremias occurring during 6 months post-HSCT (February 2014-May 2015) were prospectively collected, and analyzed for rates and risk factors...

Dangers resulting from DNA profiling of biological materials derived from patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT with regard to forensic genetic analysis

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Renata Jacewicz

2016-07-01

Full Text Available The study documents the risk that comes with DNA analysis of materials derived from patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT in forensic genetics. DNA chimerism was studied in 30 patients after allo-HSCT, based on techniques applied in contemporary forensic genetics, i.e. real-time PCR and multiplex PCR-STR with the use of autosomal DNA as well as Y-DNA markers. The results revealed that the DNA profile of the recipient’s blood was identical with the donor’s in the majority of cases. Therefore, blood analysis can lead to false conclusions in personal identification as well as kinship analysis. An investigation of buccal swabs revealed a mixture of DNA in the majority of recipients. Consequently, personal identification on the basis of stain analysis of the same origin may be impossible. The safest (but not ideal material turned out to be the hair root. Its analysis based on autosomal DNA revealed 100% of the recipient’s profile. However, an analysis based on Y-chromosome markers performed in female allo-HSCT recipients with male donors demonstrated the presence of donor DNA in hair cells – similarly to the blood and buccal swabs. In the light of potential risks arising from DNA profiling of biological materials derived from persons after allotransplantation in judicial aspects, certain procedures were proposed to eliminate such dangers. The basic procedures include abandoning the approach based exclusively on blood collection, both for kinship analysis and personal identification; asking persons who are to be tested about their history of allo-HSCT before sample collection and profile entry in the DNA database, and verification of DNA profiling based on hair follicles in uncertain cases.

Induction of tolerance and prolongation of islet allograft survival by syngeneic hematopoietic stem cell transplantation in mice.

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Yang, Shi-feng; Xue, Wu-jun; Lu, Wan-hong; Xie, Li-yi; Yin, Ai-ping; Zheng, Jin; Sun, Ji-ping; Li, Yang

2015-10-01

Syngeneic or autologous hematopoietic stem cells transplantation (HSCT) has been proposed to treat autoimmune diseases because of its immunosuppressive and immunomodulatory effects, which can also contribute to posttransplant antirejection therapy. In this study, we explored the tolerogenic effect of syngeneic HSCT on prolonging islet allograft survival. C57BL/6 mice received syngeneic HSCT plus preconditioning with sublethal irradiation. Then islets of BALB/c mice were transplanted into the renal subcapsular of C57BL/6 mice after chemically induced into diabetes. HSCT mice exhibited improved islet allograft survival and increased serum insulin compared to control mice. Islet allografts of HSCT mice displayed lower level lymphocyte infiltration and stronger insulin staining than control mice. T cells of HSCT mice proliferated poorly in response to allogeneic splenocytes compared to control mice. Mice appeared reversed interferon-γ (IFN-γ)/interleukin-4 (IL-4) ratio to a Th2 immune deviation after syngeneic HSCT. The percentage of CD8(+) T cells was lower, while percentage of CD4(+)CD25(+)Foxp3(+) T regulatory cells (Tregs) was higher in HSCT mice than control mice. HSCT mice showed higher percentage of CTLA-4(+) T cells and expression of CTLA-4 mRNA than control mice. Targeting of CTLA-4 by intraperitoneal injection of anti-CTLA-4 mAb abrogated the effect of syngeneic HSCT on prolonging islet allograft survival, inhibiting activity of T cells in response to alloantigen, promoting Th1 to Th2 immune deviation and up regulating CD4(+)CD25(+)Foxp3(+) Tregs. Syngeneic HSCT plus preconditioning of sublethal irradiation induces tolerance and improves islet allograft survival in fully mismatched mice model. Th1 to Th2 immune deviation, increased CD4(+)CD25(+)Foxp3(+) Tregs and up-regulation of CTLA-4 maybe contribute to the tolerogenic effect induced by syngeneic HSCT. Copyright © 2015 Elsevier B.V. All rights reserved.

Graft-versus-Leukemia Effect Following Hematopoietic Stem Cell Transplantation for Leukemia

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Anne M. Dickinson

2017-06-01

Full Text Available The success of hematopoietic stem cell transplantation (HSCT lies with the ability of the engrafting immune system to remove residual leukemia cells via a graft-versus-leukemia effect (GvL, caused either spontaneously post-HSCT or via donor lymphocyte infusion. GvL effects can also be initiated by allogenic mismatched natural killer cells, antigen-specific T cells, and activated dendritic cells of leukemic origin. The history and further application of this GvL effect and the main mechanisms will be discussed and reviewed in this chapter.

Clinical outcome in children with chronic granulomatous disease managed conservatively or with hematopoietic stem cell transplantation.

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Cole, Theresa; Pearce, Mark S; Cant, Andrew J; Cale, Catherine M; Goldblatt, David; Gennery, Andrew R

2013-11-01

Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by serious infections and inflammation. It can be managed conservatively with prophylactic antimicrobial agents or curatively with hematopoietic stem cell transplantation (HSCT). In the United Kingdom and Ireland there are cohorts of children managed both conservatively and curatively. This study aimed to compare clinical outcomes (mortality and morbidity) in children managed conservatively and curatively. Children were identified from specialist centers and advertising through special interest groups. Clinical data were collected from medical records regarding infections, inflammatory complications and growth, other admissions, and curative treatment. Comparisons were made for patients not undergoing HSCT and patients after HSCT. Seventy-three living children were identified, 59 (80%) of whom were recruited. Five deceased children were also identified. Clinical information was available for 62 children (4 deceased). Thirty (48%) children had undergone HSCT. Children who did not undergo transplantation had 0.71 episodes of infection/admission/surgery per CGD life year (95% CI, 0.69-0.75 events per year). Post-HSCT children had 0.15 episodes of infection/admission/surgery per transplant year (95% CI, 0.09-0.21 events per year). The mean z score for height and body mass index (BMI) for age was significantly better in post-HSCT children. Survival in the non-HSCT group was 90% at age 15 years. Survival in the post-HSCT group was 90%. Children with CGD not undergoing transplantation have more serious infections, episodes of surgery, and admissions compared with post-HSCT children. Children undergoing transplantation have better height for age. Survival is good at the end of the pediatric age range and also after HSCT. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Endocrinopathies after Allogeneic and Autologous Transplantation of Hematopoietic Stem Cells

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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.

Defective pulmonary innate immune responses post-stem cell transplantation; review and results from one model system

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Racquel eDomingo-Gonzalez

2013-05-01

Full Text Available Infectious pulmonary complications limit the success of hematopoietic stem cell transplantation (HSCT as a therapy for malignant and nonmalignant disorders. Susceptibility to pathogens in both autologous and allogeneic HSCT recipients persists despite successful immune reconstitution. As studying the causal effects of these immune defects in the human population can be limiting, a bone marrow transplant (BMT mouse model can be used to understand the defect in mounting a productive innate immune response post-transplantation. When syngeneic BMT is performed, this system allows the study of BMT-induced alterations in innate immune cell function that are independent of the confounding effects of immunosuppressive therapy and graft-versus-host disease. Studies from several laboratories, including our own show that pulmonary susceptibility to bacterial infections post-BMT are largely due to alterations in the lung alveolar macrophages. Changes in these cells post-BMT include cytokine and eicosanoid dysregulations, scavenger receptor alterations, changes in micro RNA profiles, and alterations in intracellular signaling molecules that limit bacterial phagocytosis and killing. The changes that occur highlight mechanisms that promote susceptibility to infections commonly afflicting HSCT recipients and provide insight into therapeutic targets that may improve patient outcomes post-HSCT.

Umbilical Cord-Derived Mesenchymal Stem Cells for Hematopoietic Stem Cell Transplantation

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Yu-Hua Chao

2012-01-01

Full Text Available Hematopoietic stem cell transplantation (HSCT is becoming an effective therapeutic modality for a variety of diseases. Mesenchymal stem cells (MSCs can be used to enhance hematopoietic engraftment, accelerate lymphocyte recovery, reduce the risk of graft failure, prevent and treat graft-versus-host disease, and repair tissue damage in patients receiving HSCT. Till now, most MSCs for human clinical application have been derived from bone marrow. However, acquiring bone-marrow-derived MSCs involves an invasive procedure. Umbilical cord is rich with MSCs. Compared to bone-marrow-derived MSCs, umbilical cord-derived MSCs (UCMSCs are easier to obtain without harm to the donor and can proliferate faster. No severe adverse effects were noted in our previous clinical application of UCMSCs in HSCT. Accordingly, application of UCMSCs in humans appears to be feasible and safe. Further studies are warranted.

Milestones of Hematopoietic Stem Cell Transplantation – From First Human Studies to Current Developments

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Juric, Mateja Kralj; Ghimire, Sakhila; Ogonek, Justyna; Weissinger, Eva M.; Holler, Ernst; van Rood, Jon J.; Oudshoorn, Machteld; Dickinson, Anne; Greinix, Hildegard T.

2016-01-01

Since the early beginnings, in the 1950s, hematopoietic stem cell transplantation (HSCT) has become an established curative treatment for an increasing number of patients with life-threatening hematological, oncological, hereditary, and immunological diseases. This has become possible due to worldwide efforts of preclinical and clinical research focusing on issues of transplant immunology, reduction of transplant-associated morbidity, and mortality and efficient malignant disease eradication. The latter has been accomplished by potent graft-versus-leukemia (GvL) effector cells contained in the stem cell graft. Exciting insights into the genetics of the human leukocyte antigen (HLA) system allowed improved donor selection, including HLA-identical related and unrelated donors. Besides bone marrow, other stem cell sources like granulocyte-colony stimulating-mobilized peripheral blood stem cells and cord blood stem cells have been established in clinical routine. Use of reduced-intensity or non-myeloablative conditioning regimens has been associated with a marked reduction of non-hematological toxicities and eventually, non-relapse mortality allowing older patients and individuals with comorbidities to undergo allogeneic HSCT and to benefit from GvL or antitumor effects. Whereas in the early years, malignant disease eradication by high-dose chemotherapy or radiotherapy was the ultimate goal; nowadays, allogeneic HSCT has been recognized as cellular immunotherapy relying prominently on immune mechanisms and to a lesser extent on non-specific direct cellular toxicity. This chapter will summarize the key milestones of HSCT and introduce current developments. PMID:27881982

Psychosocial Changes Associated with Participation in Art Therapy Interventions for Siblings of Pediatric Hematopoietic Stem Cell Transplant Patients

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Wallace, Jo; Packman, Wendy; Huffman, Lynne C.; Horn, Biljana; Cowan, Morton; Amylon, Michael D.; Kahn, Colleen; Cordova, Matt; Moses, Jim

2014-01-01

Hematopoietic stem cell transplantation (HSCT) is an accepted medical treatment for many serious childhood diseases. HSCT is a demanding procedure that creates both physical and emotional challenges for patients and their family members. Research has demonstrated that siblings of children undergoing HSCT are at risk for developing psychosocial…

Characterization of Regulatory Dendritic Cells That Mitigate Acute Graft-versus-Host Disease in Older Mice Following Allogeneic Bone Marrow Transplantation

OpenAIRE

Scroggins, Sabrina M.; Olivier, Alicia K.; Meyerholz, David K.; Schlueter, Annette J.

2013-01-01

Despite improvements in human leukocyte antigen matching and pharmacologic prophylaxis, acute graft-versus-host disease (GVHD) is often a fatal complication following hematopoietic stem cell transplant (HSCT). Older HSCT recipients experience significantly increased morbidity and mortality compared to young recipients. Prophylaxis with syngeneic regulatory dendritic cells (DCreg) in young bone marrow transplanted (BMT) mice has been shown to decrease GVHD-associated mortality. To evaluate thi...

Evolution, trends, outcomes, and economics of hematopoietic stem cell transplantation in severe autoimmune diseases.

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Snowden, John A; Badoglio, Manuela; Labopin, Myriam; Giebel, Sebastian; McGrath, Eoin; Marjanovic, Zora; Burman, Joachim; Moore, John; Rovira, Montserrat; Wulffraat, Nico M; Kazmi, Majid; Greco, Raffaella; Snarski, Emilian; Kozak, Tomas; Kirgizov, Kirill; Alexander, Tobias; Bader, Peter; Saccardi, Riccardo; Farge, Dominique

2017-12-26

Hematopoietic stem cell transplantation (HSCT) has evolved for >20 years as a specific treatment of patients with autoimmune disease (AD). Using European Society for Blood and Marrow Transplantation registry data, we summarized trends and identified factors influencing activity and outcomes in patients with AD undergoing first autologous HSCT (n = 1951; median age, 37 years [3-76]) and allogeneic HSCT (n = 105; median age, 12 years [<1-62]) in 247 centers in 40 countries from 1994 to 2015. Predominant countries of activity were Italy, Germany, Sweden, the United Kingdom, The Netherlands, Spain, France, and Australia. National activity correlated with the Human Development Index ( P = .006). For autologous HSCT, outcomes varied significantly between diseases. There was chronological improvement in progression-free survival (PFS, P < 10 -5 ), relapse/progression ( P < 10 -5 ), and nonrelapse mortality ( P = .01). Health care expenditure was associated with improved outcomes in systemic sclerosis and multiple sclerosis (MS). On multivariate analysis selecting adults for MS, systemic sclerosis, and Crohn disease, better PFS was associated with experience (≥23 transplants for AD, P = .001), learning (time from first HSCT for AD ≥6 years, P = .01), and Joint Accreditation Committee of the International Society for Cellular Therapy and European Society for Blood and Marrow Transplantation accreditation status ( P = .02). Despite improved survival over time ( P = .02), allogeneic HSCT use remained low and largely restricted to pediatric practice. Autologous HSCT has evolved into a treatment modality to be considered alongside other modern therapies in severe AD. Center experience, accreditation, interspecialty networking, and national socioeconomic factors are relevant for health service delivery of HSCT in AD.

Introduction of a Quality Management System and Outcome After Hematopoietic Stem-Cell Transplantation

NARCIS (Netherlands)

Gratwohl, Alois; Brand, Ronald; Niederwieser, Dietger; Baldomero, Helen; Chabannon, Christian; Cornelissen, Jan; de Witte, Theo; Ljungman, Per; McDonald, Fiona; McGrath, Eoin; Passweg, Jakob; Peters, Christina; Rocha, Vanderson; Slaper-Cortenbach, Ineke; Sureda, Anna; Tichelli, Andre; Apperley, Jane

2011-01-01

Purpose A comprehensive quality management system called JACIE (Joint Accreditation Committee International Society for Cellular Therapy and the European Group for Blood and Marrow Transplantation), was introduced to improve quality of care in hematopoietic stem-cell transplantation (HSCT). We

Oral bacteria and yeasts in relationship to oral ulcerations in hematopoietic stem cell transplant recipients

NARCIS (Netherlands)

Laheij, A.M.G.A.; de Soet, J.J.; von dem Borne, P.A.; Kuijper, E.J.; Kraneveld, E.A.; van Loveren, C.; Raber-Durlacher, J.E.

2012-01-01

BACKGROUND: Oral mucositis is a serious and debilitating side effect of conditioning regimens for hematopoietic stem cell transplant (HSCT). Through HSCT, the homeostasis in the oral cavity is disrupted. The contribution of the oral microflora to mucositis remains to be clarified. The aim of our

Acquisition and Cure of Autoimmune Disease Following Allogeneic Hematopoietic Stem Cell Transplantation

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Hsin-An Hou

2007-09-01

Full Text Available Hematopoietic stem cell transplantation (HSCT can either cause or eliminate autoimmune disease. Here, we report two cases. One was a 33-year-old woman with myelodysplastic syndrome (refractory anemia who received bone marrow transplantation from her human leukocyte antigen (HLA-identical sister who had a history of Graves' disease. Antithyroid antibodies, including antimicrosomal antibody and antithy-roglobulin antibody, appeared 4 months after transplantation. Clinical hyperthyroidism appeared 7 months after transplantation, and a hypothyroid state was noted 2 months later. The other case was a 50-year-old woman with Sjögren's syndrome and hypothyroidism who was diagnosed with peripheral T cell non-Hodgkin's lymphoma. She received allogeneic peripheral blood stem cell transplantation (PBSCT from her histocompatible sister owing to only partial response to traditional chemotherapy. Cure of lymphoma and remission of Sjögren's syndrome was noted 4 years after PBSCT. These two illustrative cases, one of acquisition of hyperthyroidism and the other of remission of Sjögren's syndrome after transplantation, highlights that HSCT can induce adoptive autoimmune disease or cure coincidental autoimmune disease. Donor selection and attentive monitoring is required in such circumstances.

Hematopoietic stem cell transplantation for isolated extramedullary relapse of acute lymphoblastic leukemia in children.

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Gabelli, Maria; Zecca, Marco; Messina, Chiara; Carraro, Elisa; Buldini, Barbara; Rovelli, Attilio Maria; Fagioli, Franca; Bertaina, Alice; Lanino, Edoardo; Favre, Claudio; Rabusin, Marco; Prete, Arcangelo; Ripaldi, Mimmo; Barberi, Walter; Porta, Fulvio; Caniglia, Maurizio; Santarone, Stella; D'Angelo, Paolo; Basso, Giuseppe; Locatelli, Franco

2018-06-13

Relapse of acute lymphoblastic leukemia (ALL) may occur in extramedullary sites, mainly central nervous system (CNS) and testis. Optimal post-remissional treatment for isolated extramedullary relapse (IEMR) is still controversial. We collected data of children treated with hematopoietic stem cell transplantation (HSCT) for ALL IEMR from 1990 to 2015 in Italy. Among 281 patients, 167 had a relapse confined to CNS, 73 to testis, 14 to mediastinum, and 27 to other organs. Ninety-seven patients underwent autologous HSCT, 79 received allogeneic HSCT from a matched family donor, 75 from a matched unrelated donor, and 30 from an HLA-haploidentical donor. The 10-year overall survival was 56% and was not influenced by gender, ALL blast immune-phenotype, age, site of relapse, duration of first remission, and type of HSCT. In multivariable analysis, the only prognostic factors were disease status at HSCT and year of transplantation. Patients transplanted in third or subsequent complete remission (CR) had a risk of death 2.3 times greater than those in CR2. Children treated after 2000 had half the risk of death than those treated before that year. Our results suggest that both autologous and allogeneic HSCT may be considered for the treatment of pediatric ALL IEMR after the achievement of CR2.

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...

Control of infectious mortality due to carbapenemase-producing Klebsiella pneumoniae in hematopoietic stem cell transplantation.

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Forcina, A; Baldan, R; Marasco, V; Cichero, P; Bondanza, A; Noviello, M; Piemontese, S; Soliman, C; Greco, R; Lorentino, F; Giglio, F; Messina, C; Carrabba, M; Bernardi, M; Peccatori, J; Moro, M; Biancardi, A; Nizzero, P; Scarpellini, P; Cirillo, D M; Mancini, N; Corti, C; Clementi, M; Ciceri, F

2017-01-01

Carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) infections are an emerging cause of death after hematopoietic stem cell transplantation (HSCT). In allogeneic transplants, mortality rate may rise up to 60%. We retrospectively evaluated 540 patients receiving a transplant from an auto- or an allogeneic source between January 2011 and October 2015. After an Institutional increase in the prevalence of KPC-Kp bloodstream infections (BSI) in June 2012, from July 2012, 366 consecutive patients received the following preventive measures: (i) weekly rectal swabs for surveillance; (ii) contact precautions in carriers (iii) early-targeted therapy in neutropenic febrile carriers. Molecular typing identified KPC-Kp clone ST512 as the main clone responsible for colonization, BSI and outbreaks. After the introduction of these preventive measures, the cumulative incidence of KPC-Kp BSI (P=0.01) and septic shocks (P=0.01) at 1 year after HSCT was significantly reduced. KPC-Kp infection-mortality dropped from 62.5% (pre-intervention) to 16.6% (post-intervention). Day 100 transplant-related mortality and KPC-Kp infection-related mortality after allogeneic HSCT were reduced from 22% to 10% (P=0.001) and from 4% to 1% (P=0.04), respectively. None of the pre-HSCT carriers was excluded from transplant. These results suggest that active surveillance, contact precautions and early-targeted therapies, may efficiently control KPC-Kp spread and related mortality even after allogeneic HSCT.

Economics and Outcome After Hematopoietic Stem Cell Transplantation: A Retrospective Cohort Study.

Science.gov (United States)

Gratwohl, Alois; Sureda, Anna; Baldomero, Helen; Gratwohl, Michael; Dreger, Peter; Kröger, Nicolaus; Ljungman, Per; McGrath, Eoin; Mohty, Mohamad; Nagler, Arnon; Rambaldi, Alessandro; de Elvira, Carmen Ruiz; Snowden, John A; Passweg, Jakob; Apperley, Jane; Niederwieser, Dietger; Stijnen, Theo; Brand, Ronald

2015-12-01

Hematopoietic stem cell transplantation (HSCT) is a lifesaving expensive medical procedure. Hence, more transplants are performed in more affluent countries. The impact of economic factors on patient outcome is less defined. We analyzed retrospectively a defined cohort of 102,549 patients treated with an allogeneic (N = 37,542; 37%) or autologous (N = 65,007; 63%) HSCT. They were transplanted by one of 404 HSCT centers in 25 European countries between 1999 and 2006. We searched for associations between center-specific microeconomic or country-specific macroeconomic factors and outcome. Center patient-volume and center program-duration were significantly and systematically associated with improved survival after allogeneic HSCT (HR 0·87; 0·84-0·91 per 10 patients; p < 0·0001; HR 0·90;0·85-0·90 per 10 years; p < 0·001) and autologous HSCT (HR 0·91;0·87-0·96 per 10 patients; p < 0·001; HR 0·93;0·87-0·99 per 10 years; p = 0·02). The product of Health Care Expenditures by Gross National Income/capita was significantly associated in multivariate analysis with all endpoints (R(2) = 18%; for relapse free survival) after allogeneic HSCT. Data indicate that country- and center-specific economic factors are associated with distinct, significant, systematic, and clinically relevant effects on survival after HSCT. They impact on center expertise in long-term disease and complication management. It is likely that these findings apply to other forms of complex treatments.

Invasive Pulmonary Aspergillosis in a Sickle Cell Patient Transplant Recipient: A Successful Treatment

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Katia Paciaroni

2015-08-01

Full Text Available Sickle Cell Anaemia (SCA is the most common inherited blood disorder and is associated with severe morbidity and decreased survival. Allogeneic Haematopoietic Stem Cell Transplantation (HSCT is the only curative approach. Nevertheless the decision to perform a marrow transplant includes the risk of major complications  and mortality transplant related. The infections represent the main cause of mortality for SCA patients undergoing transplant. Invasive Pulmonary Aspergillosis (IPA is a devastating opportunistic infection and remains a significant cause of morbidity and mortality in HSCT recipients. Data regarding IPA in the setting of SCA are lacking. In the present report,  we describe a patient with SCA who developed IPA after allogeneic bone marrow transplant. The fungal infection was treated by systemic antifungal therapy in addition to the surgery, despite  mild chronic GVHD and with continuing immunosuppression therapy. This case shows that IPA occurring in bone marrow recipient with SCA can be successful treated

Peripheral blood stem cell collection for allogeneic hematopoietic stem cell transplantation: Practical implications after 200 consequent transplants.

Science.gov (United States)

Goren Sahin, Deniz; Arat, Mutlu

2017-12-01

Proper stem cell mobilization is one of the most important steps in hematopoietic stem cell transplantation (HSCT). The aim of this paper is to share our 6 years' experience and provide practical clinical approaches particularly for stem cell mobilization and collection within the series of more than 200 successive allogeneic HSCT at our transplant center. Two hundred and seven consecutive patients who underwent allogeneic peripheral blood stem cell transplantation were included in this study. Age, sex, weight, complete blood counts, CD34 + cell counts, total collected amount of CD34 + cells, CD34 + cells per 10l processed, mobilization failure and adverse events were reviewed. Median age was 40.2±12.9 (21-68) years and 46.4±13.4 (17-67) years for donors and patients, respectively. The number of donors who had undergone adequate CD34 + cell harvesting and completed the procedure on the fourth day was 67 (32.8% of all patients). Only 12 patients required cell apheresis both on day 5 and 6. Apheresis was completed on day 4 and/or day 5 in 94.2% of all our donors. There was no significant association between CD34 + stem cell volume and age, gender and weight values of donors. Mobilization failure was not seen in our series. G-CSF is highly effective in 1/3 of the donors on the 4th day in order to collect enough number of stem cells. We propose that peripheral stem cell collection might start on day 4th of G-CSF treatment for avoiding G-CSF related side effects and complications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Oral bacteria and yeasts in relationship to oral ulcerations in hematopoietic stem cell transplant recipients

NARCIS (Netherlands)

Laheij, Alexa M. G. A.; de Soet, Johannes J.; von dem Borne, Peter A.; Kuijper, Ed J.; Kraneveld, Eefje A.; van Loveren, Cor; Raber-Durlacher, Judith E.

2012-01-01

Oral mucositis is a serious and debilitating side effect of conditioning regimens for hematopoietic stem cell transplant (HSCT). Through HSCT, the homeostasis in the oral cavity is disrupted. The contribution of the oral microflora to mucositis remains to be clarified. The aim of our study was to

IMMUNE STATE IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES AT LATE TERMS AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION

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N. V. Minaeva

2012-01-01

Full Text Available Abstract. Autologous hematopoietic stem cell transplantation (auto-HSCT is one of the most effective methods for treatment of patients with various forms of hemoblastoses, both in adults and children. However, high-dose chemotherapy protocols used in this procedure are characterized by pronounced myeloand immunotoxicity. Appropriate data concerning immune state at long terms after high-dose chemotherapy and auto-HSCT are sparse and controversial, and there is no consensus on time dynamics of immune system reconstitution. The aim of this study was a comprehensive evaluation of immunity in recipients of auto-HSCT at longer terms. Clinical and immunological testing was performed in ninety-eight patients with hematological malignancies before starting a high-dose chemotherapy, and at late post-transplant period. The state of cellular immunity was assessed as expression of surface CD3+, CD4+, CD8+, CD16+, CD19+ lymphocyte antigens. Humoral immunity was evaluated by serum IgG, IgA, and IgM levels. The studies have revealed disorders of cellular and humoral immunity, as well as nonspecific immune resistance factors in recipients of autologous hematopoietic stem cells at late terms post-transplant. Immune reconstitution in patients receiving highdose consolidation treatment followed by auto-HSCT takes longer time than in patients who did not receive autologous hematopoietic stem cells. Severity of these disturbances and immune reconstitution rates depend on the type of conditioning regimen, and the source of haematopoietic stem cells used for transplantation.

Outcomes of Children with Hemophagocytic Lymphohistiocytosis Given Allogeneic Hematopoietic Stem Cell Transplantation in Italy.

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Messina, Chiara; Zecca, Marco; Fagioli, Franca; Rovelli, Attilio; Giardino, Stefano; Merli, Pietro; Porta, Fulvio; Aricò, Maurizio; Sieni, Elena; Basso, Giuseppe; Ripaldi, Mimmo; Favre, Claudio; Pillon, Marta; Marzollo, Antonio; Rabusin, Marco; Cesaro, Simone; Algeri, Mattia; Caniglia, Maurizio; Di Bartolomeo, Paolo; Ziino, Ottavio; Saglio, Francesco; Prete, Arcangelo; Locatelli, Franco

2018-06-01

We report on 109 patients with hemophagocytic lymphohistiocytosis (HLH) undergoing 126 procedures of allogeneic hematopoietic stem cell transplantation (HSCT) between 2000 and 2014 in centers associated with the Italian Pediatric Hematology Oncology Association. Genetic diagnosis was FHL2 (32%), FHL3 (33%), or other defined disorders known to cause HLH (15%); in the remaining patients no genetic abnormality was found. Donor for first transplant was an HLA-matched sibling for 25 patients (23%), an unrelated donor for 73 (67%), and an HLA-partially matched family donor for 11 children (10%). Conditioning regimen was busulfan-based for 61 patients (56%), treosulfan-based for 21 (20%), and fludarabine-based for 26 children (24%). The 5-year probabilities of overall survival (OS) and event-free survival (EFS) were 71% and 60%, respectively. Twenty-six patients (24%) died due to transplant-related causes, whereas 14 (13%) and 10 (9%) patients experienced graft rejection and/or relapse, respectively. Twelve of 14 children given a second HSCT after graft failure/relapse are alive and disease-free. Use of HLA-partially matched family donors was associated with higher risk of graft failure and thus with lower EFS (but not with lower OS) in multivariable analysis. Active disease at transplantation did not significantly affect prognosis. These data confirm that HSCT can cure most HLH patients, active disease not precluding successful transplantation. Because in HLH patients HLA-haploidentical HSCT performed through CD34 + cell positive selection was found to be associated with poor sustained engraftment of donor cells, innovative approaches able to guarantee a more robust engraftment are warranted in patients given this type of allograft. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Hematopoietic stem cell transplantation in Niemann-Pick disease type B monitored by chitotriosidase activity.

Science.gov (United States)

Quarello, Paola; Spada, Marco; Porta, Francesco; Vassallo, Elena; Timeus, Fabio; Fagioli, Franca

2018-02-01

Here, we report a patient with Niemann-Pick disease type B, with early severe onset of disease and pulmonary involvement, treated with hematopoietic stem cell transplant (HSCT) from a bone marrow matched unrelated donor. We confirm that HSCT is feasible and potentially beneficial for patients with severe phenotype. Noteworthy, we discussed the potential usefulness of the activity of peripheral chitotriosidase for the longitudinal evaluation of HSCT success and effectiveness. © 2017 Wiley Periodicals, Inc.

Early and late endocrinologic complications of the hematopoetic stem cell transplantation performed for hematologic malignancies

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Murat Albayrak

2012-03-01

Full Text Available Hematopoietic stem cell transplantation (HSCT is usedfor various hematologic malignancies seen in childrenand adults. There may be several complications before,during, and after the HSCT. Just one of them is endocrinologiccomplications, since endocrine system (particularlythe pituitary gland, thyroid gland, adrenal glands, andgonads is highly sensitive against various stress. Chemotherapyand/or total body irradiation used as preparativeregimens and immunosuppressive agents (especiallycorticosteroids used for the graft-versus-host diseasecan cause hormonal disorders. Time elapsed after theHSCT, transplantation type (autologous or allogeneic,preparative regimen choice, age, and gender determinesthe complications. A multidisciplinary management containinga specialist of endocrinology for these patients ispreferred. In this report, we reviewed the endocrinologiccomplications that observed after the HSCT in childrenand adults referring to the recent literatures. J Clin ExpInvest 2012; 3(1: 149-156

Subsequent vitiligo after hematopoietic stem cell transplantation: A nationwide population-based cohort study from Korea.

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Bae, Jung Min; Choi, Kwang Hyun; Jung, Han Mi; Kim, Sook Young; Kim, Miri; Kim, Gyung Moon; Yu, Dong Soo; Lee, Young Bok

2017-03-01

Subsequent vitiligo after hematopoietic stem cell transplantation (HSCT) has been described sporadically in case series. To investigate the incidence and risk factors of subsequent vitiligo after HSCT. A nationwide, population-based cohort study was performed using the Korean National Health Insurance Claims Database from 2009 to 2013. All HSCT recipients who had undergone HSCT between 2010 and 2011 and not treatment for vitiligo in 2009 (to exclude preexisting active vitiligo) were included in the HSCT recipient group, and an age- and sex-matched control group without HSCT was also established. A total of 2747 HSCT recipients and 8241 controls were enrolled. Newly acquired vitiligo occurred in 1.06% of HSCT recipients between 2010 and 2013, and there was a significant increase (OR 3.130, 95% CI 1.859-5.271) in cases of vitiligo in HSCT recipients compared with controls (0.34%). Allogeneic HSCT (OR 5.593, 95% CI 1.628-19.213) and bone marrow-sourced stem cells (as compared with peripheral blood-sourced stem cells; OR 2.492, 95% CI 1.114-5.576) were independently associated with the development of vitiligo after HSCT. Medical record review was not available. Vitiligo developed at a significantly increased rate after HSCT compared with controls. Allogeneic HSCT and bone marrow-sourced stem cells were independent risk factors. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Long-term outcomes after allogeneic hematopoietic stem cell transplantation for metachromatic leukodystrophy: the largest single-institution cohort report

OpenAIRE

Boucher, Alexander A.; Miller, Weston; Shanley, Ryan; Ziegler, Richard; Lund, Troy; Raymond, Gerald; Orchard, Paul J.

2015-01-01

Background Metachromatic Leukodystrophy (MLD) is a rare, fatal demyelinating disorder with limited treatment options. Published outcomes after hematopoietic stem cell transplantation (HSCT) are scant and mixed. We report survival and function following HSCT for a large, single-center MLD cohort. Methods Transplant-related data, survival and serial measures (brain MRI, nerve conduction velocity (NCV), neurologic and neuropsychology evaluations) were reviewed. When possible, parental interviews...

The hematopoietic stem cell transplantation in Indonesia: an unsolved dilemma.

Science.gov (United States)

Hariman, H

2008-08-01

Allogeneic BMT was performed in Indonesia, but had to be stopped prematurely because of the small number of patients. In the beginning, only patients with sufficient financial resources to travel to western countries could undergo transplant procedures. When neighbouring countries (Singapore and Malaysia) began performing transplant, patients were referred to those centres. In both countries, the procedure is more economical and therefore patients come from a broader range of economic classes. The Indonesian hematologist must deal with the post-transplantation side effects, such as GVHD, which are mostly of the chronic type of GVHD. The types of the post-transplant complications do not differ too much from other centres and need the same treatment used in the transplant centres. Hematologists in Indonesia also treat complications of HSCT performed in other countries. When there is no recovery of HSCT development in Indonesia so far, many commercially oriented companies or centres from other countries see Indonesia as a good commercial market and offer services, some of which are not scientifically sound. One of the main problems is umbilical cord blood stem cell banking from foreign countries, which is eagerly offered to parents expecting a baby. Moreover, parents are not fully protected by law. In conclusion, Indonesia needs to revive its own HSCT program to serve and protect its own patients of being used as commercial targets by other countries.

Posaconazole plasma exposure correlated to intestinal mucositis in allogeneic stem cell transplant patients.

Science.gov (United States)

Vanstraelen, Kim; Prattes, Juergen; Maertens, Johan; Lagrou, Katrien; Schoemans, Hélène; Peersman, Nele; Vermeersch, Pieter; Theunissen, Koen; Mols, Raf; Augustijns, Patrick; Annaert, Pieter; Hoenigl, Martin; Spriet, Isabel

2016-08-01

Low posaconazole plasma concentrations (PPCs) are frequently encountered in allogeneic hematopoietic stem cell transplant (HSCT) patients, due to variable gastrointestinal absorption. In this study, the impact of intestinal mucositis on posaconazole exposure is investigated. A prospective pharmacokinetic study was performed including allogeneic HSCT patients receiving posaconazole prophylaxis with the oral suspension or tablets. Steady state PPCs were determined using high-performance liquid chromatography-fluorescence detection at the day of transplantation (=day 0), day +7, and +14. Citrulline was measured using liquid chromatography-tandem mass spectrometry to evaluate severity of mucositis, at baseline (day -7 or -6), and at day 0, +7 and +14. Additionally, citrulline plasma concentrations and steady state trough PPCs were determined in hematological patients without HSCT or mucositis. Thirty-four HSCT patients received posaconazole oral suspension together with 25 cL of Coca Cola, 6 HSCT patients received posaconazole tablets and 33 hematological patients not receiving HSCT received posaconazole oral suspension. The median (interquartile range) average PPC was 0.26 mg/L (0.17-0.43), 0.67 mg/L (0.27-1.38), and 1.08 mg/L (0.96-1.38), with suspension in HSCT patients, suspension in hematological patients and tablets in HSCT patients, respectively. A higher trough PPC was encountered with the oral suspension when citrulline plasma concentrations were above 10 μmol/L compared to values below 10 μmol/L (p < 0.001), whereas for tablets, average PPCs remained high with citrulline plasma concentrations below or above 10 μmol/L (p = 0.64). Posaconazole tablets should be preferred to suspension in HSCT patients immediately after transplantation to prevent insufficient plasma exposure due to intestinal mucositis.

BACTERIAL INFECTIONS IN HEMATOPOIETIC STEM CELL TRANSPLANT RECIPIENTS

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Elisa Balletto

2015-07-01

Full Text Available Bacterial infections are major complications after Hematopoietic Stem Cell Transplant (HSCT. They consist mainly of bloodstream infections (BSI, followed by pneumonia and gastrointestinal infections, including typhlitis and Clostridium difficile infection. Microbiological data come mostly from BSI. Coagulase negative staphylococci and Enterobacteriaceae are the most frequent pathogens causing approximately 25% of BSI each, followed by enterococci, P. aeruginosa and viridans streptococci. Bacterial pneumonia is frequent after HSCT, and Gram-negatives are predominant. Clostridium difficile infection affects approximately 15% of HSCT recipients, being more frequent in case of allogeneic than autologous HSCT. The epidemiology and the prevalence of resistant strains vary significantly between transplant centres. In some regions, multi-drug resistant Gram-negative rods are increasingly frequent. In others, vancomycin-resistant enterococci are predominant. In the era of an increasing resistance to antibiotics, the efficacy of fluoroquinolone prophylaxis and standard treatment of febrile neutropenia have been questioned. Therefore, thorough evaluation of local epidemiology is mandatory in order to decide the need for prophylaxis and the choice of the best regimen for empirical treatment of febrile neutropenia. For the latter, individualised approach has been proposed, consisting of either escalation or de-escalation strategy. De-escalation strategy is recommended is resistant bacteria should be covered upfront, mainly in patients with severe clinical presentation and previous infection or colonisation with a resistant pathogens. Non-pharmacological interventions, such as screening for resistant bacteria, applying isolation and contact precautions should be put in place in order to limit the spread of MDR bacteria. Antimicrobial stewardship program should be implemented in transplant centres.

Targeting the bone marrow: applications in stem cell transplantation

International Nuclear Information System (INIS)

Orchard, K.; Cooper, M.

2004-01-01

Therapeutic doses of radiation cab be selectively directed to the bone marrow either directly using vectors that bind to myeloid and/or lymphoid specific antigens or indirectly by targeting bone matrix. The combination of an accessible target tissue and relatively radiation sensitive malignant cells favours the use of targeted radiotherapy in the treatment of haematopoietic malignancies. Dose escalation of targeted radiation can increase tumour cell destruction and has led to the use of myelosuppressive and possibly myeloablative doses of targeted radiation. A natural development has been the use of targeted radiation in conditioning prior to haematopoietic stem cell transplantation (HSCT). Several groups are actively exploring the use of targeted radiotherapy in the context of HSCT as treatment for haematological malignancies. Although no randomised trials using targeted radiotherapy in HSCT have been published, phase I and II trials have shown very encouraging results stimulating further clinical research in this field. After more than a decade of translational research the optimal combination of therapeutic radioisotope and vector has not been determined. This review summarises the clinical experience of targeted radiotherapy in HSCT and discusses the problems that still need to be solved to maximise the potential of this new treatment modality in HSCT

Economics and Outcome After Hematopoietic Stem Cell Transplantation: A Retrospective Cohort Study

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Alois Gratwohl

2015-12-01

Full Text Available Hematopoietic stem cell transplantation (HSCT is a lifesaving expensive medical procedure. Hence, more transplants are performed in more affluent countries. The impact of economic factors on patient outcome is less defined. We analyzed retrospectively a defined cohort of 102,549 patients treated with an allogeneic (N = 37,542; 37% or autologous (N = 65,007; 63% HSCT. They were transplanted by one of 404 HSCT centers in 25 European countries between 1999 and 2006. We searched for associations between center-specific microeconomic or country-specific macroeconomic factors and outcome. Center patient-volume and center program-duration were significantly and systematically associated with improved survival after allogeneic HSCT (HR 0·87; 0·84–0·91 per 10 patients; p < 0·0001; HR 0·90;0·85–0·90 per 10 years; p < 0·001 and autologous HSCT (HR 0·91;0·87–0·96 per 10 patients; p < 0·001; HR 0·93;0·87–0·99 per 10 years; p = 0·02. The product of Health Care Expenditures by Gross National Income/capita was significantly associated in multivariate analysis with all endpoints (R2 = 18%; for relapse free survival after allogeneic HSCT. Data indicate that country- and center-specific economic factors are associated with distinct, significant, systematic, and clinically relevant effects on survival after HSCT. They impact on center expertise in long-term disease and complication management. It is likely that these findings apply to other forms of complex treatments.

Health-related quality of life of hematopoietic stem cell transplant childhood survivors: state of the science.

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Tanzi, Elizabeth M

2011-01-01

The notion of health-related quality of life (HRQoL) holds unique significance in the treatment of patients who have undergone hematopoietic stem cell transplantation (HSCT). Not only is transplant procedure inevitably associated with immediate and late medical effects along with high mortality and morbidity rates, but it can also significantly affect the HRQoL for the patient and family. This review of literature will assist advanced practice nurses and pediatric oncology nurses in distinguishing and targeting interventions for patients and families who are at high risk of encountering distress during and following HSCT. It provides information on the assessment of pre-HSCT variables to identify patient subgroups in need of more aggressive supportive care to improve HRQoL during transplant. Furthermore, it serves as a guideline for developing interventional strategies and the role of the advanced practice nurse and pediatric oncology nurse caring for the patient throughout and following transplant.

Outcomes of Hematopoietic Stem Cell Transplantation at a Limited-Resource Center in Mexico Are Comparable to Those in Developed Countries.

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Leon Rodriguez, Eucario; Rivera Franco, Monica M

2017-11-01

The first hematopoietic stem cell transplantation (HSCT) in Mexico was performed at our institution in 1980. Eighteen years later, our HSCT program was restructured to reduce transplantation-related mortality (TRM) and improve overall survival (OS). The aim of this study was to describe outcomes of HSCT at our institution despite limited resources. Consecutive patients undergoing HSCT, from November 1998 to February 2017, were retrospectively analyzed at the National Institute of Medical Sciences and Nutrition Salvador Zubiran in Mexico City. Three hundred nine HSCT (59% autologous) were performed in 275 patients. From 114 patients (41%) undergoing an allogeneic HSCT, acute and chronic graft-versus-host disease developed in 21% and 33%, respectively. From the entire cohort, 98 patients relapsed after HSCT and at the last follow-up, 183 (67%) patients were alive. The 100-day TRM rates were 1.9% and 6.1% for autologous and allogeneic HSCT, respectively. Ten-year relapse/progression-free survival were 54% and 65%, for autologous and allogeneic HSCT, respectively. Ten-year OS rates in autologous and allogeneic HSCT were 61% and 57%, respectively. We highlight that HSCT is feasible in developing countries, despite financial and infrastructure limitations, and conclude that our results are comparable to international literature and probably better in terms of TRM and cost-effectiveness. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

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.

Longitudinal Assessment of Hematopoietic Stem Cell Transplantation and Hyposalivation

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Laaksonen, Matti; Ramseier, Adrian; Rovó, Alicia

2011-01-01

Hyposalivation is a common adverse effect of anti-neoplastic therapy of head and neck cancer, causing impaired quality of life and predisposition to oral infections. However, data on the effects of hematopoietic stem cell transplantation (HSCT) on salivary secretion are scarce. The present study...

Immune reconstitution after allogeneic hematopoietic stem cell transplantation in children: a single institution study of 59 patients

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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.

Successful haploidentical donor hematopoietic stem cell transplant and restoration of STAT3 function in an adolescent with autosomal dominant hyper-IgE syndrome.

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Patel, N C; Gallagher, J L; Torgerson, T R; Gilman, A L

2015-07-01

Autosomal dominant hyper-IgE syndrome (AD-HIES), caused by mutations in Signal Transducer and Activator of Transcription 3 (STAT3) is associated with defective STAT3 signaling and Th17 differentiation and recurrent bacterial and fungal infections. Most patients suffer significant morbidity and premature mortality. Hematopoietic stem cell transplantation (HSCT) has been reported in a small number of cases, with mixed outcomes. We report successful haploidentical donor HSCT in a patient with AD-HIES. Evaluation of lymphocyte subsets, STAT3 signaling, and Th17 cells was performed pre- and post-HSCT. A 14-year old female with AD-HIES developed recurrent methicillin-resistant Staphylococcus aureus (MRSA) abscesses. Immunologic analysis showed elevated IgE (4331 kU/L), absent Th17 cells, and markedly decreased STAT3 phosphorylation in cytokine stimulated peripheral blood mononuclear cells. She had breakthrough abscesses despite clindamycin and trimethoprim-sulfamethoxazole prophylaxis, and developed steroid refractory autoimmune hemolytic anemia. She underwent T-cell depleted haploidentical HSCT from her father following reduced intensity conditioning. She developed one MRSA hand abscess after transplant. Twenty-four months post transplant, she had complete donor chimerism (>95 % donor), normal absolute T cell numbers, and a normal percentage of Th17 cells. IgE was normal at 25 kU/L. She remains well 42 months after transplantation off all antibacterial prophylaxis. Haploidentical HSCT led to successful bone marrow engraftment, normalization of STAT3 signaling in hematopoietic cells, normalization of IgE, and restoration of immune function in this patient with AD-HIES.

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.

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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. © 2015 John Wiley & Sons Ltd.

Effects of nonpharmacological interventions on reducing fatigue after hematopoietic stem cell transplantation

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Hedayat Jafari

2017-01-01

Full Text Available Fatigue is one of the main complaints of patients undergoing allogeneic and autologous hematopoietic stem cell transplantation (HSCT. Since nonpharmacological interventions are cost-effective and causes fewer complications, this study aimed to review the studies performed on the effects of nonpharmacological interventions on fatigue in patients undergoing HSCT during September 2016. MEDLINE, CINAHL, Scientific Information Database, IranMedex, PubMed, ScienceDirect, Scopus, Magiran, and IRANDOC databases were searched using Persian and English keywords. A total of 1217 articles were retrieved, 21 of which were used in this study. Exercise is known as an effective intervention in alleviating physical and mental problems of patients undergoing stem cell transplant. This review-based study showed that nonpharmacological methods such as exercise might be effective in decreasing fatigue in patients undergoing stem cell transplant. There is a multitude of studies on some of the complementary and alternative therapy methods, such as music therapy, yoga, relaxation, and therapeutic massage. These studies demonstrated the positive effects of the aforementioned therapies on reduction of fatigue in patients undergoing stem cell transplantation. All the investigated methods in this study were nonaggressive, safe, and cost-effective and could be used along with common treatments or even as an alternative for pharmacological treatments for the reduction, or elimination of fatigue in patients undergoing stem cell transplantation. Given the advantages of complementary and alternative medicine, conducting further studies on this issue is recommended to reduce fatigue in patients after stem cell transplantation.

Epigenetic programming of T cells impacts immune reconstitution in hematopoietic stem cell transplant recipients.

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Hardy, Kristine; Smith, Corey; Tu, Wen Juan; McCuaig, Robert; Panikkar, Archana; Dasari, Vijayendra; Wu, Fan; Tey, Siok-Keen; Hill, Geoffrey R; Khanna, Rajiv; Rao, Sudha

2018-03-27

Immune reconstitution following hematopoietic stem cell transplantation (HSCT) is critical in preventing harmful sequelae in recipients with cytomegalovirus (CMV) infection. To understand the molecular mechanisms underlying immune reconstitution kinetics, we profiled the transcriptome-chromatin accessibility landscape of CMV-specific CD8 + T cells from HCST recipients with different immune reconstitution efficiencies. CMV-specific T cells from HSCT recipients with stable antiviral immunity expressed higher levels of interferon/defense response and cell cycle genes in an interconnected network involving PI3KCG , STAT5B , NFAT , RBPJ , and lower HDAC6 , increasing chromatin accessibility at the enhancer regions of immune and T-cell receptor signaling pathway genes. By contrast, the transcriptional and epigenomic signatures of CMV-specific T cells from HSCT recipients with unstable immune reconstitution showed commonalities with T-cell responses in other nonresolving chronic infections. These signatures included higher levels of EGR and KLF factors that, along with lower JARID2 expression, maintained higher accessibility at promoter and CpG-rich regions of genes associated with apoptosis. Furthermore, epigenetic targeting via inhibition of HDAC6 or JARID2 enhanced the transcription of genes associated with differential responses, suggesting that drugs targeting epigenomic modifiers may have therapeutic potential for enhancing immune reconstitution in HSCT recipients. Taken together, these analyses demonstrate that transcription factors and chromatin modulators create different chromatin accessibility landscapes in T cells of HSCT recipients that not only affect immediate gene expression but also differentially prime cells for responses to additional signals. Epigenetic therapy may be a promising strategy to promote immune reconstitution in HSCT recipients. © 2018 by The American Society of Hematology.

Prospective assessment of bone turnover and clinical bone diseases after allogeneic hematopoietic stem-cell transplantation.

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Petropoulou, Anna D; Porcher, Raphael; Herr, Andrée-Laure; Devergie, Agnès; Brentano, Thomas Funck; Ribaud, Patricia; Pinto, Fernando O; Rocha, Vanderson; Peffault de Latour, Régis; Orcel, Philippe; Socié, Gérard; Robin, Marie

2010-06-15

Bone complications after hematopoietic stem-cell transplantation (HSCT) are relatively frequent. Evaluation of biomarkers of bone turnover and dual energy x-ray absorptiometry (DEXA) are not known in this context. We prospectively evaluated bone mineral density, biomarkers of bone turnover, and the cumulative incidence of bone complications after allogeneic HSCT. One hundred forty-six patients were included. Bone mineral density was measured by DEXA 2-month and 1-year post-HSCT. The markers of bone turnover were serum C-telopeptide (C-TP), 5 tartrate-resistant acid phosphatase (bone resorption), and osteocalcin (bone formation) determined pre-HSCT and 2 months and 1 year thereafter. Potential association between osteoporosis at 2 months, osteoporotic fracture or avascular necrosis and, individual patient's characteristics and biologic markers were tested. C-TP was high before and 2 months after transplant. At 2 months, DEXA detected osteoporosis in more than half the patients tested. Male sex, median age less than or equal to 15 years, and abnormal C-TP before HSCT were risk factors significantly associated with osteoporosis. Three-year cumulative incidences of fractures and avascular necrosis were 8% and 11%, respectively. Children were at higher risk of fracture, whereas corticosteroid treatment duration was a significant risk factor for developing a clinical bone complication post-HSCT. Bone complications and osteoporosis are frequent after HSCT. Bone biologic markers and DEXA showed that subclinical bone abnormalities appeared early post-HSCT. The risk factors, age, gender, and C-TP easily available at the time of transplantation were identified. Biphosphonates should probably be given to patients with those risk factors.

HEMATOPOIETIC STEM CELL TRANSPLANTATION IN THALASSEMIA AND SICKLE CELL DISEASE: EXPERIENCE OF MEDITERRANEAN INSTITUTE OF HEMATOLOGY IN A MULTI-ETHNIC POPULATION.

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Marco Marziali

2009-12-01

Full Text Available Hematopoietic stem cell transplantation (HSCT still remains the only definitive cure currently available for patients with thalassemia and sickle cell anemia.  Results of transplant in thalassemia  and in sickle cell anemia  have steadily improved over the last two decades due to improvements in preventive strategies, and effective control of transplant-related complications. From 2004 through  2009,  145 consecutive patients with thalassemia and sickle cell anemia, ethnically heterogeneous from Mediterranean and Middle East countries, were given HSCT in the International Center for Transplantation in Thalassemia and Sickle Cella Anemia in Rome. This experience is characterized by two peculiarities: patients were ethnically very heterogeneous and the vast majority of these patients were not regularly transfesed/chelated and therefore were highly sensitized due to RBC transfusions without leukodepletion filters. Consequently, they could have a high risk of graft rejection as a result of sensitization to HLA antigens. The Rome experience of SCT in patients with thalassemia and sickle cell anemia confirmed the results obtained in Pesaro, and most importantly showed the reproducibility of these results in other centers.

New insights into hematopoietic stem cell transplantation for chronic lymphocytic leukemia: a 2015 perspective.

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McClanahan, Fabienne; Gribben, John

2015-09-01

A considerable body of evidence demonstrates that allogeneic hematopoietic stem cell transplantation (HSCT) offers the only potentially curative treatment option for patients with chronic lymphocytic leukemia (CLL). However, this approach is suitable for only a minority of CLL patients, owing to its significant treatment-related mortality and morbidity. Until recently, internationally accepted guidelines suggested that HSCT should be considered in physically fit CLL patients who carry poor-risk features, such as TP53 abnormalities, or who had a short response to previous immunochemotherapy. However, several new agents and alternative treatment strategies are available that demonstrate impressive and durable responses, even in CLL patients who previously might have been candidates for transplant. The decision about which patients merit HSCT therefore remains important, and HSCT must now be considered in light of other less toxic therapies. Until data on the long-term efficacy of novel treatment approaches mature, the choice of HSCT vs alternative strategies must be assessed on a patient-by-patient basis, and treatment in the setting of randomized clinical trials should be pursued whenever possible.

Is there a role for B lymphocyte chimerism in the monitoring of B-acute lymphoblastic leukemia patients receiving allogeneic stem cell transplantation?

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Yi-Ning Yang

2015-03-01

Full Text Available Objective: To determine the sensitivity and significance of B-cell chimerism for the detection of early engraftment, transplant rejection, and disease relapse. Methods: The dynamic monitoring of lineage-specific cell subtypes (B, T, and NK cells was made in 20 B-cell acute lymphoblastic leukemia (B-ALL patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT. In the early period after allo-HSCT, the latest establishment of B-cell complete chimerism (CC was observed in a majority of patients. Results: The percentage of donor cells of B-cell lineage was lower than the percent of T-cell lineage in most of the mixed chimerism (MC patients. During graft rejection, the frequency of patients with decreasing MC of B-, T- and NK-cell lineage were 5/5, 2/5, and 2/5. When disease relapsed, five patients showed a faster decrease of the donor percent of B-cells than of T- or NK-cells. Only one patient displayed a more rapid decrease in NK-cells than in T- or B-cells. Conclusion: Monitoring of B-cell chimerism after HSCT seems to be valuable for insuring complete engraftment, anticipating graft rejection, and relapse in B-ALL patients. Keywords: B cell acute lymphoblastic leukemia (B-ALL, B-cell, T-cell, Chimerism, Allogeneic hematopoietic stem cell transplantation (allo-HSCT

Regulatory Immunotherapy in Bone Marrow Transplantation

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Vanessa Morales-Tirado

2011-01-01

Full Text Available Every year individuals receive hematopoietic stem cell transplantation (HSCT to eradicate malignant and nonmalignant disease. The immunobiology of allotransplantation is an area of ongoing discovery, from the recipient's conditioning treatment prior to the transplant to the donor cell populations responsible for engraftment, graft-versus-host disease, and graft-versus-tumor effect. In this review, we focus on donor-type immunoregulatory T cells, namely, natural killer T cells (NKT and regulatory T cells (Treg, and their current and potential roles in tolerance induction after allogeneic HSCT.

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

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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. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Guidelines for defining and implementing standard episode of care for hematopoietic stem cell transplantation within the context of clinical trials.

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Majhail, Navneet S; Giralt, Sergio; Bonagura, Anthony; Crawford, Stephen; Farnia, Stephanie; Omel, James L; Pasquini, Marcelo; Saber, Wael; LeMaistre, Charles F

2015-04-01

The Patient Protection and Affordable Care Act requires that health care insurers cover routine patient costs associated with participating in clinical trials for cancer and other life-threatening diseases. There is a need to better define routine costs within the context of hematopoietic stem cell transplantation (HSCT) clinical trials. This white paper presents guidance on behalf of the American Society for Blood and Marrow Transplantation for defining a standard HSCT episode and delineates components that may be considered as routine patient costs versus research costs. The guidelines will assist investigators, trial sponsors, and transplantation centers in planning for clinical trials that are conducted as a part of the HSCT episode and will inform payers who provide coverage for transplantation. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Routine Surveillance for Bloodstream Infections in a Pediatric Hematopoietic Stem Cell Transplant Cohort: Do Patients Benefit?

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Heather Rigby

2007-01-01

Full Text Available BACKGROUND: Hematopoietic stem cell transplant (HSCT recipients are at a high risk for late bloodstream infection (BSI. Controversy exists regarding the benefit of surveillance blood cultures in this immunosuppressed population. Despite the common use of this practice, the practical value is not well established in non-neutropenic children following HSCT.

Clinical Impact of Pretransplant Multidrug-Resistant Gram-Negative Colonization in Autologous and Allogeneic Hematopoietic Stem Cell Transplantation.

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Forcina, Alessandra; Lorentino, Francesca; Marasco, Vincenzo; Oltolini, Chiara; Marcatti, Magda; Greco, Raffaella; Lupo-Stanghellini, Maria Teresa; Carrabba, Matteo; Bernardi, Massimo; Peccatori, Jacopo; Corti, Consuelo; Ciceri, Fabio

2018-03-02

Multidrug-resistant Gram-negative bacteria (MDR-GNB) are an emerging cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Three-hundred forty-eight consecutive patients transplanted at our hospital from July 2012 to January 2016 were screened for a pretransplant MDR-GNB colonization and evaluated for clinical outcomes. A pretransplant MDR-GNB colonization was found in 16.9% of allo-HSCT and in 9.6% of auto-HSCT recipients. Both in auto- and in allo-HSCT, carriers of a MDR-GNB showed no significant differences in overall survival (OS), transplant-related mortality (TRM), or infection-related mortality (IRM) compared with noncarriers. OS at 2 years for carriers compared with noncarriers was 85% versus 81% (P = .262) in auto-HSCT and 50% versus 43% (P = .091) in allo-HSCT. TRM at 2 years was 14% versus 5% (P = .405) in auto-HSCT and 31% versus 25% (P = .301) in allo-HSCT. IRM at 2 years was 14% versus 2% (P = .142) in auto-HSCT and 23% versus 14% (P = .304) in allo-HSCT. In multivariate analysis, only grade III to IV acute graft-versus-host disease was an independent factor for reduced OS (P < .001) and increased TRM (P < .001) and IRM (P < .001). During the first year after transplant, we collected 73 GNB bloodstream infectious (BSI) episodes in 54 patients, 42.4% of which sustained by a MDR-GNB. Rectal swabs positivity associated with the pathogen causing subsequent MDR-GNB BSI episodes in 13 of 31 (41.9%). Overall, OS at 4 months from MDR-GNB BSI episode onset was of 67.9%, with a 14-day attributed mortality of 12.9%, not being significantly different between carriers and noncarriers (P = .207). We conclude that in this extended single-center experience, a pretransplant MDR-GNB colonization did not significantly influence OS, TRM, and IRM both in auto- and allo-HSCT settings and that MDR-GNB attributed mortality can be controlled in carriers when an early pre-emptive antimicrobial therapy is

Clinical and immunologic outcome of patients with cartilage hair hypoplasia after hematopoietic stem cell transplantation.

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Bordon, Victoria; Gennery, Andrew R; Slatter, Mary A; Vandecruys, Els; Laureys, Genevieve; Veys, Paul; Qasim, Waseem; Waseem, Qasim; Friedrich, Wilhelm; Wulfraat, Nico M; Scherer, Franziska; Cant, Andrew J; Fischer, Alain; Cavazzana-Calvo, Marina; Cavazanna-Calvo, Marina; Bredius, Robbert G M; Notarangelo, Luigi D; Mazzolari, Evelina; Neven, Benedicte; Güngör, Tayfun; Tayfun, Güngör

2010-07-08

Cartilage-hair hypoplasia (CHH) is a rare autosomal recessive disease caused by mutations in the RMRP gene. Beside dwarfism, CHH has a wide spectrum of clinical manifestations including variable grades of combined immunodeficiency, autoimmune complications, and malignancies. Previous reports in single CHH patients with significant immunodeficiencies have demonstrated that allogeneic hematopoietic stem cell transplantation (HSCT) is an effective treatment for the severe immunodeficiency, while growth failure remains unaffected. Because long-term experience in larger cohorts of CHH patients after HSCT is currently unreported, we performed a European collaborative survey reporting on 16 patients with CHH and immunodeficiency who underwent HSCT. Immune dysregulation, lymphoid malignancy, and autoimmunity were important features in this cohort. Thirteen patients were transplanted in early childhood ( approximately 2.5 years). The other 3 patients were transplanted at adolescent age. Of 16 patients, 10 (62.5%) were long-term survivors, with a median follow-up of 7 years. T-lymphocyte numbers and function have normalized, and autoimmunity has resolved in all survivors. HSCT should be considered in CHH patients with severe immunodeficiency/autoimmunity, before the development of severe infections, major organ damage, or malignancy might jeopardize the outcome of HSCT and the quality of life in these patients.

Allogeneic hematopoietic stem cell transplantation in Primary Cutaneous T Cell Lymphoma.

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Cudillo, Laura; Cerretti, Raffaella; Picardi, Alessandra; Mariotti, Benedetta; De Angelis, Gottardo; Cantonetti, Maria; Postorino, Massimiliano; Ceresoli, Eleonora; De Santis, Giovanna; Nasso, Daniela; Pisani, Francesco; Scala, Enrico; Di Piazza, Fabio; Lanti, Alessandro

2018-06-01

In our retrospective study, 16 patients affected by advanced cutaneous T cell lymphoma (CTCL) underwent allogeneic hematopoietic stem cell transplantation (HSCT). Two patients (12.5%) were in complete remission (CR), nine (56.3%) in partial remission (PR), and five (31.2%) with active disease. The patients were transplanted from an HLA-identical (n = 7) from a mismatched (n = 1) or haploidentical (n = 1) sibling, from matched unrelated donor (n = 5), or from a single cord blood unit (n = 2). Conditioning regimen was standard myeloablative in 6 patients and at reduced intensity in 10. Seven patients died from non relapse mortality (NRM) and four patients relapsed or progressed, three of them achieved a second CR after donor lymphocyte infusion (DLI) or chemotherapy plus DLI. To date, with a median follow-up of 76 months (range 6-130), nine patients are alive, eight in CR, and one with active disease. Overall survival (OS) and disease-free survival (DFS) at 1 and 10 years are 61% (95% CI 40-91%) and 54% (95% CI 33-86%), 40% (95% CI 22-74%), and 34% (95% CI 16-68%), respectively. The time from diagnosis to transplant seems to influence negatively both OS (log-rank p < 0.04) and DFS (log-rank p < 0.05). Our results confirm on a long follow-up that CTCL appears particularly susceptible to the graft versus lymphoma (GVL) effect, so that allogeneic HSCT represents a possibility of cure for advanced CTCL. The timing of HSCT in the clinical course of disease remains an open issue.

Subclinical hypothyroidism in children and adolescents after hematopoietic stem cells transplantation without irradiation

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Milenković Tatjana

2014-01-01

Full Text Available Background/Aim. Although total body irradiation (TBI was considered to be the primary cause of thyroid dysfunction following hematopoietic stem cells transplantation (HSCT, a significant prevalence of subclinical hypothyroidism after HSCT with chemotherapy-only conditioning regimens has been observed in several studies. The aim of this study was to assess changes in thyroid stimulating hormone (TSH levels in children after HSCT, without the use of irradiation at any time in the course of the treatment. Methods. Our cohort consisted of 41 children and adolescents who underwent autologous or allogeneic HSCT and were available for follow-up for at least one year after transplantation. Irradiation was not performed in any of the subjects, neither during pretransplatation therapy, nor during conditioning. The median duration of follow-up was 2.9 years. The indications for HSCT were hematologic malignancy (41.5%, solid malignant tumor (34.1%, and other disorders (24.4%. The thyroid status of all the subjects was assessed prior to HSCT and after follow-up period. Results. Thyroid dysfunction after HSCT was present in 27 (65.8% subjects. Subclinical hypothyroidism was the most common abnormality, presenting in 23 (56.1% patients, primary hypothyroidism was present in one (2.4% patient, while 3 (7.3% subjects had low free T4 with normal TSH values. Significantly (p < 0.01 higher elevations in TSH levels were present in the patients who received chemotherapy for the underlying disease prior to HSCT. Conclusion. Our findings emphasize the need for long-term monitoring of thyroid function following HSCT, regardless of whether or not irradiation was used.

Imaging spectrum of central nervous system complications of hematopoietic stem cell and solid organ transplantation

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Server, Andres [Oslo University Hospital-Rikshospitalet, Section of Neuroradiology, Department of Radiology and Nuclear Medicine, Oslo (Norway); Bargallo, Nuria [Universitat de Barcelona, Section of Neuroradiology, Department of Radiology, Hospital Clinic, Barcelona (Spain); Institut d' investigacions Biomediques August Pi i Sunyer (IDIBARS), Resonance Magnetic Image Core Facility, Barcelona (Spain); Floeisand, Yngvar [Oslo University Hospital-Rikshospitalet, Department of Hematology, Oslo (Norway); Sponheim, Jon [Oslo University Hospital-Rikshospitalet, Section of Gastroenterology, Department of Transplantation Medicine, Oslo (Norway); Graus, Francesc [Universitat de Barcelona, Department of Neurology, Hospital Clinic, Barcelona (Spain); Institut d' investigacions Biomediques August Pi i Sunyer (IDIBARS), Neuroimmunology Program, Barcelona (Spain); Hald, John K. [Oslo University Hospital-Rikshospitalet, Section of Neuroradiology, Department of Radiology and Nuclear Medicine, Oslo (Norway); University of Oslo, Faculty of Medicine, Oslo (Norway)

2017-02-15

Neurologic complications are common after hematopoietic stem cell transplantation (HSCT) and solid organ transplantation (SOT) and affect 30-60% of transplant recipients. The aim of this article is to provide a practical imaging approach based on the timeline and etiology of CNS abnormalities, and neurologic complications related to transplantation of specific organs. The lesions will be classified based upon the interval from HSCT procedure: pre-engraftment period <30 days, early post-engraftment period 30-100 days, late post-engraftment period >100 days, and the interval from SOT procedure: postoperative phase 1-4 weeks, early posttransplant syndromes 1-6 months, late posttransplant syndromes >6 months. Further differentiation will be based on etiology: infections, drug toxicity, metabolic derangements, cerebrovascular complications, and posttransplantation malignancies. In addition, differentiation will be based on complications specific to the type of transplantation: allogeneic and autologous hematopoietic stem cells (HSC), heart, lung, kidney, pancreas, and liver. Thus, in this article we emphasize the strategic role of neuroradiology in the diagnosis and response to treatment by utilizing a methodical approach in the work up of patients with neurologic complications after transplantation. (orig.)

Imaging spectrum of central nervous system complications of hematopoietic stem cell and solid organ transplantation

International Nuclear Information System (INIS)

Server, Andres; Bargallo, Nuria; Floeisand, Yngvar; Sponheim, Jon; Graus, Francesc; Hald, John K.

2017-01-01

Neurologic complications are common after hematopoietic stem cell transplantation (HSCT) and solid organ transplantation (SOT) and affect 30-60% of transplant recipients. The aim of this article is to provide a practical imaging approach based on the timeline and etiology of CNS abnormalities, and neurologic complications related to transplantation of specific organs. The lesions will be classified based upon the interval from HSCT procedure: pre-engraftment period <30 days, early post-engraftment period 30-100 days, late post-engraftment period >100 days, and the interval from SOT procedure: postoperative phase 1-4 weeks, early posttransplant syndromes 1-6 months, late posttransplant syndromes >6 months. Further differentiation will be based on etiology: infections, drug toxicity, metabolic derangements, cerebrovascular complications, and posttransplantation malignancies. In addition, differentiation will be based on complications specific to the type of transplantation: allogeneic and autologous hematopoietic stem cells (HSC), heart, lung, kidney, pancreas, and liver. Thus, in this article we emphasize the strategic role of neuroradiology in the diagnosis and response to treatment by utilizing a methodical approach in the work up of patients with neurologic complications after transplantation. (orig.)

Fungemia due to Rhodotorula mucilaginosa after allogeneic hematopoietic stem cell transplantation.

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Mori, T; Nakamura, Y; Kato, J; Sugita, K; Murata, M; Kamei, K; Okamoto, S

2012-02-01

Rhodotorula species have been increasingly recognized as emerging pathogens, particularly in immunocompromised patients. We herein report on a patient with myelodysplastic syndrome who developed fungemia due to Rhodotorula mucilaginosa after allogeneic hematopoietic stem cell transplantation (HSCT) from an unrelated donor. He developed severe acute graft-versus-host disease requiring high-dose steroids, and had serially been administered fluconazole and micafungin for the prophylaxis of fungal infection. Although several cases of Rhodotorula infection after HSCT have been reported, all of them were recipients of autologous HSCT, not allogeneic HSCT. A review of all the reported cases of Rhodotorula infection after HSCT revealed that all patients had received fluconazole or echinocandins before the onset of infection. The findings suggest that Rhodotorula species could be causative yeasts, particularly in patients receiving fluconazole or echinocandins, both of which are inactive against the species. © 2011 John Wiley & Sons A/S.

Effectiveness of Partner Social Support Predicts Enduring Psychological Distress after Hematopoietic Stem Cell Transplantation

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Rini, Christine; Redd, William H.; Austin, Jane; Mosher, Catherine E.; Meschian, Yeraz Markarian; Isola, Luis; Scigliano, Eileen; Moskowitz, Craig H.; Papadopoulos, Esperanza; Labay, Larissa E.; Rowley, Scott; Burkhalter, Jack E.; Schetter, Christine Dunkel; DuHamel, Katherine N.

2011-01-01

Objective: Hematopoietic stem cell transplant (HSCT) survivors who are 1 to 3 years posttransplant are challenged by the need to resume valued social roles and activities--a task that may be complicated by enduring transplant-related psychological distress common in this patient population. The present study investigated whether transplant…

Ovarian tissue cryopreservation in girls undergoing haematopoietic stem cell transplant: experience of a single centre.

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Biasin, E; Salvagno, F; Berger, M; Nesi, F; Quarello, P; Vassallo, E; Evangelista, F; Marchino, G L; Revelli, A; Benedetto, C; Fagioli, F

2015-09-01

Fertility after childhood haemopoietic stem cell transplant (HSCT) is a major concern. Conditioning regimens before HSCT present a high risk (>80%) of ovarian failure. Since 2000, we have proposed cryopreservation of ovarian tissue to female patients undergoing HSCT at our centre, to preserve future fertility. After clinical and haematological evaluation, the patients underwent ovarian tissue collection by laparoscopy. The tissue was analysed by histologic examination to detect any tumour contamination and then frozen following the slow freezing procedure and cryopreserved in liquid nitrogen. From August 2000 to September 2013, 47 patients planned to receive HSCT, underwent ovarian tissue cryopreservation. The median age at diagnosis was 11.1 years and at the time of procedure it was 13 years, respectively. Twenty-four patients were not pubertal at the time of storage, whereas 23 patients had already experienced menarche. The median time between laparoscopy and HSCT was 25 days. Twenty-six out of 28 evaluable patients (93%) developed hypergonadotropic hypogonadism at a median time of 23.3 months after HSCT. One patient required autologous orthotopic transplantation that resulted in one live birth. Results show a very high rate of iatrogenic hypergonadotropic hypogonadism, highlighting the need for fertility preservation in these patients.

Hematopoietic stem cell transplantation monitoring in childhood. Hematological diseases in Serbia: STR-PCR techniques

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Krstić Aleksandra D.

2007-01-01

Full Text Available Hematopoietic stem cell transplantation (HSCT is a very successful method of treatment for children with different aquired or inborn diseases. The main goal of post-transplantation chimerism monitoring in HSCT is to predict negative events (such as disease relapse and graft rejection, in order to intervene with appropriate therapy and improve the probability of long-term DFS (disease free survival. In this context, by quantifying the relative amounts of donor and recipient cells present in the peripheral blood sample, it can be determined if engraftment has taken place at all, or if full or mixed chimerism exists. In a group of patients who underwent hematopoietic stem cell transplantation at the Mother and Child Health Care Institute, we decided to use standard human identfication tests based on multiplex PCR analyses of short tandem repeats (STRs, as they are highly informative, sensitive, and fast and therefore represent an optimal methodological approach to engraftment analysis.

Hematopoietic stem cell transplantation activity worldwide in 2012 and a SWOT analysis of the Worldwide Network for Blood and Marrow Transplantation Group including the global survey.

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Niederwieser, D; Baldomero, H; Szer, J; Gratwohl, M; Aljurf, M; Atsuta, Y; Bouzas, L F; Confer, D; Greinix, H; Horowitz, M; Iida, M; Lipton, J; Mohty, M; Novitzky, N; Nunez, J; Passweg, J; Pasquini, M C; Kodera, Y; Apperley, J; Seber, A; Gratwohl, A

2016-06-01

Data on 68 146 hematopoietic stem cell transplants (HSCTs) (53% autologous and 47% allogeneic) gathered by 1566 teams from 77 countries and reported through their regional transplant organizations were analyzed by main indication, donor type and stem cell source for the year 2012. With transplant rates ranging from 0.1 to 1001 per 10 million inhabitants, more HSCTs were registered from unrelated 16 433 donors than related 15 493 donors. Grafts were collected from peripheral blood (66%), bone marrow (24%; mainly non-malignant disorders) and cord blood (10%). Compared with 2006, an increase of 46% total (57% allogeneic and 38% autologous) was observed. Growth was due to an increase in reporting teams (18%) and median transplant activity/team (from 38 to 48 HSCTs/team). An increase of 167% was noted in mismatched/haploidentical family HSCT. A Strengths, Weaknesses, Opportunities, Threats (SWOT) analysis revealed the global perspective of WBMT to be its major strength and identified potential to be the key professional body for patients and authorities. The limited data collection remains its major weakness and threat. In conclusion, global HSCT grows over the years without plateauing (allogeneic>autologous) and at different rates in the four World Health Organization regions. Major increases were observed in allogeneic, haploidentical HSCT and, to a lesser extent, in cord blood transplantation.

Disseminated Nocardia cyriacigeorgia causing pancreatitis in a haploidentical stem cell transplant recipient

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Jason Chen

2017-01-01

Full Text Available We report the first published case of acute pancreatitis secondary to disseminated nocardiosis in a hematopoietic stem cell transplant (HSCT recipient on chronic immunosuppression for graft-versus-host disease (GVHD. Nocardiosis in the HSCT population is relatively rare, and has not yet been described in haploidentical HSCT recipients. Our patient is a 28-year-old male with a history of haploidentical HSCT and GVHD of the skin and lung who was admitted to the hospital with acute pancreatitis. The workup for the etiology of his pancreatitis was initially unrevealing. He subsequently developed worsening sepsis and respiratory failure despite broad spectrum antimicrobials. After multiple bronchoscopies and pancreatic fluid sampling, he was found to have disseminated nocardiosis with Nocardia cyriacigeorgia.

The impact of posttraumatic stress symptoms on social support and social conflict during hematopoietic stem cell transplant.

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Gerhart, James I; Asvat, Yasmin; Lillis, Teresa A; Fung, Henry; Grosse, Johanna; Hobfoll, Stevan E

2018-01-01

Social support and its relationship to psychological distress are of interest in hematopoietic stem cell transplant (HSCT) as patients are dependent on caregivers pre-, during, and posttransplant.  Although social support is critical for managing stress and trauma, posttraumatic stress symptoms (PTSS) may erode social support and evoke conflict and abandonment within the support system. This study aimed to evaluate whether PTSS were associated with lower support and social conflict in a sample of patients undergoing HSCT. Prospective relationships between PTSS, perceived social support, and social conflict were assessed in 88 participants across the first three months of HSCT (T0 Baseline; T1 +30; T2 +60; T3 +90). When individuals experienced increase above their own average levels of PTSS, they reported concurrent increase in social conflict (p social support in the following month (p = .026). Results suggest PTSS during stem cell transplantation may evoke social conflict, but over time, the support system may recalibrate to be more supportive. Patients undergoing HSCT may benefit from family and social-level interventions that specifically target the incidence of interpersonal conflict as it unfolds during the initial stages of HSCT.

Clinical impact of pre-transplant gut microbial diversity on outcomes of allogeneic hematopoietic stem cell transplantation.

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Doki, Noriko; Suyama, Masahiro; Sasajima, Satoshi; Ota, Junko; Igarashi, Aiko; Mimura, Iyo; Morita, Hidetoshi; Fujioka, Yuki; Sugiyama, Daisuke; Nishikawa, Hiroyoshi; Shimazu, Yutaka; Suda, Wataru; Takeshita, Kozue; Atarashi, Koji; Hattori, Masahira; Sato, Eiichi; Watakabe-Inamoto, Kyoko; Yoshioka, Kosuke; Najima, Yuho; Kobayashi, Takeshi; Kakihana, Kazuhiko; Takahashi, Naoto; Sakamaki, Hisashi; Honda, Kenya; Ohashi, Kazuteru

2017-09-01

Post-transplant microbial diversity in the gastrointestinal tract is closely associated with clinical outcomes following allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, little is known about the impact of the fecal microbiota before allo-HSCT. We analyzed fecal samples approximately 2 weeks before conditioning among 107 allo-HSCT recipients between 2013 and 2015. Microbial analysis was performed using 16S rRNA gene sequencing. Operational taxonomic unit-based microbial diversity was estimated by calculating the Shannon index. Patients were classified into three groups based on the diversity index: low (3) diversity (18 (16.8%), 48 (44.9%), and 41 (38.3%) patients, respectively). There were no significant differences in the 20-month overall survival, cumulative incidence of relapse, and non-relapse mortality among three groups. The cumulative incidence of grade II to IV acute graft-versus-host disease (aGVHD) was similar among the three groups (low 55.6%; intermediate 35.4%; high 48.8%, p = 0.339, at day 100). Furthermore, we found no differences in the cumulative incidence of grade II to IV acute gastrointestinal GVHD among the three groups (low 38.9%; intermediate 21.3%; high 24.4%, p = 0.778, at day 100). Regarding the composition of microbiota before allo-HSCT, aGVHD patients showed a significantly higher abundance of phylum Firmicutes (p strategy to prevent aGVHD.

Genetic Background of Immune Complications after Allogeneic Hematopoietic Stem Cell Transplantation in Children

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Szymon Skoczen

2016-01-01

Full Text Available Immune reactions are among the most serious complications observed after hematopoietic stem cell transplantation (HSCT in children. Microarray technique allows for simultaneous assessment of expression of nearly all human genes. The objective of the study was to compare the whole genome expression in children before and after HSCT. A total of 33 children referred for HSCT were enrolled in the study. In 70% of the patients HSCT was performed for the treatment of neoplasms. Blood samples were obtained before HSCT and six months after the procedure. Subsequently, the whole genome expression was assessed in leukocytes using GeneChip Human Gene 1.0 ST microarray. The analysis of genomic profiles before and after HSCT revealed altered expression of 124 genes. Pathway enrichment analysis revealed upregulation of five pathways after HSCT: allograft rejection, graft-versus-host disease, type I diabetes mellitus, autoimmune thyroid disease, and viral myocarditis. The activation of those pathways seems to be related to immune reactions commonly observed after HSCT. Our results contribute to better understanding of the genomic background of the immunologic complications of HSCT.

Long-term outcomes after allogeneic hematopoietic stem cell transplantation for metachromatic leukodystrophy: the largest single-institution cohort report.

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Boucher, Alexander A; Miller, Weston; Shanley, Ryan; Ziegler, Richard; Lund, Troy; Raymond, Gerald; Orchard, Paul J

2015-08-07

Metachromatic Leukodystrophy (MLD) is a rare, fatal demyelinating disorder with limited treatment options. Published outcomes after hematopoietic stem cell transplantation (HSCT) are scant and mixed. We report survival and function following HSCT for a large, single-center MLD cohort. Transplant-related data, survival and serial measures (brain MRI, nerve conduction velocity (NCV), neurologic and neuropsychology evaluations) were reviewed. When possible, parental interviews informed current neurologic status, quality-of-life, and adaptive functioning. Gross motor and expressive functions for late-infantile (LI-MLD) and juvenile (J-MLD) patients were described using previously reported, MLD-specific scales. Forty patients with confirmed MLD have undergone HSCT at our center. Twenty-one (53 %) survive at a median 12 years post-HSCT. Most deaths (n = 17) were treatment-related; two died from disease progression. Survival did not depend upon MLD subtype or symptom status at transplant. LI-MLD patients survive beyond reported life expectancy in untreated disease. Abnormal brain MRI and peripheral nerve conduction velocities (NCV) were common before HSCT. Following transplant, fewer patients experienced MRI progression compared to NCV deterioration. Sixteen LI-MLD and J-MLD survivors were evaluable for long-term gross motor and/or expressive language functioning using existing MLD clinical scoring systems. While most J-MLD patients regressed, the aggregate cohort demonstrated superior retention of function compared to published natural history. Seventeen LI-MLD, J-MLD and adult subtype (A-MLD) survivors were evaluable for long-term adaptive functioning, activities of daily living, and/or cognition. Relative cognitive sparing was observed despite overall global decline. Five sibling pairs (one LI-MLD and four J-MLD), in which at least one underwent transplant in our cohort, were evaluable. Within each familial dyad, survival or function was superior for the treated

Will Post-Transplantation Cell Therapies for Pediatric Patients Become Standard of Care?

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Lankester, Arjan C.; Locatelli, Franco; Bader, Peter; Rettinger, Eva; Egeler, Maarten; Katewa, Satyendra; Pulsipher, Michael A.; Nierkens, Stefan; Schultz, Kirk; Handgretinger, Rupert; Grupp, Stephan A.; Boelens, Jaap Jan; Bollard, Catherine M.

Although allogeneic hematopoietic stem cell transplantation (HSCT) is a curative approach for many pediatric patients with hematologic malignancies and some nonmalignant disorders, some critical obstacles remain to be overcome, including relapse, engraftment failure, graft-versus-host disease

Oral complaints and dental care of haematopoietic stem cell transplant patients: a qualitative survey of patients and their dentists

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Bos-den Braber, J.; Potting, C.M.J.; Bronkhorst, E.M.; Huysmans, M.C.D.N.J.M.; Blijlevens, N.M.A.

2015-01-01

PURPOSE: Little is known about the understanding of the oral and dental needs of haematopoietic stem cell transplant (HSCT) patients or about dentists' views and experiences regarding this patient group. This information is essential if we want to improve the standard of peri-HSCT dental care. The

Endocrine complications after busulphan and cyclophosphamide based hematopoietic stem cell transplant: A single tertiary care centre experience

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Abhay Gundgurthi

2013-01-01

Full Text Available Introduction: Endocrine complications are common after hematopoietic stem cell transplant (HSCT. Although HSCT is performed at various centers in India, no study is available for endocrine dysfunctions among them. This study was carried out with the objective to evaluate endocrine dysfunction among patients undergone HSCT in the past. Materials and Methods: We carried out a cross-sectional study in a 50 post-HSCT recipients (39 allogenic, 11 autologous. All relevant data were collected from patient′s records. Samples for hormonal estimation were collected and stimulation tests for cortisol and growth hormone were interpreted based on peak values achieved during insulin tolerance test. Results: The mean age of patients was 26.3 ± 16.9 years (range 4-74. Adrenal insufficiency (AI was present in 60%, hypergonadotropic hypogonadism (HH in 60%, growth hormone deficiency (GHD in 54%, hypothyroidism in 4%, hyperprolactinemia in 4%, new onset diabetes after transplant in 4%, and impaired fasting glucose in 6%. Multiple endocrine complications were common. GHD was present in 77% of children (n = 22 although height standard deviation score was not statistically different compared to those who didn′t have GHD. HH was present in 36% of children. In adults (n = 28, 36% had GHD, all females had HH, and 89% of males had HH. Germ cell dysfunction with compensated Leydig cell dysfunction was the most common pattern of HH in males. Fifteen patients had graft versus host disease (GVHD. GVHD had no bearing on development of endocrine deficiencies. AI was related to duration after and type of transplant, but was unrelated to steroid intake. Conclusions: Endocrine manifestations are common after HSCT; they can occur as early or late complications. All HSCT recipients should have endocrine evaluation as per prevailing guidelines.

Having a sibling as donor: patients' experiences immediately before allogeneic hematopoietic stem cell transplantation.

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Kisch, Annika; Bolmsjö, Ingrid; Lenhoff, Stig; Bengtsson, Mariette

2014-08-01

Allogeneic hematopoietic stem cell transplantation (HSCT) offers a potential cure for a variety of diseases but is also associated with significant risks. With HSCT the donor is either a relative, most often a sibling, or an unrelated registry donor. The aim was to explore patients' experiences, immediately before transplantation, regarding having a sibling as donor. Ten adult patients with sibling donors were interviewed before admission for HSCT. The interviews were digitally recorded, transcribed verbatim and subjected to qualitative content analysis. The main theme Being in no man's land is a metaphor for the patients' complex situation with its mixture of emotions and thoughts prior to transplantation. The three subthemes Trust in the sibling donor, Concern about others and Loss of control cover the various experiences. The patient's experiences are influenced by their personal situation and the quality of the relationship with the sibling donor. While patients feel secure in having a sibling donor, they are dependent for their survival on the cell donation and feel responsible for the donor's safety during donation. These emotions intensify the patients' sense of dependency and loss of control. In caring for HSCT patients the nurses should be aware of the complexity of the patients' situation and keep in mind that having a sibling donor might imply extra pressure, including a sense of responsibility. Caring for both patients and sibling donors optimally is a challenge, which needs further improvement and exploration. Copyright © 2014 Elsevier Ltd. All rights reserved.

Defibrotide prevents the activation of macrovascular and microvascular endothelia caused by soluble factors released to blood by autologous hematopoietic stem cell transplantation.

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Palomo, Marta; Diaz-Ricart, Maribel; Rovira, Montserrat; Escolar, Ginés; Carreras, Enric

2011-04-01

Endothelial activation and damage occur in association with autologous hematopoietic stem cell transplantation (HSCT). Several of the early complications associated with HSCT seem to have a microvascular location. Through the present study, we have characterized the activation and damage of endothelial cells of both macro (HUVEC) and microvascular (HMEC) origin, occurring early after autologous HSCT, and the potential protective effect of defibrotide (DF). Sera samples from patients were collected before conditioning (Pre), at the time of transplantation (day 0), and at days 7, 14, and 21 after autologous HSCT. Changes in the expression of endothelial cell receptors at the surface, presence and reactivity of extracellular adhesive proteins, and the signaling pathways involved were analyzed. The expression of ICAM-1 at the cell surface increased progressively in both HUVEC and HMEC. However, a more prothrombotic profile was denoted for HMEC, in particular at the time of transplantation (day 0), reflecting the deleterious effect of the conditioning treatment on the endothelium, especially at a microvascular location. Interestingly, this observation correlated with a higher increase in the expression of both tissue factor and von Willebrand factor on the extracellular matrix, together with activation of intracellular p38 MAPK and Akt. Previous exposure and continuous incubation of cells with DF prevented the signs of activation and damage induced by the autologous sera. These observations corroborate that conditioning treatment in autologous HSCT induces a proinflammatory and a prothrombotic phenotype, especially at a microvascular location, and indicate that DF has protective antiinflammatory and antithrombotic effects in this setting. Copyright © 2011 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial.

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van Laar, Jacob M; Farge, Dominique; Sont, Jacob K; Naraghi, Kamran; Marjanovic, Zora; Larghero, Jérôme; Schuerwegh, Annemie J; Marijt, Erik W A; Vonk, Madelon C; Schattenberg, Anton V; Matucci-Cerinic, Marco; Voskuyl, Alexandre E; van de Loosdrecht, Arjan A; Daikeler, Thomas; Kötter, Ina; Schmalzing, Marc; Martin, Thierry; Lioure, Bruno; Weiner, Stefan M; Kreuter, Alexander; Deligny, Christophe; Durand, Jean-Marc; Emery, Paul; Machold, Klaus P; Sarrot-Reynauld, Francoise; Warnatz, Klaus; Adoue, Daniel F P; Constans, Joël; Tony, Hans-Peter; Del Papa, Nicoletta; Fassas, Athanasios; Himsel, Andrea; Launay, David; Lo Monaco, Andrea; Philippe, Pierre; Quéré, Isabelle; Rich, Éric; Westhovens, Rene; Griffiths, Bridget; Saccardi, Riccardo; van den Hoogen, Frank H; Fibbe, Willem E; Socié, Gérard; Gratwohl, Alois; Tyndall, Alan

2014-06-25

High-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation (HSCT) have shown efficacy in systemic sclerosis in phase 1 and small phase 2 trials. To compare efficacy and safety of HSCT vs 12 successive monthly intravenous pulses of cyclophosphamide. The Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial, a phase 3, multicenter, randomized (1:1), open-label, parallel-group, clinical trial conducted in 10 countries at 29 centers with access to a European Group for Blood and Marrow Transplantation-registered transplant facility. From March 2001 to October 2009, 156 patients with early diffuse cutaneous systemic sclerosis were recruited and followed up until October 31, 2013. HSCT vs intravenous pulse cyclophosphamide. The primary end point was event-free survival, defined as time from randomization until the occurrence of death or persistent major organ failure. A total of 156 patients were randomly assigned to receive HSCT (n = 79) or cyclophosphamide (n = 77). During a median follow-up of 5.8 years, 53 events occurred: 22 in the HSCT group (19 deaths and 3 irreversible organ failures) and 31 in the control group (23 deaths and 8 irreversible organ failures). During the first year, there were more events in the HSCT group (13 events [16.5%], including 8 treatment-related deaths) than in the control group (8 events [10.4%], with no treatment-related deaths). At 2 years, 14 events (17.7%) had occurred cumulatively in the HSCT group vs 14 events (18.2%) in the control group; at 4 years, 15 events (19%) had occurred cumulatively in the HSCT group vs 20 events (26%) in the control group. Time-varying hazard ratios (modeled with treatment × time interaction) for event-free survival were 0.35 (95% CI, 0.16-0.74) at 2 years and 0.34 (95% CI, 0.16-0.74) at 4 years. Among patients with early diffuse cutaneous systemic sclerosis, HSCT was associated with increased treatment-related mortality in the first year

A survey of fertility and sexual health following allogeneic haematopoietic stem cell transplantation in New South Wales, Australia.

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Dyer, Gemma; Gilroy, Nicole; Bradford, Jennifer; Brice, Lisa; Kabir, Masura; Greenwood, Matt; Larsen, Stephen R; Moore, John; Hertzberg, Mark; Kwan, John; Brown, Louisa; Hogg, Megan; Huang, Gillian; Tan, Jeff; Ward, Christopher; Kerridge, Ian

2016-02-01

Four hundred and twenty-one adult allogeneic haematopoietic stem cell transplant (HSCT) survivors participated in a cross-sectional study to assess sexual dysfunction and infertility post-transplant. Survey instruments included the Sydney Post-Blood and Marrow Transplant (BMT) Survey, Functional Assessment of Cancer Treatment (FACT) - BMT, the Depression, Anxiety, Stress Scales (DASS 21), the Chronic Graft-versus-Host Disease (cGVHD) Activity Assessment- Patient Self Report (Form B), the Lee cGVHD Symptom Scale and The Post-Traumatic Growth Inventory. Most HSCT survivors reported sexual difficulties (51% of males; 66% of females). Men reported erectile dysfunction (79%) and decreased libido (61·6%) and women reported loss of libido (83%), painful intercourse (73%) and less enjoyment of sex (68%). Women also commonly reported vaginal dryness (73%), vaginal narrowing (34%) and vaginal irritation (26%). Woman had much higher rates of genital cGvHD than men (22% vs. 5%). Age and cGVHD were significantly associated with sexual dysfunction. Few survivors had children following transplant (3·3%). However, for those of reproductive age at HSCT, 22% reported trying to conceive, with 10·3% reporting success. This study is the largest to date exploring sexual function in survivors of allo-HSCT. This data provides the basis for health service reform to better meet the needs of HSCT survivors, including evidence to support counselling and education both pre- and post-transplant. © 2015 John Wiley & Sons Ltd.

Lung function after allogeneic hematopoietic stem cell transplantation in children

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Uhlving, Hilde Hylland; Larsen Bang, Cæcilie; Christensen, Ib Jarle

2013-01-01

Reduction in pulmonary function (PF) has been reported in up to 85% of pediatric patients during the first year after hematopoietic stem cell transplantation (HSCT). Our understanding of the etiology for this decrease in lung function is, however, sparse. The aim of this study was to describe PF...

Long term follow up of patients after allogeneic stem cell transplantation and transfusion of HSV-Tk transduced T-cells.

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Eva Maria Weissinger

2015-04-01

Full Text Available Allogeneic stem cell transplantation (allo-HSCT is one of the curative treatments for hematologic malignancies, but is hampered by severe complications, such as acute or chronic graft-versus-host-disease (aGvHD; cGvHD and infections. CD34-selcetion of stem cells reduces the risk of aGvHD, but also leads to increased infectious complications and relapse. Thus, we studied the efficacy, safety and feasibility of transfer of gene modified donor T-cells shortly after allo-HSCT in two clinical trials between 2002 and 2007 and here we compare the results to unmodified donor leukocyte transfusion (DLI. The aim of these trials was to provide patients with the protection of T-cells after T-cell-depleted allo-HSCT in the matched or mismatched donor setting with an option to delete transduced T-cells, if severe aGvHD occurred within the trial period. Donor-T-cells were transduced with the replication-deficient retrovirus SFCMM-3, expressing HSV-Tk and the truncated LNGFR for selection of transduced cells. Transduced cells were transfused either after day +60 (matched donors or on day +42 (haploidentical donors.Nine patients were included in the first trial (MHH; 2002 until 2007 2 were included in TK007 (2005-2009 and 6 serve as a control group for outcome after haploidentical transplantation without HSV-TK-transduced DLI. Three patients developed acute GvHD, two had grade I of the skin, one had aGvHD on day +131 (post-HSCT; +89 post-HSV-Tk DLI grade II, which was successfully controlled by ganciclovir (GCV. Donor chimerism was stabilized after transfusion of the transduced cells in all patients treated. Functionality of HSV-Tk gene expressing T-cells was shown by loss of bcr-abl gene expression as well as by control of cytomegalovirus-reactivation. To date, 6patients have relapsed and died, 2 after a second HSCT without T-cell depletion or administration of unmodified T-cells. Eleven patients (7 post-HSV-Tk DLI are alive and well to date.

Donor Selection for Allogenic Hemopoietic Stem Cell Transplantation: Clinical and Ethical Considerations

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Irene Riezzo

2017-01-01

Full Text Available Allogenic hematopoietic progenitor cell transplantation (allo-HSCT is an established treatment for many diseases. Stem cells may be obtained from different sources: mobilized peripheral blood stem cells, bone marrow, and umbilical cord blood. The progress in transplantation procedures, the establishment of experienced transplant centres, and the creation of unrelated adult donor registries and cord blood banks gave those without an human leucocyte antigen- (HLA- identical sibling donor the opportunity to find a donor and cord blood units worldwide. HSCT imposes operative cautions so that the entire donation/transplantation procedure is safe for both donors and recipients; it carries with it significant clinical, moral, and ethical concerns, mostly when donors are minors. The following points have been stressed: the donation should be excluded when excessive risks for the donor are reasonable, donors must receive an accurate information regarding eventual adverse events and health burden for the donors themselves, a valid consent is required, and the recipient’s risks must be outweighed by the expected benefits. The issue of conflict of interest, when the same physician has the responsibility for both donor selection and recipient care, is highlighted as well as the need of an adequate insurance protection for all the parties involved.

Outcomes after Unrelated Umbilical Cord Blood Transplantation for Children with Osteopetrosis

NARCIS (Netherlands)

Chiesa, Robert; Ruggeri, Annalisa; Paviglianiti, Annalisa; Zecca, Marco; Gónzalez-Vicent, Marta; Bordon, Victoria; Stein, Jerry; Lawson, Sarah; Dupont, Sophie; Lanino, Edoardo; Abecasis, Manuel; Al-Seraihy, Amal; Kenzey, Chantal; Bierings, Marc; Locatelli, Franco; Gluckman, Eliane; Schulz, Ansgar; Gennery, Andrew; Page, Kristin; Kurtzberg, Joanne; Rocha, Vanderson

2016-01-01

Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for most children with osteopetrosis (OP). Timing of HSCT is critical; therefore, umbilical cord blood transplantation (UCBT) is an attractive option. We analyzed outcomes after UCBT in 51 OP children. Median age at UCBT

Health related quality of life and emotional health in children with chronic granulomatous disease: a comparison of those managed conservatively with those that have undergone haematopoietic stem cell transplant.

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Cole, Theresa; McKendrick, Fiona; Titman, Penny; Cant, Andrew J; Pearce, Mark S; Cale, Catherine M; Goldblatt, David; Gennery, Andrew R

2013-01-01

Chronic Granulomatous Disease (CGD) is a rare primary immunodeficiency that predisposes to life-threatening infections and inflammation. Haematopoietic stem cell transplant (HSCT) can cure CGD. Chronic illness reduces quality of life. Children with haematological malignancies report improved quality of life post-HSCT. There are no data for children with CGD. This study evaluated quality of life and emotional well-being in CGD children treated conventionally or transplanted. Parents and children completed the Pediatric Quality of Life Inventory v4.0 (PedsQL) and Strengths and Difficulties Questionnaires (SDQ). Mean scores were compared with published UK norms. Comparisons were made for those that had or had not undergone HSCT. Forty-seven parents completed PedsQL (children aged 3-15). Twenty-one were post-HSCT. Forty-two completed SDQ (children aged 3-15). Nineteen post-HSCT. Median age for non-HSCT group 9 years. Median age for post-HSCT group 10 years. The HSCT group were median 3 years post-HSCT (range 1-9 years). HSCT survival was 90 %-two died without completing questionnaires Parent and self-reported quality of life for non-transplanted children was significantly lower than healthy children. Parents reported increased emotional difficulties compared to published norms. PedsQL and SDQ scores for transplanted children were not significantly different from healthy norms. This study demonstrates the quality of life is reduced in CGD. Transplanted patients have quality of life comparable to levels reported in healthy children. This data will help inform families and clinicians when deciding about treatment and may have relevance for other immunodeficiencies treated with transplant.

Strength Training Following Hematopoietic Stem Cell Transplantation

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Hacker, Eileen Danaher; Larson, Janet; Kujath, Amber; Peace, David; Rondelli, Damiano; Gaston, Lisa

2010-01-01

Background Patients receiving high-dose chemotherapy and hematopoietic stem cell transplantation (HSCT) experience considerable reductions in physical activity and deterioration of their health status. Objective The purpose of this pilot study was to test the effects of strength training compared to usual activity on physical activity, muscle strength, fatigue, health status perceptions, and quality of life following HSCT. Interventions/Methods Nineteen subjects were randomized to the exercise or control group. Moderate intensity strength training began following discharge from the hospital. Dependent variables included physical activity, muscle strength, fatigue, health status perceptions and quality of life. Variables were measured prior to admission to the hospital for HSCT, day 8 following HSCT, and six weeks following discharge from the hospital. Results Significant time effects were noted for many variables with anticipated declines in physical activity, muscle strength, fatigue, and health status perceptions immediately after HSCT with subsequent improvements six weeks following hospital discharge. One group effect was noted with subjects in the exercise group reporting less fatigue than subjects in the control group. Although no significant interactions were detected, the trends suggest that the exercise group may be more physically active following the intervention compared to the usual activity group. Conclusions This study demonstrates the potential positive effects of strength training on physical activity, fatigue, and quality of life in people receiving high-dose chemotherapy and HSCT. Implications for Practice Preliminary evidence is provided for using strength training to enhance early recovery following HSCT. Elastic resistance bands are easy to use and relatively inexpensive. PMID:21116175

Umbilical cord blood as an alternative source of reduced-intensity hematopoietic stem cell transplantation for chronic Epstein-Barr virus-associated T or natural killer cell lymphoproliferative diseases.

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Sawada, Akihisa; Inoue, Masami; Koyama-Sato, Maho; Kondo, Osamu; Yamada, Kayo; Shimizu, Mariko; Isaka, Kanako; Kimoto, Tomiko; Kikuchi, Hiroaki; Tokimasa, Sadao; Yasui, Masahiro; Kawa, Keisei

2014-02-01

Chronic Epstein-Barr virus-associated T/natural killer cell lymphoproliferative diseases represented by chronic active Epstein-Barr virus infection are lethal but are curable with several courses of chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT). Recently, we reported that reduced-intensity conditioning (RIC) provided better outcomes than myeloablative conditioning because RIC was less toxic. However, it was unclear whether cord blood transplantation (CBT) works in the context of RIC. We retrospectively analyzed 17 patients who underwent RIC followed by bone marrow transplantation (RIC-BMT) and 15 patients who underwent RIC followed by CBT (RIC-CBT). The representative regimen was fludarabine and melphalan based. The overall survival rates with RIC-BMT and RIC-CBT were 92.9% ± 6.9% and 93.3% ± 6.4%, respectively (P = .87). One patient died of lung graft-versus-host disease after RIC-BMT, and 1 patient died of multiple viral infections after RIC-CBT. Although cytotoxic chemotherapy was also immunosuppressive and might contribute to better donor cell engraftment after RIC-HSCT, the rate of engraftment failure after RIC-CBT was still higher than that after RIC-BMT (not significant); however, patients who had experienced graft failure were successfully rescued with a second HSCT. Unrelated cord blood can be an alternative source for RIC-HSCT if a patient has no family donor. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Prediction of Allogeneic Hematopoietic Stem-Cell Transplantation Mortality 100 Days After Transplantation Using a Machine Learning Algorithm: A European Group for Blood and Marrow Transplantation Acute Leukemia Working Party Retrospective Data Mining Study.

Science.gov (United States)

Shouval, Roni; Labopin, Myriam; Bondi, Ori; Mishan-Shamay, Hila; Shimoni, Avichai; Ciceri, Fabio; Esteve, Jordi; Giebel, Sebastian; Gorin, Norbert C; Schmid, Christoph; Polge, Emmanuelle; Aljurf, Mahmoud; Kroger, Nicolaus; Craddock, Charles; Bacigalupo, Andrea; Cornelissen, Jan J; Baron, Frederic; Unger, Ron; Nagler, Arnon; Mohty, Mohamad

2015-10-01

Allogeneic hematopoietic stem-cell transplantation (HSCT) is potentially curative for acute leukemia (AL), but carries considerable risk. Machine learning algorithms, which are part of the data mining (DM) approach, may serve for transplantation-related mortality risk prediction. This work is a retrospective DM study on a cohort of 28,236 adult HSCT recipients from the AL registry of the European Group for Blood and Marrow Transplantation. The primary objective was prediction of overall mortality (OM) at 100 days after HSCT. Secondary objectives were estimation of nonrelapse mortality, leukemia-free survival, and overall survival at 2 years. Donor, recipient, and procedural characteristics were analyzed. The alternating decision tree machine learning algorithm was applied for model development on 70% of the data set and validated on the remaining data. OM prevalence at day 100 was 13.9% (n=3,936). Of the 20 variables considered, 10 were selected by the model for OM prediction, and several interactions were discovered. By using a logistic transformation function, the crude score was transformed into individual probabilities for 100-day OM (range, 3% to 68%). The model's discrimination for the primary objective performed better than the European Group for Blood and Marrow Transplantation score (area under the receiver operating characteristics curve, 0.701 v 0.646; Prisk evaluation of patients with AL before HSCT, and is available online (http://bioinfo.lnx.biu.ac.il/∼bondi/web1.html). It is presented as a continuous probabilistic score for the prediction of day 100 OM, extending prediction to 2 years. The DM method has proved useful for clinical prediction in HSCT. © 2015 by American Society of Clinical Oncology.

Evaluation of febrile neutropenia in patients undergoing hematopoietic stem cell transplantation.

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Shahideh Amini

2014-01-01

Full Text Available The aim of this study was to determine the incidence and causes of fever as a major problem contributing to transplantation related mortality among patients undergoing hematopoietic stem cell transplantation (HSCT and evaluation of antibiotic use, according to reliable guidelines.We retrospectively reviewed hospital records of 195 adult patients who underwent HSCT between 2009-2011 at hematology-oncology and bone marrow transplantation research center. Baseline information and also data related to fever and neutropenia, patient's outcomes, duration of hospitalization and antibiotic use pattern were documented.A total of 195 patients were analyzed and a total of 268 febrile episodes in 180 patients were recorded (mean 1.5 episodes per patient. About 222 episodes (82% were associated with neutropenia which one-fourth of them were without any documented infection sources. Microbiologic documents showed that the relative frequencies of gram positive and gram negative bacteria were 62.5% and 37.5%, respectively. The hospital stay duration was directly related to the numbers of fever episodes (P<0.0001.The rate of febrile episodes in autologous stem cell transplantation was significantly higher compared to allogeneic type (P<0.05.It is necessary to determine not only the local profile of microbiologic pattern, but also antibiotic sensitivities in febrile neutropenic patients following hematopoietic stem cell transplantation, and reassess response to antibiotic treatment to establish any necessity for modifications to treatment guidelines in order to prevent any fatal complications from infection.

Transplantation in patients with iron overload: is there a place for magnetic resonance imaging? : Transplantation in iron overload.

Science.gov (United States)

Mavrogeni, Sophie; Kolovou, Genovefa; Bigalke, Boris; Rigopoulos, Angelos; Noutsias, Michel; Adamopoulos, Stamatis

2018-03-01

In iron overload diseases (thalassemia, sickle cell, and myelodysplastic syndrome), iron is deposited in all internal organs, leading to functional abnormalities. Hematopoietic stem cell transplantation (HSCT) is the only treatment offering a potential cure in these diseases. Our aim was to describe the experience in the field and the role of magnetic resonance imaging in the evaluation of iron overload before and after HSCT. Magnetic resonance imaging (MRI), using T2*, is the most commonly used tool to diagnose myocardial-liver iron overload and guide tailored treatment. Currently, HSCT offers complete cure in thalassemia major, after overcoming the immunologic barrier, and should be considered for all patients who have a suitable donor. The overall thalassemia-free survival of low-risk, HLA-matched sibling stem cell transplantation patients is 85-90%, with a 95% overall survival. The problems of rejection and engraftment are improving with the use of adequate immunosuppression. However, a detailed iron assessment of both heart and liver is necessary for pre- and post-transplant evaluation. In iron overload diseases, heart and liver iron evaluation is indispensable not only for the patients' survival, but also for evaluation before and after HSCT.

Defibrotide for children and adults with hepatic veno-occlusive disease post hematopoietic cell transplantation.

Science.gov (United States)

Corbacioglu, Selim; Richardson, Paul G

2017-10-01

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a complication that is typically associated with conditioning for hematopoietic stem cell transplantation (HSCT). In patients with concomitant multi-organ dysfunction, mortality may be >80%. Recently, the European Society for Blood and Marrow Transplantation established separate criteria for diagnosis and severity of VOD/SOS for adults and children, to better reflect current understanding of the disease. Areas covered: This review provides an overview of post-HSCT hepatic VOD/SOS and defibrotide, including its pharmacological, clinical, and regulatory profile. In children and adults following HSCT, defibrotide is approved for the treatment of hepatic VOD/SOS with concomitant renal or pulmonary dysfunction in the United States and for the treatment of severe hepatic VOD/SOS in the European Union. Day +100 survival rates with defibrotide are superior to those of historical controls receiving best supportive care only, and safety profiles are similar. Expert commentary: Defibrotide appears to act through multiple mechanisms to restore thrombo-fibrinolytic balance and protect endothelial cells, and there are promising data on the use of defibrotide for VOD/SOS prophylaxis in high-risk children undergoing HSCT. An ongoing randomized controlled trial in children and adults will better assess the clinical value of defibrotide as a preventive medication.

Long-term outcome of patients with newly diagnosed chronic myeloid leukemia: a randomized comparison of stem cell transplantation with drug treatment.

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Gratwohl, A; Pfirrmann, M; Zander, A; Kröger, N; Beelen, D; Novotny, J; Nerl, C; Scheid, C; Spiekermann, K; Mayer, J; Sayer, H G; Falge, C; Bunjes, D; Döhner, H; Ganser, A; Schmidt-Wolf, I; Schwerdtfeger, R; Baurmann, H; Kuse, R; Schmitz, N; Wehmeier, A; Fischer, J Th; Ho, A D; Wilhelm, M; Goebeler, M-E; Lindemann, H W; Bormann, M; Hertenstein, B; Schlimok, G; Baerlocher, G M; Aul, C; Pfreundschuh, M; Fabian, M; Staib, P; Edinger, M; Schatz, M; Fauser, A; Arnold, R; Kindler, T; Wulf, G; Rosselet, A; Hellmann, A; Schäfer, E; Prümmer, O; Schenk, M; Hasford, J; Heimpel, H; Hossfeld, D K; Kolb, H-J; Büsche, G; Haferlach, C; Schnittger, S; Müller, M C; Reiter, A; Berger, U; Saußele, S; Hochhaus, A; Hehlmann, R

2016-03-01

Tyrosine kinase inhibitors represent today's treatment of choice in chronic myeloid leukemia (CML). Allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as salvage therapy. This prospective randomized CML-study IIIA recruited 669 patients with newly diagnosed CML between July 1997 and January 2004 from 143 centers. Of these, 427 patients were considered eligible for HSCT and were randomized by availability of a matched family donor between primary HSCT (group A; N=166 patients) and best available drug treatment (group B; N=261). Primary end point was long-term survival. Survival probabilities were not different between groups A and B (10-year survival: 0.76 (95% confidence interval (CI): 0.69-0.82) vs 0.69 (95% CI: 0.61-0.76)), but influenced by disease and transplant risk. Patients with a low transplant risk showed superior survival compared with patients with high- (Ptreatment (56% vs 6%; P<0.001). Differences in symptoms and Karnofsky score were not significant. In the era of tyrosine kinase inhibitors, HSCT remains a valid option when both disease and transplant risk are considered.

[Molecular diagnosis and hematopoietic stem cell transplantation in 17 children with inherited bone marrow failure syndrome].

Science.gov (United States)

Li, Qian; Li, Benshang; Luo, Changying; Wang, Jianmin; Luo, Chengjuan; Ding, Lixia; Chen, Jing

2015-11-01

To enrich our national database with data of rare diseases by analyzing molecular diagnosis and hematopoietic stem cell transplantation (HSCT) in children with inherited bone marrow failure syndromes (IBMFS). Next-generation sequencing (NGS)-based genetic diagnosis panel was applied for the clinical diagnosis and management of IBMFS. Retrospective analysis was performed on clinical and genetic data of 17 consecutive children who received HSCT over a long time interval (November. 2005-June 2015). Three patients were diagnosed only by clinical manifestation before 2012. After that NGS-based genetic diagnosis panel was used to identify IBMFS-related genes in 12/14.IBMFS patients (except two Diamond-Blackfan anemia (DBA) patients). Two Fanconi anemia (FA) patients were confirmed to be new variations through family-genotype-analysis and 3 families accepted prenatal diagnosis to avoid birth of affected fetuses. Seventeen IBMFS patients (10 FA,5 DBA and 2 dyskeratosis congenital (DKC)) were treated with HSCT from matched sibling donors (n=2), matched unrelated donors (n=8) or mismatched unrelated donors (n=7). The source of stem cells for transplantation included peripheral blood (n=12) and cord blood (n=5). With regard to the conditioning regimens, FA and DKC patients received fludarabine-based reduced intensity conditioning, while DBA patients received classical busulfan-based myeloablative conditioning. Median age at the time of HSCT was 36 months (7-156 months). The number of infused mononuclear cells and CD34⁺ cells was (10.6 ± 6.7) × 10⁸ and (5.9 ± 7.0) × 10⁶ per kilogram of recipient body weight, respectively. The median number of days to neutrophil recovery was 13 days after HSCT (range: 10-19 days). Platelet recovery was faster in the PBSCT group than in the CBT group ((16.3 ± 6.0) days vs. (30.0 ± 17.1) days,t=-2.487,P=0.026). During a median follow-up of 17 months (range: 2-114 months), except one FA patient who was transplanted with HLA

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

Allogeneic hematopoietic stem cell transplant in adult patients with myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) overlap syndromes.

Science.gov (United States)

Sharma, Prashant; Shinde, Shivani S; Damlaj, Moussab; Hefazi Rorghabeh, Mehrdad; Hashmi, Shahrukh K; Litzow, Mark R; Hogan, William J; Gangat, Naseema; Elliott, Michelle A; Al-Kali, Aref; Tefferi, Ayalew; Patnaik, Mrinal M

2017-04-01

MDS/MPN (myelodysplastic syndrome/myeloproliferative neoplasm) overlap syndromes are myeloid malignancies for which allogeneic hematopoietic stem cell transplant (allo-HSCT) is potentially curative. We describe transplant outcomes of 43 patients - 35 with chronic myelomonocytic leukemia, CMML (of which 17 had blast transformation, BT) and eight with MDS/MPN-unclassifiable (MDS/MPN,U). At median follow-up of 21 months, overall survival (OS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were 55%, 29%, and 25% respectively in CMML without BT and 47%, 40%, and 34% respectively in CMML with BT. Higher HSCT-comorbidity index (HSCT-CI >3 versus ≤3; p = 0.015) and splenomegaly (p = 0.006) predicted worse OS in CMML without BT. In CMML with BT, engraftment failure (p = 0.006) and higher HSCT-CI (p = 0.03) were associated with inferior OS, while HSCT within 1-year of diagnosis was associated with improved OS (p = 0.045). In MDS/MPN,U, at median follow-up of 15 months, OS, CIR, and NRM were 62%, 30%, and 14%, respectively.

Early determinants of long-term T-cell reconstitution after hematopoietic stem cell transplantation for severe combined immunodeficiency

NARCIS (Netherlands)

Borghans, José A.; Bredius, Robbert G.; Hazenberg, Mette D.; Roelofs, Helene; Jol-van der Zijde, Els C.; Heidt, Jeroen; Otto, Sigrid A.; Kuijpers, Taco W.; Fibbe, Willem E.; Vossen, Jaak M.; Miedema, Frank; van Tol, Maarten J.

2006-01-01

The immune system of patients with severe combined immunodeficiency (SCID) reconstitutes to a large extent during the first years after hematopoietic stem cell transplantation (HSCT). It was suggested, however, that accelerated loss of thymus output may cause impaired immune function at the long

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

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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.

Treatment of massive gastrointestinal bleeding occurred during autologous stem cell transplantation with recombinant activated factor VII and octreotide

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Erman Atas

2015-01-01

Full Text Available After hematopoietic stem cell transplantation (HSCT, patients may suffer from bleeding. One of the bleeding type is gastrointestinal (GI which has serious morbidity and mortality in children with limited treatment options. Herein, we presented a child with upper GI bleeding post autologous HSCT controlled successfully by using recombinant activated factor VII (rFVIIa and octreotide infusion.

Oral features and dental health in Hurler Syndrome following hematopoietic stem cell transplantation.

LENUS (Irish Health Repository)

McGovern, Eleanor

2010-09-01

Hurler Syndrome is associated with a deficiency of a specific lysosomal enzyme involved in the degradation of glycosaminoglycans. Hematopoietic stem cell transplantation (HSCT) in early infancy is undertaken to help prevent the accumulation of glycosaminoglycans and improve organ function.

Successful Sequential Liver and Hematopoietic Stem Cell Transplantation in a Child With CD40 Ligand Deficiency and Cryptosporidium-Induced Liver Cirrhosis.

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Quarello, Paola; Tandoi, Francesco; Carraro, Francesca; Vassallo, Elena; Pinon, Michele; Romagnoli, Renato; David, Ezio; Dell Olio, Dominic; Salizzoni, Mauro; Fagioli, Franca; Calvo, Pier Luigi

2018-05-01

Hematopoietic stem cell transplantation (HSCT) is curative in patients with primary immunodeficiencies. However, pre-HSCT conditioning entails unacceptably high risks if the liver is compromised. The presence of a recurrent opportunistic infection affecting the biliary tree and determining liver cirrhosis with portal hypertension posed particular decisional difficulties in a 7-year-old child with X-linked CD40-ligand deficiency. We aim at adding to the scanty experience available on such rare cases, as successful management with sequential liver transplantation (LT) and HSCT has been reported in detail only in 1 young adult to date. A closely sequential strategy, with a surgical complication-free LT, followed by reduced-intensity conditioning, allowed HSCT to be performed only one month after LT, preventing Cryptosporidium parvum recolonization of the liver graft. Combined sequential LT and HSCT resolved the cirrhotic evolution and corrected the immunodeficiency so that the infection responsible for the progressive sclerosing cholangitis did not recur. Hopefully, this report of the successful resolution of a potentially fatal combination of immunodeficiency and chronic opportunistic infection with end-stage organ damage in a child will encourage others to adapt a sequential transplant approach to this highly complex pathology. However, caution is to be exercised to carefully balance the risks intrinsic to transplant surgery and immunosuppression in primary immunodeficiencies.

Terminal Complement Blockade after Hematopoietic Stem Cell Transplantation Is Safe without Meningococcal Vaccination.

Science.gov (United States)

Jodele, Sonata; Dandoy, Christopher E; Danziger-Isakov, Lara; Myers, Kasiani C; El-Bietar, Javier; Nelson, Adam; Wallace, Gregory; Teusink-Cross, Ashley; Davies, Stella M

2016-07-01

Eculizumab inhibits terminal complement-mediated intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria and complement-mediated thrombotic microangiopathy (TMA) in patients with atypical hemolytic uremic syndrome and is now used as a first-line therapy in these diseases. Eculizumab is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) because of an increased risk of meningococcal infections in persons without adequate functional complement. Administration of meningococcal vaccine is required at least 2 weeks before administering the first dose of eculizumab, and this advice is included in the product label. Eculizumab use for treatment of TMA in hematopoietic stem cell transplantation (HSCT) recipients brings a significant dilemma regarding REMS required meningococcal vaccination. TMA after HSCT usually occurs within the first 100 days after transplantation when patients are severely immunocompromised and are not able to mount a response to vaccines. We evaluated 30 HSCT recipients treated with eculizumab for high-risk TMA without meningococcal vaccine. All patients received antimicrobial prophylaxis adequate for Neisseria meningitides during eculizumab therapy and for 8 weeks after discontinuation of the drug. Median time to TMA diagnosis was 28 days after transplant (range, 13.8 to 48.5). Study subjects received a median of 14 eculizumab doses (range, 2 to 38 doses) for HSCT-associated TMA therapy. There were no incidences of meningococcal infections. The incidences of bacterial and fungal bloodstream infections were similar in patients treated with eculizumab (n = 30) as compared with those with HSCT-associated TMA who did not receive any complement blocking therapy (n = 39). Our data indicate that terminal complement blockade in the early post-transplant period can be performed without meningococcal vaccination while using appropriate antimicrobial prophylaxis until complement

Central nervous system infection following allogeneic hematopoietic stem cell transplantation.

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Hanajiri, Ryo; Kobayashi, Takeshi; Yoshioka, Kosuke; Watanabe, Daisuke; Watakabe, Kyoko; Murata, Yutaka; Hagino, Takeshi; Seno, Yasushi; Najima, Yuho; Igarashi, Aiko; Doki, Noriko; Kakihana, Kazuhiko; Sakamaki, Hisashi; Ohashi, Kazuteru

2017-03-01

Here, we described the clinical characteristics and outcomes of central nervous system (CNS) infections occurring after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in a single institution over the previous 6 years. Charts of 353 consecutive allogeneic transplant recipients were retrospectively reviewed for CNS infection. A total of 17 cases of CNS infection were identified at a median of 38 days (range, 10-1028 days) after allo-HSCT. Causative pathogens were human herpesvirus-6 (n=6), enterococcus (n=2), staphylococcus (n=2), streptococcus (n=2), varicella zoster virus (n=1), cytomegalovirus (n=1), John Cunningham virus (n=1), adenovirus (n=1), and Toxoplasma gondii (n=1). The cumulative incidence of CNS infection was 4.1% at 1 year and 5.5% at 5 years. Multivariate analysis revealed that high-risk disease status was a risk factor for developing CNS infection (p=.02), and that overall survival at 3 years after allo-HSCT was 33% in patients with CNS infection and 53% in those without CNS infection (p=.04). Copyright © 2016 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.

Bone marrow MR imaging as predictors of outcome in hemopoietic stem cell transplantation

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Shen, Jun; Cheng, Li-Na; Duan, Xiao-Hui; Liang, Bi-Ling [Sun Yat-sen University, Department of Radiology, Guangzhou, Guangdong (China); Second Affiliated Hospital, Guangzhou, Guangdong (China); Griffith, James F. [Chinese University of Hong Kong, Prince of Wales Hospital, Department of Diagnostic Radiology and Organ Imaging, Shatin, Hong Kong SAR (China); Xu, Hong-Gui [Sun Yat-sen University, Department of Pediatrics, Guangzhou, Guangdong (China); Second Affiliated Hospital, Guangzhou, Guangdong (China)

2008-09-15

The purpose of this study is to investigate the role of femoral marrow MR imaging as predictor of outcome for hemopoietic stem cell transplantation (HSCT) in beta-thalassemia major. MR imaging of the proximal femur, including T1- and T2-weighted spin echo and short-tau inversion recovery and in-phase and out-of-phase fast field echo images, was prospectively performed in 27 thalassemia major patients being prepared for HSCT. The area of red marrow and its percentage of the proximal femur were measured, and the presence of marrow hemosiderosis was assessed. Age-adjusted multivariate logistic regression was used to determine the relationship between red marrow area percentage and marrow hemosiderosis and HSCT outcome. Red area percentage were less in patients with successful (90.25{+-}4.14%) compared to unsuccessful transplants (94.54% {+-}2.93%; p=0.01). Red marrow area percentage correlated positively with duration of symptoms(r=0.428, p=0.026) and serum ferritin (r=0.511, p=0.006). In multivariate-adjusted logistic regression analyses, red marrow area percentage was significantly inversely associated with successful HSCT (OR=1.383, 95% CI: 1.059-1.805, p=0.005). Marrow hemosidersosis and duration of sympotms and serum ferritin were not associated with HSCT outcome(p=0.174, 0.974, 0.762, respectively). Red marrow area percentage of proximal femur on MR imaging is a useful predictor of HSCT outcome. (orig.)

Bone marrow MR imaging as predictors of outcome in hemopoietic stem cell transplantation

International Nuclear Information System (INIS)

Shen, Jun; Cheng, Li-Na; Duan, Xiao-Hui; Liang, Bi-Ling; Griffith, James F.; Xu, Hong-Gui

2008-01-01

The purpose of this study is to investigate the role of femoral marrow MR imaging as predictor of outcome for hemopoietic stem cell transplantation (HSCT) in beta-thalassemia major. MR imaging of the proximal femur, including T1- and T2-weighted spin echo and short-tau inversion recovery and in-phase and out-of-phase fast field echo images, was prospectively performed in 27 thalassemia major patients being prepared for HSCT. The area of red marrow and its percentage of the proximal femur were measured, and the presence of marrow hemosiderosis was assessed. Age-adjusted multivariate logistic regression was used to determine the relationship between red marrow area percentage and marrow hemosiderosis and HSCT outcome. Red area percentage were less in patients with successful (90.25±4.14%) compared to unsuccessful transplants (94.54% ±2.93%; p=0.01). Red marrow area percentage correlated positively with duration of symptoms(r=0.428, p=0.026) and serum ferritin (r=0.511, p=0.006). In multivariate-adjusted logistic regression analyses, red marrow area percentage was significantly inversely associated with successful HSCT (OR=1.383, 95% CI: 1.059-1.805, p=0.005). Marrow hemosidersosis and duration of sympotms and serum ferritin were not associated with HSCT outcome(p=0.174, 0.974, 0.762, respectively). Red marrow area percentage of proximal femur on MR imaging is a useful predictor of HSCT outcome. (orig.)

Late non-infectious lung damage in children after allogeneic hematopoietic stem cells transplantation

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Yu. V. Skvortsova

2015-06-01

Full Text Available Hematopoietic stem cells transplantation (HSCT technology currently allows curing a lot of malignant and non-malignant diseases in adults and children. However, HSCT is highly toxic treatment. HSCT complications include the possibility of prolonged immunodeficiency, alloand autoimmune reactions and various organs dysfunction. These conditions require careful monitoring by specialists, early diagnosis and appropriate treatment. This article discusses the clinical features, diagnosis and treatment options of such late complications as non-infectious lung disease. These conditions can lead to disability of patients. Relevance and importance of timely diagnosis of these pathological conditions, including the range of clinical tests available on a residence, with a view to effective treatment can improve the quality of life ofchildren with complications after HSCT. Theoretical issues are illustrated by case report.

Gastrointestinal toxicity, systemic inflammation, and liver biochemistry in allogeneic hematopoietic stem cell transplantation

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Jordan, Karina; Pontoppidan, Peter; Uhlving, Hilde Hylland

2017-01-01

Liver toxicity is frequently seen in relation to allogeneic hematopoietic stem cell transplantation (HSCT), but pathogenesis and the risk factors are poorly understood. The purpose of this study was to investigate associations between liver toxicity, gastrointestinal toxicity, and levels of immun...

Localized extramedullary relapse after autologous hematopoietic stem cell transplantation in multiple myeloma

International Nuclear Information System (INIS)

Erkus, Muhan; Meteoglu, Ibrahim; Bolaman, Zahit; Kadikoylu, Gurhan

2005-01-01

Extramedullary plasmacytomas are rare manifestation of plasma cell malignancies. After hematopoietic stem cell transplantation HSCT, presentation of localized plasmacytoma with extramedullary growth is very unusual. We report a case of a 56-year-old woman with Dune-Salmon stage IIIA immunoglobulin A-kappa multiple myeloma, which presented 120 days after autologous HSCT with extramedullary plasmacytoma arising from a lymph node in supraclavicular region. The patient had no pretransplant-history related with extramedullary disease. There was no increase of plasma cells in bone marrow or monoclonal protein in urine or serum. Aspiration smears of lymph node revealed a population of plasmacytoid cells at various stages of maturation. The patient was successfully treated with local radiotherapy and has remained progression-free for more than 20 months. (author)

Human CD134 (OX40) expressed on T cells plays a key role for human herpesvirus 6B replication after allogeneic hematopoietic stem cell transplantation.

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Nagamata, Satoshi; Nagasaka, Miwako; Kawabata, Akiko; Kishimoto, Kenji; Hasegawa, Daiichiro; Kosaka, Yoshiyuki; Mori, Takeshi; Morioka, Ichiro; Nishimura, Noriyuki; Iijima, Kazumoto; Yamada, Hideto; Kawamoto, Shinichiro; Yakushijin, Kimikazu; Matsuoka, Hiroshi; Mori, Yasuko

2018-05-01

CD134 (OX40), which is a cellular receptor for human herpesvirus-6B (HHV-6B) and expresses on activated T cells, may play a key role for HHV-6B replication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Therefore, we examined the CD134 expression on T cells and HHV-6B replication after allo-HSCT, and analyzed the correlation between them. Twenty-three patients after allo-HSCT were enrolled. The percentages of CD134-positive cells within the CD4 + and CD8 + cell populations were measured by flow cytometry, and the viral copy number of HHV-6B was simultaneously quantified by real-time PCR. The correlation between CD134 and HHV-6B viral load was then statistically analyzed. HHV-6B reactivation occurred in 11 of 23 patients (47.8%). CD134 expression was seen on T cells and was coincident with the time of peak viral load. The percentage of CD134-positive cells decreased significantly when HHV-6B DNA disappeared (p = .005 in CD4 + T cells, p = .02 in CD8 + T cells). In the 4 patients who underwent umbilical cord blood transplantation (UCBT), the viral load varied with the percentage of CD134-positive cells. In the comparison between the HHV-6B reactivation group and non-reactivation group, maximum percentages of CD134-positive cells among CD4 + T cells in reactivation group were significantly higher than those in non-reactivation group (p = .04). This is the first study to show that a correlation of CD134 expression on T cells with HHV-6B replication after allo-HSCT, especially in UCBT. The results possibly indicate that CD134 on T cells plays a key role for HHV-6B replication after allo-HSCT. Copyright © 2018 Elsevier B.V. All rights reserved.

The role of gamma delta T cells in haematopoietic stem cell transplantation

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Minculescu, L; Sengeløv, H

2015-01-01

transplantation modalities increasingly focuses on selective cell depletion and graft engineering with the aim of retaining beneficial immune donor cells for the graft-versus-leukaemia (GVL) effect. In this context, the adoptive and especially innate effector functions of γδ T cells together with clinical studies...... recognition independent from the major histocompatibility complex (MHC) allows for the theoretical possibility of mediating GVL without an allogeneic response in terms of GVHD. Early studies on the impact of γδ T cells in HSCT have reported conflicting results. Recent studies, however, do suggest an overall...

Nurses' competences in the critical care of children undergoing hematopoietic stem cell transplantation

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Marianna Ferreira

2017-11-01

Full Text Available This is a descriptive study, with qualitative data analysis, in order to identify and analyze the experiences and competencies required by nurses in the care of transplanted child, who demand critical care. Nine nurses were interviewed. We analyzed the data according to the procedures for qualitative content analysis, and then we elaborated the following themes: Critical care to the transplanted child: a double challenge for the nurse; Nurses' competences for the care towards the critically ill child submitted to hematopoietic stem cell transplantation (HSCT. The identified competencies based on scientific knowledge, skills and natural abilities and relate to specific knowledge about pediatric HSCT; technical-scientific, interactive and communication skills; management of material resources and equipment; emotional control, empathy and leadership. Such competences help in the construction of a specific profile for the care offered to this clientele, with a view to therapeutic success.

Evolving Hematopoietic Stem Cell Transplantation Strategies in Severe Aplastic Anemia

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Dietz, Andrew C.; Lucchini, Giovanna; Samarasinghe, Sujith; Pulsipher, Michael A.

2016-01-01

Purpose of Review Significant improvements in unrelated donor hematopoietic stem cell transplantation (HSCT) in recent years has solidified its therapeutic role in severe aplastic anemia (SAA) and led to evolution of treatment algorithms, particularly for children. Recent Findings Advances in understanding genetics of inherited bone marrow failure syndromes (IBMFS) have allowed more confidence in accurately diagnosing SAA and avoiding treatments that could be dangerous and ineffective in individuals with IBMFS, which can be diagnosed in 10–20% of children presenting with a picture of SAA. Additionally long-term survival after matched sibling donor (MSD) and matched unrelated donor (MUD) HSCT now exceed 90% in children. Late effects after HSCT for SAA are minimal with current strategies and compare favorably to late effects after up-front immunosuppressive therapy (IST), except for patients with chronic graft versus host disease (GVHD). Summary 1) Careful assessment for signs or symptoms of IBMFS along with genetic screening for these disorders is of major importance. 2) MSD HSCT is already considered standard of care for up-front therapy and some groups are evaluating MUD HSCT as primary therapy. 3) Ongoing studies will continue to challenge treatment algorithms and may lead to an even more expanded role for HSCT in SAA. PMID:26626557

A human monoclonal antibody drug and target discovery platform for B-cell chronic lymphocytic leukemia based on allogeneic hematopoietic stem cell transplantation and phage display.

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Baskar, Sivasubramanian; Suschak, Jessica M; Samija, Ivan; Srinivasan, Ramaprasad; Childs, Richard W; Pavletic, Steven Z; Bishop, Michael R; Rader, Christoph

2009-11-12

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only potentially curative treatment available for patients with B-cell chronic lymphocytic leukemia (B-CLL). Here, we show that post-alloHSCT antibody repertoires can be mined for the discovery of fully human monoclonal antibodies to B-CLL cell-surface antigens. Sera collected from B-CLL patients at defined times after alloHSCT showed selective binding to primary B-CLL cells. Pre-alloHSCT sera, donor sera, and control sera were negative. To identify post-alloHSCT serum antibodies and subsequently B-CLL cell-surface antigens they recognize, we generated a human antibody-binding fragment (Fab) library from post-alloHSCT peripheral blood mononuclear cells and selected it on primary B-CLL cells by phage display. A panel of Fab with B-CLL cell-surface reactivity was strongly enriched. Selection was dominated by highly homologous Fab predicted to bind the same antigen. One Fab was converted to immunoglobulin G1 and analyzed for reactivity with peripheral blood mononuclear cells from B-CLL patients and healthy volunteers. Cell-surface antigen expression was restricted to primary B cells and up-regulated in primary B-CLL cells. Mining post-alloHSCT antibody repertoires offers a novel route to discover fully human monoclonal antibodies and identify antigens of potential therapeutic relevance to B-CLL and possibly other cancers. Trials described herein were registered at www.clinicaltrials.gov as nos. NCT00055744 and NCT00003838.

Gastrointestinal toxicity, systemic inflammation, and liver biochemistry in allogeneic hematopoietic stem cell transplantation

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Liver toxicity is frequently seen in relation to allogeneic hematopoietic stem cell transplantation (HSCT), but pathogenesis and the risk factors are poorly understood. The purpose of this study was to investigate associations between liver toxicity, gastrointestinal toxicity, and levels of immune-r...

Defibrotide: a review of its use in severe hepatic veno-occlusive disease following haematopoietic stem cell transplantation.

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Keating, Gillian M

2014-12-01

Defibrotide (Defitelio(®)) was recently approved in the EU for the treatment of severe hepatic veno-occlusive disease (VOD), also known as sinusoidal obstructive syndrome, in haematopoietic stem cell transplantation (HSCT) therapy. It is indicated in adults, adolescents, children and infants over 1 month of age. Defibrotide is also available in the US via an expanded-access protocol. Defibrotide is thought to protect endothelial cells and restore the thrombo-fibrinolytic balance in VOD. In a multicentre, phase III trial, the complete response rate by day +100 (primary endpoint) was significantly higher, and mortality at day +100 was significantly lower, in patients with severe hepatic VOD and multiorgan failure following HSCT who received intravenous defibrotide 6.25 mg/kg every 6 h than in a group of historical controls. The efficacy of defibrotide in severe hepatic VOD following HSCT was also supported by findings from a phase II dose-finding study, compassionate-use data and information provided from an independent transplant registry. Intravenous defibrotide was generally well tolerated in patients with severe hepatic VOD following HSCT, and was not associated with an increased risk of haemorrhagic adverse events. In conclusion, defibrotide is the only agent approved (in the EU) for use in severe hepatic VOD following HSCT and represents a useful advance in the treatment of this condition.

Haematopoietic Stem Cell Transplantation Arrests the Progression of Neurodegenerative Disease in Late-Onset Tay-Sachs Disease.

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Stepien, Karolina M; Lum, Su Han; Wraith, J Edmond; Hendriksz, Christian J; Church, Heather J; Priestman, David; Platt, Frances M; Jones, Simon; Jovanovic, Ana; Wynn, Robert

2017-12-07

Tay-Sachs disease is a rare metabolic disease caused by a deficiency of hexosaminidase A that leads to accumulation of GM2 gangliosides predominantly in neural tissue. Late-onset Tay-Sachs disease variant is associated with a higher level of residual HexA activity. Treatment options are limited, and there are a few described cases who have undergone haematopoietic stem cell transplantation (HSCT) with variable outcome.We describe a case of a 23-year-old male patient who presented with a long-standing tremor since 7 years of age. He had gait ataxia, a speech stammer and swallowing problems. His condition had had a static course apart from his tremor that had been gradually deteriorating. Because of the deterioration in his neurological function, the patient had an uneventful, matched-sibling donor bone marrow transplant at the age of 15 years. Eight years post-HSCT, at the age of 23, he retains full donor engraftment, and his white cell beta-HexA of 191 nmol/mg/h is comparable to normal controls (in-assay control = 187). He continues to experience some intentional tremor that is tolerable for daily life and nonprogressive since HSCT. HSCT is a potential treatment option which might arrest neurodegeneration in patients with LOTS.

Neurological outcomes after hematopoietic stem cell transplantation for cerebral X-linked adrenoleukodystrophy, late onset metachromatic leukodystrophy and Hurler syndrome

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Jonas Alex Morales Saute

Full Text Available ABSTRACT Hematopoietic stem cell transplantation (HSCT is the only available treatment for the neurological involvement of disorders such as late-onset metachromatic leukodystrophy (MLD, mucopolysaccharidosis type I-Hurler (MPS-IH, and X-linked cerebral adrenoleukodystrophy (CALD. Objective To describe survival and neurological outcomes after HSCT for these disorders. Methods Seven CALD, 2 MLD and 2 MPS-IH patients underwent HSCT between 2007 and 2014. Neurological examinations, magnetic resonance imaging, molecular and biochemical studies were obtained at baseline and repeated when appropriated. Results Favorable outcomes were obtained with 4/5 related and 3/6 unrelated donors. Two patients died from procedure-related complications. Nine transplanted patients were alive after a median of 3.7 years: neurological stabilization was obtained in 5/6 CALD, 1/2 MLD, and one MPS-IH patient. Brain lesions of the MPS-IH patient were reduced four years after HSCT. Conclusion Good outcomes were obtained when HSCT was performed before adulthood, early in the clinical course, and/or from a related donor.

Transplante de células-tronco hematopoéticas e leucemia mieloide aguda: diretrizes brasileiras Hematopoietic stem cells transplantation and acute myeloid leukemia: Brazilian guidelines

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Lucia Mariano R. Silla

2010-05-01

Full Text Available O objetivo deste trabalho foi definir diretrizes para a indicação do transplante de células-tronco hematopoéticas (TCTH no tratamento da leucemia mieloide aguda (LMA no Brasil. O papel do TCTH no tratamento da LMA foi discutido pelosautores e apresentado para a Sociedade Brasileira de Transplante de Medula Óssea na reunião sobre Diretrizes Brasileiras para o TCTH, que o ratificou. Este consenso foi baseado na revisão da literatura internacional e na experiência brasileira em TCTH para o tratamento da LMA. O tratamento ideal para leucemia mieloide aguda em primeira remissão completa (1RC ainda não está definido. Há consenso na indicação do TCTH alogênico, com condicionamento mieloablativo, para pacientes que apresentem alterações citogenéticas consideradas de alto risco. O TCTH alogênico não está indicado na 1RC para pacientes de baixo risco citogenético e, aparentemente, o TCTH alogênico, autólogo ou a quimioterapia de consolidação são equivalentes para os pacientes de risco intermediário.The objective of this work was to define guidelines for the indication of hematopoietic stem cells transplantation (HSCT in the treatment of acute myeloid leukemia (AML in Brazil. The role of HSCT in the treatment of AML was discussed by the authors and presented to the Brazilian Society of Bone Marrow Transplantation in a meeting to formulate and ratify the Brazilian Guidelines on HSCT. This consensus was based on a review of international publications and on the Brazilian experience in HSCT for the treatment of AML. The optimal treatment for AML in first complete remission (1CR has not been defined yet. There is consensus on the indication of allogeneic HSCT with myeloablative conditioning for patients who present high risk cytogenetic changes. Allogeneic HSCT is not indicated for low cytogenetic risk 1RC patients and, apparently, allogeneic and autologous HSCT and consolidation chemotherapy are similar for intermediate risk

Proceedings from the National Cancer Institute's Second International Workshop on the Biology, Prevention, and Treatment of Relapse after Hematopoietic Stem Cell Transplantation: Part I. Biology of relapse after transplantation.

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Gress, Ronald E; Miller, Jeffrey S; Battiwalla, Minoo; Bishop, Michael R; Giralt, Sergio A; Hardy, Nancy M; Kröger, Nicolaus; Wayne, Alan S; Landau, Dan A; Wu, Catherine J

2013-11-01

In the National Cancer Institute's Second Workshop on the Biology, Prevention, and Treatment of Relapse after Hematopoietic Stem Cell Transplantation, the Scientific/Educational Session on the Biology of Relapse discussed recent advances in understanding some of the host-, disease-, and transplantation-related contributions to relapse, emphasizing concepts with potential therapeutic implications. Relapse after hematopoietic stem cell transplantation (HSCT) represents tumor escape, from the cytotoxic effects of the conditioning regimen and from immunologic control mediated by reconstituted lymphocyte populations. Factors influencing the biology of the therapeutic graft-versus-malignancy (GVM) effect-and relapse-include conditioning regimen effects on lymphocyte populations and homeostasis, immunologic niches, and the tumor microenvironment; reconstitution of lymphocyte populations and establishment of functional immune competence; and genetic heterogeneity within the malignancy defining potential for clonal escape. Recent developments in T cell and natural killer cell homeostasis and reconstitution are reviewed, with implications for prevention and treatment of relapse, as is the application of modern genome sequencing to defining the biologic basis of GVM, clonal escape, and relapse after HSCT. Published by Elsevier Inc.

Pre-Transplantation Blockade of TNF-α-Mediated Oxygen Species Accumulation Protects Hematopoietic Stem Cells.

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Ishida, Takashi; Suzuki, Sachie; Lai, Chen-Yi; Yamazaki, Satoshi; Kakuta, Shigeru; Iwakura, Yoichiro; Nojima, Masanori; Takeuchi, Yasuo; Higashihara, Masaaki; Nakauchi, Hiromitsu; Otsu, Makoto

2017-04-01

Hematopoietic stem cell (HSC) transplantation (HSCT) for malignancy requires toxic pre-conditioning to maximize anti-tumor effects and donor-HSC engraftment. While this induces bone marrow (BM)-localized inflammation, how this BM environmental change affects transplanted HSCs in vivo remains largely unknown. We here report that, depending on interval between irradiation and HSCT, residence within lethally irradiated recipient BM compromises donor-HSC reconstitution ability. Both in vivo and in vitro we demonstrate that, among inflammatory cytokines, TNF-α plays a role in HSC damage: TNF-α stimulation leads to accumulation of reactive oxygen species (ROS) in highly purified hematopoietic stem/progenitor cells (HSCs/HSPCs). Transplantation of flow-cytometry-sorted murine HSCs reveals damaging effects of accumulated ROS on HSCs. Short-term incubation either with an specific inhibitor of tumor necrosis factor receptor 1 signaling or an antioxidant N-acetyl-L-cysteine (NAC) prevents TNF-α-mediated ROS accumulation in HSCs. Importantly, pre-transplantation exposure to NAC successfully demonstrats protective effects in inflammatory BM on graft-HSCs, exhibiting better reconstitution capability than that of nonprotected control grafts. We thus suggest that in vivo protection of graft-HSCs from BM inflammation is a feasible and attractive approach, which may lead to improved hematopoietic reconstitution kinetics in transplantation with myeloablative conditioning that inevitably causes inflammation in recipient BM. Stem Cells 2017;35:989-1002. © 2016 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Total lymphoid irradiation based conditioning for hematopoietic stem cell transplantation in severe aplastic anemia

International Nuclear Information System (INIS)

Lee, Yun Hee; Kim, Ji Yoon; Choi, Byung Ock; Ryu, Mi Ryeong; Chung, Su Mi

2012-01-01

To retrospectively evaluate the outcome and toxicity of total lymphoid irradiation (TLI) based conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in severe aplastic anemia (SAA) patients who experienced an engraftment failure from prior HSCT or were heavily transfused. Between 1995 and 2006, 20 SAA patients received TLI for conditioning of HSCT. All patients were multi-transfused or had long duration of disease. Fifteen (75%) patients had graft failure from prior HSCT. In 18 (90%) patients, the donors were human leukocyte antigen identical siblings. The stem cell source was the peripheral blood stem cell in 15 (75%) patients. The conditioning regimen was composed of antithymocyte globulin plus TLI with a median dose of 750 cGy in 1 fraction. The graft-versus-host disease (GVHD) prophylaxis used cyclosporine with methotrexate. With a median follow-up of 10.8 years, graft failures developed in 6 patients. Among them, 3 patients received their third HSCT to be engrafted finally. The Kaplan-Meier overall survival rate was 85.0% and 83.1% at 5 and 10 years, respectively. The incidence of acute and chronic GVHD was 20% and 20%, respectively. None of the patients have developed a malignancy after HSCT. In our study, TLI based conditioning in allogeneic HSCT was feasible with acceptable rates of GVHD in SAA patients who experienced graft failure from prior HSCT or was at a high risk of graft rejection. We achieved relatively better results of engraftment and survival with a long term follow-up.

Total lymphoid irradiation based conditioning for hematopoietic stem cell transplantation in severe aplastic anemia

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Lee, Yun Hee; Kim, Ji Yoon; Choi, Byung Ock; Ryu, Mi Ryeong; Chung, Su Mi [Dept. of Radiation Oncology, The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

2012-12-15

To retrospectively evaluate the outcome and toxicity of total lymphoid irradiation (TLI) based conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in severe aplastic anemia (SAA) patients who experienced an engraftment failure from prior HSCT or were heavily transfused. Between 1995 and 2006, 20 SAA patients received TLI for conditioning of HSCT. All patients were multi-transfused or had long duration of disease. Fifteen (75%) patients had graft failure from prior HSCT. In 18 (90%) patients, the donors were human leukocyte antigen identical siblings. The stem cell source was the peripheral blood stem cell in 15 (75%) patients. The conditioning regimen was composed of antithymocyte globulin plus TLI with a median dose of 750 cGy in 1 fraction. The graft-versus-host disease (GVHD) prophylaxis used cyclosporine with methotrexate. With a median follow-up of 10.8 years, graft failures developed in 6 patients. Among them, 3 patients received their third HSCT to be engrafted finally. The Kaplan-Meier overall survival rate was 85.0% and 83.1% at 5 and 10 years, respectively. The incidence of acute and chronic GVHD was 20% and 20%, respectively. None of the patients have developed a malignancy after HSCT. In our study, TLI based conditioning in allogeneic HSCT was feasible with acceptable rates of GVHD in SAA patients who experienced graft failure from prior HSCT or was at a high risk of graft rejection. We achieved relatively better results of engraftment and survival with a long term follow-up.

Identification of Heme Oxygenase-1 as a Novel Predictor of Hematopoietic Stem Cell Transplantation Outcomes in Acute Leukemia

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Yinghao Lu

2016-09-01

Full Text Available Objective: The main aim of this study was to determine the correlation between clinical outcome and heme oxygenase-1 (HO-1 expression before and after hematopoietic stem cell transplantation (HSCT in acute leukemia. Methods: HO-1 mRNA levels in 83 patients were measured using qRT-PCR. In a comparative analysis of HO-1 levels in relation to different post-transplant outcomes, the HO-1 threshold, determined via the receiver operating characteristic (ROC curve, was effectively used to predict clinical relapse and acute graft-versus-host disease (aGVHD. The correlations among clinical relapse, aGVHD and HO-1 expression were analyzed based on this threshold. Results: Leukemia risk stratification and relative expression of HO-1 before pretreatment had significant effects on clinical relapse. Leukemia risk stratification, relative expression of HO-1 after HSCT and the interval from diagnosis to transplantation had a significant influence on aGVHD. Both relapse and aGVHD appeared to be associated with relative HO-1 expression. The relative expression rate of HO-1 was 1.131-1.186 before pretreatment, and strongly associated with post-transplantation relapse. The relative expression rate of HO-1 was 1.102-1.144 after transplantation, and closely related to aGVHD. ROC curve analysis revealed high specificity and sensitivity of HO-1 expression in predicting relapse and aGVHD after allo-HSCT. Conclusions: HO-1 expression can be effectively used as a predictor of relapse as well as a diagnostic factor of aGVHD after transplantation for allo-HSCT patients with acute leukemia.

Neurological complications of hematopoietic stem cell transplantation (HSCT: a retrospective study in a HSCT center in Brazil Complicações neurológicas do transplante de células tronco hematopoiéticas (TCTH: estudo retrospectivo em um centro de TCTH no Brasil

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Hélio A.G. Teive

2008-01-01

Full Text Available We present the neurological complications evaluated in a series of 1000 patients who underwent hematopoietic stem cell transplantation (HSCT. Central nervous system (CNS neurological complications, particularly brain hemorrhages, were the most common, followed by seizures and CNS infections. An unusual neurological complication was Wernicke's encephalopathy. Less frequent neurological complications were metabolic encephalopathy, neuroleptic malignant syndrome, reversible posterior leukoencephalopathy syndrome, brain infarct and movement disorders. The most common neurological complication of the peripheral nervous system was herpes zoster radiculopathy, while peripheral neuropathies, inflammatory myopathy and myotonia were very rarely found.Apresentamos as complicações neurológicas avaliadas em uma série de 1000 pacientes submetidos ao transplante de células tronco hematopoiéticas (TCTH. As complicações neurológicas do sistema nervoso central foram as mais encontradas, particularmente as hemorragias encefálicas, seguidas por crises convulsivas e por infecções. Uma complicação peculiar foi a encefalopatia de Wernicke. Menos freqüentemente foram encontrados casos de encefalopatia metabólica, síndrome maligna neuroléptica, leucoencefalopatia posterior reversível, infarto cerebral e os distúrbios do movimento. Entre as complicações neurológicas do sistema nervoso periférico a mais encontrada foi a radiculopatia pelo herpes zoster, enquanto que raramente se observaram casos de polineuropatias periféricas, miopatia inflamatória e de miotonia.

The effects of hematopoietic stem cell transplant on splenic extramedullary hematopoiesis in patients with myeloproliferative neoplasm-associated myelofibrosis.

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Pizzi, Marco; Gergis, Usama; Chaviano, Felicia; Orazi, Attilio

2016-09-01

Hematopoietic stem cell transplant (HSCT) is the only curative treatment for myeloproliferative neoplasm-associated myelofibrosis (MPN-MF). The main clinical manifestation of MPN-MF is splenomegaly secondary to extramedullary hematopoiesis (EMH). The effects of HSCT on splenic EMH and associated vascular and stromal changes are unknown. This study compares the findings seen in spleens following HSCT with those of nontransplanted patients, normal controls, and matched bone marrow (BM) samples. This study included three transplanted MPN-MF spleens, three nontransplanted MPN-MF spleens, and three normal controls. Spleens were assessed for: (a) presence/extent of EMH; (b) presence of Gamna-Gandy bodies; (c) splenic fibrosis; (d) CD34-positive microvessel density; (e) CD8-positive sinusoids; (f) frequency of smooth muscle actin-positive myoid cells; and (g) nerve growth factor receptor-positive adventitial reticulum cells. In two cases, matched BM samples were assessed for cellularity, presence of atypical megakaryocytes, and fibrosis. Compared with normal controls, all MPN-MF spleens were larger in size, had EMH, red pulp fibrosis, higher CD34-positive microvessel density, and decreased CD8-positive sinusoids. Compared with nontransplanted cases, post-HSCT spleens showed disappearance or reduction of EMH. Gamna-Gandy bodies were increased; no differences in the remaining parameters were found. A reduction of splenic EMH was associated with normalization of BM cellularity and megakaryopoiesis. HSCT reduces/abrogates splenic EMH and is associated with an increased number of Gamna-Gandy bodies, which may suggest vascular damage. The lack of stromal changes in spleens removed shortly after transplant is in line with similar observations in the BM, where a longer interval is often necessary for resolution of fibrosis. Copyright © 2016 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.

Herpesvirus-associated central nervous system diseases after allogeneic hematopoietic stem cell transplantation.

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Wu, Meiqing; Huang, Fen; Jiang, Xinmiao; Fan, Zhiping; Zhou, Hongsheng; Liu, Can; Jiang, Qianli; Zhang, Yu; Zhao, Ke; Xuan, Li; Zhai, Xiao; Zhang, Fuhua; Yin, Changxin; Sun, Jing; Feng, Ru; Liu, Qifa

2013-01-01

Herpesvirus infections of the central nervous system (CNS) are associated with encephalitis/myelitis and lymphoproliferative diseases in immunocompromised individuals. As of now, data of herpesvirus-associated CNS diseases in transplant recipients is limited. Hence, in this prospective study, we investigated the incidence of herpesvirus-associated CNS diseases and explored the diagnosis of these diseases in 281 allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Herpesvirus-DNA and cerebrospinal fluid (CSF) cells were sampled from 58 recipients with herpesvirus-associated diseases or with unexplainable CNS manifestations. Results showed that 23 patients were diagnosed as herpesvirus-associated CNS diseases, including 15 Epstein-Barr virus (EBV)-associated diseases (4 encephalitis and 11 lymphoproliferative diseases), 5 herpes simplex virus type 1 encephalitis, 2 cytomegalovirus encephalitis/myelitis and 1 varicella zoster virus encephalitis. The median time of diseases onset was 65 (range 22-542) days post-transplantation. The 3-year cumulative incidence of herpesvirus-associated encephalitis/myelitis and post-transplant lymphoproliferative disorder (PTLD) was 6.3% ± 1.9% and 4.1% ± 1.2%, respectively. Of the evaluable cases, CSF cells mainly consisted of CD19(+)CD20(+) B cells (7/11) and had clonal rearrangement of immunoglobulin genes (3/11) in patients with CNS-PTLD. On the contrary, in patients with encephalitis/myelitis, CSF cells were comprised of different cell populations and none of the gene rearrangement was detected. Herpesvirus-associated CNS diseases are common in the early stages of allo-HSCT, wherein EBV is the most frequent causative virus. The immunophenotypic and clonal analysis of CSF cells might be helpful in the differential diagnosis between encephalitis and lymphoproliferative diseases.

Disturbances in dental development and craniofacial growth in children treated with hematopoietic stem cell transplantation.

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Vesterbacka, M; Ringdén, O; Remberger, M; Huggare, J; Dahllöf, G

2012-02-01

To investigate the correlation between age, degree of disturbances in dental development, and vertical growth of the face in children treated with hematopoietic stem cell transplantation (HSCT). 39 long-term survivors of HSCT performed in childhood and transplanted before the age of 12, at a mean age of 6.8±3.3 years. Panoramic and cephalometric radiographs were taken at a mean age of 16.2 years. For each patient two age- and sex-matched healthy controls were included. The area of three mandibular teeth was measured and a cephalometric analysis was performed. The mean area of the mandibular central incisor, first and second molar was significantly smaller in the HSCT group, and the vertical growth of the face was significantly reduced, especially in the lower third, compared to healthy controls. A statistically significant correlation between age at HSCT, degree of disturbances in dental development, and vertical growth of the face was found. Children subjected to pre-HSCT chemotherapy protocols had significantly more growth reduction in vertical craniofacial variables compared to children without pre-HSCT chemotherapy. Conditioning regimens including busulfan or total body irradiation had similar deleterious effects on tooth area reduction and craniofacial parameters. The younger the child is at HSCT, the greater the impairment in dental and vertical facial development. This supports the suggestion that the reduction in lower facial height found in SCT children mainly is a result of impaired dental development and that young age is a risk factor for more severe disturbances. © 2012 John Wiley & Sons A/S.

Comprehensive evaluation of nutritional status before and after hematopoietic stem cell transplantation in 170 patients with hematological diseases.

Science.gov (United States)

Liu, Peng; Wang, Boshi; Yan, Xia; Cai, Jingjing; Wang, Yu

2016-12-01

To investigate the nutritional status of patients before and after hematopoietic stem cell transplantation (HSCT), and explore optimal methods for assessing nutritional status in patients with hematological diseases. This cohort study enrolled 170 patients who were diagnosed with hematological diseases and underwent allogeneic HSCT in the Department of Hematology, Peking University People's Hospital between May 2011 and April 2013. We used fixed-point continuous sampling and four nutritional screening tools, Nutritional Risk Screening 2002 (NRS-2002), Mini Nutritional Assessment (MNA), Subjective Global Assessment (SGA) and Malnutrition Universal Screening Tools (MUST), in combination with body measurements, to extensively screen and evaluate nutritional risks and status in patients receiving HSCT before entering and after leaving laminar air flow rooms. After HSCT, patients had significant reduction in weight, hip circumference, waist-hip ratio, calf circumference, mid-upper arm circumference, and suprailiac skinfold thickness compared with pre-HSCT measurements. Before HSCT, NRS-2002 identified that 21.2% of patients were at nutritional risks, compared with 100% after HSCT. MUST indicated that before HSCT, 11.77% of patients were at high nutritional risk, compared with 59.63% after HSCT. MNA assessed that 0.06% of patients were malnourished before HSCT, compared with 19.27% after HSCT. SGA identified that before HSCT, 1.76% of patients had mild to severe malnutrition, which increased to 83.3% after HSCT. There is a significant increase in the nutritional risk and malnutrition in patients who received HSCT. Before HSCT, some patients already had nutritional risk or nutritional deficiencies, and prompt and close nutritional screening or assessment should be performed. The nutritional status of patients after HSCT was generally deteriorated compared with that before transplantation. Body measurements should be taken more frequently during the subsequent treatment

[Distribution of Pathogenic Bacteria and Its Influence on Expression of BCL-2 and BAX Protein after HSCT in the Patients with Hematological Malignancies].

Science.gov (United States)

Su, Gui-Ping; Dai, Yan; Huang, Lai-Quan; Jiang, Yi-Zhi; Geng, Liang-Quan; Ding, Kai-Yang; Huang, Dong-Ping

2016-06-01

To investigate the distribution of pathogenic bacteria in the patients with hematologic malignancies received hematopoietic stem cell transplantation (HSCT) and its influence on the expression of BCL-2 and BAX proteins. The clinical data of 64 patients with malignant lymphoma (ML) received auto-HSCT from January 2011 to December 2015 in our hospital were analyzed. On basis of post-treansplant infection, the patients were divided into infection group (36 cases) and non-infection group (28 cases). The distribution of pathogenic bacteria in 2 groups was identified, the T lymphocyte subsets of peripheral blood, expression level of apoptotic proteins and C-reaction protein (CRP) in 2 group were detected. Thirty-six strains of pathogenic bacteria were isolated from 36 case of hematological malignancy after HSCT, including 24 strains of Gram-negative bacteria (66.67%) with predominamce of klebsiella pneumoniae (19.44%). The periperal blood CD4+ (t=2.637, Ppathogenic bacteria infecting ML patients after HSCT were mainly Gram-negative bacteria. The post-transplant infection can promote the expression up-regulation of related inflammatory factors and apoptotic proteins. The pathogens may be involved in cell apoptisis that provides a new strategy to treat the hematologic malignancies.

Early highly aggressive MS successfully treated by hematopoietic stem cell transplantation

DEFF Research Database (Denmark)

Fagius, J.; Lundgren, J.; Oberg, G.

2009-01-01

BACKGROUND: During the last 15 years, high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HSCT) has globally been performed for severe multiple sclerosis (MS). Most patients have been in progressive phase with long disease duration. As a rule, treatment effect has been...... minor or moderate. PATIENTS: Since 2004, we have performed HSCT in nine young patients with "malignant" relapsing-remitting MS. Criteria for treatment were short duration of disease; very frequent, severe relapses; recent improvement periods indicating potential for recovery after strong...... immunosuppression. FINDINGS: Median age at treatment was 27 (range 9-34) years, MS duration 26 (4-100) months, and annualized relapse rate 10 (4-12). Median Disability Status Scale (extended disability status scale, EDSS) at HSCT was 7.0 (3.5-8.0). Median follow-up time April 2008 is 29 (23-47) months. Median EDSS...

Allogeneic Hematopoietic Stem Cell Transplantation Is an Effective Salvage Therapy for Patients with Chronic Myeloid Leukemia Presenting with Advanced Disease or Failing Treatment with Tyrosine Kinase Inhibitors.

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Nair, Anish P; Barnett, Michael J; Broady, Raewyn C; Hogge, Donna E; Song, Kevin W; Toze, Cynthia L; Nantel, Stephen H; Power, Maryse M; Sutherland, Heather J; Nevill, Thomas J; Abou Mourad, Yasser; Narayanan, Sujaatha; Gerrie, Alina S; Forrest, Donna L

2015-08-01

Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only known curative therapy for chronic myeloid leukemia (CML); however, it is rarely utilized given the excellent long-term results with tyrosine kinase inhibitor (TKI) treatment. The purpose of this study is to examine HSCT outcomes for patients with CML who failed TKI therapy or presented in advanced phase and to identify predictors of survival, relapse, and nonrelapse mortality (NRM). Fifty-one patients with CML underwent HSCT for advanced disease at diagnosis (n = 15), TKI resistance as defined by the European LeukemiaNet guidelines (n = 30), TKI intolerance (n = 2), or physician preference (n = 4). At a median follow-up of 71.9 months, the 8-year overall survival (OS), event-free survival (EFS), relapse, and NRM were 68%, 46%, 41%, and 23%, respectively. In univariate analysis, predictors of OS included first chronic phase (CP1) disease status at HSCT (P = .0005), European Society for Blood and Marrow Transplantation score 1 to 4 (P = .04), and complete molecular response (CMR) to HSCT (P treatment to optimize transplantation outcomes. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

State-of-the-art fertility preservation in children and adolescents undergoing haematopoietic stem cell transplantation

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Dalle, J-H; Lucchini, G; Balduzzi, A

2017-01-01

Nowadays, allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a well-established treatment procedure and often the only cure for many patients with malignant and non-malignant diseases. Decrease in short-term complications has substantially contributed to increased survival. Theref...

Strange Bedfellows No More: How Integrated Stem-Cell Transplantation and Palliative Care Programs Can Together Improve End-of-Life Care.

Science.gov (United States)

Levine, Deena R; Baker, Justin N; Wolfe, Joanne; Lehmann, Leslie E; Ullrich, Christina

2017-09-01

In the intense, cure-oriented setting of hematopoietic stem-cell transplantation (HSCT), delivery of high-quality palliative and end-of-life care is a unique challenge. Although HSCT affords patients a chance for cure, it carries a significant risk of morbidity and mortality. During HSCT, patients usually experience high symptom burden and a significant decrease in quality of life that can persist for long periods. When morbidity is high and the chance of cure remote, the tendency after HSCT is to continue intensive medical interventions with curative intent. The nature of the complications and overall condition of some patients may render survival an unrealistic goal and, as such, continuation of artificial life-sustaining measures in these patients may prolong suffering and preclude patient and family preparation for end of life. Palliative care focuses on the well-being of patients with life-threatening conditions and their families, irrespective of the goals of care or anticipated outcome. Although not inherently at odds with HSCT, palliative care historically has been rarely offered to HSCT recipients. Recent evidence suggests that HSCT recipients would benefit from collaborative efforts between HSCT and palliative care services, particularly when initiated early in the transplantation course. We review palliative and end-of-life care in HSCT and present models for integrating palliative care into HSCT care. With open communication, respect for roles, and a spirit of collaboration, HSCT and palliative care can effectively join forces to provide high-quality, multidisciplinary care for these highly vulnerable patients and their families.

Prospective study establishing a management plan for impacted third molar in patients undergoing hematopoietic stem cell transplantation

OpenAIRE

Yamagata, Kenji; Onizawa, Kojiro; Yanagawa, Toru; Takeuchi, Yasutoshi; Hasegawa, Yuichi; Chiba, Shigeru; Bukawa, Hiroki

2011-01-01

ObjectiveAlthough dental treatment before hematopoietic stem cell transplantation (HSCT) is essential to prevent serious infections from oral sources, the best management plan for impacted third molar (ITM) is unclear.Study designThis study was planned to establish a management plan for ITM. Eighty-four candidates for HSCT therapy were consecutively enrolled in the prospective trial. The management plan, which was evidence based and prospectively decided, was to extract the symptomatic ITMs a...

Impact of oral gut decontamination on Staphylococcus aureus colonisation in patients undergoing allogeneic haematopoietic stem cell transplantation.

Science.gov (United States)

Wilk, C Matthias; Weber, Isabel; Seidl, Kati; Rachmühl, Carole; Holzmann-Bürgel, Anne; Müller, Antonia M S; Kuster, Stefan P; Schanz, Urs; Zinkernagel, Annelies S

2017-12-01

Recipients of allogeneic haematopoietic stem cell transplantation (allo-HSCT) are severely immunocompromised and are at increased risk of infection. In this prospective, observational, single-centre study including 110 allo-HSCT recipients, the rate of Staphylococcus aureus colonisation was reduced from 11.8% to 0% (P <0.001) following peritransplant oral gut decontamination. No invasive S. aureus infections were observed. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Signal one and two blockade are both critical for non-myeloablative murine HSCT across a major histocompatibility complex barrier.

Directory of Open Access Journals (Sweden)

Kia J Langford-Smith

Full Text Available Non-myeloablative allogeneic haematopoietic stem cell transplantation (HSCT is rarely achievable clinically, except where donor cells have selective advantages. Murine non-myeloablative conditioning regimens have limited clinical success, partly through use of clinically unachievable cell doses or strain combinations permitting allograft acceptance using immunosuppression alone. We found that reducing busulfan conditioning in murine syngeneic HSCT, increases bone marrow (BM:blood SDF-1 ratio and total donor cells homing to BM, but reduces the proportion of donor cells engrafting. Despite this, syngeneic engraftment is achievable with non-myeloablative busulfan (25 mg/kg and higher cell doses induce increased chimerism. Therefore we investigated regimens promoting initial donor cell engraftment in the major histocompatibility complex barrier mismatched CBA to C57BL/6 allo-transplant model. This requires full myeloablation and immunosuppression with non-depleting anti-CD4/CD8 blocking antibodies to achieve engraftment of low cell doses, and rejects with reduced intensity conditioning (≤75 mg/kg busulfan. We compared increased antibody treatment, G-CSF, niche disruption and high cell dose, using reduced intensity busulfan and CD4/8 blockade in this model. Most treatments increased initial donor engraftment, but only addition of co-stimulatory blockade permitted long-term engraftment with reduced intensity or non-myeloablative conditioning, suggesting that signal 1 and 2 T-cell blockade is more important than early BM niche engraftment for transplant success.

Signal one and two blockade are both critical for non-myeloablative murine HSCT across a major histocompatibility complex barrier.

Science.gov (United States)

Langford-Smith, Kia J; Sandiford, Zara; Langford-Smith, Alex; Wilkinson, Fiona L; Jones, Simon A; Wraith, J Ed; Wynn, Robert F; Bigger, Brian W

2013-01-01

Non-myeloablative allogeneic haematopoietic stem cell transplantation (HSCT) is rarely achievable clinically, except where donor cells have selective advantages. Murine non-myeloablative conditioning regimens have limited clinical success, partly through use of clinically unachievable cell doses or strain combinations permitting allograft acceptance using immunosuppression alone. We found that reducing busulfan conditioning in murine syngeneic HSCT, increases bone marrow (BM):blood SDF-1 ratio and total donor cells homing to BM, but reduces the proportion of donor cells engrafting. Despite this, syngeneic engraftment is achievable with non-myeloablative busulfan (25 mg/kg) and higher cell doses induce increased chimerism. Therefore we investigated regimens promoting initial donor cell engraftment in the major histocompatibility complex barrier mismatched CBA to C57BL/6 allo-transplant model. This requires full myeloablation and immunosuppression with non-depleting anti-CD4/CD8 blocking antibodies to achieve engraftment of low cell doses, and rejects with reduced intensity conditioning (≤75 mg/kg busulfan). We compared increased antibody treatment, G-CSF, niche disruption and high cell dose, using reduced intensity busulfan and CD4/8 blockade in this model. Most treatments increased initial donor engraftment, but only addition of co-stimulatory blockade permitted long-term engraftment with reduced intensity or non-myeloablative conditioning, suggesting that signal 1 and 2 T-cell blockade is more important than early BM niche engraftment for transplant success.

Hematopoietic stem cell transplantation in children and young adults with secondary myelodysplastic syndrome and acute myelogenous leukemia after aplastic anemia.

Science.gov (United States)

Yoshimi, Ayami; Strahm, Brigitte; Baumann, Irith; Furlan, Ingrid; Schwarz, Stephan; Teigler-Schlegel, Andrea; Walther, Joachim-Ulrich; Schlegelberger, Brigitte; Göhring, Gudrun; Nöllke, Peter; Führer, Monika; Niemeyer, Charlotte M

2014-03-01

Secondary myelodysplastic syndrome and acute myelogenous leukemia (sMDS/sAML) are the most serious secondary events occurring after immunosuppressive therapy in patients with aplastic anemia. Here we evaluate the outcome of hematopoietic stem cell transplantation (HSCT) in 17 children and young adults with sMDS/sAML after childhood aplastic anemia. The median interval between the diagnosis of aplastic anemia and the development of sMDS/sAML was 2.9 years (range, 1.2 to 13.0 years). At a median age of 13.1 years (range, 4.4 to 26.7 years), patients underwent HSCT with bone marrow (n = 6) or peripheral blood stem cell (n = 11) grafts from HLA-matched sibling donors (n = 2), mismatched family donors (n = 2), or unrelated donors (n = 13). Monosomy 7 was detected in 13 patients. The preparative regimen consisted of busulfan, cyclophosphamide, and melphalan in 11 patients and other agents in 6 patients. All patients achieved neutrophil engraftment. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 47%, and that of chronic GVHD was 70%. Relapse occurred in 1 patient. The major cause of death was transplant-related complication (n = 9). Overall survival and event-free survival at 5 years after HSCT were both 41%. In summary, this study indicates that HSCT is a curative therapy for some patients with sMDS/sAML after aplastic anemia. Future efforts should focus on reducing transplantation-related mortality. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Impact of Allogeneic Stem Cell Transplantation in First Complete Remission in Acute Myeloid Leukemia

DEFF Research Database (Denmark)

Østgård, Lene Sofie Granfeldt; Lund, Jennifer L; Nørgaard, Jan Maxwell

2018-01-01

To examine the outcome of allogeneic stem cell transplantation (HSCT) in first complete remission (CR1) compared to chemotherapy alone in a population-based setting, we identified a cohort of acute myeloid leukemia (AML) patients aged 15-70 years diagnosed between 2000-2014 in Denmark. Using...... the Danish National Acute Leukemia Registry, we compared relapse risk, relapse-free survival (RFS), and overall survival between patients with non-favorable cytogenetic features receiving post-remission therapy with conventional chemotherapy-only versus those undergoing HSCT in CR1. To minimize immortal time...

Pre-emptive rituximab for Epstein-Barr virus reactivation after haplo-hematopoietic stem cell transplantation.

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Kobayashi, Shogo; Sano, Hideki; Mochizuki, Kazuhiro; Ohara, Yoshihiro; Takahashi, Nobuhisa; Ohto, Hitoshi; Kikuta, Atsushi

2017-09-01

Epstein-Barr virus-related post-transplantation lymphoproliferative disease (EBV-PTLD) is a serious complication in hematopoietic stem cell transplantation (HSCT) recipients. We conducted a retrospective study to investigate the incidence and potential risk factors for EBV reactivation and to assess the efficacy of the management of EBV reactivation with pre-emptive rituximab in children who had T-cell-replete haploidentical HSCT (TCR-haplo-SCT) with low-dose anti-thymocyte globulin (ATG). EBV-DNA level in peripheral blood (PB) was measured when suspected EBV reactivation were observed. When the EBV-DNA level in PB increased to >1,000 copies/10 6 peripheral blood mononuclear cells (PBMC), patients were pre-emptively treated with rituximab (375 mg/m 2 /dose). A total of 19 (50%) of 38 patients received rituximab infusion at a median time of 56 days after HSCT (range, 17-270 days). The median viral load at initiation of therapy was 2,900 copies/10 6 PBMC (range, 1,000-650 000). Pre-emptive therapy was started after a median of 2 days (range, 0-7 days). The median number of weekly treatment cycles was 2 (range, 1-3). None of the patients developed PTLD or other EBV-associated diseases. Pre-emptive rituximab therapy could be a useful strategy for EBV-PTLD in TCR-haplo-SCT recipients with low-dose ATG. © 2017 Japan Pediatric Society.

Hematopoietic stem cell transplantation from unrelated donors in children with DOCK8 deficiency.

Science.gov (United States)

Uygun, Dilara Fatma K; Uygun, Vedat; Reisli, İsmail; Keleş, Sevgi; Özen, Ahmet; Yılmaz, Mustafa; Sayar, Esra H; Daloğlu, Hayriye; Öztürkmen, Seda I; Çakı, Suar; Karasu, Gülsün T; Yeşilipek, Akif

2017-11-01

DIDS is a unique form of combined immune deficiency characterized by an unusual susceptibility to cutaneous viral infections, severe allergies with eosinophilia and elevated immunoglobulin E titers, autoimmunity, and cancer. HSCT is considered the standard of care for this deadly disease. We have retrospectively analyzed the outcome of allogeneic HSCT from unrelated donors in patients with DIDS. Data from four patients, with five transplants, are presented. All patients received transplants from unrelated donors' BM, except for one patient who received a cord blood transplant. The conditioning regimens were based on myeloablative protocols for BM derived transplants; a NM regimen was pursued for the patient who received a cord blood transplant, which resulted in graft rejection. Although recurrent pneumonia and skin infections resolved immediately after transplantation, all patients subsequently developed human herpesvirus infection, including cutaneous herpetic lesions, cytomegalovirus reactivation, and zona zoster, which could be attributed to the use of ATG. Despite the presence of serious morbidities prior to transplantation, all patients recovered successfully. DIDS can be successfully treated with allogeneic HSCT from unrelated donors following a myeloablative conditioning regimen, with a reasonable safety profile. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prolonged Survival of a Refractory Acute Myeloid Leukemia Patient after a Third Hematopoietic Stem Cell Transplantation with Umbilical Cord Blood following a Second Relapse

Directory of Open Access Journals (Sweden)

Suk-young Lee

2014-01-01

Full Text Available Although hematopoietic stem cell transplantation (HSCT has been considered to be the only way for potential cure of relapsed acute myeloid leukemia (AML, there has been no report on a third HSCT in patients with multiple relapsed AML. Here, we report a case of 53-year-old female who received a successful third allogeneic HSCT after relapse of AML following a second allogeneic HSCT. She was treated with a toxicity reduced conditioning regimen and received direct intrabone cord blood transplantation (CBT using a single unit of 5/6 HLA-matched cord blood as a graft source. Graft-versus-host disease prophylaxis was performed with a single agent of tacrolimus to increase graft-versus-leukemia effect. She is in remission for 8 months since the direct intrabone CBT. This report highlights not only the importance of individually adjusted approach but also the need for further investigation on the role of HSCT as a treatment modality in patients with refractory or multiple relapsed AML.

Safety and effects of prophylactic defibrotide for sinusoidal obstruction syndrome in hematopoietic stem cell transplantation.

Science.gov (United States)

Park, Meerim; Park, Hyeon Jin; Eom, Hyeon-Seok; Kwon, Young Joo; Park, Jeong A; Lim, Yeon Jung; Yoon, Jong Hyung; Kong, Sun-Young; Ghim, Thad T; Lee, Hye Won; Yun, Tak; Park, Byung-Kiu

2013-01-28

Sinusoidal obstruction syndrome (SOS) is a serious complication of hematopoietic stem cell transplantation (HSCT), with a mortality rate of up to 90%. We report our experience on the use of defibrotide for SOS prophylaxis in HSCT. We retrospectively reviewed data of 49 patients who received defibrotide as SOS prophylaxis during the course of HSCT at the National Cancer Center, Goyang, Korea, between August 2005 and July 2008. Thirty-four patients (69.4%) were classified as a high-risk group for developing SOS. Defibrotide was well-tolerated, without any grade 3 or 4 toxicity. The median value of maximum total bilirubin within 100 days after HSCT was within the normal range. SOS was diagnosed in only 1 patient, who underwent autologous HSCT due to relapsed medulloblastoma. There was no day 100 treatment-related mortality in our study. Defibrotide appears to be a safe prophylaxis for SOS. This study suggests that it could be effective to use prophylactic defibrotide in advance to improve HSCT outcomes in patients at risk of SOS.

Impact of cytomegalovirus reactivation on relapse and survival in patients with acute leukemia who received allogeneic hematopoietic stem cell transplantation in first remission

OpenAIRE

Yoon, Jae-Ho; Lee, Seok; Kim, Hee-Je; Jeon, Young-Woo; Lee, Sung-Eun; Cho, Byung-Sik; Lee, Dong-Gun; Eom, Ki-Seong; Kim, Yoo-Jin; Min, Chang-Ki; Cho, Seok-Goo; Min, Woo-Sung; Lee, Jong Wook

2016-01-01

Cytomegalovirus (CMV)-reactivation is associated with graft-vs-leukemia (GVL) effect by stimulating natural-killer or T-cells, which showed leukemia relapse prevention after hematopoietic stem cell transplantation (HSCT). We enrolled patients with acute myeloid leukemia (n = 197) and acute lymphoid leukemia (n = 192) who underwent allogeneic-HSCT in first remission. We measured RQ-PCR weekly to detect CMV-reactivation and preemptively used ganciclovir (GCV) when the titer increased twice cons...

Where does allogeneic stem cell transplantation fit in the treatment of chronic lymphocytic leukemia?

Science.gov (United States)

Dreger, Peter; Montserrat, Emili

2015-03-01

Allogeneic hematopoietic stem cell transplantation (alloHSCT) has been considered as the treatment of choice for patients with high-risk chronic lymphocytic leukemia (CLL) (i.e., refractory to purine analogs, short response (CLL treatment armamentarium. These signal transduction inhibitors (STI) will change the algorithms of high-risk CLL (HR-CLL) management. Despite the limited body of evidence, there is sufficient rationale for withholding alloHSCT in patients with 17p-/TP53mut CLL in first remission. In contrast, the perspectives of patients with relapsed 17p-/TP53mut CLL remain uncertain even if responding to STI. The same accounts for patients with HR-CLL progressing under STI. In both scenarios, it is reasonable to consider alloHSCT, ideally after response to alternative STI regimens.

Hematopoietic stem cell transplantation in Switzerland: a comprehensive quality control report on centre effect.

Science.gov (United States)

Passweg, Jakob; Baldomero, Helen; Stern, Martin; Bargetzi, Mario; Ghielmini, Michele; Leibundgut, Kurt; Duchosal, Michel; Hess, Urs; Seger, Reinhard; Buhrfeind, Eva; Schanz, Urs; Gratwohl, Alois

2010-06-12

Interest groups advocate centre-specific outcome data as a useful tool for patients in choosing a hospital for their treatment and for decision-making by politicians and the insurance industry. Haematopoietic stem cell transplantation (HSCT) requires significant infrastructure and represents a cost-intensive procedure. It therefore qualifies as a prime target for such a policy. We made use of the comprehensive database of the Swiss Blood Stem Cells Transplant Group (SBST) to evaluate potential use of mortality rates. Nine institutions reported a total of 4717 HSCT - 1427 allogeneic (30.3%), 3290 autologous (69.7%) - in 3808 patients between the years 1997 and 2008. Data were analysed for survival- and transplantation-related mortality (TRM) at day 100 and at 5 years. The data showed marked and significant differences between centres in unadjusted analyses. These differences were absent or marginal when the results were adjusted for disease, year of transplant and the EBMT risk score (a score incorporating patient age, disease stage, time interval between diagnosis and transplantation, and, for allogeneic transplants, donor type and donor-recipient gender combination) in a multivariable analysis. These data indicate comparable quality among centres in Switzerland. They show that comparison of crude centre-specific outcome data without adjustment for the patient mix may be misleading. Mandatory data collection and systematic review of all cases within a comprehensive quality management system might, in contrast, serve as a model to ascertain the quality of other cost-intensive therapies in Switzerland.

The role of iron in patients after bone marrow transplantation.

NARCIS (Netherlands)

Witte, T.J.M. de

2008-01-01

Haemopoietic stem cell transplantation (HSCT) is an important intervention for malignant and non-malignant blood diseases. However, HSCT is also associated with considerable morbidity and mortality, some of which may be related to iron overload. Levels of serum iron are elevated in patients

Immune Reconstitution After Autologous Hematopoietic Stem Cell Transplantation in Crohn’s Disease: Current Status and Future Directions. A Review on Behalf of the EBMT Autoimmune Diseases Working Party and the Autologous Stem Cell Transplantation In Refractory CD—Low Intensity Therapy Evaluation Study Investigators

Directory of Open Access Journals (Sweden)

Alan Graham Pockley

2018-04-01

Full Text Available Patients with treatment refractory Crohn’s disease (CD suffer debilitating symptoms, poor quality of life, and reduced work productivity. Surgery to resect inflamed and fibrotic intestine may mandate creation of a stoma and is often declined by patients. Such patients continue to be exposed to medical therapy that is ineffective, often expensive and still associated with a burden of adverse effects. Over the last two decades, autologous hematopoietic stem cell transplantation (auto-HSCT has emerged as a promising treatment option for patients with severe autoimmune diseases (ADs. Mechanistic studies have provided proof of concept that auto-HSCT can restore immunological tolerance in chronic autoimmunity via the eradication of pathological immune responses and a profound reconfiguration of the immune system. Herein, we review current experience of auto-HSCT for the treatment of CD as well as approaches that have been used to monitor immune reconstitution following auto-HSCT in patients with ADs, including CD. We also detail immune reconstitution studies that have been integrated into the randomized controlled Autologous Stem cell Transplantation In refractory CD—Low Intensity Therapy Evaluation trial, which is designed to test the hypothesis that auto-HSCT using reduced intensity mobilization and conditioning regimens will be a safe and effective means of inducing sustained control in refractory CD compared to standard of care. Immunological profiling will generate insight into the pathogenesis of the disease, restoration of responsiveness to anti-TNF therapy in patients with recurrence of endoscopic disease and immunological events that precede the onset of disease in patients that relapse after auto-HSCT.

Small airways dysfunction in long-term survivors of pediatric stem cell transplantation

DEFF Research Database (Denmark)

Uhlving, Hilde Hylland; Mathiesen, Sidsel; Buchvald, Frederik

2015-01-01

BACKGROUND: Chronic graft-versus-host disease (cGvHD) in the lungs is a life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT). Pulmonary cGvHD is initiated in the peripheral airways, and diagnosis may be delayed by low sensitivity of standard pulmonary function...... performed spirometry, whole-body plethysmography and MBWN2 . From MBWN2 the lung clearance index (LCI) and indices reflecting ventilation inhomogeneity arising close to the acinar lung zone (Sacin ) and in the conductive airway zone (Scond ) were derived. Subjective respiratory morbidity was assessed using...... tests. Multiple breath nitrogen washout (MBWN2 ) is a promising, sensitive method to assess small airways function. This is the first report on MBWN2 in survivors of pediatric HSCT. METHODS: This cross-sectional study undertaken 3-10 years post-HSCT, included 64 patients and 64 matched controls who all...

Outcome of children with high-risk acute myeloid leukemia given autologous or allogeneic hematopoietic cell transplantation in the aieop AML-2002/01 study.

Science.gov (United States)

Locatelli, F; Masetti, R; Rondelli, R; Zecca, M; Fagioli, F; Rovelli, A; Messina, C; Lanino, E; Bertaina, A; Favre, C; Giorgiani, G; Ripaldi, M; Ziino, O; Palumbo, G; Pillon, M; Pession, A; Rutella, S; Prete, A

2015-02-01

We analyzed the outcome of 243 children with high-risk (HR) AML in first CR1 enrolled in the AIEOP-2002/01 protocol, who were given either allogeneic (ALLO; n=141) or autologous (AUTO; n=102) hematopoietic SCT (HSCT), depending on the availability of a HLA-compatible sibling. Infants, patients with AML-M7, or complex karyotype or those with FLT3-ITD, were eligible to be transplanted also from alternative donors. All patients received a myeloablative regimen combining busulfan, cyclophosphamide and melphalan; [corrected] AUTO-HSCT patients received BM cells in most cases, while in children given ALLO-HSCT stem cell source was BM in 96, peripheral blood in 19 and cord blood in 26. With a median follow-up of 57 months (range 12-130), the probability of disease-free survival (DFS) was 73% and 63% in patients given either ALLO- or AUTO-HSCT, respectively (P=NS). Although the cumulative incidence (CI) of relapse was lower in ALLO- than in AUTO-HSCT recipients (17% vs 28%, respectively; P=0.043), the CI of TRM was 7% in both groups. Patients transplanted with unrelated donor cord blood had a remarkable 92.3% 8-year DFS probability. Altogether, these data confirm that HSCT is a suitable option for preventing leukemia recurrence in HR children with CR1 AML.

Absence of VOD in paediatric thalassaemic HSCT recipients using defibrotide prophylaxis and intravenous Busulphan.

Science.gov (United States)

Cappelli, Barbara; Chiesa, Robert; Evangelio, Costanza; Biffi, Alessandra; Roccia, Tito; Frugnoli, Ilaria; Biral, Erika; Noè, Anna; Fossati, Marco; Finizio, Valentina; Miniero, Roberto; Napolitano, Sara; Ferrua, Francesca; Soliman, Clara; Ciceri, Fabio; Roncarolo, Maria G; Marktel, Sarah

2009-11-01

Hepatic veno-occlusive disease (VOD) is a common complication of haematopoietic stem cell transplantation (HSCT), with reported incidences of 5-40% in children. Recently, defibrotide (DF) has been successfully used as prophylaxis and treatment of VOD. This study reports data on 63 human leucocyte antigen-matched HSCT performed in 57 children affected by beta thalassemia at very high risk for developing VOD (liver fibrosis, iron overload, hepatitis C virus infections, busulphan-based conditioning, methotraexate + ciclosporine). All patients received a busulphan-based conditioning regimen, either orally (four HSCT) or intravenously (59 HSCT). All patients received oral DF (40 mg/kg per day, final dose) as VOD prophylaxis from median day -9 to median day +29. In order to overcome the lack of oral paediatric formulations, a galenic formulation was administered. DF was well tolerated. Only one patient fulfilled Seattle Criteria for VOD diagnosis. This patient had discontinued DF 6 d prior to VOD onset, due to high risk of haemorrhage. We concluded that oral defibrotide prophylaxis and i.v. busulphan safely abated VOD incidence in high-risk patients who had undergone HSCT. A galenic preparation of oral DF also permits this treatment in low-weight patients. Costs of DF prophylaxis are acceptable considering the reduced incidence of VOD.

Generation of induced pluripotent stem cells as a potential source of hematopoietic stem cells for transplant in PNH patients.

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Phondeechareon, Tanapol; Wattanapanitch, Methichit; U-Pratya, Yaowalak; Damkham, Chanapa; Klincumhom, Nuttha; Lorthongpanich, Chanchao; Kheolamai, Pakpoom; Laowtammathron, Chuti; Issaragrisil, Surapol

2016-10-01

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia caused by lack of CD55 and CD59 on blood cell membrane leading to increased sensitivity of blood cells to complement. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for PNH, however, lack of HLA-matched donors and post-transplant complications are major concerns. Induced pluripotent stem cells (iPSCs) derived from patients are an attractive source for generating autologous HSCs to avoid adverse effects resulting from allogeneic HSCT. The disease involves only HSCs and their progeny; therefore, other tissues are not affected by the mutation and may be used to produce disease-free autologous HSCs. This study aimed to derive PNH patient-specific iPSCs from human dermal fibroblasts (HDFs), characterize and differentiate to hematopoietic cells using a feeder-free protocol. Analysis of CD55 and CD59 expression was performed before and after reprogramming, and hematopoietic differentiation. Patients' dermal fibroblasts expressed CD55 and CD59 at normal levels and the normal expression remained after reprogramming. The iPSCs derived from PNH patients had typical pluripotent properties and differentiation capacities with normal karyotype. After hematopoietic differentiation, the differentiated cells expressed early hematopoietic markers (CD34 and CD43) with normal CD59 expression. The iPSCs derived from HDFs of PNH patients have normal levels of CD55 and CD59 expression and hold promise as a potential source of HSCs for autologous transplantation to cure PNH patients.

Quality of life in Arab Muslim cancer survivors following hematopoietic stem cell transplantation: comparison with matched healthy group.

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Alaloul, Fawwaz; Brockopp, Dorothy Y; Andrykowski, Michael A; Hall, Lynne A; Al Nusairat, Taghreed S

2015-07-01

The aims of this study were to determine if quality of life (QOL) among Arab Muslim hematopoietic stem cell transplantation (HSCT) survivors differs from that of a healthy matched comparison group and to examine the relationships of demographic and medical variables and perceived social support with post-HSCT QOL. HSCT survivors (n = 63) were recruited from the King Hussein Cancer Center outpatient clinic. A matched (age, gender, education), healthy comparison group (n = 63) was recruited through public advertisements. Participants completed the EORTC-30 QOL scale and the Medical Outcomes Study Social Support Survey. Differences were found between the Arab Muslim HSCT survivor and healthy comparison groups for physical functioning (p Western HSCT survivors in the social and emotional QOL domains. Given growing numbers of Arab and Muslim cancer survivors in the USA and other Western countries, future research is warranted.

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.

Holding back moderates the association between health symptoms and social well-being in patients undergoing hematopoietic stem cell transplantation.

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Bartley, Emily J; Edmond, Sara N; Wren, Anava A; Somers, Tamara J; Teo, Irene; Zhou, Sicong; Rowe, Krista A; Abernethy, Amy P; Keefe, Francis J; Shelby, Rebecca A

2014-09-01

Holding back, or withholding discussion of disease-related thoughts and emotions, is associated with negative outcomes including lower quality of life, diminished well-being, and relational distress. For patients undergoing hematopoietic stem cell transplantation (HSCT), the degree to which one holds back from discussing illness-related concerns may be an important determinant of social well-being and health; however, this has not been systematically assessed in this population. The purpose of the present study was to assess the moderating effects of holding back discussion of disease-related concerns on the relationship between health-related symptoms and social well-being in adult patients undergoing HSCT. Seventy autologous (n = 55) and allogeneic (n = 15) HSCT patients completed measures of holding back, social well-being, and health symptoms (i.e., pain, fatigue, sleep problems, cognitive problems) both before and after transplantation (i.e., three months after transplantation and six months after transplantation). In patients with average to high levels of holding back, health symptoms were significantly related to lower levels of social well-being; however, for patients with low levels of holding back, the relationship between health symptoms and social well-being was not significant. The results of the present study suggest that the level of holding back may be important in understanding how health-related symptoms relate to social well-being in patients undergoing HSCT. These findings underscore the importance of addressing how patients undergoing HSCT communicate about their disease with others as this may be related to their adjustment to illness and treatment. Copyright © 2014 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Hypothyroidism following allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia.

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Medinger, Michael; Zeiter, Deborah; Heim, Dominik; Halter, Jörg; Gerull, Sabine; Tichelli, André; Passweg, Jakob; Nigro, Nicole

2017-07-01

Hypothyroidism may complicate allogeneic hematopoietic stem cell transplantation (allo-HSCT); we therefore analyzed risk factors in this study. We studied 229 patients with acute myeloid leukemia (AML) who underwent an allo-HSCT between 2003 and 2013 with different conditioning regimens (myeloablative, reduced-intensity, chemotherapy-based, or total body irradiation-based). Thyroid-stimulating hormone (TSH) and free thyroxine levels (fT4) were available in 104 patients before and after allo-HSCT. The median age at transplantation (n=104) was 47 (IQR 40-59)], 37 (35.6%) patients were female, and the overall mortality was 34.6% (n=36). After a median follow-up period of 47 (IQR 25-84) months, overt hypothyroidism (basal TSH>4.49mIU/l, FT4hypothyroidism (basal TSH>4.49mIU/l, normal fT4) was observed in 20 patients (19.2%). Positive thyroperoxidase (TPO) antibodies were found in 5 (4.8%) patients. A total of 13 patients (12.5%) were treated with thyroid hormone replacement. Acute graft-versus-host disease (aGvHD) ≥grade 2 occurred in 55 (52.9%) and chronic GvHD (cGvHD) in 74 (71.2%) of the patients. The risk of developing hypothyroidism was higher in the patients with repeated allo-HSCTs (P=0.024) and with positive TPO antibodies (P=0.045). Furthermore, the development of overt hypothyroidism was inversely proportional to age (P=0.043). No correlation was found with GvHD, HLA-mismatch, total body irradiation, and gender. After allo-HSCT, a significant number of patients experience thyroid dysfunction, including subclinical and overt hypothyroidism. Long-term and continuous follow-up for thyroid function after HSCT is important to provide timely and appropriate treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Perspectives on the co-treatment with GnRHa in female patients undergoing hematopoietic stem cell transplantation

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Luminita Nicoleta Cima

2017-10-01

Full Text Available Outcomes after hematopoietic stem cell transplantation (HSCT for patients with both malignant and nonmalignant diseases have improved significantly in recent years. However, the endocrine system is highly susceptible to damage by the high-dose chemotherapy and/or irradiation used in the conditioning regimen before HSCT. Ovarian failure and subsequent infertility are frequent complications that long-term HSCT survivors and their partners face with a negative impact on their QoL. Several meta-analyses of randomized clinical trials showed that gonadotropin-releasing hormone agonist (GnRHa administration in advance of starting standard chemotherapy decreases the risk of gonadal dysfunction and infertility in cancer patients, but GnRHa use for ovarian protection in HSCT patients is not fully determined. In this review, we are discussing the potential preservation of ovarian function and fertility in pubertal girls/premenopausal women who undergo HSCT using GnRHa in parallel with conditioning chemotherapy, focusing on the current data available and making some special remarks regarding the use of GnRHa.

Pre- and post-transplant minimal residual disease predicts relapse occurrence in children with acute lymphoblastic leukaemia.

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Lovisa, Federica; Zecca, Marco; Rossi, Bartolomeo; Campeggio, Mimma; Magrin, Elisa; Giarin, Emanuela; Buldini, Barbara; Songia, Simona; Cazzaniga, Giovanni; Mina, Tommaso; Acquafredda, Gloria; Quarello, Paola; Locatelli, Franco; Fagioli, Franca; Basso, Giuseppe

2018-03-01

Relapse remains the leading cause of treatment failure in children with acute lymphoblastic leukaemia (ALL) undergoing allogeneic haematopoietic stem cell transplantation (HSCT). We retrospectively investigated the prognostic role of minimal residual disease (MRD) before and after HSCT in 119 children transplanted in complete remission (CR). MRD was measured by polymerase chain reaction in bone marrow samples collected pre-HSCT and during the first and third trimesters after HSCT (post-HSCT1 and post-HSCT3). The overall event-free survival (EFS) was 50%. The cumulative incidence of relapse and non-relapse mortality was 41% and 9%. Any degree of detectable pre-HSCT MRD was associated with poor outcome: EFS was 39% and 18% in patients with MRD positivity <1 × 10 -3 and ≥1 × 10 -3 , respectively, versus 73% in MRD-negative patients (P < 0·001). This effect was maintained in different disease remissions, but low-level MRD had a very strong negative impact only in patients transplanted in second or further CR. Also, MRD after HSCT enabled patients to be stratified, with increasing MRD between post-HSCT1 and post-HSCT3 clearly defining cohorts with a different outcome. MRD is an important prognostic factor both before and after transplantation. Given that MRD persistence after HSCT is associated with dismal outcome, these patients could benefit from early discontinuation of immunosuppression, or pre-emptive immuno-therapy. © 2018 John Wiley & Sons Ltd.

Autoimmune hematological diseases after allogeneic hematopoietic stem cell transplantation in children: an Italian multicenter experience.

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Faraci, Maura; Zecca, Marco; Pillon, Marta; Rovelli, Attilio; Menconi, Maria Cristina; Ripaldi, Mimmo; Fagioli, Franca; Rabusin, Marco; Ziino, Ottavio; Lanino, Edoardo; Locatelli, Franco; Daikeler, Thomas; Prete, Arcangelo

2014-02-01

Autoimmune hematological diseases (AHDs) may occur after allogeneic hematopoietic stem cell transplantation (HSCT), but reports on these complications in large cohorts of pediatric patients are lacking. Between 1998 and 2011, 1574 consecutive children underwent allogeneic HSCT in 9 Italian centers. Thirty-three children (2.1%) developed AHDs: 15 autoimmune hemolytic anemia (45%), 10 immune thrombocytopenia (30%), 5 Evans' syndrome (15%), 2 pure red cell aplasia (6%), and 1 immune neutropenia (3%). The 10-year cumulative incidence of AHDs was 2.5% (95% confidence interval, 1.7 to 3.6). In a multivariate analysis, the use of alternative donor and nonmalignant disease was statistically associated with AHDs. Most patients with AHDs (64%) did not respond to steroids. Sustained complete remission was achieved in 87% of cases with the anti-CD20 monoclonal antibody (rituximab). Four patients (9%) (1 autoimmune hemolytic anemia, 1 Evans' syndrome, 2 immune thrombocytopenia) died at a median of 87 days after AHD diagnosis as a direct or indirect consequence of their disorder. Our data suggest that AHDs are a relatively rare complication occurring after HSCT that usually respond to treatment with rituximab. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Managing high-risk CLL during transition to a new treatment era: stem cell transplantation or novel agents?

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Dreger, Peter; Schetelig, Johannes; Andersen, Niels; Corradini, Paolo; van Gelder, Michel; Gribben, John; Kimby, Eva; Michallet, Mauricette; Moreno, Carol; Stilgenbauer, Stephan; Montserrat, Emili

2014-12-18

Allogeneic hematopoietic stem cell transplantation (HSCT) has been considered as the treatment of choice for patients with high-risk chronic lymphocytic leukemia (HR-CLL; ie, refractory to purine analogs, short response [CLL are being challenged by the introduction of novel classes of drugs. Among them, BCR signal inhibitors (BCRi) and B-cell lymphoma 2 antagonists (BCL2a) appear particularly promising. As a result of the growing body of favorable outcome data reported for BCRi/BCL2a, uncertainty is emerging on how to advise patients with HR-CLL about indication for and timing of HSCT. This article provides an overview of currently available evidence and theoretical considerations to guide this difficult decision process. Until the risks and benefits of different treatment strategies are settled, all patients with HR-CLL should be considered for treatment with BCRi/BCL2a. For patients who respond to these agents, there are 2 treatment possibilities: (1) performing an HSCT or (2) continuing treatment with the novel drug. Individual disease-specific and transplant-related risk factors, along with patient's preferences, should be taken into account when recommending one of these treatments over the other. © 2014 by The American Society of Hematology.

Prevalence of dry eye syndrome after allogeneic hematopoietic stem cell transplantation.

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Ivanir, Yair; Shimoni, Avichai; Ezra-Nimni, Orit; Barequet, Irina S

2013-05-01

To evaluate the prevalence, severity, and effect of dry eye in patients after allogeneic hematopoietic stem cell transplantation (aHSCT) and to correlate the findings to the duration after transplantation. A total of 222 eyes of 111 patients after aHSCT at the Department of Bone Marrow Transplantation, Sheba Medical Center, Israel in a consecutive 3-year period. All patients underwent a full ophthalmic examination and filled the ocular surface disease index (OSDI) questionnaire to assess ocular involvement in the form of dry eye syndrome or any other ocular manifestation. The main outcome measures were best-corrected visual acuity, tear break-up time, corneal fluorescein staining, Schirmer test, and OSDI questionnaire. A total of 111 patients were recruited. In 37%, a diagnosis of ocular graft versus host disease was previously made and 46% had no previous ocular examination. Schirmer test was less than 5 mm in 50% of all patients, and in 30% of patients with undiagnosed ocular involvement. The mean OSDI score was 13, and in 28% it was above 20. Correlation was found between visual acuity decrease and high OSDI score to the diagnosis of ocular graft versus host disease and signs of dry eye syndrome. A trend of worsening dry eye was observed up to the second half of the second year posttransplantation. Although many patients are either asymptomatic or do not seek ophthalmic examination, severe dry eye is a common finding after aHSCT. Mandatory follow-up, patient education, and early treatment may improve the quality of life.

Stem cell Transplantation for Eradication of Minimal PAncreatic Cancer persisting after surgical Excision (STEM PACE Trial, ISRCTN47877138): study protocol for a phase II study

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Schmitz-Winnenthal, Friedrich H; Schmidt, Thomas; Lehmann, Monika; Beckhove, Philipp; Kieser, Meinhard; Ho, Anthony D; Dreger, Peter; Büchler, Markus W

2014-01-01

Pancreatic cancer is the third most common cancer related cause of death. Even in the 15% of patients who are eligible for surgical resection the outlook is dismal with less than 10% of patients surviving after 5 years. Allogeneic hematopoietic (allo-HSCT) stem cell transplantation is an established treatment capable of to providing cure in a variety of hematopoietic malignancies. Best results are achieved when the underlying neoplasm has been turned into a stage of minimal disease by chemotherapy. Allo-HSCT in advanced solid tumors including pancreatic cancer have been of limited success, however studies of allo-HSCT in solid tumors in minimal disease situations have never been performed. The aim of this trial is to provide evidence for the clinical value of allo-HSCT in pancreatic cancer put into a minimal disease status by effective surgical resection and standard adjuvant chemotherapy. The STEM PACE trial is a single center, phase II study to evaluate adjuvant allogeneic hematopoietic stem cell transplantation in pancreatic cancer after surgical resection. The study will evaluate as primary endpoint 2 year progression free survival and will generate first time state-of-the-art scientific clinical evidence if allo-HSCT is feasible and if it can provide long term disease control in patients with effectively resected pancreatic cancer. Screened eligible patients after surgical resection and standard adjuvant chemotherapy with HLA matched related stem cell donor can participate. Patients without a matched donor will be used as a historical control. Study patients will undergo standard conditioning for allo-HSCT followed by transplantation of allogeneic unmanipulated peripheral blood stem cells. The follow up of the patients will continue for 2 years. Secondary endpoints will be evaluated on 7 postintervention visits. The principal question addressed in this trial is whether allo-HSCT can change the unfavourable natural course of this disease. The underlying

Mesenchymal Stem Cells May Ameliorate Nephrotic Syndrome Post-Allogeneic Hematopoietic Stem Cell Transplantation-Case Report

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Xin Zhang

2017-08-01

Full Text Available IntroductionBecause of their immunomodulatory and anti-inflammatory effects, mesenchymal stem cells (MSCs have been considered as potential therapeutic agents for treating immune-related or autoimmune diseases, such as graft-versus-host disease (GVHD. Nephrotic syndrome (NS after allogeneic hematopoietic stem cell transplantation (allo-HSCT is an uncommon complication with unclear etiology and pathogenesis. It may be an immune disorder involving immune complex deposition, B cells, regulatory T cells (Tregs, and Th1 cytokines and be a manifestation of chronic GVHD. Corticosteroids and calcium antagonists, alone or in combination, are the most common therapeutic agents in this setting. Rituximab is commonly administered as salvage treatment. However, treatment failure and progressive renal function deterioration has been reported to occur in approximately 20% of patients in a particular cohort.Case presentationWe present a patient who developed NS 10 months after allo-HSCT. After treatment failure with cyclosporine A, prednisone, and rituximab, she achieved a complete response with MSC treatment. The clinical improvement of this patient was accompanied by a decreased B cell population together with an increased frequency of regulatory B cells (Bregs and Tregs after MSC treatment.ConclusionMSCs could modulate NS after allo-HSCT by suppressing B cell proliferation, inducing Tregs and Bregs, and inhibiting inflammatory cytokine production by monocytes and NK cells. Among all these, Bregs might play an important role in ameliorating the NS of this patient.

Successful autologous hematopoietic stem cell transplantation for a patient with rapidly progressive localized scleroderma.

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Nair, Velu; Sharma, Ajay; Sharma, Sanjeevan; Das, Satyaranjan; Bhakuni, Darshan S; Narayanan, Krishnan; Nair, Vivek; Shankar, Subramanian

2015-03-01

Autologous hematopoietic stem cell transplant (HSCT) for rapidly progressive disease has not been reported in localized scleroderma. Our patient, a 16-year-old girl had an aggressive variant of localized scleroderma, mixed subtype (linear-generalized) with Parry Romberg syndrome, with no internal organ involvement, that was unresponsive to immunosuppressive therapy and was causing rapid disfigurement. She was administered autologous HSCT in June 2011 and has maintained drug-free remission with excellent functional status at almost 3.5 years of follow-up. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Total-body irradiation - role and indications. Results from the German Registry for Stem Cell Transplantation (DRST)

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Heinzelmann, F.; Bamberg, M.; Belka, C.; Ottinger, H.; Mueller, C.H.; Allgaier, S.; Faul, C.

2006-01-01

Background and purpose: total-body irradiation (TBI) is a key part of the conditioning regimen before hematopoietic stem cell transplantation (HSCT). The exact role of TBI as part of the conditioning regimen is largely unclear. In order to determine the relevance of TBI, the status of TBI utilization was analyzed on the basis of a nationwide registry. Material and methods: 14,371 patients (1998-2002) documented in the German Stem Cell Transplantation Registry (DRST) were analyzed regarding TBI utilization prior to autologous or allogeneic transplantation, underlying disorder, type of donor, stem cell source, and size of the treatment center. Results: for autologous HSCT ∝10% of the patients (873/8,167) received TBI, with chronic lymphocytic leukemia (CLL, ∝80%, 171/214) and low-grade non-Hodgkin's lymphoma (l-NHL, ∝35%, 330/929) being the most important disorders. In the allogeneic setting 50% of the patients (2,399/4,904) received TBI, with acute lymphocytic leukemia (ALL, 85%, 794/930), acute myeloid leukemia (AML, 45%, 662/1,487) and chronic myeloid leukemia (CML, 49%, 561/1,156) being the key indications. The type of donor, stem cell source and center size did not strongly influence the use of TBI. Conclusion: TBI has only a limited role for the conditioning prior to autologous HCST. For allogeneic HSCT TBI is widely accepted with no major changes over the observation time. The use of TBI is generally accepted for ALL, whereas approximately half of the patients with CML or AML received TBI. Although a considerably large database was analyzed, no clear determinants for the use of TBI could be distinguished. (orig.)

Total-body irradiation - role and indications. Results from the German Registry for Stem Cell Transplantation (DRST)

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Heinzelmann, F.; Bamberg, M.; Belka, C. [Dept. of Radiation Oncology, Univ. of Tuebingen (Germany); Ottinger, H. [German Registry for Stem Cell Transplantation (DRST) Secretary, Univ. of Essen (Germany); Mueller, C.H.; Allgaier, S. [DRST Datacenter, DRK Bloodbank Center Ulm (Germany); Faul, C. [Dept. of Internal Medicine II, Univ. of Tuebingen (Germany)

2006-04-15

Background and purpose: total-body irradiation (TBI) is a key part of the conditioning regimen before hematopoietic stem cell transplantation (HSCT). The exact role of TBI as part of the conditioning regimen is largely unclear. In order to determine the relevance of TBI, the status of TBI utilization was analyzed on the basis of a nationwide registry. Material and methods: 14,371 patients (1998-2002) documented in the German Stem Cell Transplantation Registry (DRST) were analyzed regarding TBI utilization prior to autologous or allogeneic transplantation, underlying disorder, type of donor, stem cell source, and size of the treatment center. Results: for autologous HSCT {proportional_to}10% of the patients (873/8,167) received TBI, with chronic lymphocytic leukemia (CLL, {proportional_to}80%, 171/214) and low-grade non-Hodgkin's lymphoma (l-NHL, {proportional_to}35%, 330/929) being the most important disorders. In the allogeneic setting 50% of the patients (2,399/4,904) received TBI, with acute lymphocytic leukemia (ALL, 85%, 794/930), acute myeloid leukemia (AML, 45%, 662/1,487) and chronic myeloid leukemia (CML, 49%, 561/1,156) being the key indications. The type of donor, stem cell source and center size did not strongly influence the use of TBI. Conclusion: TBI has only a limited role for the conditioning prior to autologous HCST. For allogeneic HSCT TBI is widely accepted with no major changes over the observation time. The use of TBI is generally accepted for ALL, whereas approximately half of the patients with CML or AML received TBI. Although a considerably large database was analyzed, no clear determinants for the use of TBI could be distinguished. (orig.)

Pre-existing anti-HLA antibodies negatively impact survival of pediatric aplastic anemia patients undergoing HSCT.

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Zhu, Hua; He, Jun; Cai, Junchao; Yuan, Xiaoni; Jiang, Hua; Luo, Changying; Wang, Jianmin; Luo, Chengjuan; Pan, Zhijuan; Terasaki, Paul I; Ding, Lixia; Chen, Jing

2014-11-01

Graft failure and survival are the major problems for patients with aplastic anemia undergoing hematopoietic stem cell transplantation (HSCT). Previous studies showed that anti-HLA antibodies negatively impact engraftment in HSCT. This retrospective study of 51 pediatric patients with acquired aplastic anemia who underwent allogeneic HSCT at a single institution between 2006 and 2012 investigated the influence of anti-HLA antibodies on the outcome of HSCT. Serum samples collected before HSCT were tested for the presence of anti-HLA antibodies. Pre-existing anti-HLA antibodies were detected in 54.9% (28/51) of patients, among whom 39.2% (20/51) had anti-HLA class I antibodies. Anti-HLA antibodies were associated with worse five-yr survival (78.6% vs. 100%, p = 0.021) and higher treatment-related mortality (21.4% vs. 0%, p = 0.028) compared with antibody-negative patients. Anti-HLA class I antibody-positive patients had poorer five-yr survival (75.0%) than anti-HLA class I&II antibody-positive and antibody-negative patients (87.5% and 100.0%, respectively, p = 0.039). Presence of anti-HLA class I antibodies (p = 0.024) and older age (10 yr or more; p = 0.027) significantly increased the risk of post-HSCT mortality. Pre-existing anti-HLA antibodies negatively affect the outcome of HSCT in pediatric patients with aplastic anemia. Routine testing for anti-HLA antibodies concurrent with efficient treatment should be conducted prior to HSCT. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Marked in Vivo Donor Regulatory T Cell Expansion via Interleukin-2 and TL1A-Ig Stimulation Ameliorates Graft-versus-Host Disease but Preserves Graft-versus-Leukemia in Recipients after Hematopoietic Stem Cell Transplantation.

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Wolf, Dietlinde; Barreras, Henry; Bader, Cameron S; Copsel, Sabrina; Lightbourn, Casey O; Pfeiffer, Brent J; Altman, Norman H; Podack, Eckhard R; Komanduri, Krishna V; Levy, Robert B

2017-05-01

Regulatory T cells (Tregs) are critical for self-tolerance. Although adoptive transfer of expanded Tregs limits graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT), ex vivo generation of large numbers of functional Tregs remains difficult. Here, we demonstrate that in vivo targeting of the TNF superfamily receptor TNFRSF25 using the TL1A-Ig fusion protein, along with IL-2, resulted in transient but massive Treg expansion in donor mice, which peaked within days and was nontoxic. Tregs increased in multiple compartments, including blood, lymph nodes, spleen, and colon (GVHD target tissue). Tregs did not expand in bone marrow, a critical site for graft-versus-malignancy responses. Adoptive transfer of in vivo-expanded Tregs in the setting of MHC-mismatched or MHC-matched allogeneic HSCT significantly ameliorated GVHD. Critically, transplantation of Treg-expanded donor cells facilitated transplant tolerance without GVHD, with complete sparing of graft-versus-malignancy. This approach may prove valuable as a therapeutic strategy promoting transplantation tolerance. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Does defibrotide induce a delay to polymorphonuclear neutrophil engraftment after hematopoietic stem cell transplantation? Observation in a pediatric population.

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Maximova, Natalia; Pizzol, Antonio; Giurici, Nagua; Granzotto, Marilena

2015-04-01

In recent years, defibrotide (DFT) has emerged as a promising therapy for veno-occlusive disease (VOD). The aim of this study was to investigate whether DFT prophylaxis affects neutrophil engraftment in patients undergoing hematopoietic stem cell transplantation (HSCT). A cohort of 44 consecutive pediatric patients who underwent HSCT was retrospectively analyzed to see the role of DFT on engraftment. Patients were assigned into two groups based on the use or non-use of prophylaxis with DFT. The mean time to engraftment was statistically different between the two groups for both polymorphonuclear neutrophils (PMN) and white blood cells. Our study supports the hypothesis that prophylaxis with DFT for VOD leads to a delay to the engraftment of PMN in pediatric patients that underwent HSCT.

Donor-Cell Origin High-Risk Myelodysplastic Syndrome Synchronous with an Intracranial Meningioma-Like Tumor, 8 Years after Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Lymphocytic Leukemia

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G. Brás

2017-01-01

Full Text Available Secondary neoplasias are well known consequences of radiotherapy or chemotherapy for a primary cancer. In this report, we describe two rare secondary neoplasias occurring in the same patient: a meningioma-like intracranial tumor and high-risk myelodysplastic syndrome (MDS of donor-cells origin, both diagnosed simultaneously, 8 years after an allogeneic hematopoietic stem cell transplantation (allo-HSCT for chronic lymphocytic leukemia (CLL. Due to an engraftment failure during the first allo-HSCT of a matched related donor for CLL treatment, the salvage treatment was a second allo-HSCT. At the moment of meningioma-like tumor diagnosis, the patient was pancytopenic due to high-risk MDS, so it was decided to postpone a surgical intervention until hematological improvement. For the high-risk MDS of donor-cells origin the chosen treatment was induction with intensive chemotherapy. Due to refractory disease, the patient was treated with 5-azacitidine and donor-lymphocytes infusion with no response and, finally, a third allo-HSCT of a matched unrelated donor was performed. The patient died 6 months after the third allo-HSCT, in cytogenetic remission but without hematological recovery, due to an intracranial hemorrhage with origin in the meningioma-like tumor.

[Reduced intensity conditioning allogeneic hematopoietic stem cell transplantation in chronic lymphocytic leukemia (CLL) patients with the aberration of p53 gene].

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Wang, Li; Miao, Kourong; Fan, Lei; Xu, Ji; Wu, Hanxin; Li, Jianyong; Xu, Wei

2016-04-01

To investigate the effectiveness and safety of reduced intensity conditioning allogeneic hematopoietic stem cell transplantation (RIC allo-HSCT) in ultra high risk chronic lymphocytic leukemia (CLL) patients with the deletion of p53 to deepen the understanding of allo-HSCT in the treatment of CLL. In this retrospective study, a total of 4 ultra high risk CLL patients with the deletion of p53 in our center between July 2012 and Jan 2014 were enrolled. The RIC regimen was administered and the hematopoietic reconstitution, transplantation related mortality (TRM), overall survival (OS), progress free survival (PFS) were evaluated. We registered 4 patients with the median age of 56 years (49-61 years), including 3 males and 1 female. The median mononuclear cells (MNC) and CD34(+) cells were 6.54 (2.85-14.7) × 10(8)/kg (recipient body weight) and 5.81 (2.85-7.79) × 10(6)/kg (recipient body weight), respectively. The median time of the neutrophil recovery was 11 days (range of 9-12 days), and the median time of the platelet recovery 5.5 days (range of 0-11 days). Three patients (75%) attained a full donor chimerism at day 28 after transplantation and one (25%) got a mixed chimerism of donor and recipient. During the follow-up at a median time of 26.5 months (range of 21-39 months), 2 (50%) patients developed acute graft versus host disease (aGVHD) grade I and 2 (50%) patients got CMV infection. One patient got herpes zoster virus and EB virus infections. No transplantation related mortality was found in the 4 patients. One patient who was in partial response status progressed 5 months after transplantation, and the other 3 patients remained in durable remission after allo-HSCT. These results suggested that RIC allo-HSCT showed durable remission, good tolerance and acceptable toxicity, which could be a better option for the treatment of ultra high risk CLL patients with the deletion of p53 and was worth to be investigated and applied widely in future.

Virus reactivations after autologous hematopoietic stem cell transplantation detected by multiplex PCR assay.

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Inazawa, Natsuko; Hori, Tsukasa; Nojima, Masanori; Saito, Makoto; Igarashi, Keita; Yamamoto, Masaki; Shimizu, Norio; Yoto, Yuko; Tsutsumi, Hiroyuki

2017-02-01

Several studies have indicated that viral reactivations following allogeneic hematopoietic stem cell transplantation (allo-HSCT) are frequent, but viral reactivations after autologous HSCT (auto-HSCT) have not been investigated in detail. We performed multiplex polymerase chain reaction (PCR) assay to examine multiple viral reactivations simultaneously in 24 patients undergoing auto-HSCT between September 2010 and December 2012. Weekly whole blood samples were collected from pre- to 42 days post-HSCT, and tested for the following 13 viruses; herpes simplex virus 1 (HSV-1), HSV-2, varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), HHV-7, HHV-8, adeno virus (ADV), BK virus (BKV), JC virus (JCV), parvovirus B19 (B19V), and hepatitis B virus (HBV).  Fifteen (63%) patients had at least one type of viral reactivation. HHV6 (n = 10; 41.7%) was most frequently detected followed by EBV (n = 7; 29.2%). HHV-6 peaked on day 21 after HSCT and promptly declined. In addition, HBV, CMV, HHV7, and B19V were each detected in one patient. HHV6 reactivation was detected in almost half the auto-HSCT patients, which was similar to the incidence in allo-HSCT patients. The incidence of EBV was unexpectedly high. Viral infections in patients undergoing auto-HSCT were higher than previously reported in other studies. Although there were no particular complications of viral infection, we should pay attention to possible viral reactivations in auto-HSCT patients. J. Med. Virol. 89:358-362, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Epidemiology of neglected tropical diseases in transplant recipients: review of the literature and experience of a Brazilian HSCT center Epidemiologia das doenças tropicais negligenciadas em receptores de transplantes: revisão da literatura e experiência de um centro brasileiro

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Clarisse Martins Machado

2009-12-01

Full Text Available The rising success rate of solid organ (SOT and haematopoietic stem cell transplantation (HSCT and modern immunosuppression make transplants the first therapeutic option for many diseases affecting a considerable number of people worldwide. Consequently, developing countries have also grown their transplant programs and have started to face the impact of neglected tropical diseases (NTDs in transplant recipients. We reviewed the literature data on the epidemiology of NTDs with greatest disease burden, which have affected transplant recipients in developing countries or may represent a threat to transplant recipients living in other regions. Tuberculosis, Leprosy, Chagas disease, Malaria, Leishmaniasis, Dengue, Yellow fever and Measles are the topics included in this review. In addition, we retrospectively revised the experience concerning the management of NTDs at the HSCT program of Amaral Carvalho Foundation, a public transplant program of the state of São Paulo, Brazil.O sucesso crescente dos transplantes de órgãos sólidos (TOS e de células tronco-hematopoiéticas (TCTH e as novas drogas imunossupressoras fizeram dos transplantes a primeira opção terapêutica para muitas doenças que afetam milhares de pessoas em todo o mundo. Também os populosos países em desenvolvimento investiram no crescimento de seus programas de transplante e desde então começaram a vivenciar o impacto das doenças tropicais negligenciadas (DTNs nestes pacientes. Revisamos os dados da literatura sobre a epidemiologia das DTNs de maior impacto clinico e social que afetam receptores de transplante de países em desenvolvimento, ou que podem representar um risco para receptores de transplante vivendo em outras regiões não afetadas por estas doenças. Tuberculose, hanseníase, doença de Chagas, malaria, leishmaniose, dengue, febre amarela e sarampo são os tópicos incluídos nesta revisão. Além disso, revisamos retrospectivamente a experiência referente ao

Life coaching following haematopoietic stem cell transplantation: a mixed-method investigation of feasibility and acceptability.

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Kenyon, M; Young, F; Mufti, G J; Pagliuca, A; Lim, Z; Ream, E

2015-07-01

Haematopoietic stem cell transplantation (HSCT) cures many haematological cancers. Recovery post-HSCT is physically and psychologically challenging, lasting several months. Beyond the first post-transplant year, a fifth report difficulties encompassing practical, social and emotional domains, including finance and employment. We investigated the feasibility, acceptability and impact of a life coaching intervention designed to address psychosocial 'survivor' concerns of HSCT recipients and facilitate transition to life post-treatment. A concurrent embedded experimental mixed-method design was employed. Pre- and post-intervention data collection comprised qualitative semi-structured telephone interviews and quantitative postal questionnaires. Seven purposively sampled HSCT recipients (life coaching delivered by a professional life coach fortnightly over 8 weeks. Participants reported less anxiety, depression and fewer survivor concerns post-intervention, with a trend for lower social difficulties and increased functional well-being. Perceived self-efficacy was unchanged. Life coaching was feasible to deliver and acceptable to the participants who indicated it was a positive experience, with benefits described in diverse areas including work, lifestyle and hobbies. Life coaching within cancer services potentially offers the means to address psychosocial concerns and support transition to life after treatment, enabling patients to reach their potential, e.g. returning to employment and financial independence. Further investigation of this intervention in cancer survivors is warranted. © 2015 John Wiley & Sons Ltd.

АВ0-INCOMPATIBILITY IN ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION: 15-YEARS EXPERIENCE OF R.M. GORBACHEVA MEMORIAL RESEARCH INSTITUTE FOR CHILDREN ONCOLOGY, HEMATOLOGY AND TRANSPLANTATION

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M. A. Kucher

2016-01-01

Full Text Available Introduction. AB0-incompatibility in different types of allogeneic hematopoietic stem cell transplantation (HSCT may be an additional aggravating factor for the development of immunological complications and decrease treatment efficacy.Materials and methods. From May 1999 to December 2015 in R.M. Gorbacheva Memorial Research Institute for Children Oncology, Hematology and Transplantation 1131 patients with malignancies and hereditary diseases were included to the study, which were performed 1428 allogeneic HSCT: allogeneic unrelated – 814 (57.0 %, allogeneic related – 344 (24.1 %, haploidentical – 267 (18.7 %, umbilical cord blood in 3 patients (0.2 %. Age was 0–76 years, median – 25 years.Results. In 54.6 % of cases (n = 780 АВ0-incompatibility was determined: major – 37.8 % (n = 295; minor – 45.4 % (n = 354; combined – 16.8 % (n = 131. АВ0-incompatibility in allogeneic HSCT did not influence overall survival (p = 0.56, frequency of acute graftversus-host disease (GVHD (p = 0.2. There was an increased frequency of acute GVHD in combination with reduced intensity conditioning regimens and АВ0-incompatibility (30.8 % compared with myeloablative regimens (15.3 %; p = 0.002.Conclusion. The presence of АВ0-incompatibility is not a limiting factor to perform allogeneic HSCT, however, it demands high quality prophylaxis and sophisticated transfusion therapy to prevent immune complications.

The Role of Hematopoietic Stem-Cell Transplantation in First Remission in Pediatric Acute Lymphoblastic Leukemia: A Narrative Review

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Neel S. Bhatt

2017-05-01

Full Text Available Context Survival after allogeneic hematopoietic stem-cell transplantation (HSCT for children with hematologic malignancies including acute lymphoblastic leukemia (ALL continues to improve in part due to advancement in HLA typing and enhanced supportive care. Despite improved outcomes with HSCT, the decision to offer it in first remission (CR1 in children with ALL remains a topic of debate and uncertainty. This review aims to discuss the role of HSCT in CR1 for children with high-risk subsets of ALL in the current era. Evidence Acquisition A thorough review of the literature was performed using electronic databases: PubMed, Google Scholar, and bibliographies. Studies focusing on high-risk subsets of ALL (Primary Induction Failure, Severe Hypodiploidy, Philadelphia-chromosome positive ALL, T-Cell ALL, Infant ALL, ALL with persistent minimal residual disease (MRD, and Philadelphia-like ALL were included. Publications in non- English language were excluded. Results Based on our review of the current literature, HSCT should be considered in first remission for patients with primary induction failure, severe hypodiploidy, T-cell ALL with poor response, high-risk infant ALL, and persistently positive MRD. In contrast, HSCT in CR1 may not be warranted for patients with early T-cell progenitor ALL or Philadelphia-chromosome positive ALL. Further data are needed to make specific recommendations regarding Philadelphia-like ALL. Conclusions As our understanding of high-risk leukemia biology continues to develop, the role of HSCT in ALL CR1 will need to be revisited.

Current practices for screening, consent and care of related donors in France: Haematopoietic stem cell transplantation coordinator nurses' perceptions.

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Polomeni, A; Bompoint, C; Gomez, A; Brissot, E; Ruggeri, A; Belhocine, R; Mohty, M

2017-11-01

Haematopoietic stem cell transplantation-coordinating nurses (HSCT-CNs) play an important role in informing related donors (RDs) and in organising human leucocyte antigen (HLA) tests, pre-donation workup and stem cells collection. Our pilot study aimed to explore French HSCT-CNs' perceptions of RD care issues. Twenty-nine French HSCT adult units were sent a questionnaire on the subject of donation procedures, HSCT-CNs' data and their professional experience of related donation issues. Twenty-two HSCT-CNs returned a completed questionnaire, and 90% of HSCT units were involved to some degree in both patient and donor care. Responses indicated that the provision of information to potential donors prior to HLA tests was insufficient, while donors were given a medical consultation only during the pre-donation workup. Questions were raised about the consent and voluntary status of RDs. None of the HSCT teams organised a post-donation consultation, while 57% provided follow-up by phone or via a questionnaire. Our results draw attention to the conflict of interest experienced by HSCT-CNs when caring simultaneously for patients and donors. The specific psychosocial difficulties associated with becoming an RD are also highlighted. French HSCT-CNs' perceptions of related donation reveal many ethical and clinical problems that have yet to be fully explored. Data on this topic remain scarce, and our pilot study may contribute to the current debate on the organisation of RD care. © 2016 John Wiley & Sons Ltd.

Disease-specific hematopoietic stem cell transplantation in children with inherited bone marrow failure syndromes.

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Li, Qian; Luo, Changying; Luo, Chengjuan; Wang, Jianmin; Li, Benshang; Ding, Lixia; Chen, Jing

2017-08-01

Hematopoietic stem cell transplantation (HSCT) using an optimized conditioning regimen is essential for the long-term survival of patients with inherited bone marrow failure syndromes (IBMFS). We report HSCT in 24 children with Fanconi anemia (FA, n = 12), Diamond-Blackfan anemia (DBA, n = 7), and dyskeratosis congenita (DC, n = 5) from a single HSCT center. The graft source was peripheral blood stem cells (n = 19) or cord blood stem cells (n = 5). FA and DC patients received reduced-intensity conditioning, while DBA patients had myeloablative conditioning. The median numbers of infused mononuclear cells and CD34+ cells were 14.20 × 10 8 /kg and 4.3 × 10 6 /kg, respectively. The median time for neutrophil and platelet recovery was 12 and 18 days, respectively. Complete donor engraftment was achieved in 23 of 24 patients. There was one primary graft failure. During a median follow-up of 27.5 months (range, 2-130 months), the overall survival in all patients was 95.8%. The incidence of grade II-III acute graft versus host disease (GvHD) and chronic GvHD was 29.2% and 16.7%, respectively. We conclude that HSCT can be a curative option for patients with IBMFS. Modification of the conditioning regimen based on the type of disease may lead to encouraging long-term outcomes.

HLA-C incompatibilities in allogeneic unrelated hematopoietic stem cell transplantation

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Jean-Marie eTIERCY

2014-05-01

Full Text Available An increasingly larger fraction of patients with hematological diseases are treated by hematopoietic stem cells transplantation (HSCT from HLA matched unrelated donors. Polymorphism of HLA genes represent a major barrier to HSCT because HLA-A,B,C and DRB1 incompatibilities confer a higher risk of aGVHD and mortality. Although >22 million volunteer HLA-typed donors are available worldwide, still a significant number of patients do not find a highly matched HSC donor. Because of the large haplotypic diversity in HLA-B-C associations, incompatibilities occur most frequently at HLA-C, so that unrelated donors with a single HLA-C mismatch often represent the only possible choice. The ratio of HLA-C-mismatched HSCT over the total number of transplants varies from 15-30%, as determined in 12 multicenter studies. Six multicenter studies involving >1800 patients have reported a 21-43% increase in mortality risk. By using in vitro cellular assays a large heterogeneity in T-cell allorecognition has been observed. Yet the permissiveness of individual HLA-C mismatches remains poorly defined. It could be linked to the position and nature of the mismatched residues on HLA-C molecules, but also to variability in the expression levels of the mismatched alleles. The permissive C*03:03-03:04 mismatch is caracterized by full compatibility at residues 9, 97, 99, 116, 152, 156 and 163 reported to be key positions influencing T-cell allorecognition. With a single difference in these key residues the C*07:01-07:02 mismatch might also be considered by analogy as permissive. High variability of HLA-C expression as determined by quantitative RT-PCR has been observed within individual allotypes and shows some correlation with A-B-C-DRB1 haplotypes. Thus in addition to the position of mismatched amino acid residues, expression level of patient’s mismatched HLA-C allotype might influence T-cell allorecognition, with patient's low expression-C alleles representing possible

High body mass index among patients undergoing hematopoietic stem cell transplantation: results of a cross-sectional evaluation of nutritional status in a private hospital

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Pereira, Andrea Z.; Victor, Elivane S.; Campregher, Paulo Vidal; Piovacari, Silvia M. F.; Barban, Juliana S. Bernardo; Pedreira Jr, Wilson L; Hamerschlak, Nelson

2015-01-01

Background: nutritional status before hematopoietic stem cell transplantation (HSCT) affects prognosis: better nourished patients have shorter time to engraftment, while malnutrition is associated with increase of mortality rates, complications, medical costs, poor quality of life and hospitalization stay. Furthermore, underweight patients have increased risk of death in the early post- HSCT period, and non-relapse mortality is greater for those who are extremely underweight, overweight and o...

T cells for viral infections after allogeneic hematopoietic stem cell transplant.

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Bollard, Catherine M; Heslop, Helen E

2016-06-30

Despite recent advances in the field of allogeneic hematopoietic stem cell transplantation (HSCT), viral infections are still a major complication during the period of immune suppression that follows the procedure. Adoptive transfer of donor-derived virus-specific cytotoxic T cells (VSTs) is a strategy to rapidly restore virus-specific immunity to prevent or treat viral diseases after HSCT. Early proof of principle studies demonstrated that the administration of donor-derived T cells specific for cytomegalovirus or Epstein-Barr virus (EBV) could effectively restore virus-specific immunity and control viral infections. Subsequent studies using different expansion or direct selection techniques have shown that donor-derived VSTs confer protection in vivo after adoptive transfer in 70% to 90% of recipients. Because a major cause of failure is lack of immunity to the infecting virus in a naïve donor, more recent studies have infused closely matched third-party VSTs and reported response rates of 60% to 70%. Current efforts have focused on broadening the applicability of this approach by: (1) extending the number of viral antigens being targeted, (2) simplifying manufacture, (3) exploring strategies for recipients of virus-naïve donor grafts, and (4) developing and optimizing "off the shelf" approaches. © 2016 by The American Society of Hematology.

Oral features and dental health in Hurler Syndrome following hematopoietic stem cell transplantation.

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McGovern, Eleanor

2012-02-01

BACKGROUND: Hurler Syndrome is associated with a deficiency of a specific lysosomal enzyme involved in the degradation of glycosaminoglycans. Hematopoietic stem cell transplantation (HSCT) in early infancy is undertaken to help prevent the accumulation of glycosaminoglycans and improve organ function. AIM: To investigate the oral features and dental health of patients with Hurler Syndrome who have undergone successful HSCT. MATERIALS AND METHODS: Twenty-five patients (median age 8.6 years) post-HSCT (mean age 9.4 months) underwent oral assessment (mean of 7.5 years post-HSCT). RESULTS: Dental development was delayed. Numerous occlusal anomalies were noted including: open-bite, class III skeletal base, dental spacing, primary molar infra-occlusion and ectopic tooth eruption. Dental anomalies included hypodontia, microdontia, enamel defects, thin tapering canine crowns, pointed molar cusps, bulbous molar crowns and molar taurodontism. Tooth roots were usually short\\/blunted\\/spindle-like in permanent molars. The prevalence of dental caries was low in the permanent dentition (mean DMFT 0.7) but high in the primary dentition (mean dmft 2.4). Oral hygiene instruction with plaque and or calculus removal was indicated in 71% of those that were dentate. CONCLUSION: Patients with Hurler Syndrome post-HSCT are likely to have delayed dental development, a malocclusion, and dental anomalies, particularly hypodontia and microdontia.

Selective Depletion of αβ T Cells and B Cells for Human Leukocyte Antigen-Haploidentical Hematopoietic Stem Cell Transplantation. A Three-Year Follow-Up of Procedure Efficiency.

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Li Pira, Giuseppina; Malaspina, David; Girolami, Elia; Biagini, Simone; Cicchetti, Elisabetta; Conflitti, Gianpiero; Broglia, Manuel; Ceccarelli, Stefano; Lazzaro, Stefania; Pagliara, Daria; Meschini, Antonella; Bertaina, Alice; Montanari, Mauro; Locatelli, Franco

2016-11-01

HLA-haploidentical family donors represent a valuable option for children requiring allogeneic hematopoietic stem cell transplantation (HSCT). Because graft-versus-host diseases (GVHD) is a major complication of HLA-haploidentical HSCT because of alloreactive T cells in the graft, different methods have been used for ex vivo T cell depletion. Removal of donor αβ T cells, the subset responsible for GVHD, and of B cells, responsible for post-transplantation lymphoproliferative disorders, have been recently developed for HLA-haploidentical HSCT. This manipulation preserves, in addition to CD34 +  progenitors, natural killer, γδ T, and monocytes/dendritic cells, contributing to anti-leukemia activity and protection against infections. We analyzed depletion efficiency and cell yield in 200 procedures performed in the last 3 years at our center. Donors underwent CD34 +   hematopoietic stem cell (HSC) peripheral blood mobilization with granulocyte colony-stimulating factor (G-CSF). Poor CD34 +  cell mobilizers (48 of 189, 25%) received plerixafor in addition to G-CSF. Aphereses containing a median of 52.5 × 10 9 nucleated cells and 494 × 10 6 CD34 +  HSC were manipulated using the CliniMACS device. In comparison to the initial product, αβ T cell depletion produced a median 4.1-log reduction (range, 3.1 to 5.5) and B cell depletion led to a median 3.4-log reduction (range, 2.0 to 4.7). Graft products contained a median of 18.5 × 10 6 CD34 +  HSC/kg recipient body weight, with median values of residual αβ T cells and B cells of 29 × 10 3 /kg and 33 × 10 3 /kg, respectively. Depletion efficiency monitored at 6-month intervals demonstrated steady performance, while improved recovery of CD34 +  cells was observed after the first year (P = .0005). These data indicate that αβ T cell and B cell depletion of HSC grafts from HLA-haploidentical donors was efficient and reproducible. Copyright © 2016 The American Society for Blood and Marrow

The need for endodontic treatment and systemic characteristics of hematopoietic stem cell transplantation patients.

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Braga-Diniz, Julia Mourão; Santa-Rosa, Caroline Christine; Martins, Renata de Castro; Silva, Maria Elisa Souza E; Vieira, Leda Quercia; Ribeiro Sobrinho, Antônio Paulino

2017-07-03

The aim of this study is to investigate the relationship between the epidemiological and clinical profiles of patients before and after hematopoietic stem cell transplantation (HSCT) and the need for endodontic treatment. The subjects included 188 individuals enrolled in the dental care program for transplanted patients of the School of Dentistry, Federal University of Minas Gerais (Faculdade de Odontologia da Universidade Federal de Minas Gerais, FO-UFMG) from March 2011 through March 2016. The patients were subjected to an HSCT conditioning dental regimen based on a thorough clinical and radiographic evaluation. Intraoral periapical and bite-wing X-rays were obtained, and after evaluation, specific dental treatment was planned and performed. The following demographic and clinical data were collected from the patients' medical records: age, gender, transplantation stage, primary disease, transplant type, medication used, complete blood count at the time of visit, and need for endodontic treatment. The Kolmogorov-Smirnov and the chi-square tests were used. Leukemia (31.3%) and multiple myeloma (17.9%) were the most prevalent primary diseases. Most patients were subjected to allogeneic-related transplantation (83.6%). Most patients exhibited platelet counts and hemoglobin concentrations below the reference values in the pre-transplantation stage, while the neutrophil and platelet counts and the hemoglobin levels were within the reference ranges in the post-transplantation stage. The proportions of individuals requiring endodontic treatment were similar between the pre- and post-transplantation groups: 24.3% and 24.7%, respectively. The systemic conditions of the patients referred for dental treatment were compromised.

A relevância das células natural killer (NK e killer immunoglobulin-like receptors (KIR no transplante de células-tronco hematopoéticas (TCTH The relevance of natural killer (NK cells and killer immunoglobulin-like receptors (KIR in hematopoietic stem cell transplantation (HSCT

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Aline Almeida-Oliveira

2008-08-01

cell transplantation (HSCT. HLA disparities between the donor and patient in HSCT may be distinguished by NK cells leading to alloreactivity. Even though there are some promising results, until now existing studies have not reached any consensus. Here, we will review the relevance of NK cells and KIR in the different types of HSC.

Predominant or complete recipient T-cell chimerism following alemtuzumab-based allogeneic transplantation is reversed by donor lymphocytes and not associated with graft failure.

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Mohamedbhai, Sajir G; Edwards, Noha; Morris, Emma C; Mackinnon, Stephen; Thomson, Kirsty J; Peggs, Karl S

2012-02-01

The clinical significance of mixed chimerism following allogeneic haematopoietic stem cell transplantation (HSCT) remains controversial. Its relevance and incidence are probably influenced by the conditioning regimen and incorporation of T-cell depletion. The presence of recipient chimerism levels >40-50% following T-cell replete reduced intensity transplantation correlates with a high risk of graft rejection, regardless of donor-lymphocyte infusions, but it is unclear whether this finding translates to T-cell depleted transplants. We conducted a retrospective single-institution analysis of patients receiving alemtuzumab-based HSCT. 27/152 (18%) evaluable cases had predominantly recipient T-cell chimerism at 3 months or beyond. By contrast, coincident chimerism in the granulocyte lineage was predominantly of donor origin (median 100%) in all but one patient. Donor lymphocyte infusion effectively converted predominantly recipient T-cell chimerism to ful donor chimerism in all evaluable cases including three cases with no detectable donor T cells. The only graft failure occurred in the patient with predominantly recipient myeloid chimerism in whom rejection occurred rapidly before donor lymphocytes could be administered. We conclude that predominant or complete recipient T-cell chimerism following alemtuzumab-based regimens does not have the same clinical implications as that following T-cell replete transplants and can be effectively converted with donor lymphocytes without the need for lympho-depleting agents or re-conditioning. © 2011 Blackwell Publishing Ltd.

Health-related quality of life (HRQoL): the impact of medical and demographic variables upon pediatric recipients of hematopoietic stem cell transplantation.

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Brice, Lisa; Weiss, Rebecca; Wei, Ying; Satwani, Prakash; Bhatia, Monica; George, Diane; Garvin, James; Morris, Erin; Harrison, Lauren; Cairo, Mitchell S; Sands, Stephen A

2011-12-15

The trajectory of Heath-Related Quality of Life (HRQoL) in pediatric recipients who have undergone hematopoietic stem cell transplantation (HSCT), as well as the demographic and medical factors that predict HRQoL, has lagged behind the adult research. A prospective longitudinal study of HRQoL in pediatric HSCT recipients was conducted with 95 patients at the Columbia University Medical Center between 2002 and 2009. Both children and parents completed the PedsQL 4.0 prior to HSCT and at days 100, 180, and 365-post-HSCT. The majority of patients and their parents reported linear improvements in HRQoL in the first year post-transplant; however, a portion of patients were in the at-risk group at each time point. Latent growth modeling was utilized to examine demographic and medical factors that predicted initial HRQoL and its trajectory. Older age at transplant significant predicted lowered HRQoL at baseline for self- and parent-report. Female gender significantly impacted lowered self-reported physical HRQoL over time. Ethnicity was a significant predictor of HRQoL at baseline and over time for self- and parent-report, with African-American children reporting the highest HRQoL; whereas, the worst decline in psychosocial HRQoL was often reported by parents and children of Asian descent. This research identifies the significant impact of ethnicity upon HRQoL following pediatric HSCT. It is likely that an individual's pre-morbid experiences and expectations, particularly with regard to culture, behaviors, and values, influence the parent and child's perceptions and expectations of the HSCT process. Copyright © 2011 Wiley Periodicals, Inc.

Parvovirus B19 in the Context of Hematopoietic Stem Cell Transplantation: Evaluating Cell Donors and Recipients

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Gama, Bianca E.; Emmel, Vanessa E.; Oliveira-Silva, Michelle; Gutiyama, Luciana M.; Arcuri, Leonardo; Colares, Marta; de Cássia Tavares, Rita; Bouzas, Luis F.; Abdelhay, Eliana; Hassan, Rocio

2017-01-01

Background Parvovirus B19 (B19V) is a common human pathogen, member of the family Parvoviridae. Typically, B19V has been found to infect erythroid progenitors and cause hematological disorders, such as anemia and aplastic crisis. However, the persistence of genomic deoxyribonucleic acid (DNA) has been demonstrated in tonsils, liver, skin, brain, synovial, and testicular tissues as well as bone marrow, for both symptomatic and asymptomatic subjects. Although the molecular and cellular mechanisms of persistence remain undefined, it raises questions about potential virus transmissibility and its effects in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Methods With this aim, we retrospectively screened allogeneic stem cell donors from 173 patients admitted for allo-HSCT from January 2008 to May 2013 using a seminested polymerase chain reaction approach. Results We found 8 positive donor samples, yielding a 4.6% of parvovirus prevalence (95% confidence interval, 2.36-8.85). Pre- and post-HSCT samples (n = 51) from the 8 recipients of the positive donors were also investigated, and 1 case exhibited B19V DNA in the post-HSCT follow-up (D + 60). Direct DNA sequencing was performed to determine the genotype of isolates and classification, performed by phylogenetic reconstruction, showed a predominance of genotype 1a, whereas the rare genotype 3b was detected in 2 additional patients. By molecular cloning, different B19V 1a substrains polymorphisms were evidenced in the single case in which donor and its recipient were B19V+. Conclusions Our results suggest that HSCT allografts are not a main source for B19V transmission, pointing to potential events of reinfection or endogenous viral reactivation. PMID:29184906

Parvovirus B19 in the Context of Hematopoietic Stem Cell Transplantation: Evaluating Cell Donors and Recipients.

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Gama, Bianca E; Emmel, Vanessa E; Oliveira-Silva, Michelle; Gutiyama, Luciana M; Arcuri, Leonardo; Colares, Marta; de Cássia Tavares, Rita; Bouzas, Luis F; Abdelhay, Eliana; Hassan, Rocio

2017-11-01

Parvovirus B19 (B19V) is a common human pathogen, member of the family Parvoviridae. Typically, B19V has been found to infect erythroid progenitors and cause hematological disorders, such as anemia and aplastic crisis. However, the persistence of genomic deoxyribonucleic acid (DNA) has been demonstrated in tonsils, liver, skin, brain, synovial, and testicular tissues as well as bone marrow, for both symptomatic and asymptomatic subjects. Although the molecular and cellular mechanisms of persistence remain undefined, it raises questions about potential virus transmissibility and its effects in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. With this aim, we retrospectively screened allogeneic stem cell donors from 173 patients admitted for allo-HSCT from January 2008 to May 2013 using a seminested polymerase chain reaction approach. We found 8 positive donor samples, yielding a 4.6% of parvovirus prevalence (95% confidence interval, 2.36-8.85). Pre- and post-HSCT samples (n = 51) from the 8 recipients of the positive donors were also investigated, and 1 case exhibited B19V DNA in the post-HSCT follow-up (D + 60). Direct DNA sequencing was performed to determine the genotype of isolates and classification, performed by phylogenetic reconstruction, showed a predominance of genotype 1a, whereas the rare genotype 3b was detected in 2 additional patients. By molecular cloning, different B19V 1a substrains polymorphisms were evidenced in the single case in which donor and its recipient were B19V+. Our results suggest that HSCT allografts are not a main source for B19V transmission, pointing to potential events of reinfection or endogenous viral reactivation.

Prospective study establishing a management plan for impacted third molar in patients undergoing hematopoietic stem cell transplantation.

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Yamagata, Kenji; Onizawa, Kojiro; Yanagawa, Toru; Takeuchi, Yasutoshi; Hasegawa, Yuichi; Chiba, Shigeru; Bukawa, Hiroki

2011-02-01

Although dental treatment before hematopoietic stem cell transplantation (HSCT) is essential to prevent serious infections from oral sources, the best management plan for impacted third molar (ITM) is unclear. This study was planned to establish a management plan for ITM. Eighty-four candidates for HSCT therapy were consecutively enrolled in the prospective trial. The management plan, which was evidence based and prospectively decided, was to extract the symptomatic ITMs and to leave the asymptomatic ones untreated, regardless of their impacted position. Eighty-seven ITMs were observed in 35 patients. The ITMs were in the maxilla of 25 patients and the mandible of 28 patients. Dental extraction of 7 teeth was performed in 6 patients without complications. All of the patients received the scheduled HSCT therapy and none experienced odontogenic infection while myelosuppressed. This management plan for ITM appears to be appropriate for pre-HSCT patients. Moreover, the experienced dental provider is suggested as a necessary and valuable part of the HSCT team. Crown Copyright © 2011. Published by Mosby, Inc. All rights reserved.

Comparison of matched sibling donors versus unrelated donors in allogeneic stem cell transplantation for primary refractory acute myeloid leukemia: a study on behalf of the Acute Leukemia Working Party of the EBMT

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Eolia Brissot

2017-06-01

Full Text Available Abstract Background Primary refractory acute myeloid leukemia (PRF-AML is associated with a dismal prognosis. Allogeneic stem cell transplantation (HSCT in active disease is an alternative therapeutic strategy. The increased availability of unrelated donors together with the significant reduction in transplant-related mortality in recent years have opened the possibility for transplantation to a larger number of patients with PRF-AML. Moreover, transplant from unrelated donors may be associated with stronger graft-mediated anti-leukemic effect in comparison to transplantations from HLA-matched sibling donor, which may be of importance in the setting of PRF-AML. Methods The current study aimed to address the issue of HSCT for PRF-AML and to compare the outcomes of HSCT from matched sibling donors (n = 660 versus unrelated donors (n = 381, for patients with PRF-AML between 2000 and 2013. The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate. Results HSCT provide patients with PRF-AML a 2-year leukemia-free survival and overall survival of about 25 and 30%, respectively. In multivariate analysis, two predictive factors, cytogenetics and time from diagnosis to transplant, were associated with lower leukemia-free survival, whereas Karnofsky performance status at transplant ≥90% was associated with better leukemia-free survival (LFS. Concerning relapse incidence, cytogenetics and time from diagnosis to transplant were associated with increased relapse. Reduced intensity conditioning regimen was the only factor associated with lower non-relapse mortality. Conclusions HSCT was able to rescue about one quarter of the patients with PRF-AML. The donor type did not have any impact on PRF patients’ outcomes. In contrast, time to transplant was a major prognostic factor for LFS. For patients with PRF-AML who do not have a matched sibling donor, HSCT from an

Compassionate presence: The meaning of hematopoietic stem cell transplant nursing.

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Sabo, Brenda M

2011-04-01

Within oncology, working with patients who are suffering or at end-of-life has been recognized repeatedly as stress-inducing, yet there is little agreement on what specifically nurses may experience as a result of their work. Further, research focused on caring work within the context of hematopoietic stem cell transplant (HSCT) nursing is almost non-existent. In light of the gap, this interpretative phenomenological study focused on enhancing the knowledge and understanding of the effect(s) of nursing work on the psychosocial health and well being of HSCT nurses. An interpretative phenomenological design grounded in the work of Heidegger and van Manen was used to explore nursing work among HSCT nurses. Twelve nurses from three Canadian tertiary healthcare facilities participated in multiple interviews and focus groups. Thematic analysis resulted in the emergence of four core themes and one overarching novel theme, compassionate presence. The discussion provides an overview of the novel finding, compassionate presence, which challenges the notion that working with individuals who are suffering or at end-of-life inevitably leads to adverse psychosocial effects. Implications for practice, education and research are also provided. Compassionate presence emerged to suggest a potential buffering effect against adverse consequences of HSCT nursing work. This finding underscored the value of the relationship as an integral component of nursing work. Copyright © 2010 Elsevier Ltd. All rights reserved.

Potential contribution of a novel Tax epitope-specific CD4+ T cells to graft-versus-Tax effect in adult T cell leukemia patients after allogeneic hematopoietic stem cell transplantation.

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Tamai, Yotaro; Hasegawa, Atsuhiko; Takamori, Ayako; Sasada, Amane; Tanosaki, Ryuji; Choi, Ilseung; Utsunomiya, Atae; Maeda, Yasuhiro; Yamano, Yoshihisa; Eto, Tetsuya; Koh, Ki-Ryang; Nakamae, Hirohisa; Suehiro, Youko; Kato, Koji; Takemoto, Shigeki; Okamura, Jun; Uike, Naokuni; Kannagi, Mari

2013-04-15

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for adult T cell leukemia/lymphoma (ATL) caused by human T cell leukemia virus type 1 (HTLV-1). We previously reported that Tax-specific CD8(+) cytotoxic T lymphocyte (CTL) contributed to graft-versus-ATL effects in ATL patients after allo-HSCT. However, the role of HTLV-1-specific CD4(+) T cells in the effects remains unclear. In this study, we showed that Tax-specific CD4(+) as well as CD8(+) T cell responses were induced in some ATL patients following allo-HSCT. To further analyze HTLV-1-specific CD4(+) T cell responses, we identified a novel HLA-DRB1*0101-restricted epitope, Tax155-167, recognized by HTLV-1-specific CD4(+) Th1-like cells, a major population of HTLV-1-specific CD4(+) T cell line, which was established from an ATL patient at 180 d after allo-HSCT from an unrelated seronegative donor by in vitro stimulation with HTLV-1-infected cells from the same patient. Costimulation of PBMCs with both the identified epitope (Tax155-167) and known CTL epitope peptides markedly enhanced the expansion of Tax-specific CD8(+) T cells in PBMCs compared with stimulation with CTL epitope peptide alone in all three HLA-DRB1*0101(+) patients post-allo-HSCT tested. In addition, direct detection using newly generated HLA-DRB1*0101/Tax155-167 tetramers revealed that Tax155-167-specific CD4(+) T cells were present in all HTLV-1-infected individuals tested, regardless of HSCT. These results suggest that Tax155-167 may be the dominant epitope recognized by HTLV-1-specific CD4(+) T cells in HLA-DRB1*0101(+)-infected individuals and that Tax-specific CD4(+) T cells may augment the graft-versus-Tax effects via efficient induction of Tax-specific CD8(+) T cell responses.

The role of missing killer cell immunoglobulin-like receptor ligands in T cell replete peripheral blood stem cell transplantation from HLA-identical siblings.

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Clausen, Johannes; Kircher, Brigitte; Auberger, Jutta; Schumacher, Petra; Ulmer, Hanno; Hetzenauer, Gabriele; Wolf, Dominik; Gastl, Günther; Nachbaur, David

2010-02-01

The contribution of natural killer (NK) cells to graft-versus-malignancy (GVM) effects following hematopoietic stem cell transplantation (HSCT) remains uncertain, particularly in the HLA-identical setting. A model considering missing HLA ligands to the donor's inhibitory killer cell immunoglobulin-like receptor (KIR), termed the missing KIR ligand model, has been established in T cell depleted bone marrow transplantation (BMT), but lacks validity in other cohorts with different treatment characteristics. We hypothesized that the impact of missing KIR ligands on relapse-free survival (RFS) and overall survival (OS) in T cell replete peripheral blood SCT (PBSCT) differs from that in the T cell depleted BMT setting, and retrospectively evaluated 100 consecutive, HLA-identical sibling transplantations for hematologic malignancies. In addition to KIR ligand status, we considered the donors' activating KIRs and grafted NK, T, and CD34(+) cell doses. Our findings demonstrate noninferiority for OS (P = .005) and RFS (P = .002) for the heterozygous HLA-C group KIR ligand status (C1/2; n = 47) compared with patients missing either C1 or C2 (n = 53). Similarly, OS (P = .031) and RFS (P = .034) of Bw4-positive patients was noninferior to that of patients missing a Bw4 ligand to KIR3DL1. By multivariate analysis, C1/2 heterozygous patients had a favorable risk ratio (RR) for relapse (RR = 0.28; P = .003), RFS (RR = 0.56; P = .046), and acute graft-versus-host disease grade II-IV (RR = 0.36; P = .05). Following reduced-intensity conditioning (RIC), but not standard-intensity conditioning, myeloablative (MA) transplantation, a grafted NK cell dose above the median (3.4 x 10(7)/kg) was associated with a lower risk of relapse (RR = 0.57; P = .003) and improved survival (RR = 0.78; P = .03). Overall, our findings support a role for NK alloreactivity in HLA-identical HSCT, but argue against a favorable impact of missing KIR ligands in the given setting. We conclude that the mechanism

Recent Developments in Cellular Immunotherapy for HSCT-associated Complications

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Monica Reis

2016-11-01

Full Text Available Allogeneic HSCT is associated with serious complications and improvement of the overall clinical outcome of patients with hematological malignancies is necessary. During the last decades, post-transplant donor-derived adoptive cellular immunotherapeutic strategies have been progressively developed for the treatment of graft versus host disease (GvHD, infectious complications, and tumor relapses. To date, the common challenge of all these cell-based approaches is their implementation for clinical application. Establishing an appropriate manufacturing process, to guarantee safe and effective therapeutics with simultaneous consideration of economic requirements is one of the most critical hurdles. In this review we will discuss the recent scientific findings, clinical experiences, and technological advances for cell processing, towards the application of MSC as a therapy for treatment of severe GvHD, virus-specific T cells for targeting life-threating infections, and of CAR-engineered T cells to treat relapsed leukemia.

Invasive fungal infection among hematopoietic stem cell transplantation patients with mechanical ventilation in the intensive care unit

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Hung Chen-Yiu

2012-02-01

Full Text Available Abstract Background Invasive fungal infection (IFI is associated with high morbidity and high mortality in hematopoietic stem cell transplantation (HSCT patientsThe purpose of this study was to assess the characteristics and outcomes of HSCT patients with IFIs who are undergoing MV at a single institution in Taiwan. Methods We performed an observational retrospective analysis of IFIs in HSCT patients undergoing mechanical ventilation (MV in an intensive care unit (ICU from the year 2000 to 2009. The characteristics of these HSCT patients and risk factors related to IFIs were evaluated. The status of discharge, length of ICU stay, date of death and cause of death were also recorded. Results There were 326 HSCT patients at the Linkou Chang-Gung Memorial Hospital (Taipei, Taiwan during the study period. Sixty of these patients (18% were transferred to the ICU and placed on mechanical ventilators. A total of 20 of these 60 patients (33% had IFIs. Multivariate analysis indicated that independent risk factors for IFI were admission to an ICU more than 40 days after HSCT, graft versus host disease (GVHD, and high dose corticosteroid (p p = 0.676. Conclusion There was a high incidence of IFIs in HSCT patients requiring MV in the ICU in our study cohort. The independent risk factors for IFI are ICU admission more than 40 days after HSCT, GVHD, and use of high-dose corticosteroid.

Validation of chimerism in pediatric recipients of allogeneic hematopoietic stem cell transplantation (HSCT) a comparison between two methods: real-time PCR (qPCR) vs. variable number tandem repeats PCR (VNTR PCR).

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Kletzel, Morris; Huang, Wei; Olszewski, Marie; Khan, Sana

2013-01-01

Post-hematopoietic stem cell transplantation (HSCT) chimerism monitoring is important to assess relapse and therapeutic intervention. The purpose of our study is to compare two methods variable number tandem repeats (VNTR) vs. quantitative real- time polymerase chain reaction (qPCR) in terms of determining chimerism. 127 (peripheral blood n=112, bone marrow n=15) samples were simultaneously tested by VNTR using APO-B, D1S80, D1S111, D17S30, gene loci SRY and ZP3 and qPCR using 34 assays (CA001-CA034) that are designed to a bi-allelic insertion/deletion (indel) polymorphism in the human genome. Samples were separated in three subsets: total WBC, T-cell and Myeloid cells. Extraction of DNA was performed then quantified. We analyzed column statistics, paired t-test and regression analysis for both methods. There was complete correlation between the two methods. The simplicity and rapidity of the test results from the qPCR method is more efficient and accurate to assess chimerism.

Healing stories: narrative characteristics in cancer survivorship narratives and psychological health among hematopoietic stem cell transplant survivors.

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Benish-Weisman, Maya; Wu, Lisa M; Weinberger-Litman, Sarah L; Redd, William H; Duhamel, Katherine N; Rini, Christine

2014-08-01

Survivors of hematopoietic stem cell transplant (HSCT) have experienced a life threatening and potentially traumatic illness and treatment that make them vulnerable to long lasting negative psychological outcomes, including anxiety and depression. Nevertheless, studies show that overcoming cancer and its treatment can present an opportunity for personal growth and psychological health (reduced symptoms of anxiety and depression and high levels of emotional well-being) through resilience. However, research has not yet clarified what differentiates HSCT survivors who experience psychological growth from those who do not. By analyzing recovery narratives, we examined whether HSCT survivors' interpretation of their experiences helps explain differences in their post-treatment psychological health. Guided by narrative psychology theory, we analyzed the narratives of 23 HSCT survivors writing about their experience of cancer treatment. Psychological health was measured by: (1) emotional well-being subscale part of the Functional Assessment of Cancer Therapy Bone Marrow Transplant (FACT-BMT), (2) depression, and (3) anxiety subscales of the Brief Symptom Inventory. Findings revealed a positive relation between psychological health and a greater number of redemption episodes (going from an emotionally negative life event to an emotionally positive one) as well as fewer negative emotional expressions. SIGNIFICANCE OF THE RESULTS: Theoretical and practical implications of these findings are discussed, showing how narratives can inform interventions to assist cancer survivors with their psychological recovery.

Haematopoietic stem cell transplantation survivorship and quality of life: is it a small world after all?

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Brice, Lisa; Gilroy, Nicole; Dyer, Gemma; Kabir, Masura; Greenwood, Matt; Larsen, Stephen; Moore, John; Kwan, John; Hertzberg, Mark; Brown, Louisa; Hogg, Megan; Huang, Gillian; Tan, Jeff; Ward, Christopher; Gottlieb, David; Kerridge, Ian

2017-02-01

The aim of this qualitative study was to gain a rich understanding of the impact that haematopoietic stem cell transplantation (HSCT) has on long-term survivor's quality of life (QoL). Participants included 441 survivors who had undergone HSCT for a malignant or non-malignant disease. Data were obtained by a questionnaire positing a single open-ended question asking respondents to list the three issues of greatest importance to their QoL in survivorship. Responses were analysed and organised into QoL themes and subthemes. Major themes identified included the following: the failing body and diminished physical effectiveness, the changed mind, the loss of social connectedness, the loss of the functional self and the patient for life. Each of these themes manifests different ways in which HSCT survivor's world and opportunities had diminished compared to the unhindered and expansive life that they enjoyed prior to the onset of disease and subsequent HSCT. HSCT has a profound and pervasive impact on the life of survivors-reducing their horizons and shrinking various parts of their worlds. While HSCT survivors can describe the ways in which their life has changed, many of their fears, anxieties, regrets and concerns are existential in nature and are ill-defined-making it exceeding unlikely that they would be adequately captured by standard psychometric measures of QoL post HSCT.

Consenso brasileiro para transplante de células-tronco hematopoéticas para tratamento de doenças autoimunes Brazilian consensus on hematopoietic stem cell transplantation for autoimmune diseases

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Júlio C. Voltarelli

2010-05-01

Full Text Available Neste trabalho, foram revisadas a literatura internacional e a experiência nacional com transplante de células-tronco hematopoéticas (TCTH para doenças autoimunes. A evidência acumulada indica que o TCTH autólogo pode beneficiar pacientes com esclerose múltipla em fase inflamatória, refratária aos tratamentos medicamentosos disponíveis, e pacientes com esclerose sistêmica cutânea difusa de caráter progressivo, com ou sem comprometimento sistêmico. Esse tratamento deveria ser disponibilizado na rede pública de saúde, numa fase inicial, em centros de referência com experiência em TCTH e no manejo clínico de doenças autoimunes sistêmicas graves.In this paper, international literature and national experience on hematopoietic stem cell transplantation (HSCT for autoimmune diseases were reviewed. Cumulative evidence indicates that autologous HSCT may benefit patients with inflammatory multiple esclerosis, refractory to available drug therapy, and progressive forms of diffuse cutaneous systemic sclerosis with or without systemic involvement. Initially, this treatment should be available in reference centers of the public health system, with experience in performing HSCT and in treating severe systemic autoimmune diseases.

[Role of long-term follow-up in management of late-onset post-hematopoietic stem cell transplant complications].

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Asano-Mori, Yuki

As the number of long-term survivors after allogeneic hematopoietic stem cell transplantation (HSCT) has increased owing to advances in transplantation and supportive care techniques, the health and welfare of these survivors have come into focus. However, they are still at risks for various complications, including chronic graft-versus-host disease, infectious diseases, and secondary cancers even in the late period, which can not only interfere with the patient's quality of life (QOL) but also lead to death. The importance of long-term follow-up (LTFU) and management have been recently recognized, and nationwide systems to promote LTFU care in patients receiving HSCT, such as medical fee revision, publication of a LTFU guideline unique to Japan, and preparation of patient pocketbook, is under consideration. The number of medical facilities at LTFU outpatient clinic is also increasing; therefore, an optimal comprehensive support system may be established sooner or later. However, self-management by patients is essential to overcome late complications as well as to improve QOL after HSCT. Healthcare professionals should collaborate and continue to make the greatest possible efforts to educate patients regarding the risks of late complications and their prevention.

Spiritual absence and 1-year mortality after hematopoietic stem cell transplant.

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Pereira, Deidre B; Christian, Lisa M; Patidar, Seema; Bishop, Michelle M; Dodd, Stacy M; Athanason, Rebecca; Wingard, John R; Reddy, Vijay S

2010-08-01

Religiosity and spirituality have been associated with better survival in large epidemiologic studies. This study examined the relationship between spiritual absence and 1-year all-cause mortality in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Depression and problematic compliance were examined as possible mediators of a significant spiritual absence-mortality relationship. Eighty-five adults (mean = 46.85 years old, SD = 11.90 years) undergoing evaluation for allogeneic HSCT had routine psychologie evaluation prior to HSCT admission. The Millon Behavioral Medicine Diagnostic was used to assess spiritual absence, depression, and problematic compliance, the psychosocial predictors of interest. Patient status at 1 year and survival time in days were abstracted from medical records. Cox regression analysis was used to examine the relationship between the psychosocial factors of interest and mortality after adjusting for relevant biobehavioral factors. Twenty-nine percent (n = 25) of participants died within 1 year of HSCT. After covarying for disease type, individuals with the highest spiritual absence and problematic compliance scores were significantly more likely to die 1-year post-HSCT (hazard ratio [HR] = 2.49, P = .043 and HR = 3.74, P = .029, respectively), particularly secondary to infection, sepsis, or graft-versus-host disease (GVHD) (HR = 4.56, P = .01 and HR = 5.61, P = .014), relative to those without elevations on these scales. Depression was not associated with 1-year mortality, and problematic compliance did not mediate the relationship between spiritual absence and mortality. These preliminary results suggest that both spiritual absence and problematic compliance may be associated with poorer survival following HSCT. Future research should examine these relations in a larger sample using a more comprehensive assessment of spirituality.

Allogeneic Hematopoietic Stem Cell Transplantation in the Treatment of Human C1q Deficiency: The Karolinska Experience.

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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.

Nonmyeloablative HLA-matched sibling allogeneic hematopoietic stem cell transplantation for severe sickle cell phenotype.

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Hsieh, Matthew M; Fitzhugh, Courtney D; Weitzel, R Patrick; Link, Mary E; Coles, Wynona A; Zhao, Xiongce; Rodgers, Griffin P; Powell, Jonathan D; Tisdale, John F

2014-07-02

Myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) is curative for children with severe sickle cell disease, but toxicity may be prohibitive for adults. Nonmyeloablative transplantation has been attempted with degrees of preparative regimen intensity, but graft rejection and graft-vs-host disease remain significant. To determine the efficacy, safety, and outcome on end-organ function with this low-intensity regimen for sickle cell phenotype with or without thalassemia. From July 16, 2004, to October 25, 2013, 30 patients aged 16-65 years with severe disease enrolled in this nonmyeloablative transplant study, consisting of alemtuzumab (1 mg/kg in divided doses), total-body irradiation (300 cGy), sirolimus, and infusion of unmanipulated filgrastim mobilized peripheral blood stem cells (5.5-31.7 × 10(6) cells/kg) from human leukocyte antigen-matched siblings. The primary end point was treatment success at 1 year after the transplant, defined as a full donor-type hemoglobin for patients with sickle cell disease and transfusion independence for patients with thalassemia. The secondary end points were the level of donor leukocyte chimerism; incidence of acute and chronic graft-vs-host disease; and sickle cell-thalassemia disease-free survival, immunologic recovery, and changes in organ function, assessed by annual brain imaging, pulmonary function, echocardiographic image, and laboratory testing. Twenty-nine patients survived a median 3.4 years (range, 1-8.6), with no nonrelapse mortality. One patient died from intracranial bleeding after relapse. As of October 25, 2013, 26 patients (87%) had long-term stable donor engraftment without acute or chronic graft-vs-host disease. The mean donor T-cell level was 48% (95% CI, 34%-62%); the myeloid chimerism levels, 86% (95% CI, 70%-100%). Fifteen engrafted patients discontinued immunosuppression medication with continued stable donor chimerism and no graft-vs-host disease. The normalized hemoglobin and

Treatment of hip dysplasia in patients with mucopolysaccharidosis type I after hematopoietic stem cell transplantation: results of an international consensus procedure

NARCIS (Netherlands)

Langereis, Eveline J.; Borgo, Andrea; Crushell, Ellen; Harmatz, Paul R.; van Hasselt, Peter M.; Jones, Simon A.; Kelly, Paula M.; Lampe, Christina; van der Lee, Johanna H.; Odent, Thierry; Sakkers, Ralph; Scarpa, Maurizio; Schafroth, Matthias U.; Struijs, Peter A.; Valayannopoulos, Vassili; White, Klane K.; Wijburg, Frits A.

2013-01-01

Mucopolysaccharidosis type I (MPS-I) is a lysosomal storage disorder characterized by progressive multi-organ disease. The standard of care for patients with the severe phenotype (Hurler syndrome, MPS I-H) is early hematopoietic stem cell transplantation (HSCT). However, skeletal disease, including

Haematopoietic stem cell transplantation for Diamond Blackfan anaemia: a report from the Italian Association of Paediatric Haematology and Oncology Registry.

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Fagioli, Franca; Quarello, Paola; Zecca, Marco; Lanino, Edoardo; Corti, Paola; Favre, Claudio; Ripaldi, Mimmo; Ramenghi, Ugo; Locatelli, Franco; Prete, Arcangelo

2014-06-01

Allogeneic haematopoietic stem cell transplantation (HSCT) is the only curative option for patients with Diamond Blackfan anaemia (DBA). We report the transplantation outcome of 30 Italian DBA patients referred to the Italian Association of Paediatric Haematology and Oncology Registry between 1990 and 2012. This is one of the largest national registry cohorts of transplanted DBA patients. Most patients (83%) were allografted after 2000. A matched sibling donor was employed in 16 patients (53%), the remaining 14 patients (47%) were transplanted from matched unrelated donors. Twenty-eight of the 30 patients engrafted. One patient died at day +6 due to veno-occlusive disease without achieving neutrophil recovery and another patient remained transfusion-dependent despite the presence of a full donor chimerism. The 5-year overall survival and transplant-related mortality was 74·4% and 25·6%, respectively. Patients younger than 10 years as well as those transplanted after 2000 showed a significantly higher overall survival and a significantly lower risk of transplant-related mortality. No difference between donor type was observed. Our data suggest that allogeneic HSCT from a related or unrelated donor was a reasonable alternative to transfusion therapy in young and well chelated DBA patients. © 2014 John Wiley & Sons Ltd.

The impact of HLA matching on long-term transplant outcome after allogeneic hematopoietic stem cell transplantation for CLL: a retrospective study from the EBMT registry

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Michallet, M; Sobh, M; Milligan, D

2010-01-01

We analyzed 368 chronic lymphocytic leukemia patients who underwent allogeneic hematopoietic stem cell transplantation reported to the EBMT registry between 1995 and 2007. There were 198 human leukocyte antigen (HLA)-identical siblings; among unrelated transplants, 31 were well matched in high...... worsened significantly when EBMT risk score increased. HLA matching had no significant impact on relapse (siblings: 24% (21-27); WMUD: 35% (26-44), P=0.11 and MM: 21% (18-24), P=0.81); alemtuzumab T-cell depletion and stem cell source (peripheral blood) were associated with an increased risk. Our findings...... support the use of WMUD as equivalent alternative to HLA-matched sibling donors for allogeneic HSCT in CLL, and justify the application of EBMT risk score in this disease....

The budget impact and cost-effectiveness of defibrotide for treatment of veno-occlusive disease with multi-organ dysfunction in patients post-hematopoietic stem cell transplant.

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Veenstra, David L; Guzauskas, Gregory F; Villa, Kathleen F; Boudreau, Denise M

2017-05-01

A Phase-3 study of defibrotide compared with historical controls demonstrated a 23% improvement in 100-day survival post-hematopoietic stem cell transplantation (HSCT) among patients with veno-occlusive disease with multi-organ dysfunction (VOD with MOD). To estimate the budget impact and cost-effectiveness of introducing defibrotide to a transplant center. The authors developed a budget impact model from the perspective of a bone-marrow transplant center. It was estimated that 2.3% of adults and 4.2% of children would develop VOD with MOD following HSCT based on a retrospective hospital database analysis and the effect that treating patients with defibrotide would have on costs for adult and pediatric centers was estimated. A cost-utility analysis (CUA) was also developed to capture the long-term cost-effectiveness of defibrotide. Projected life expectancies in the two groups were estimated based on trial data, transplant registry data, studies of long-term survival among HSCT patients, and US population life-tables. There was an estimated 3% increase ($330,706) per year in total adult transplantation center costs associated with adopting defibrotide, and a incremental cost-effectiveness ratio (ICER) was $47,736 per QALY gained; 88% probability defibrotide was cost-effective at a $100,000/QALY threshold. The budget impact of defibrotide for a transplant center is relatively modest compared to the overall cost of transplantation. Defibrotide provides an important survival advantage for VOD with MOD patients, and the life years gained lead to defibrotide being highly cost-effective.

Successful Reduced Intensity Allogeneic Transplant With Full Donor Chimerism and Good Quality of Life in Adolescent Patient With Wiskott-Aldrich Syndrome.

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Ali, Salah; Gacsadi, Anna; McDougall, Elizabeth; Armstrong, Christine; Krueger, Joerg; Schechter, Tal; Ali, Muhammad

2017-07-01

Wiskott-Aldrich syndrome (WAS) is an X-linked disease characterized by microthrombocytopenia, eczema, immune deficiency, and autoimmune phenomena. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment. Myeloablative conditioning is the most common regimen used for HSCT in patients with WAS to avoid the risk of mixed donor chimerism and autoimmunity post-HSCT. There is limited data on the use of reduced intensity conditioning for HSCT in patients with WAS. Here, we report a case with severe phenotype of WAS transplanted successfully with reduced intensity conditioning, which is an acceptable conditioning regimen and can be considered in patients with WAS with significantly impaired organ functions.

Next-generation sequencing-based detection of circulating tumour DNA After allogeneic stem cell transplantation for lymphoma.

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Herrera, Alex F; Kim, Haesook T; Kong, Katherine A; Faham, Malek; Sun, Heather; Sohani, Aliyah R; Alyea, Edwin P; Carlton, Victoria E; Chen, Yi-Bin; Cutler, Corey S; Ho, Vincent T; Koreth, John; Kotwaliwale, Chitra; Nikiforow, Sarah; Ritz, Jerome; Rodig, Scott J; Soiffer, Robert J; Antin, Joseph H; Armand, Philippe

2016-12-01

Next-generation sequencing (NGS)-based circulating tumour DNA (ctDNA) detection is a promising monitoring tool for lymphoid malignancies. We evaluated whether the presence of ctDNA was associated with outcome after allogeneic haematopoietic stem cell transplantation (HSCT) in lymphoma patients. We studied 88 patients drawn from a phase 3 clinical trial of reduced-intensity conditioning HSCT in lymphoma. Conventional restaging and collection of peripheral blood samples occurred at pre-specified time points before and after HSCT and were assayed for ctDNA by sequencing of the immunoglobulin or T-cell receptor genes. Tumour clonotypes were identified in 87% of patients with adequate tumour samples. Sixteen of 19 (84%) patients with disease progression after HSCT had detectable ctDNA prior to progression at a median of 3·7 months prior to relapse/progression. Patients with detectable ctDNA 3 months after HSCT had inferior progression-free survival (PFS) (2-year PFS 58% vs. 84% in ctDNA-negative patients, P = 0·033). In multivariate models, detectable ctDNA was associated with increased risk of progression/death (Hazard ratio 3·9, P = 0·003) and increased risk of relapse/progression (Hazard ratio 10·8, P = 0·0006). Detectable ctDNA is associated with an increased risk of relapse/progression, but further validation studies are necessary to confirm these findings and determine the clinical utility of NGS-based minimal residual disease monitoring in lymphoma patients after HSCT. © 2016 John Wiley & Sons Ltd.

Vascular and perivascular niches, but not the osteoblastic niche, are numerically restored following allogeneic hematopoietic stem cell transplantation in patients with aplastic anemia.

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Wu, Liangliang; Mo, Wenjian; Zhang, Yuping; Zhou, Ming; Li, Yumiao; Zhou, Ruiqing; Xu, Shiling; Pan, Shiyi; Deng, Hui; Mao, Ping; Wang, Shunqing

2017-07-01

Bone marrow (BM) niches, including the osteoblastic, vascular, and perivascular niches, are numerically impaired in patients with aplastic anemia (AA). It remains unclear whether these niches are numerically restored in AA patients after allogenic hematopoietic stem cell transplantation (allo-HSCT). To investigate changes in BM niches, we monitored 52 patients with AA who had undergone allo-HSCT and performed immunohistochemical studies of BM niches using antibodies against CD34, CD146, and osteopontin. After allo-HSCT, patients with AA exhibited a remarkable increase in the number of cellular elements in the BM niches, including the vascular and perivascular cells. However, no significant differences in endosteal cells were detected. We explored the cause of this restoration by analyzing the origin of BM mesenchymal stem cells (BM-MSCs) and the expression of cytokines in BM plasma. STR-PCR revealed that the BM-MSCs were derived from the host, not the donor. In addition, significantly elevated levels of vascular endothelial growth factor (VEGF) were found after allo-HSCT. Our data indicates that vascular and perivascular niches are numerically restored, but the endosteal niche remains numerically impaired in patients with AA after allo-HSCT, and that levels of VEGF, but not donor-derived BM-MSCs, may correlate with the restoration of BM niches.

Assessment of cardiotoxicity during haemopoietic stem cell transplantation with plasma brain natriuretic peptide.

Science.gov (United States)

Snowden, J A; Hill, G R; Hunt, P; Carnoutsos, S; Spearing, R L; Espiner, E; Hart, D N

2000-08-01

Cardiac failure is a known complication of haemopoietic stem cell transplantation (HSCT) and is often difficult to diagnose as patients may have multiple medical problems. Since brain natriuretic peptide (BNP) is largely a hormone of cardiac ventricular origin and is released early in the course of ventricular dysfunction, we have examined the value of serial plasma BNP levels for detecting cardiac failure in patients undergoing cytotoxic conditioning for HSCT. Fifteen patients undergoing HSCT were evaluated (10 undergoing autologous HSCT; five undergoing allogeneic HSCT). BNP was measured by radioimmunoassay prior to therapy and weekly for 5 weeks. Seven patients had a significant rise in BNP level (above a previously established threshold of 43 pmol/l associated with cardiac failure), occurring 1-4 weeks post commencement of conditioning. In three of these patients, cardiac failure was subsequently diagnosed clinically 3, 9 and 23 days after a BNP level of 43 pmol/l had been detected. These three patients had the highest peak BNP levels for the group and in each case elevation in BNP level occurred for a period exceeding 1 week. Although numbers were relatively small, a BNP >43 pmol/l was significantly associated with the inclusion of high-dose cyclophosphamide in the preparative regimen (P = 0.02). BNP levels showed no relationship to febrile episodes. In conclusion, these results show that plasma BNP may be used as a marker for early detection of cardiac dysfunction in patients undergoing HSCT, particularly if levels are increased for periods exceeding 1 week. Measurement of BNP during HSCT may be helpful in patients at risk of cardiac failure, in complex clinical situations and in monitoring the cardiotoxicity of preparative regimens.

Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: a phase 1 study.

Science.gov (United States)

Cruz, Conrad Russell Y; Micklethwaite, Kenneth P; Savoldo, Barbara; Ramos, Carlos A; Lam, Sharon; Ku, Stephanie; Diouf, Oumar; Liu, Enli; Barrett, A John; Ito, Sawa; Shpall, Elizabeth J; Krance, Robert A; Kamble, Rammurti T; Carrum, George; Hosing, Chitra M; Gee, Adrian P; Mei, Zhuyong; Grilley, Bambi J; Heslop, Helen E; Rooney, Cliona M; Brenner, Malcolm K; Bollard, Catherine M; Dotti, Gianpietro

2013-10-24

Autologous T cells expressing a CD19-specific chimeric antigen receptor (CD19.CAR) are active against B-cell malignancies, but it is unknown whether allogeneic CD19.CAR T cells are safe or effective. After allogeneic hematopoietic stem cell transplantation (HSCT), infused donor-derived virus-specific T cells (VSTs) expand in vivo, persist long term, and display antiviral activity without inducing graft-vs-host disease; therefore, we determined whether donor VSTs, engineered to express CD19.CAR, retained the characteristics of nonmanipulated allogeneic VSTs while gaining antitumor activity. We treated 8 patients with allogeneic (donor-derived) CD19.CAR-VSTs 3 months to 13 years after HSCT. There were no infusion-related toxicities. VSTs persisted for a median of 8 weeks in blood and up to 9 weeks at disease sites. Objective antitumor activity was evident in 2 of 6 patients with relapsed disease during the period of CD19.CAR-VST persistence, whereas 2 patients who received cells while in remission remain disease free. In 2 of 3 patients with viral reactivation, donor CD19.CAR-VSTs expanded concomitantly with VSTs. Hence CD19.CAR-VSTs display antitumor activity and, because their number may be increased in the presence of viral stimuli, earlier treatment post-HSCT (when lymphodepletion is greater and the incidence of viral infection is higher) or planned vaccination with viral antigens may enhance disease control.

Combination antifungal therapy and surgery for the treatment of invasive pulmonary aspergillosis after hematopoietic stem cell transplantation

Directory of Open Access Journals (Sweden)

Tiziana Toffolutti

2011-06-01

Full Text Available An 8-year old boy, affected by severe aplastic anemia, developed a probable pulmonary invasive aspergillosis (IA early after a second unrelated allogeneic hematopoietic stem cell transplant (HSCT. He was treated promptly with the combination of liposomal amphotericin B and caspofungin. Despite the initial stabilization, the patient deteriorated and the antifungal therapy was switched to voriconazole and caspofungin. The patient gradually improved and was discharged home on day +29 post-HSCT on oral voriconazole. On day +119, a sudden episode of hemoptysis occurred and a right superior lobectomy was decided to remove the residual aspergilloma. The patient is now alive and well more than 24 months from HSCT. This case demonstrated that antifungal combination therapy and surgery are valid options to cure pulmonary IA even in patients at high-risk and severely immunosuppressed.

Non-traditional CD4+CD25-CD69+ regulatory T cells are correlated to leukemia relapse after allogeneic hematopoietic stem cell transplantation.

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Zhao, Xiao-su; Wang, Xu-hua; Zhao, Xiang-yu; Chang, Ying-jun; Xu, Lan-ping; Zhang, Xiao-hui; Huang, Xiao-jun

2014-07-01

Non-traditional CD4+CD25-CD69+ T cells were found to be involved in disease progression in tumor-bearing mouse models and cancer patients recently. We attempted to define whether this subset of T cells were related to leukemia relapse after allogeneic hematopoietic cell transplantation (allo-HSCT). The frequency of CD4+CD25-CD69+ T cells among the CD4+ T cell population from the bone marrow of relapsed patients, patients with positive minimal residual disease (MRD+) and healthy donors was examined by flow cytometry. The CD4+CD25-CD69+ T cells were also stained with the intracellular markers to determine the cytokine (TGF-β, IL-2 and IL-10) secretion. The results showed that the frequency of CD4+CD25-CD69 + T cells was markedly increased in patients in the relapsed group and the MRD + group compared to the healthy donor group. The percentage of this subset of T cells was significantly decreased after effective intervention treatment. We also analyzed the reconstitution of CD4+CD25-CD69+ T cells at various time points after allo-HSCT, and the results showed that this subset of T cells reconstituted rapidly and reached a relatively higher level at +60 d in patients compared to controls. The incidence of either MRD+ or relapse in patients with a high frequency of CD4+CD25-CD69+ T cells (>7%) was significantly higher than that of patients with a low frequency of CD4+CD25-CD69+ T cells at +60 d, +90 d and +270 d after transplant. However, our preliminary data indicated that CD4+CD25-CD69+ T cells may not exert immunoregulatory function via cytokine secretion. This study provides the first clinical evidence of a correlation between non-traditional CD4+CD25-CD69+ Tregs and leukemia relapse after allo-HSCT and suggests that exploration of new methods of adoptive immunotherapy may be beneficial. Further research related to regulatory mechanism behind this phenomenon would be necessary.

Importance of Nongovernmental Organizations for the Establishment of a Successful Hematopoietic Stem-Cell Transplantation Program in a Developing Country

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Monica M. Rivera Franco

2018-02-01

Full Text Available Purpose: In low- and middle-income countries with limited resources, the success of a hematopoietic stem-cell transplantation (HSCT program relies directly on its affordability while obtaining similar outcomes to developed regions. The objective of this study was to describe the experience of a tertiary/referral center in Mexico City performing HSCT with the subsidy of a nongovernmental organization (NGO. Patients and Methods: We performed a retrospective analysis including 146 patients who underwent HSCT at the National Institutes of Health Sciences and Nutrition Salvador Zubiran and were subsidized by the NGO Unidos. Results: Seventy-five patients (51% and 71 patients (49% underwent autologous and allogeneic HSCT, respectively. The median age was 30 years, 56% did not obtain a bachelor’s degree, 79% had a low socioeconomic level, and 75% were unemployed. None had any health coverage. According to the real patient out-of-pocket expense, the subsidy by Unidos corresponded to 88% and 72% in autologous and allogeneic HSCT, respectively. Conclusion: Our results highlight that undergoing an HSCT was feasible for vulnerable patients because of the subsidy of medications and chemotherapy by Unidos. Therefore, creating NGOs in developing countries is important to provide complex medical procedures, such as HSCT, at limited-resource centers to underserved populations while obtaining good outcomes.

Patient-Reported Measures of Hearing Loss and Tinnitus in Pediatric Cancer and Hematopoietic Stem Cell Transplantation: A Systematic Review

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Stark, Daniel; Rosenberg, Abby R.; Johnston, Donna; Knight, Kristin; Caperon, Lizzie; Uleryk, Elizabeth; Frazier, A. Lindsay; Sung, Lillian

2016-01-01

Purpose: We identified studies that described use of any patient-reported outcome scale for hearing loss or tinnitus among children and adolescents and young adults (AYAs) with cancer or hematopoietic stem cell transplantation (HSCT) recipients. Method: In this systematic review, we performed electronic searches of OvidSP MEDLINE, EMBASE, and…

Periodontal status and bacteremia with oral viridans streptococci and coagulase negative staphylococci in allogeneic hematopoietic stem cell transplantation recipients: a prospective observational study

NARCIS (Netherlands)

Raber-Durlacher, Judith E.; Laheij, Alexa M. G. A.; Epstein, Joel B.; Epstein, Matthew; Geerligs, Gerard M.; Wolffe, Gordon N.; Blijlevens, Nicole M. A.; Donnelly, J. Peter

2013-01-01

This study was aimed to investigate whether any association could be found between the presence of an inflamed and infected periodontium (e.g., gingivitis and periodontitis) and the development of bacteremia during neutropenia following allogeneic hematopoietic stem cell transplantation (HSCT).

Mind and body practices for fatigue reduction in patients with cancer and hematopoietic stem cell transplant recipients : A systematic review and meta-analysis

NARCIS (Netherlands)

Duong, Nathan; Davis, Hailey; Robinson, Paula D; Oberoi, Sapna; Cataudella, Danielle; Culos-Reed, S Nicole; Gibson, Faith; Götte, Miriam; Hinds, Pamela; Nijhof, Sanne L; Tomlinson, Deborah; van der Torre, Patrick; Ladas, Elena; Cabral, Sandra; Dupuis, Lee L.; Sung, Lillian

2017-01-01

PURPOSE: To determine whether non-physical activity mind and body practices reduce the severity of fatigue in patients with cancer or hematopoietic stem cell transplant (HSCT) recipients compared to control interventions. METHODS: We included randomized trials which compared non-physical activity

Cost utility analysis of reduced intensity hematopoietic stem cell transplantation in adolescence and young adult with severe thalassemia compared to hypertransfusion and iron chelation program.

Science.gov (United States)

Sruamsiri, Rosarin; Chaiyakunapruk, Nathorn; Pakakasama, Samart; Sirireung, Somtawin; Sripaiboonkij, Nintita; Bunworasate, Udomsak; Hongeng, Suradej

2013-02-05

Hematopoieticic stem cell transplantation is the only therapeutic option that can cure thalassemia disease. Reduced intensity hematopoietic stem cell transplantation (RI-HSCT) has demonstrated a high cure rate with minimal complications compared to other options. Because RI-HSCT is very costly, economic justification for its value is needed. This study aimed to estimate the cost-utility of RI-HSCT compared with blood transfusions combined with iron chelating therapy (BT-ICT) for adolescent and young adult with severe thalassemia in Thailand. A Markov model was used to estimate the relevant costs and health outcomes over the patients' lifetimes using a societal perspective. All future costs and outcomes were discounted at a rate of 3% per annum. The efficacy of RI-HSCT was based a clinical trial including a total of 18 thalassemia patients. Utility values were derived directly from all patients using EQ-5D and SF-6D. Primary outcomes of interest were lifetime costs, quality adjusted life-years (QALYs) gained, and the incremental cost-effectiveness ratio (ICER) in US ($) per QALY gained. One-way and probabilistic sensitivity analyses (PSA) were conducted to investigate the effect of parameter uncertainty. In base case analysis, the RI-HSCT group had a better clinical outcomes and higher lifetime costs. The incremental cost per QALY gained was US $3,236 per QALY. The acceptability curve showed that the probability of RI-HSCT being cost-effective was 71% at the willingness to pay of 1 time of Thai Gross domestic product per capita (GDP per capita), approximately US $4,210 per QALY gained. The most sensitive parameter was utility of severe thalassemia patients without cardiac complication patients. At a societal willingness to pay of 1 GDP per capita, RI-HSCT was a cost-effective treatment for adolescent and young adult with severe thalassemia in Thailand compared to BT-ICT.

Clinical assessment of anti-viral CD8+ T cell immune monitoring using QuantiFERON-CMV® assay to identify high risk allogeneic hematopoietic stem cell transplant patients with CMV infection complications.

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Siok-Keen Tey

Full Text Available The reconstitution of anti-viral cellular immunity following hematopoietic stem cell transplantation (HSCT is crucial in preventing cytomegalovirus (CMV-associated complications. Thus immunological monitoring has emerged as an important tool to better target pre-emptive anti-viral therapies. However, traditional laboratory-based assays are too cumbersome and complicated to implement in a clinical setting. Here we conducted a prospective study of a new whole blood assay (referred to as QuantiFERON-CMV® to determine the clinical utility of measuring CMV-specific CD8+ T-cell responses as a prognostic tool. Forty-one evaluable allogeneic HSCT recipients underwent weekly immunological monitoring from day 21 post-transplant and of these 21 (51.2% showed CMV reactivation and 29 (70.7% developed acute graft-versus-host disease (GvHD. Patients with acute GvHD (grade ≥ 2 within 6 weeks of transplant showed delayed reconstitution of CMV-specific T-cell immunity (p = 0.013 and a higher risk of CMV viremia (p = 0.026. The median time to stable CMV-specific immune reconstitution was 59 days and the incidence of CMV reactivation was lower in patients who developed this than those who did not (27% versus 65%; p = 0.031. Furthermore, a failure to reconstitute CMV-specific immunity soon after the onset of CMV viraemia was associated with higher peak viral loads (5685 copies/ml versus 875 copies/ml; p = 0.002. Hence, QuantiFERON-CMV® testing in the week following CMV viremia can be useful in identifying HSCT recipients at risk of complicated reactivation.

First successful automated red cell exchange (erythrocytapheresis ...

African Journals Online (AJOL)

INTRODUCTION: Despite several documented challenges, Hematopoietic Stem cell Transplantation (HSCT) remains the only curative therapy for Sickle Cell Disease (SCD). However HSCT is expensive with its complications, therefore supportive care remains the main available option to many Nigerians. Frequent blood ...

Establishing an Inpatient Gym for Recipients of Stem Cell Transplantation: A Multidisciplinary Collaborative.

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Blackburn, Roxann; Presson, Kimberly; Laufman, Robin; Tomczak, Nancy; Brassil, Kelly J

2016-02-01

Evidence suggests that exercise can have a profound impact on physiologic and quality-of-life outcomes for patients undergoing hematopoietic stem cell transplantation (HSCT). Despite this, implementation of a gym on inpatient HSCT units may be limited because of space, infrastructure, and budget. This article presents the design, implementation, and evaluation of the gym and highlights its use for individual and group patient activities. An interprofessional team at a National Cancer Institute-designated comprehensive cancer center collaborated to design and implement gym space on an inpatient HSCT unit servicing as many as 86 beds. Informal feedback from patients, as well as metrics on use of the space, indicates that the gym is well received and frequently used. Limitations include the absence of a designated physical therapy technician to supervise individual activity, which may limit patient access when a staff member is unavailable. The cost associated with the implementation of such space may be offset by benefits to patients, including enhanced conditioning, quality of life, and time to discharge, as evidenced in the literature.

Evolution of human cytomegalovirus-seronegative donor/-seropositive recipient high-risk combination frequency in allogeneic hematopoietic stem cell transplantations at Institute of Hematology and Blood Transfusion during 1995-2014.

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Nemeckova, S; Sroller, V; Stastna-Markova, M

2016-04-01

Human cytomegalovirus (HCMV) establishes lifelong latent infection that can result in severe life-threatening disease in immunosuppressed patients after hematopoietic stem cell transplantation (HSCT). An HCMV-seropositive transplant recipient who receives a graft from a seronegative donor (R+/D-) is at high risk of recurrent HCMV reactivation. To assess the incidence of R+/D- combination, we retrospectively evaluated HCMV-seronegative donors for 746 allogeneic HSCT treatments carried out at our center during 1995-2014. In our cohort, 20% HCMV-seronegative HSCT recipients, 21% HCMV-seronegative related graft donors, and 52% HCMV-seronegative unrelated graft donors were included. Analyses of the HCMV serostatus of hematopoietic stem cell donors during 2 consecutive calendar periods (1995-2005 and 2006-2014) showed a significant increase in the proportion of seronegative donors (odds ratio [OR] = 1.947). In addition, the number of HSCT treatments using an unrelated donor increased (OR = 2.376). Finally, the use of grafts from countries with a very low HCMV prevalence increased. This increase in HCMV seronegativity in unrelated donors and the increased proportion of unrelated donors were responsible for the increased occurrence of the high-risk combination R+/D- (OR = 1.680). If the reduction in the rate of HCMV-seropositive graft donors continues, an increased frequency of HCMV reactivation events in our transplant recipients can be expected, because of the increasing occurrence of the high-risk R+/D- combination. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Comparison of chemotherapy and hematopoietic stem cell ...

African Journals Online (AJOL)

2013-02-19

Feb 19, 2013 ... scores before and after hematopoietic stem cell transplantation (HSCT) and chemotherapy. Materials and Methods: Thirty-six patients undergoing HSCT were included in the study. A pre-HSCT dental treatment protocol was implemented that consisted of restoration of all active carious lesions, treatment of ...

Allogeneic Stem Cell Transplantation in Congenital Hemoglobinopathies Using a Tailored Busulfan-Based Conditioning Regimen: Single-Center Experience.

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Zaidman, Irina; Rowe, Jacob M; Khalil, Abdalla; Ben-Arush, Myriam; Elhasid, Ronit

2016-06-01

Hematopoietic stem cell transplantation (HSCT) is the only proven curative option for patients with hemoglobinopathies, both thalassemia and sickle cell anemia (SCA). A busulfan-based myeloablative conditioning regimen is the standard of care for HSCT in these patients, although increased treatment-related morbidity, including veno-occlusive disease (VOD), has been demonstrated. Thirty-eight pediatric patients, median age 8 years (range, 6 months to 22 years), suffering from hemoglobinopathy were treated at Rambam Medical Center in Haifa, Israel, between 1998 and 2011. Thirty-four patients had thalassemia major and 4 had SCA. The 38 patients underwent 40 HSCTs, 34 of which were first transplants and 6 second transplants. Most transplants (32/40) were from matched sibling donors. Sources of stem cells were peripheral blood in 30 transplants, bone marrow in 7 transplants, and cord blood in 3 transplants. All received different customized busulfan-based conditioning regimens tailored by pharmacokinetic analysis of busulfan levels. Primary engraftment occurred in 37 of 40 transplants. Neutrophil engraftment (>.5 × 10(9)/L) occurred at a median of 15.3 days post-transplantation (range, 10 to 45). Platelet transfusion independence (>20 × 10(9)/L) occurred at a median of 22.3 days (range, 11 to 60). The rate of 5-year overall survival for thalassemia patients after first transplantation was 90.5% ± 5.3%. The rate of 5-year thalassemia-free survival was 81.7% ± 6.8%. Cumulative incidence of acute graft-versus-host disease (GVHD) was 17.6%. Rate of grades III to IV GVHD was 8.8%. Cumulative incidence of chronic GVHD was 23.5%, with 11.8% incidence of extensive chronic GVHD. One patient developed VOD. Full donor chimerism occurred in 36.4% of patients with class 1 + 2 thalassemia, compared with 78.6% in class 3 thalassemia (P = .049). Overall survival above 90% in patients undergoing their first transplant was demonstrated using busulfan

Long-term control of recurrent or refractory viral infections after allogeneic HSCT with third-party virus-specific T cells.

Science.gov (United States)

Withers, Barbara; Blyth, Emily; Clancy, Leighton E; Yong, Agnes; Fraser, Chris; Burgess, Jane; Simms, Renee; Brown, Rebecca; Kliman, David; Dubosq, Ming-Celine; Bishop, David; Sutrave, Gaurav; Ma, Chun Kei Kris; Shaw, Peter J; Micklethwaite, Kenneth P; Gottlieb, David J

2017-11-14

Donor-derived adoptive T-cell therapy is a safe and effective treatment of viral infection posttransplant, but it is limited by donor serostatus and availability and by its personalized nature. Off-the-shelf, third-party virus-specific T cells (VSTs) appear promising, but the long-term safety and durability of responses have yet to be established. We conducted a prospective study of 30 allogeneic hemopoietic stem cell transplant (HSCT) patients with persistent or recurrent cytomegalovirus (CMV) (n = 28), Epstein-Barr virus (n = 1), or adenovirus (n = 1) after standard therapy. Patients were treated with infusions of partially HLA-matched, third-party, ex vivo-expanded VSTs (total = 50 infusions) at a median of 75 days post-HSCT (range, 37 to 349 days). Safety, viral dynamics, and immune recovery were monitored for 12 months. Infusions were safe and well tolerated. Acute graft versus host disease occurred in 2 patients, despite a median HLA match between VSTs and the recipient of 2 of 6 antigens. At 12 months, the cumulative incidence of overall response was 93%. Virological control was durable in the majority of patients; the reintroduction of antiviral therapy after the final infusion occurred in 5 patients. CMV-specific T-cell immunity rose significantly and coincided with a rise in CD8 + terminal effector cells. PD-1 expression was elevated on CD8 + lymphocytes before the administration of third-party T cells and remained elevated at the time of viral control. Third-party VSTs show prolonged benefit, with virological control achieved in association with the recovery of CD8 + effector T cells possibly facilitated by VST infusion. This trial was registered at www.clinicaltrials.gov as #NCT02779439 and www.anzctr.org.au as #ACTRN12613000603718.

Captopril to Mitigate Chronic Renal Failure After Hematopoietic Stem Cell Transplantation: A Randomized Controlled Trial

International Nuclear Information System (INIS)

Cohen, Eric P.; Irving, Amy A. B.A.; Drobyski, William R.; Klein, John P.; Passweg, Jakob; Talano, Julie-An M.; Juckett, Mark B.; Moulder, John E.

2008-01-01

Purpose: To test whether the angiotensin-converting enzyme inhibitor captopril was effective in mitigating chronic renal failure after hematopoietic stem cell transplantation (HSCT). Methods and Materials: A total of 55 subjects undergoing total body irradiation (TBI)-HSCT were enrolled in this randomized controlled trial. Captopril or identical placebo was started at engraftment and continued as tolerated until 1 year after HSCT. Results: The baseline serum creatinine and calculated glomerular filtration rate (GFR) did not differ between groups. The 1-year serum creatinine level was lower and the GFR higher in the captopril compared with the placebo group (p = 0.07 for GFR). Patient survival was higher in the captopril compared with the placebo group, but this was also not statistically significant (p = 0.09). In study subjects who received the study drug for more than 2 months, the 1-year calculated GFRs were 92 mL/min and 80 mL/min, for the captopril and placebo groups, respectively (p = 0.1). There was no adverse effect on hematologic outcome. Conclusions: There is a trend in favor of captopril in mitigation of chronic renal failure after radiation-based HSCT

Music Therapy for Patients Who Have Undergone Hematopoietic Stem Cell Transplant

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Chelsea G. Ratcliff

2014-01-01

Full Text Available Objectives. This study examines the short- and long-term QOL benefits of a music therapy intervention for patients recovering from hematopoietic stem cell transplantation (HSCT. Methods. Ninety allogeneic HSCT patients, after transplant, were randomized to receive ISO-principle (i.e., mood matching based music therapy (MT; n=29, unstructured music (UM; n=30, or usual care (UC; n=31 for four weeks. The ISO principle posits that patients may shift their mood from one state to another by listening to music that is “equal to” the individual’s initial mood state and subsequently listening to music selections that gradually shift in tempo and mood to match the patient’s desired disposition. Participants in MT and UM groups developed two audio CDs to help them feel more relaxed and energized and were instructed to use the CDs to improve their mood as needed. Short-term effects on mood and long-term effects on QOL were examined. Results. MT and UM participants reported improved mood immediately after listening to CDs; the within-group effect was greater for UM participants compared to MT participants. Participant group was not associated with long-term QOL outcomes. Conclusions. Music listening improves mood acutely but was not associated with long-term benefits in this study.

Music therapy for patients who have undergone hematopoietic stem cell transplant.

Science.gov (United States)

Ratcliff, Chelsea G; Prinsloo, Sarah; Richardson, Michael; Baynham-Fletcher, Laura; Lee, Richard; Chaoul, Alejandro; Cohen, Marlene Z; de Lima, Marcos; Cohen, Lorenzo

2014-01-01

Objectives. This study examines the short- and long-term QOL benefits of a music therapy intervention for patients recovering from hematopoietic stem cell transplantation (HSCT). Methods. Ninety allogeneic HSCT patients, after transplant, were randomized to receive ISO-principle (i.e., mood matching) based music therapy (MT; n = 29), unstructured music (UM; n = 30), or usual care (UC; n = 31) for four weeks. The ISO principle posits that patients may shift their mood from one state to another by listening to music that is "equal to" the individual's initial mood state and subsequently listening to music selections that gradually shift in tempo and mood to match the patient's desired disposition. Participants in MT and UM groups developed two audio CDs to help them feel more relaxed and energized and were instructed to use the CDs to improve their mood as needed. Short-term effects on mood and long-term effects on QOL were examined. Results. MT and UM participants reported improved mood immediately after listening to CDs; the within-group effect was greater for UM participants compared to MT participants. Participant group was not associated with long-term QOL outcomes. Conclusions. Music listening improves mood acutely but was not associated with long-term benefits in this study.

Results of allogeneic stem cell transplantation in the Spanish MDS registry: prognostic factors for low risk patients.

Science.gov (United States)

Díez Campelo, M; Sánchez-Barba, M; de Soria, V Gómez-García; Martino, R; Sanz, G; Insunza, A; Bernal, T; Duarte, R; Amigo, M L; Xicoy, B; Tormo, M; Iniesta, F; Bailén, A; Benlloch, L; Córdoba, I; López-Villar, O; Del Cañizo, M C

2014-10-01

Although new agents have been approved for the treatment of MDS, the only curative approach is allogeneic hematopoietic stem cell transplantation (HSCT) and thus, in particular circumstances this procedure has been proposed as a treatment option for low risk patients. We have retrospectively analyzed the results of HSCT in 291 patients from the Spanish MDS registry with special attention to low risk MDS (LR-MDS) in order to define the variables that could impact their clinical evolution after transplantation. At 2 years OS was 51% and EFS was 50% (95% CI 0.7-4.5 years for OS and 95% CI 0.1-3.9 years for EFS). Among 43 LR-MDS, transplant-related mortality was 28%. At 3 years, OS was 67% (95% CI 264.7-8927.2 days for OS) and EFS was 64% (95% CI 0-9697.2 days for EFS). In the multivariate analysis only cytogenetics retained statistical significant effect on both OS (p=.047) and EFS (p=.046). Conditioning regimen could improve outcome among this subset of patients (OS 86% and RFS 100% for patients receiving RIC regimen). The present study confirms that specific disease characteristic as well as transplant characteristics have a significant impact on transplant outcome. Regarding low risk patients a non-myeloablative conditioning would be preferable especially in cases without high-risk cytogenetics. Copyright © 2014 Elsevier Ltd. All rights reserved.

Utilization of Collaborative Practice Agreements between Physicians and Pharmacists as a Mechanism to Increase Capacity to Care for Hematopoietic Stem Cell Transplant Recipients

Science.gov (United States)

Merten, Julianna A.; Shapiro, Jamie F.; Gulbis, Alison M.; Rao, Kamakshi V.; Bubalo, Joseph; Lanum, Scott; Engemann, Ashley Morris; Shayani, Sepideh; Williams, Casey; Leather, Helen; Walsh-Chocolaad, Tracey

2013-01-01

Survival following hematopoietic stem cell transplantation (HSCT) has improved and the number of allogeneic HSCTs performed annually in the United States is expected to reach 10,000 by 2015. The National Marrow Donor Program created the System Capacity Initiative to formulate mechanisms to care for the growing number of HSCT recipients. One proposed method to increase capacity is utilization of pharmacists to manage drug therapy via collaborative practice agreements (CPAs). Pharmacists have managed drug therapy in oncology patients with CPAs for decades; however, there are limited HSCT centers that employ this practice. Engaging in collaborative practice and billing agreements with credentialed pharmacists to manage therapeutic drug monitoring, chronic medical conditions and supportive care in HSCT recipients may be cost-effective and enable physicians to spend more time on new or more complex patients. The goal of this paper is to provide a framework for implementation of a CPA and address how it may improve HSCT program capacity. PMID:23419976

Response to rituximab-based therapy and risk factor analysis in epstein barr virus-related lymphoproliferative disorder after hematopoietic stem cell transplant in children and adults: a study from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation.

NARCIS (Netherlands)

Styczynski, J.; Gil, L.; Tridello, G.; Ljungman, P.; Donnelly, J.P.; Velden, W. van der; Omar, H.; Martino, R.; Halkes, C.; Faraci, M.; Theunissen, K.; Kalwak, K.; Hubacek, P.; Sica, S.; Nozzoli, C.; Fagioli, F.; Matthes, S.; Diaz, M.A.; Migliavacca, M.; Balduzzi, A.; Tomaszewska, A.; amara Rde, L. C; Biezen, A. van; Hoek, J. van den; Iacobelli, S.; Einsele, H.; Cesaro, S.

2013-01-01

BACKGROUND: The objective of this analysis was to investigate prognostic factors that influence the outcome of Epstein-Barr virus (EBV)-related posttransplant lymphoproliferative disorder (PTLD) after a rituximab-based treatment in the allogeneic hematopoietic stem cell transplant (HSCT) setting.

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.

Microbiota Manipulation With Prebiotics and Probiotics in Patients Undergoing Stem Cell Transplantation

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Andermann, Tessa M.; Rezvani, Andrew; Bhatt, Ami S.

2016-01-01

Hematopoietic stem cell transplantation (HSCT) is a potentially life-saving therapy that often comes at the cost of complications such as graft-versus-host disease and post-transplant infections. With improved technology to under-stand the ecosystem of microorganisms (viruses, bacteria, fungi, and microeukaryotes) that make up the gut microbiota, there is increasing evidence of the microbiota’s contribution to the development of post-transplant complications. Antibiotics have traditionally been the mainstay of microbiota-altering therapies available to physicians. Recently, interest is increasing in the use of prebiotics and probiotics to support the development and sustainability of a healthier microbiota. In this review, we will describe the evidence for the use of prebiotics and probiotics in combating microbiota dysbiosis and explore the ways in which they may be used in future research to potentially improve clinical outcomes and decrease rates of graft-versus-host disease (GVHD) and post-transplant infection. PMID:26780719

Successful Combination of Sequential Gene Therapy and Rescue Allo-HSCT in Two Children with X-CGD - Importance of Timing.

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Siler, Ulrich; Paruzynski, Anna; Holtgreve-Grez, Heidi; Kuzmenko, Elena; Koehl, Ulrike; Renner, Eleonore D; Alhan, Canan; de Loosdrecht, Arjan A van; Schwäble, Joachim; Pfluger, Thomas; Tchinda, Joelle; Schmugge, Markus; Jauch, Anna; Naundorf, Sonja; Kühlcke, Klaus; Notheis, Gundula; Güngor, Tayfun; Kalle, Christof V; Schmidt, Manfred; Grez, Manuel; Seger, Reinhard; Reichenbach, Janine

2015-01-01

We report on a series of sequential events leading to long-term survival and cure of pediatric X-linked chronic granulomatous disease (X-CGD) patients after gamma-retroviral gene therapy (GT) and rescue HSCT. Due to therapyrefractory life-threatening infections requiring hematopoietic stem cell transplantation (HSCT) but absence of HLAidentical donors, we treated 2 boys with X-CGD by GT. Following GT both children completely resolved invasive Aspergillus nidulans infections. However, one child developed dual insertional activation of ecotropic viral integration site 1 (EVI1) and signal transducer and activator of transcription 3 (STAT3) genes, leading to myelodysplastic syndrome (MDS) with monosomy 7. Despite resistance to mismatched allo-HSCT with standard myeloablative conditioning, secondary intensified rescue allo-HSCT resulted in 100 % donor chimerism and disappearance of MDS. The other child did not develop MDS despite expansion of a clone with a single insertion in the myelodysplasia syndrome 1 (MDS1) gene and was cured by early standard allo-HSCT. The slowly developing dominance of clones harboring integrations in MDS1-EVI1 may guide clinical intervention strategies, i.e. early rescue allo-HSCT, prior to malignant transformation. GT was essential for both children to survive and to clear therapy-refractory infections, and future GT with safer lentiviral self-inactivated (SIN) vectors may offer a therapeutic alternative for X-CGD patients suffering from life-threatening infections and lacking HLA-identical HSC donors.

Source, pattern and antibiotic resistance of blood stream infections in hematopoietic stem cell transplant recipients

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El-Mahallawy, H.; Samir, I.; Kadry, D.; Abdel Fattah, R.; El-Kholy, A.

2014-01-01

Mucositis developing as a result of myelo-ablative high dose therapy administered prior to hematopoietic stem cell transplantation (HSCT) is associated with the risk of bacteremia. The aim of the present study was to detect the pattern of bacteremia coinciding with the present practice of HSCT, to study the contribution of health-care associated infection (HAI) to the pattern of infection, in the context of the problem of antibiotic resistance in HSCT recipients. Patients and methods: This is a retrospective, single center study including patients who developed febrile neutropenia (FN) among HSCT recipients in one year duration. Results: Ninety FN episodes were recorded in 50 patients. Out of 39 positive blood cultures, Gram negative rods (GNR) were the predominant pathogens, constituting 67% (n =26) of isolated organisms, while 33% of infections were caused by gram positive cocci (GPC) (n= 13). Bacteremia was significantly associated with central venous line (CVL) infections and gastroenteritis (diarrhea and vomiting) with a p-value 0.024, 0.20 and 0.0001, respectively. Multi-drug resistant organisms (MDROs) were identified in 27 (69%) of the 39 positive blood cultures. Conclusion: In one year duration, gram negative pathogens were the predominant causes of infection in HSCT recipients with high rates of MDROs in our institution. Gastroenteritis and central venous line infections are the main sources of bacteremia

The impact of hematopoietic stem cell transplantation on sexuality: a systematic review of the literature

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Thygesen, Kristina Holmegaard; Schiødt, Ida; Jarden, M

2012-01-01

In this paper we review evidence concerning the impact of hematopoietic SCT (HSCT) on sexuality. The aims are to determine: (1) the sexual changes experienced by patients following allogeneic or autologous HSCT, and its consequences; (2) changes in the sexual function over time and (3) the impact...... in sexual dysfunction with specific reliable validated instruments and more adequate sample sizes will be required to definitively evaluate the impact of HSCT on sexuality.Bone Marrow Transplantation advance online publication, 29 August 2011; doi:10.1038/bmt.2011.169....

CD4+CD25highCD127low Regulatory T Cells in Peripheral Blood Are Not an Independent Factor for Chronic Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation

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Jolanta B. Perz

2012-01-01

Full Text Available Background. The therapeutic efficacy of allogeneic hemopoietic stem cell transplantation (HSCT largely relies on the graft-versus-leukemia (GVL effect. Uncontrolled graft-versus-host disease (GVHD is a feared complication of HSCT. Regulatory T cells (Treg are a subset of CD4+ T-helper cells believed to maintain tolerance after HSCT. It remains unclear whether low peripheral blood Treg have an impact on the risk for acute (aGVHD and chronic GVHD (cGVHD. Methods. In this paper we enumerated the CD4+CD25highCD127low Treg in the peripheral blood of 84 patients after at least 150 days from HSCT and in 20 healthy age-matched controls. Results. Although similar mean lymphocyte counts were found in patients and controls, CD3+CD4+ T-cell counts were significantly lower in patients. Patients also had significantly lower Treg percentages among lymphocytes as compared to controls. Patients with cGVHD had even higher percentages of Treg if compared to patients without cGVHD. In multivariate analysis, Treg percentages were not an independent factor for cGVHD. Conclusions. This paper did not show a relation between deficient peripheral blood Treg and cGVHD, therefore cGVHD does not seem to occur as a result of peripheral Treg paucity.

Comparison of survival outcome between donor types or stem cell sources for childhood acute myeloid leukemia after allogenic hematopoietic stem cell transplantation: A multicenter retrospective study of Study Alliance of Yeungnam Pediatric Hematology-oncology.

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Shim, Ye Jee; Lee, Jae Min; Kim, Heung Sik; Jung, Nani; Lim, Young Tak; Yang, Eu Jeen; Hah, Jeong Ok; Lee, Young-Ho; Chueh, Hee Won; Lim, Jae Young; Park, Eun Sil; Park, Jeong A; Park, Ji Kyoung; Park, Sang Kyu

2018-06-19

We compared transplant outcomes between donor types and stem cell sources for childhood acute myeloid leukemia (AML). The medical records of children with AML in the Yeungnam region of Korea from January 2000 to June 2017 were reviewed. In all, 76 children with AML (male-to-female ratio = 46:30) received allogenic hematopoietic stem cell transplantation (allo-HSCT). In total, 29 patients received HSCT from either a matched-related donor or a mismatched-related donor, 32 patients received an unrelated donor, and 15 patients received umbilical cord blood. In term of stem cell sources, bone marrow was used in 15 patients and peripheral blood in 46 patients. For all HSCT cases, the 5-year overall survival (OS) was 73.1% (95% CI: 62.7-83.5) and the 5-year event-free survival (EFS) was 66.1% (95% CI: 54.5-77.7). There was no statistical difference in 5-year OS according to the donor types or stem cell sources (P = .869 and P = .911). There was no statistical difference in 5-year EFS between donor types or stem cell sources (P = .526 and P = .478). For all HSCT cases, the 5-year relapse rate was 16.1% (95% CI: 7.3-24.9) and the 5-year non-relapse mortality (NRM) was 13.3% (95% CI: 5.1-21.5). There was no statistical difference in the 5-year relapse rate according to the donor types or stem cell sources (P = .971 and P = .965). There was no statistical difference in the 5-year NRM between donor types or stem cell sources (P = .461 and P = .470). © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Tolerance induction between two different strains of parental mice prevents graft-versus-host disease in haploidentical hematopoietic stem cell transplantation to F1 mice

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Guo, Yixian; Zhang, Lanfang; Wan, Suigui; Sun, Xuejing; Wu, Yongxia; Yu, Xue-Zhong; Xia, Chang-Qing

2014-01-01

Highlights: • Injection of UVB-irradiated iDCs induces alloantigen tolerance. • This alloantigen tolerance may be associated regulatory T cell induction. • Tolerant mice serve as bone marrow donors reduces GVHD to their F1 recipients in allo-HSCT. • Tolerance is maintained in F1 recipients for long time post HSCT. - Abstract: Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) has been employed worldwide in recent years and led to favorable outcome in a group of patients who do not have human leukocyte antigen (HLA)-matched donors. However, the high incidence of severe graft-versus-host disease (GVHD) is a major problem for Haplo-HSCT. In the current study, we performed a proof of concept mouse study to test whether induction of allogeneic tolerance between two different parental strains was able to attenuate GVHD in Haplo-HSCT to the F1 mice. We induced alloantigen tolerance in C3H mice (H-2k) using ultraviolet B (UVB) irradiated immature dendritic cells (iDCs) derived from the cultures of Balb/c bone marrow cells. Then, we performed Haplo-HSCT using tolerant C3H mice as donors to F1 mice (C3H × Balb/c). The results demonstrated that this approach markedly reduced GVHD-associated death and significantly prolonged the survival of recipient mice in contrast to the groups with donors (C3H mice) that received infusion of non-UVB-irradiated DCs. Further studies showed that there were enhanced Tregs in the tolerant mice and alloantigen-specific T cell response was skewed to more IL-10-producing T cells, suggesting that these regulatory T cells might have contributed to the attenuation of GVHD. This study suggests that it is a feasible approach to preventing GVHD in Haplo-HSCT in children by pre-induction of alloantigen tolerance between the two parents. This concept may also lead to more opportunities in cell-based immunotherapy for GVHD post Haplo-HSCT

Tolerance induction between two different strains of parental mice prevents graft-versus-host disease in haploidentical hematopoietic stem cell transplantation to F1 mice

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Guo, Yixian; Zhang, Lanfang; Wan, Suigui; Sun, Xuejing; Wu, Yongxia [Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Yu, Xue-Zhong [Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425 (United States); Xia, Chang-Qing, E-mail: cqx65@yahoo.com [Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China)

2014-04-18

Highlights: • Injection of UVB-irradiated iDCs induces alloantigen tolerance. • This alloantigen tolerance may be associated regulatory T cell induction. • Tolerant mice serve as bone marrow donors reduces GVHD to their F1 recipients in allo-HSCT. • Tolerance is maintained in F1 recipients for long time post HSCT. - Abstract: Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) has been employed worldwide in recent years and led to favorable outcome in a group of patients who do not have human leukocyte antigen (HLA)-matched donors. However, the high incidence of severe graft-versus-host disease (GVHD) is a major problem for Haplo-HSCT. In the current study, we performed a proof of concept mouse study to test whether induction of allogeneic tolerance between two different parental strains was able to attenuate GVHD in Haplo-HSCT to the F1 mice. We induced alloantigen tolerance in C3H mice (H-2k) using ultraviolet B (UVB) irradiated immature dendritic cells (iDCs) derived from the cultures of Balb/c bone marrow cells. Then, we performed Haplo-HSCT using tolerant C3H mice as donors to F1 mice (C3H × Balb/c). The results demonstrated that this approach markedly reduced GVHD-associated death and significantly prolonged the survival of recipient mice in contrast to the groups with donors (C3H mice) that received infusion of non-UVB-irradiated DCs. Further studies showed that there were enhanced Tregs in the tolerant mice and alloantigen-specific T cell response was skewed to more IL-10-producing T cells, suggesting that these regulatory T cells might have contributed to the attenuation of GVHD. This study suggests that it is a feasible approach to preventing GVHD in Haplo-HSCT in children by pre-induction of alloantigen tolerance between the two parents. This concept may also lead to more opportunities in cell-based immunotherapy for GVHD post Haplo-HSCT.

The Use of Intravenous Antibiotics at the Onset of Neutropenia in Patients Receiving Outpatient-Based Hematopoietic Stem Cell Transplants

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Hamadah, Aziz; Schreiber, Yoko; Toye, Baldwin; McDiarmid, Sheryl; Huebsch, Lothar; Bredeson, Christopher; Tay, Jason

2012-01-01

Empirical antibiotics at the onset of febrile neutropenia are one of several strategies for management of bacterial infections in patients undergoing Hematopoietic Stem Cell Transplant (HSCT) (empiric strategy). Our HSCT program aims to perform HSCT in an outpatient setting, where an empiric antibiotic strategy was employed. HSCT recipients began receiving intravenous antibiotics at the onset of neutropenia in the absence of fever as part of our institutional policy from 01 Jan 2009; intravenous Prophylactic strategy. A prospective study was conducted to compare two consecutive cohorts [Year 2008 (Empiric strategy) vs. Year 2009 (Prophylactic strategy)] of patients receiving HSCT. There were 238 HSCTs performed between 01 Jan 2008 and 31 Dec 2009 with 127 and 111 in the earlier and later cohorts respectively. Infection-related mortality pre- engraftment was similar with a prophylactic compared to an empiric strategy (3.6% vs. 7.1%; p = 0.24), but reduced among recipients of autologous HSCT (0% vs. 6.8%; p = 0.03). Microbiologically documented, blood stream infections and clinically documented infections pre-engraftment were reduced in those receiving a prophylactic compared to an empiric strategy, (11.7% vs. 28.3%; p = 0.001), (9.9% vs. 24.4%; p = 0.003) and (18.2% vs. 33.9% p = 0.007) respectively. The prophylactic use of intravenous once-daily ceftriaxone in patients receiving outpatient based HSCT is safe and may be particularly effective in patients receiving autologous HSCT. Further studies are warranted to study the impact of this Prophylactic strategy in an outpatient based HSCT program. PMID:23029441

Impact of autologous hematopoietic stem cell transplantation on the quality of life of type 1 diabetes mellitus patients Impacto do transplante de células-tronco hematopoéticas sobre a qualidade de vida de pacientes com diabetes mellitus tipo 1

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Manoel Antônio dos Santos

2011-01-01

Full Text Available The present study aimed at assessing the health-related quality of life (HRQoL of patients with type 1 diabetes mellitus (DM1 submitted to autologous hematopoietic stem cell transplantation (HSCT. This study is part of a pioneering research protocol which tests the applicability of autologous hematopoietic stem cell transplantation as a new therapeutic approach to DM1. The study was conducted on 14 patients admitted to the ward of the Bone Marrow Transplantation Unit of a university hospital during the period from October 2006 to December 2007. The patients were evaluated at admission and on the occasion of the ambulatory return visit 100 days after transplantation. They answered the SF-36 quality of life questionnaire and the data were analyzed according to literature recommendations. The results showed that 100 days after transplantation the value of the patients' quality of life was higher compared to the pre-HSCT value, with significant differences in the Physical Domains (Role Limitations due to Physical Problems (p = .009, Vitality (p = .02 and Mental Health (p = .04, demonstrating significant appreciation of those domains after the procedure. The results indicate an improvement in HRQoL after HSCT. The SF-36 proved to be a useful instrument for the assessment of quality of life in patients with DM1 submitted to HSCT.Este estudo teve como objetivo avaliar a qualidade de vida relacionada à saúde (QVRS de pacientes com diabetes mellitus tipo 1 (DM1 submetidos ao Transplante de Células-Tronco Hematopoéticas (TCTH. O estudo é parte de um protocolo de pesquisa pioneiro no mundo, que testa a aplicabilidade do TCTH como nova abordagem terapêutica no DM1. Foram investigados 14 pacientes, que constituíram a população de pessoas internadas na enfermaria da Unidade de Transplante de Medula Óssea de um hospital universitário, no período de outubro de 2006 a dezembro de 2007. Os pacientes foram avaliados na admissão e no retorno

Epidemiologic Profile of Patients Transplanted With Hematopoietic Stem Cells in a Reference Service in the State of Rio Grande do Norte, Brazil.

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Campos de Azevedo, I; Ferreira Júnior, M A; Pereira de Aquino, L A; de Oliveira, A A; Cruz, G K P; de Queiroz Cardoso, A I; Ivo, M L; Santos, V E P

2018-04-01

Hematopoietic stem cell transplantation (HSCT) consists of the intravenous infusion of healthy hematopoietic stem cells to restore the medullary and immunologic function of patients affected by a series of hematologic, oncologic, immunologic, malignant and nonmalignant inherited or acquired diseases, with the possibility of cure or increase of disease-free survival. To characterize the epidemiologic profile and the cases of death of patients who underwent HSCT. This is a cohort quantitative study, nested with a retrospective, descriptive, and analytical study of a hospital-based cohort that included the patients who underwent HSCT at a referral service in the state of Rio Grande do Norte, a region of northeastern Brazil. There was a slight male prevalence (52.94%), the age of the patients ranged from 2 to 73 years old, 18.38% were brown, 47.06% were married, 15.07% were students, 78.31% had a diagnosis of multiple myeloma, 93.38% developed gastrointestinal toxicities, all patients received chemotherapeutic treatment, 54.78% had allogeneic HSCT, and the cause of the most recorded deaths was septic shock (48.19%). This study showed relevant scientific evidence on the clinical and epidemiologic profile of patients who underwent HSCT. In general, sociodemographic data are similar to national and international research results. Copyright © 2018 Elsevier Inc. All rights reserved.

Acyclovir-resistant herpes simplex virus 1 infection early after allogeneic hematopoietic stem cell transplantation with T-cell depletion.

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Akahoshi, Yu; Kanda, Junya; Ohno, Ayumu; Komiya, Yusuke; Gomyo, Ayumi; Hayakawa, Jin; Harada, Naonori; Kameda, Kazuaki; Ugai, Tomotaka; Wada, Hidenori; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Sato, Miki; Terasako-Saito, Kiriko; Kimura, Shun-Ichi; Kikuchi, Misato; Nakasone, Hideki; Kako, Shinichi; Shiraki, Kimiyasu; Kanda, Yoshinobu

2017-07-01

We previously reported that oral low-dose acyclovir (200 mg/day) for the prevention of herpes simplex virus (HSV) infections after allogenic hematopoietic stem cell transplantation (HSCT) is effective without the emergence of acyclovir-resistant HSV infections. However, HSV infections are of significant concern because the number of allogeneic HSCT with T-cell depletion, which is a risk factor of the emergence of drug-resistant HSV infections, has been increasing. We experienced a 25-year-old female who received allogenic HSCT from an unrelated donor with 1-antigen mismatch using anti-thymocyte globulin. Despite acyclovir prophylaxis (200 mg/day), she developed the right palatal ulcer that was positive for HSV-1 specific antigen by fluorescent antibody on day 20 and developed new hypoglossal and tongue ulcers on day 33. Replacement of acyclovir with foscarnet improved her ulcers. We isolated 2 acyclovir-resistant and foscarnet-sensitive strains from the right palatal and hypoglossal ulcers, which had the same frame shift mutation in the thymidine kinase genes. The rate of proliferation of the isolate from the hypoglossal ulcer was faster than that from the right palatal ulcer in the plaque reduction assay. HSV strains that acquired acyclovir-resistant mutations at the right palatal ulcer with larger plaque might spread to the hypoglossal ulcer as the secondary site of infection because of better growth property. Second-line antiviral agents should be considered when we suspect treatment failure of HSV infection, especially in HSCT with T-cell depletion. Further studies are required whether low-dose acyclovir prophylaxis leads to the emergence of virological resistance. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

A Pediatric Case of Systemic Lupus Erythematosus Developed 10 Years after Cord Blood Transplantation for Juvenile Myelomonocytic Leukemia

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Masayuki Nagasawa

2012-01-01

Full Text Available Allogeneic hematopoietic stem cell transplantation (allo-HSCT is a most powerful immunotherapy for hematological malignancies. However, the impact of immunological disturbances as a result of allo-HSCT is not understood well. We experienced an 11-year-old boy who presented with systemic lupus erythemathosus (SLE 10 years after unrelated cord blood transplantation of male origin for juvenile myelomonocytic leukemia (JMML with monosomy 7. Bone marrow examination showed complete remission without monosomy 7. Genetic analysis of peripheral blood revealed mixed chimera with recipient cells consisting of <5% of T cells, 50–60% of B cells, 60–75% of NK cells, 70–80% of macrophages, and 50–60% of granulocytes. Significance of persistent mixed chimera as a cause of SLE is discussed.

Short-term Assessment of HSCT Effects on the Hypothalamus-Pituitary Axis in Pediatric Thalassemic Patients.

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Hamidieh, Amir Ali; Mohseni, Fariba; Behfar, Maryam; Hamidi, Zohreh; Alimoghaddam, Kamran; Pajouhi, Mohamad; Larijani, Bagher; Mohajeri-Tehrani, Mohammad-Reza; Ghavamzadeh, Ardeshir

2018-02-01

Beta thalassemia major (BTM) and its treatment by hematopoietic stem cell transplantation (HSCT) may have deleterious effects on the endocrine systems. We assessed endocrine complications of HSCT in pediatric patients for 3 months. In 20 (6 female) pediatric major thalassemic patients (mean age of 10.8 ± 3.9 years old), prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), T4, T3, thyroid-stimulating hormone (TSH), IGF-1, testosterone (in males) or estradiol (in females) were measured as a batch at the Endocrinology and Metabolism Research Center (EMRC) of Tehran University of Medical Sciences (TUMS) laboratories before HSCT and 1 and 3 months afterwards. The cosyntropin test for all and the clonidine test for short stature patients was conducted before HSCT. Before HSCT, delayed puberty and hypogonadotropic hypogonadism was found in 10% and 20% of patients, respectively. GH deficiency, low IGF1 and short stature was found in 25%, 55% and 40% of patients, respectively. Hypocortisolism, hypothyroidism and panhypopituitarism was found in 15%, 10% and 15% of patients, respectively. Prevalence of hypogonadotropic hypogonadism, low IGF1, hypothyroidism and panhypopituitarism was found in 20%, 40%, 10% and 10% of patients after 3 months, respectively (delayed puberty and short stature prevalence do not change after 3 months). HSCT caused lower T3 and estradiol and higher TSH. Corticosteroid users (15) had higher GH and lower T3 and testosterone or estradiol. Ferritin had a significant (negative) correlation with (before) prolactin and a significant correlation with T3 and T4 after HSCT. Age and acute graft-versus-host disease (GVHD) had no significant effect. Considering the small sample size and short duration of the study, it is difficult to reach any conclusion however it seems HSCT does not appear to have an overall positive or negative effect on prevalence of pituitary- hypothalamus axis disorders in pediatric thalassemic patients in 3 months. �

Cost utility analysis of reduced intensity hematopoietic stem cell transplantation in adolescence and young adult with severe thalassemia compared to hypertransfusion and iron chelation program

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Sruamsiri Rosarin

2013-02-01

Full Text Available Abstract Background Hematopoieticic stem cell transplantation is the only therapeutic option that can cure thalassemia disease. Reduced intensity hematopoietic stem cell transplantation (RI-HSCT has demonstrated a high cure rate with minimal complications compared to other options. Because RI-HSCT is very costly, economic justification for its value is needed. This study aimed to estimate the cost-utility of RI-HSCT compared with blood transfusions combined with iron chelating therapy (BT-ICT for adolescent and young adult with severe thalassemia in Thailand. Methods A Markov model was used to estimate the relevant costs and health outcomes over the patients’ lifetimes using a societal perspective. All future costs and outcomes were discounted at a rate of 3% per annum. The efficacy of RI-HSCT was based a clinical trial including a total of 18 thalassemia patients. Utility values were derived directly from all patients using EQ-5D and SF-6D. Primary outcomes of interest were lifetime costs, quality adjusted life-years (QALYs gained, and the incremental cost-effectiveness ratio (ICER in US ($ per QALY gained. One-way and probabilistic sensitivity analyses (PSA were conducted to investigate the effect of parameter uncertainty. Results In base case analysis, the RI-HSCT group had a better clinical outcomes and higher lifetime costs. The incremental cost per QALY gained was US $ 3,236 per QALY. The acceptability curve showed that the probability of RI-HSCT being cost-effective was 71% at the willingness to pay of 1 time of Thai Gross domestic product per capita (GDP per capita, approximately US $ 4,210 per QALY gained. The most sensitive parameter was utility of severe thalassemia patients without cardiac complication patients. Conclusion At a societal willingness to pay of 1 GDP per capita, RI-HSCT was a cost-effective treatment for adolescent and young adult with severe thalassemia in Thailand compared to BT-ICT.

O transplante de células-tronco hematopoéticas na leucemia linfoide crônica, uma proposta do I Encontro de Diretrizes do Transplante de Medula Óssea da Sociedade Brasileira de Transplante de Medula Óssea, Rio de Janeiro 2009 Hematopoietic stem cell transplantation in chronic lymphoid leukemia: a proposal by the Brazilian Consensus on Bone Marrow Transplantation of the Brazilian Society of Bone Marrow Transplantation, Rio de Janeiro 2009

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Milton A. Ruiz

2010-05-01

disease. Younger patients with high-risk criteria may benefit with a more aggressive treatment that includes hematopoietic stem cell transplantation (HSCT. Autologous transplantation, despite of the encouraging results with cases of molecular and/or cytogenetic remission and low mortality rates, does not present a plateau in survival curves and has a high relapse rate. Allogeneic transplantations using myeloablative regimens, have high toxicity and mortality rates, but also demonstrate the graft-versus-leukemia effect that increases the possibility of cure of these individuals. So the option of allogeneic transplants for patients with CLL is directed to conditioning using non-myeloablative regimens, which can also be applied to older patients or those with comorbidities, and maintain a potential graft-versus-leukemia effect. The identification of patients who may benefit from these procedures and the characterization of new prognostic markers remain the subjects of many clinical studies and were the objective of the group responsible for discussing guidelines for CLL of the consensus on HSCT SBTMO. Thus we believe that HSCT for CLL should follow the criteria of the EBMT. When a sibling donor is available the best option is allogeneic HSCT with a myeloablative regimen. The strategy of unrelated allogeneic or autologous HSCT must be considered as a second option when no donor is available, for special situations and clinical trials.

Combination of High-Dose Methylprednisolone and Defibrotide for Veno-Occlusive Disease in Pediatric Hematopoietic Stem Cell Transplant Recipients.

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Gloude, Nicholas J; Jodele, Sonata; Teusink-Cross, Ashley; Grimley, Michael; Davies, Stella M; Lane, Adam; Myers, Kasiani C

2018-01-01

Veno-occlusive disease (VOD) is a serious complication of hematopoietic stem cell transplant (HSCT), with high mortality in severe cases and until recently very limited therapeutic options consisting largely of supportive care. Defibrotide was recently approved in the United States for the treatment of severe VOD in patients with renal or pulmonary dysfunction after HSCT. Our group previously published on the use of high-dose methylprednisolone (500 mg/m 2 per dose every 12 hours for 6 doses) in patients with VOD, showing good success. A small subset of these individuals were also treated with defibrotide, but additional studies using the combination of high-dose methylprednisolone and defibrotide for the treatment of VOD are lacking. We present a single-institution retrospective chart review of 15 HSCT patients with VOD treated with the combination of high-dose methylprednisolone and defibrotide. VOD developed at a median of 17 days post-HSCT, and combination therapy was initiated within 1 day of VOD diagnosis. Twelve of 15 patients (80%) had multiorgan failure. Our single-center experience using both high-dose methylprednisolone and defibrotide showed a day +100 survival rate of 73% and an overall VOD complete resolution rate of 66.7%, higher than the rates reported in the recent literature using defibrotide alone (40% to 50% day +100 overall survival). These data suggest that the combination of high-dose steroids and defibrotide may be superior to defibrotide alone and warrant further investigation. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Outcome of Allogeneic Stem Cell Transplantation for Patients Transformed to Myelodysplastic Syndrome or Leukemia from Severe Aplastic Anemia: A Report from the MDS Subcommittee of the Chronic Malignancies Working Party and the Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation

NARCIS (Netherlands)

Hussein, A.A.; Halkes, C.M.; Socie, G.; Tichelli, A.; Borne, P.A. von dem; Schaap, M.N.; Foa, R.; Ganser, A.; Dufour, C.; Bacigalupo, A.; Locasciulli, A.; Aljurf, M.; Peters, C.; Robin, M.; Biezen, A.A. van; Volin, L.; Witte, T.J. de; Marsh, J.; Passweg, J.R.; Kroger, N.; et al.,

2014-01-01

One hundred and forty patients who had undergone hematopoietic stem cell transplantation (HSCT) for myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) transformation after treatment of severe aplastic anemia (SAA) were identified in the European Group for Blood and Marrow

IIVP salvage regimen induces high response rates in patients with relapsed lymphoma before autologous stem cell transplantation.

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Abali, Huseyin; Oyan, Basak; Koc, Yener; Kars, Ayse; Barista, Ibrahim; Uner, Aysegul; Turker, Alev; Demirkazik, Figen; Tekin, Fatma; Tekuzman, Gulten; Kansu, Emin

2005-06-01

Patients with relapsed lymphoma can be cured with high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HSCT). New therapeutic approaches with better cytoreductive capacity are needed for relapsed patients to keep their chance for cure with transplantation. We report 30 patients with relapsed lymphoma, median age 43 years, treated with IIVP salvage regimen consisting of ifosfamide, mesna, idarubicin, and etoposide for 2 or 3 cycles. Seventeen patients had non-Hodgkin lymphoma (NHL) and 13 patients had Hodgkin disease (HD). Fourteen (47%) patients were at their first relapse. Overall response rate was 86.6% (n = 26) with 19 patients (63.3%) achieving complete response. Overall response rate was 92% in patients with HD and 82% in NHL. The most frequent side effects observed were grade III-IV neutropenia (87%) and thrombocytopenia (73%). IIVP regimen is a highly effective salvage therapy for patients with relapsed HD or NHL who are candidates for autologous HSCT. Close follow up is necessary because of the high incidence of grade III-IV hematologic toxicity.

[Comparative study on the usefulness of antibacterial prophylaxis with levofloxacin in patients submitted to hematopoietic stem cell transplantation].

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Fernandez Sojo, Jesús; Batlle Massana, Montserrat; Morgades, Mireia; Vives Polo, Susana; Quesada, María Dolores; Ribera Santasusana, Josep María

2016-01-01

Bacterial infection remains a frequent complication in patients receiving a hematopoietic stem cell transplantation (HSCT). However, the impact of the antibacterial prophylaxis mortality in these patients is controversial. Retrospective comparison of 2 consecutive groups of patients undergoing HSCT receiving (n=132) or not (n=107) antibacterial prophylaxis with levofloxacin. 41% of patients receiving prophylaxis with levofloxacin had microbiologically documented infection (MDI) with bacteremia, compared with 40% of those not receiving levofloxacin. The frequency of gram-negative bacteremia was 11 and 38%, the resistance to levofloxacin was 39 and 14%, and the mortality was 8 and 7%, respectively. In our experience, the use of levofloxacin as prophylaxis in HSCT was associated with a lower frequency of gram-negative bacteremia but was not associated with a decreased rate of MDI and did not influence their outcome. In contrast, there was an increase in quinolone resistance in patients treated with levofloxacin. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Effect of donor STAT4 polymorphism rs7574865 on clinical outcomes of pediatric acute leukemia patients after hematopoietic stem cell transplant.

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Wun, Cheng Mun; Piao, Zhe; Hong, Kyung Taek; Choi, Jung Yoon; Hong, Che Ry; Park, June Dong; Park, Kyung Duk; Shin, Hee Young; Kang, Hyoung Jin

2017-02-01

STAT4 polymorphism, rs7574865 is linked to various autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. Its T minor allele is associated with higher STAT4 mRNA and protein expression, indicating a stronger skewed immune response than the norm. Although widely studied in autoimmune disease patients and the general population, its effect on immunocompromised subjects is still unknown. Especially in situations, i.e. post-hematopoietic stem cell transplantation (post-HSCT), where control of the immune response is crucial. Hence, this study investigates if the presence of the T minor allele in donors would affect immunological response and clinical outcomes post-HSCT. Samples from 161 pediatric patients who underwent allogeneic HSCT for acute leukemia and showed complete chimerism by donor cells were obtained. Six clinical outcomes were investigated; hepatic veno-occlusive disease, acute graft-vs-host disease, chronic graft-vs-host disease, cytomegalovirus (CMV) infection, relapse and overall survival. The TT genotype was found to be significant in the occurrence of CMV infection (P=0.049), showing higher incidence of CMV infection compared to the others. Multivariate analysis confirmed that association of the TT genotype is independent from other variables in CMV infection occurrence (P=0.010). This is the first study on STAT4 polymorphism rs7574865 in allogeneic HSCT as well as immunocompromised patients. As the TT genotype is associated with autoimmune diseases, our results seem at a paradox with current evidence hinting at a different role of STAT4 in normal circumstances versus immunocompromised patients. Further investigation is needed to elicit the reason behind this and discover novel applications for better post-transplant outcomes. Copyright © 2016 Elsevier B.V. All rights reserved.

Daunorubicin, Cytarabine, and Cladribine Regimen Plus Radiotherapy and Donor Lymphocyte Infusion for Extramedullary Relapse of Acute Myeloid Leukemia after Hematopoietic Stem Cell Transplantation

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Marco Sanna

2013-01-01

Full Text Available Myeloid sarcoma is a rare tumor consisting of myeloid blasts that involve anatomic sites outside the bone marrow. Fatal prognosis is inevitable in patients with extramedullary relapse after hematopoietic stem cell transplantation (HSCT, and no standard treatments are available yet. We report the first case of extramedullary relapse after HSCT treated with a combination of daunorubicin, cytarabine, and cladribine (DAC regimen plus radiotherapy and donor lymphocyte infusion (DLI. This treatment induced a new and durable remission in our patient. The favorable toxicity profile and the reduced cost make this combination worthy of further investigations.

Defibrotide in the prevention and treatment of veno-occlusive disease in autologous and allogeneic stem cell transplantation in children.

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Qureshi, Amrana; Marshall, Lynley; Lancaster, Donna

2008-04-01

Hepatic veno-occlusive disease (VOD) is a common (10-50%) and serious complication of haematological stem cell transplantation (HSCT), with up to 90% mortality rates. We carried out a study to assess whether the use of prophylactic defibrotide in paediatric patients undergoing HSCT results in a lower frequency or severity of hepatic VOD. Forty-seven successive patients who underwent transplantation between April 2004 and December 2005 were given defibrotide prophylaxis and were compared with 56 historical controls transplanted between November 2001 and April 2004. No serious side effects were reported. High risk patients in the control group received ursodeoxycholic acid and tinzaparin as VOD prophylaxis. The groups were matched for sex, age, type of transplant and risk. In the defibrotide group, four patients developed clinical VOD (Seattle criteria) although two had liver biopsies which showed graft versus host disease (GvHD). Defibrotide dose was increased and symptoms resolved within 14 days. Of the control group four patients had VOD. Two of these patients had reversed hepatic vein flow and died 30 days post-transplant, partly due to VOD. VOD was associated with busulfan conditioning (P = 0.001) and not with age, sex, type of transplant, GvHD, abnormal liver function prior to transplant or type of antifungal prophylaxis. VOD incidence and severity was reduced in the defibrotide group which suggests that defibrotide might be effective in preventing and treating VOD. Sufficiently powered randomised trials are now required to definitively test the role of defibrotide in this setting. (c) 2008 Wiley-Liss, Inc.

Late-onset Epstein-Barr virus-related disease in acute leukemia patients after haploidentical hematopoietic stem cell transplantation is associated with impaired early recovery of T and B lymphocytes.

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Liu, Jiangying; Yan, Chenhua; Zhang, Chunli; Xu, Lanping; Liu, Yanrong; Huang, Xiaojun

2015-10-01

Epstein-Barr virus-related disease (EBVD) is a serious clinical complication in patients who have undergone haploidentical hematopoietic stem cell transplantation (haploHSCT). Some recipients develop EBVD relatively late after haploHSCT, and most of these patients suffer a poor outcome. This retrospective cohort study characterized the early adaptive immune recovery of patients with acute leukemia presenting with EBVD more than 100 d after haploHSCT. Patients with acute leukemia who received haploHSCT and developed EBVD 100 d later (n = 8) were compared with a matched control group without EBVD (n = 24) with regard to peripheral WBC, lymphocytes, and neutrophils (at 30, 60, and 90 d) and recoveries of B and T lymphocytes (at 30 and 90 d, via immunophenotyping/flow cytometry). Ninety days after haploHSCT, the median values of WBCs and lymphocytes, and the recoveries of CD19(+) B cells and CD4(+) , CD8(+) , and CD4(+) CD45RO(+) T cells, were significantly lower in patients who developed EBVD, relative to the control group. These results suggest a significant association between deficient early recovery of B and T lymphocytes and the development of late-onset EBVD after haploHSCT. Our observation could facilitate clinical intervention and the improvement of overall survival of patients undergoing haploHSCT. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Moxa-stick suffumigation for disinfecting air in hematology and hematopoietic stem cell transplantation wards with class 100 laminar flow.

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He, Jing-song; Yang, Qing; Huang, Wei-jia; Hu, Xiao-rong

2014-04-01

To evaluate the effect of moxa-stick suffumigation in the hematology and hematopoietic stem cell transplantation (HSCT) wards with luminar flow. The plate exposure method was used to measure the effect of air-disinfection of moxa-stick suffumigation in hematology and HSCT wards. The yearly average qualified rates of air sampling in HSCT wards were evaluated from 2007 to 2010. To further investigate the disinfecting effect of moxa-stick suffumigation, the colony counts of common pathogens (including Staphylcoccus aureus and Pseudomonas aeruginosa) before and after moxa-stick suffumigation were compared. The mean air quality rates of the HSCT wards with class 100 laminar flow were all above 90.0% (91.2%-96.2%) from 2007 to 2010. Moxa-stick suffumigation effectively decreased the presence of bacteria in the hematology ward's air (Pplates exposed to air treated with moxa-stick suffumigation (77.1±52.9 cfu/m(2) vs 196.1±87.5 cfu/m(2), P<0.01; and 100.2±35.3 cfu/m(2) vs 371.5±35.3 cfu/m(2), P<0.01). Moxa-stick suffumigation proved to be a reliable and effective airdisinfection method for hematology and HSCT wards, and hence, it should be employed extensively.

INVASIVE CANDIDA INFECTIONS IN PATIENTS WITH HAEMATOLOGICAL MALIGNANCIES AND HEMATOPOIETIC STEM CELL TRANSPLANT RECIPIENTS: CURRENT EPIDEMIOLOGY AND THERAPEUTIC OPTIONS.

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Corrado Girmenia

2011-03-01

Full Text Available In the last decades, the global epidemiological impact of invasive candidiasis (IC in patients with hematologic malignancies (HM and in hematopoietic stem cell transplant (HSCT recipients has decreased and the incidence of invasive aspergillosis  exceeded that of Candida infections. The use of prevention strategies, first of all antifungal prophylaxis with triazoles,  contributed to the reduction of IC in these populations as demonstrated by several  epidemiological studies. However, relatively little is known about the current epidemiological patterns of IC in HM and HSCT populations, because recent epidemiological data almost exclusively derive from retrospective experiences and few prospective data are available. Several prospective, controlled studies in the prophylaxis of invasive fungal diseases have been conducted in both the HM and HSCT setting. On the contrary, most of the prospective controlled trials that demonstrated the efficacy of the antifungal drugs echinocandins and voriconazole in the treatment of candidemia and invasive candidiasis mainly involved  patients with underlying conditions other than HM or  HSCT.  For these reasons, international guidelines provided specific indications for the prophylaxis strategies in HM and HSCT patients, whereas the  recommendations on therapy of documented Candida infections are based on the results observed in the general population and should be considered with caution.

Clinical characteristics and computed tomography findings of pulmonary toxoplasmosis after hematopoietic stem cell transplantation.

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Sumi, Masahiko; Norose, Kazumi; Hikosaka, Kenji; Kaiume, Hiroko; Takeda, Wataru; Kirihara, Takehiko; Kurihara, Taro; Sato, Keijiro; Ueki, Toshimitsu; Hiroshima, Yuki; Kuraishi, Hiroshi; Watanabe, Masahide; Kobayashi, Hikaru

2016-12-01

The prognosis of pulmonary toxoplasmosis, including disseminated toxoplasmosis involving the lungs, following hematopoietic stem cell transplantation (HSCT) is extremely poor due to the difficulties associated with early diagnosis and the rapidly progressive deterioration of multiorgan function. In our institution, we identified nine cases of toxoplasmosis, representing incidences of 2.2 and 19.6 % among all HSCT recipients and seropositive HSCT recipients, respectively. Of the patients with toxoplasmosis, six had pulmonary toxoplasmosis. Chest computed tomography (CT) findings revealed centrilobular, patchy ground-glass opacities (n = 3), diffuse ground-glass opacities (n = 2), ground-glass opacities with septal thickening (n = 1), and marked pleural effusion (n = 1). All cases died, except for one with suspected pulmonary toxoplasmosis who was diagnosed by a polymerase chain reaction assay 2 days after the onset of symptoms. In pulmonary toxoplasmosis, CT findings are non-specific and may mimic pulmonary congestion, atypical pneumonia, viral pneumonitis, and bronchopneumonia. Early diagnosis and treatment is crucial for overcoming this serious infectious complication. Pulmonary toxoplasmosis should be considered during differential diagnosis in a recipient with otherwise unexplained signs of infection and CT findings with ground-glass opacities, regardless of the distribution.

'Crazy-Paving' Patterns on High-Resolution CT Scans in Patients with Pulmonary Complications after Hematopoietic Stem Cell Transplantation

International Nuclear Information System (INIS)

Marchiori, Edson; Escuissato, Dante L.; Gasparetto, Taisa Davaus; Considera, Daniela Peixoto; Franquet, Tomas

2009-01-01

To describe the pulmonary complications following hematopoietic stem cell transplantation (HSCT) that can present with a 'crazy-paving' pattern in high-resolution CT scans. Retrospective review of medical records from 2,537 patients who underwent HSCT. The 'crazy-paving' pattern consists of interlobular and intralobular septal thickening superimposed on an area of ground-glass attenuation on high-resolution CT scans. The CT scans were retrospectively reviewed by two radiologists, who reached final decisions by consensus. We identified 10 cases (2.02%), seven male and three female, with pulmonary complications following HSCT that presented with the 'crazy-paving' pattern. Seven (70%) patients had infectious pneumonia (adenovirus, herpes simplex, influenza virus, cytomegalovirus, respiratory syncytial virus, and toxoplasmosis), and three patients presented with non-infectious complications (idiopathic pneumonia syndrome and acute pulmonary edema). The 'crazy-paving' pattern was bilateral in all cases, with diffuse distribution in nine patients (90%), predominantly in the middle and inferior lung regions in seven patients (70%), and involving the anterior and posterior regions of the lungs in nine patients (90%). The 'crazy-paving' pattern is rare in HSCT recipients with pulmonary complications and is associated with infectious complications more commonly than non-infectious conditions

Characteristics and risk of chronic graft-versus-host disease of liver in allogeneic hematopoietic stem cell transplant recipients.

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Chien-Ting Chen

Full Text Available Chronic graft-versus-host-disease (cGvHD is a serious complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT. Among various organ-specific cGvHD, the cGvHD of liver is less well-characterized. In this study, we applied the National Institutes of Health 2014 scoring criteria of cGvHD to analyze a retrospective cohort of 362 allo-HSCT recipients focusing on cGvHD of liver. The overall incidence of liver cGvHD with a score of 3 by 1.5 years post-transplant was 5.8% (21/362. Poor outcome, in terms of overall survival (OS, were observed in patients with scores of 3 liver cGvHD, comparing to those with scores less than 3 (hazard ratio [HR] 2.037, 95% confidence interval [CI] 1.123-3.696, P = 0.019. In multivariate analysis, male gender (HR 4.004, P = 0.042 and chronic hepatitis C virus (HCV infection status (HR 19.087, P < 0.001 were statistically significant risk factors for scores of 3 liver cGvHD. Our results indicate that liver cGvHD with scores of 3 has a grave prognosis following allo-HSCT, and that HCV carrier status and male are risk factors. Early recognition of this devastating complication might help in prompt immunosuppressive therapy and reducing late poor outcome.

[Pathogenesis and therapy of hydronephrosis after hematopoietic stem cell transplantation].

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Yu, Lu-ping; Xu, Tao; Huang, Xiao-bo; Wang, Xiao-feng

2014-08-18

To investigate the pathogenesis and therapy of hydronephrosis after hematopoietic stem cell transplantation (HSCT). From March 2004 to March 2014, 23 patients with hydronephrosis after HSCT were identified. With these data, the pathogenesis of hydronephrosis after HSCT were analyzed. According to the surgical intervention of hydronephrosis and ureteral dialation of ureteral stricture, the patients were divided into two groups, rank-sum test and exact probability test were used to evaluate whether there were significant differences in the time of hemorrhagic cystitis (HC) occurred, ureteritis and viremia. HC, ureteritis, ureteral stenosis were all the causes of hydronephrosis after HSCT. In this study, 69.6% (16/23) of the patients suffered from HSCT were cured by conservative treatment, 30.4% (7/23) by surgical intervention, and 13.0% (3/23) by insertion DJ stent or nephrostomy.Of the patients [17.4% (4/23)] who suffered ureteral stenosis, 2 were cured after the balloon dialation of ureter, 1 needed DJ tube long-term insertion, and 1 was still followed-up. rank-sum test and exact probability test results showed that the patients who needed surgical intervention might suffer from HC later than other patients, and their incidences of viremia and ureteritis were higher, but the differences between the two groups were not statistically significant (P = 0.524, P = 0.169, and P = 0.124, respectively). The results also showed that the ureteritis incidences of the patients who suffered from ureteral stricture and needed ureteral dialation were higher than that of the other patients, and the difference between the two groups was statistically significant (P = 0.024). The patients who needed ureteral dialation suffered from HC later and their incidences of viremia was higher, but the differences between the two groups were not statistically significant (P = 0.73 and P = 0.27). HC, ureteritis and ureteral stenosis may cause hydronephrosis after HSCT. Patients may treated by

l-asparaginase-based regimens followed by allogeneic hematopoietic stem cell transplantation improve outcomes in aggressive natural killer cell leukemia

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Ki Sun Jung

2016-04-01

Full Text Available Abstract Aggressive nature killer cell leukemia (ANKL is a mature NK-T cell lymphoma with worse prognosis, but optimal treatment is unclear. Therefore, we analyzed the efficacy of l-asparaginase-based regimens for ANKL patients. Twenty-one patients who received dexamethasone, methotrexate, ifosfamide, l-asparaginase, and etoposide (SMILE or etoposide, ifosfamide, dexamethasone, and l-asparaginase (VIDL chemotherapy at Samsung Medical Center were selected. The overall response rate for all patients was 33 % (7/21; 38 % (5/13 in SMILE and 40 % (2/5 in VIDL, respectively. The median progression-free survival was 3.9 months (95 % CI 0.0–8.1 months and median overall survival was 7.0 months (95 % CI 2.3–11.7 months. Treatment response (P = 0.001, hematopoietic stem cell transplantation (HSCT (P = 0.007 and negative conversion of Epstein-Barr virus (EBV DNA titer after treatment (P = 0.004 were significantly associated with survival. Thus, l-asparaginase-based regimens followed by allogeneic HSCT seem to improve the outcome for ANKL patients.

Prevalence of chimerism after non-myeloablative hematopoietic stem cell transplantation

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Azulamara da Silva Ruiz

Full Text Available CONTEXT AND OBJECTIVE: Non-myeloablative hematopoietic stem cell transplantation (NMA-HSCT is performed in onco-hematological patients who cannot tolerate ablative conditioning because of older age or comorbidities. This approach does not completely eliminate host cells and initially results in mixed chimerism. Long-term persistence of mixed chimerism results in graft rejection and relapse. Involvement of graft-versus-host disease is concomitant with complete chimerism and graft-versus-tumor effect. The aim of this study was to evaluate the prevalence of chimerism in onco-hematological patients who underwent NMA-HSCT. DESIGN AND SETTING: Observational clinical study on chimerism status after human leukocyte antigen-identical NMA-HSCT at the Discipline of Hematology and Hemotherapy of Universidade Federal de São Paulo. METHODS: We sequentially analyzed the amplification of APO-B, D1S80, DxS52, FVW, 33.6, YNZ-2 and H-ras primers using variable number of tandem repeats (VNTR on 17 pairs and fluorescent in situ hybridization (FISH with the XY probe and SRY primer on 13 sex-unmatched pairs. RESULTS: The informativeness of the primers using VNTR was 60% for APO-B, 75% D1S80, 36% DxS52, 14% FVW, 40% YNZ-22 and 16% H-ras. The SRY primer was informative in female receptors with male donors. The XY-FISH method was informative in 100% of the sex-unmatched pairs. CONCLUSION: These methods were sensitive and informative. In VNTR, the association of APO-B with D1S80 showed 88% informativeness. The quantitative FISH method was more sensitive, but had the disadvantage of only being used for sex-unmatched pairs.

Sequence typing of human adenoviruses isolated from Polish patients subjected to allogeneic hematopoietic stem cell transplantation - a single center experience.

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Przybylski, Maciej; Rynans, Sylwia; Waszczuk-Gajda, Anna; Bilinski, Jarosław; Basak, Grzegorz W; Jędrzejczak, Wiesław W; Wróblewska, Marta; Młynarczyk, Grażyna; Dzieciątkowski, Tomasz

2018-03-28

Human adenoviruses (HAdV) from species A, B and C are commonly recognized as pathogens causing severe morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. The purpose of the present study was to determine HAdV types responsible for viremia in HSCT recipients at a large tertiary hospital in Poland. Analysis of partial nucleotide sequences of HAdV hexon gene was used to type 40 clinical isolates of HAdV obtained from 40 HSCT recipients. We identified six different HAdV serotypes belonging to species B, C and E. We demonstrated high variability in sequences of detected HAdV types, and patients infected with the same HAdV types were not hospitalized at the same time, which suggests the low possibility of cross-infection. In almost all patients, anti-HAdV antibodies in IgG class were detected, which indicates a history of HAdV infection in the past. Clinical symptoms accompanying HAdV viremia were in 89%, and in 61.5% of individuals, HAdV was a sole pathogen detected. There were no cases with high-level HAdV viremia and severe systemic or organ infections. Graft-versus-host disease (GvHD) was present in patients infected with species B and C, but grade II of GvHD was observed only in patients infected with HAdV-B. The predominance of HAdV-C and common presence of anti-HAdV antibodies in IgG class may strongly suggest that most infections in the present study were reactivations of HAdV persisting into the patient's mucosa-associated lymphoid tissues. Variability of HAdV sequences suggests that cross-infections between patients were very rare. GvHD: graft-versus-host disease; HAdV: human adenoviruses; HSCT: hematopoietic stem cell transplantation.

Donor cytomegalovirus status influences the outcome of allogeneic stem cell transplant: a study by the European group for blood and marrow transplantation.

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Ljungman, Per; Brand, Ronald; Hoek, Jennifer; de la Camara, Rafael; Cordonnier, Catherine; Einsele, Hermann; Styczynski, Jan; Ward, Katherine N; Cesaro, Simone

2014-08-15

The use of a cytomegalovirus (CMV)-seronegative donor for a CMV-seronegative allogeneic hematopoietic stem cell transplant (HSCT) recipient is generally accepted. However, the importance of donor serostatus in CMV-seropositive patients is controversial. A total of 49 542 HSCT patients, 29 349 seropositive and 20 193 seronegative, were identified from the European Group for Blood and Marrow Transplantation database. Cox multivariate models were fitted to estimate the effect of donor CMV serological status on outcome. Seronegative patients receiving seropositive unrelated-donor grafts had decreased overall survival (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.06-1.21; P donors, whereas no difference was seen in patients receiving HLA-matched sibling grafts. Seropositive patients receiving grafts from seropositive unrelated donors had improved overall survival (HR, 0.92; 95% CI, .86-.98; P donors, if they had received myeloablative conditioning. This effect was absent when they received reduced-intensity conditioning. No effect was seen in patients grafted from HLA-identical sibling donors. The same association was found if the study was limited to patients receiving transplants from the year 2000 onward. We confirm the negative impact on overall survival if a CMV-seropositive unrelated donor is selected for a CMV-seronegative patient. For a CMV-seropositive patient, our data support selecting a CMV-seropositive donor if the patient receives a myeloablative conditioning regimen. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Oral complaints and dental care of haematopoietic stem cell transplant patients: a qualitative survey of patients and their dentists.

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Bos-den Braber, Jacolien; Potting, Carin M J; Bronkhorst, Ewald M; Huysmans, Marie-Charlotte D N J M; Blijlevens, Nicole M A

2015-01-01

Little is known about the understanding of the oral and dental needs of haematopoietic stem cell transplant (HSCT) patients or about dentists' views and experiences regarding this patient group. This information is essential if we want to improve the standard of peri-HSCT dental care. The primary objective of this qualitative survey was to explore the following: (1) The understanding of dental care pre- and post-HSCT (2) The subjective oral complaints of HSCT patients both short- and long-term (3) The relationship of these oral complaints to the severity of oral mucositis during hospitalization The secondary objective was to explore the opinions of dentists regarding dental care before and after HSCT. All adult patients who survived HSCT at the Radboud University Medical Centre between 2010 and 2011 (n = 101) received a questionnaire. During hospitalization, mucositis scores were recorded daily in the patient's chart. The patients' dentist (n = 88) was also sent a questionnaire after permission of the patient. Ninety-six out of 101 patients (95%) responded. The average period since HSCT was 19 months (range 8-31 months). The overall mean maximum mucositis score was 6.6 (sd = 3.3). Only eight patients reported not having visited a dentist pre-HSCT. The majority of the patients (59%) reported short-term oral complaints, and 28% reported long-term oral complaints. Fifty-two dentists responded (59%). Nine had not performed pre-HSCT screening and eight dentists reported screening their patients but could not complete the necessary treatments. Only 44 dentists succeeded in completing the required treatments. The most important advice of the dentist was to reinforce the importance of regular dental care. Most patients report short-term and/or long-term oral complaints after HSCT. Most dentists stress the importance of regular dental care before and after HSCT but report not being familiar with the particular dental care needs of this patient group. The high

Haploidentical hematopoietic stem cell transplant with umbilical cord-derived multipotent mesenchymal cell infusion for the treatment of high-risk acute leukemia in children.

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Zhu, Ling; Wang, Zhidong; Zheng, Xiaoli; Ding, Li; Han, Dongmei; Yan, Hongmin; Guo, Zikuan; Wang, Hengxiang

2015-05-01

In this study, 25 children with high-risk acute leukemia received haploidentical hematopoietic stem cell transplant (haplo-HSCT) with co-transfusion of umbilical cord multipotent mesenchymal cells (UC-MSCs). Adverse effects, hematopoietic recovery, complications and outcome were observed during a median follow-up of 12.8 months (range: 3-25 months). Myeloid engraftment was rapid, and the median time to neutrophil and platelet recovery was 15.12 days and 20.08 days, respectively. Eight patients developed grade I skin acute graft-versus-host disease (aGVHD) that responded well to standard steroid therapy. Of note, cytomegalovirus viremia was observed in most patients (23/25 cases). Patients died mainly of leukemia relapse and pulmonary complication. Fourteen patients are currently alive and remain with full donor chimerism at the time of reporting. The present results suggest further clinical trials to testify the effectiveness of UC-MSCs to prevent aGVHD in haplo-HSCT for treating children with high-risk leukemia.

Spectrum of Epstein-Barr virus-associated diseases in recipients of allogeneic hematopoietic stem cell transplantation.

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Xuan, Li; Jiang, Xinmiao; Sun, Jing; Zhang, Yu; Huang, Fen; Fan, Zhiping; Guo, Xutao; Dai, Min; Liu, Can; Yu, Guopan; Zhang, Xian; Wu, Meiqing; Huang, Xiaojun; Liu, Qifa

2013-09-01

Epstein-Barr virus (EBV) infection may result in a spectrum of diseases in recipients of transplant. The aim of this study is to investigate the incidence, clinical characteristics, and prognosis of the spectrum of EBV-associated diseases in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). A total of 263 recipients undergoing allo-HSCT were prospectively enrolled. The blood EBV-DNA loads were regularly monitored by quantitative real-time polymerase chain reaction. The 3-year cumulative incidence of total EBV-associated diseases, posttransplantation lymphoproliferative diseases (PTLD), EBV fever, and EBV end-organ diseases (pneumonia, encephalitis/myelitis, and hepatitis) were 15.6%±2.5%, 9.9%±2.0%, 3.3%±1.3%, and 3.3%±1.2% (2.2%±1.0%, 1.6%±0.8%, and 0.9%±0.6%), respectively. Fever was the most common symptom of EBV-associated diseases. Patients with PTLD had better response rate to rituximab-based treatments compared with those with EBV end-organ diseases (including PTLD accompanied by EBV end-organ diseases) (P=0.014). The 3-year overall survival was 37.3%±13.7%, 100.0%, and 0.0%±0.0% in patients with PTLD, EBV fever, and EBV end-organ diseases (P=0.001). EBV-associated diseases other than PTLD are not rare in the recipients of allo-HSCT. The clinical manifestations of EBV end-organ diseases are similar to PTLD. EBV end-organ diseases had poorer response to rituximab-based therapy compared with PTLD.

Cord stem-cell transplantation in Ontario: do we need a public bank?

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Gassas, A

2011-06-01

It has been 21 years since the first successful use of umbilical cord blood as a source of donor cells for hematopoietic stem cell transplantation (HSCT). Over those years, cord blood transplantation (CBT) has shown marked success as an effective modality in the treatment of children and adults with hematologic malignancies, marrow failure, immunodeficiency, hemoglobinopathy, and inherited metabolic diseases. Furthermore, transplantation without full human leukocyte antigen (HLA) matching is possible and, despite a lower incidence of graft-versus-host disease, graft-versus-leukemia effect is preserved. More than 20,000 cbts have been performed worldwide. Ontario is the most populated province in Canada, and its cbt numbers have increased dramatically in recent years, but most of the umbilical cord blood units are purchased from unrelated international registries. There is no public cord bank in Ontario, but there is a private cord banking option, and notably, Ontario has the largest number of live births in Canada [approximately 40% of all Canadian live births per year occur in Ontario (Statistics Canada, 2007)]. In this brief review, the pros and cons of private and public cord banking and the feasibility of starting an Ontario public cord bank are discussed.

Enzyme Replacement Therapy and/or Hematopoietic Stem Cell Transplantation at diagnosis in patients with Mucopolysaccharidosis type I: results of a European consensus procedure

LENUS (Irish Health Repository)

de Ru, Minke H

2011-08-10

Abstract Background Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder that results in the accumulation of glycosaminoglycans causing progressive multi-organ dysfunction. Its clinical spectrum is very broad and varies from the severe Hurler phenotype (MPS I-H) which is characterized by early and progressive central nervous system (CNS) involvement to the attenuated Scheie phenotype (MPS I-S) with no CNS involvement. Indication, optimal timing, safety and efficacy of the two available treatment options for MPS I, enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT), are subject to continuing debate. A European consensus procedure was organized to reach consensus about the use of these two treatment strategies. Methods A panel of specialists, including 8 specialists for metabolic disorders and 7 bone marrow transplant physicians, all with acknowledged expertise in MPS I, participated in a modified Delphi process to develop consensus-based statements on MPS I treatment. Fifteen MPS I case histories were used to initiate the discussion and to anchor decisions around either treatment mode. Before and at the meeting all experts gave their opinion on the cases (YES\\/NO transplantation) and reasons for their decisions were collected. A set of draft statements on MPS I treatment options composed by a planning committee were discussed and revised during the meeting until full consensus. Results Full consensus was reached on several important issues, including the following: 1) The preferred treatment for patients with MPS I-H diagnosed before age 2.5 yrs is HSCT; 2) In individual patients with an intermediate phenotype HSCT may be considered if there is a suitable donor. However, there are no data on efficacy of HSCT in patients with this phenotype; 3) All MPS I patients including those who have not been transplanted or whose graft has failed may benefit significantly from ERT; 4) ERT should be started at diagnosis and may be

Oral Complications in Hematopoietic Stem Cell Recipients: The Role of Inflammation

Directory of Open Access Journals (Sweden)

T. M. Haverman

2014-01-01

Full Text Available Hematopoietic stem cell transplantation (HSCT is widely used as a potentially curative treatment for patients with various hematological malignancies, bone marrow failure syndromes, and congenital immune deficiencies. The prevalence of oral complications in both autologous and allogeneic HSCT recipients remains high, despite advances in transplant medicine and in supportive care. Frequently encountered oral complications include mucositis, infections, oral dryness, taste changes, and graft versus host disease in allogeneic HSCT. Oral complications are associated with substantial morbidity and in some cases with increased mortality and may significantly affect quality of life, even many years after HSCT. Inflammatory processes are key in the pathobiology of most oral complications in HSCT recipients. This review article will discuss frequently encountered oral complications associated with HSCT focusing on the inflammatory pathways and inflammatory mediators involved in their pathogenesis.

stem cell research: applications in haematological conditions

African Journals Online (AJOL)

Dr. E. P. Gharoro

chemotherapy and radiation. This has allowed HSCT to be conducted in older patients without the need for hospitalization. STEM CELL COLLECTION. Types of Donors. There are two major types of bone marrow transplantation namely;. Autologous and Allogenic transplantations. Autologous: Bone marrow transplantation.

Travel risk assessment, advice and vaccinations in immunocompromised travellers (HIV, solid organ transplant and haematopoeitic stem cell transplant recipients): A review.

Science.gov (United States)

Aung, A K; Trubiano, J A; Spelman, D W

2015-01-01

International travellers with immunocompromising conditions such as human immunodeficiency virus (HIV) infection, solid organ transplantation (SOT) and haematopoietic stem cell transplantation (HSCT) are at a significant risk of travel-related illnesses from both communicable and non-communicable diseases, depending on the intensity of underlying immune dysfunction, travel destinations and activities. In addition, the choice of travel vaccinations, timing and protective antibody responses are also highly dependent on the underlying conditions and thus pose significant challenges to the health-care providers who are involved in pre-travel risk assessment. This review article provides a framework of understanding and approach to aforementioned groups of immunocompromised travellers regarding pre-travel risk assessment and management; in particular travel vaccinations, infectious and non-infectious disease risks and provision of condition-specific advice; to reduce travel-related mortality and morbidity. Copyright © 2014 Elsevier Ltd. All rights reserved.

The role of social and cognitive processes in the relationship between fear network and psychological distress among parents of children undergoing hematopoietic stem cell transplantation.

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Virtue, Shannon Myers; Manne, Sharon; Mee, Laura; Bartell, Abraham; Sands, Stephen; Ohman-Strickland, Pamela; Gajda, Tina Marie

2014-09-01

The current study examined whether cognitive and social processing variables mediated the relationship between fear network and depression among parents of children undergoing hematopoietic stem cell transplant (HSCT). Parents whose children were initiating HSCT (N = 179) completed survey measures including fear network, Beck Depression Inventory, cognitive processing variables (positive reappraisal and self-blame) and social processing variables (emotional support and holding back from sharing concerns). Fear network was positively correlated with depression (p fear network and depression. Together they accounted for 34.3% of the variance in the relationship between fear network and depression. Positive reappraisal and emotional support did not have significant mediating effects. Social and cognitive processes, specifically self-blame and holding back from sharing concerns, play a negative role in parents' psychological adaptation to fears surrounding a child's HSCT.

Acquisition of vernal and atopic keratoconjunctivitis after bone marrow transplantation.

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Tabbara, Khalid F; Nassar, Amr; Ahmed, Syed Osman; Al Mohareb, Fahad; Aljurf, Mahmoud

2008-09-01

Vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC) result from genetic and environmental factors. We present patients who had no history of atopic disorders before bone marrow transplantation (BMT) and who seem to have acquired VKC or AKC from their donors, who had atopic disorders. Observational case series. The patients in this study were part of a cohort of patients who had undergone allogeneic hemapoietic stem cell transplantation (HSCT) from January 1997 through December 2007. Of 621 HSCT recipients, four recipients who were free of allergic disorders acquired VKC or AKC from their afflicted donors after HSCT. Each patient underwent complete ophthalmologic examination, determination of the total serum immunoglobulin (Ig) E, and conjunctival scrapings. Four (0.64%) of 621 patients who had undergone HSCT acquired VKC or AKC after BMT. The donors had VKC or atopic dermatitis. In addition, in two of these four patients, asthma developed. One patient had elevated total serum IgE. Conjunctival scrapings of all four patients revealed the presence of eosinophils. One patient had concurrent graft-versus-host disease. VKC and AKC are systemic allergic disorders characterized by local ocular manifestations. This report suggests the possibility of the acquisition of VKC or AKC after BMT by adoptive transfer.

Features of transfusion therapy in patients undergoing hematopoietic stem cell transplantation. Review of the literature

Directory of Open Access Journals (Sweden)

D. N. Balashov

2014-07-01

Full Text Available The indications for transfusion of blood components support after stem cell transplantation (SCT usually do not differ form other clinical situations, but the rules for such therapy have a number of features. One of them is the possibility of inconsistence of AB0 group between donor and recipient of hematopoietic stem cells, which is not only fraught with the development of various alloimmune complications, but also fundamentally changes the standards for the selection of blood components for transfusion. A major problem after HSCT is a secondary immunodeficiency, which is important to consider for ensuring prevention of transfusion-transmitted infections (eg, CMV, as well as to carry out activities aimed for the prevention of transfusion- associated graft-versus-host disease. HSCT is a medical technology today, the effectiveness of which is often dependent on the accuracy and integrity of its implementation. So, serious attitude to various supportive therapy, including transfusions of blood components is an important component which determines the success of the treatment.

Features of transfusion therapy in patients undergoing hematopoietic stem cell transplantation. Review of the literature

Directory of Open Access Journals (Sweden)

D. N. Balashov

2013-01-01

Full Text Available The indications for transfusion of blood components support after stem cell transplantation (SCT usually do not differ form other clinical situations, but the rules for such therapy have a number of features. One of them is the possibility of inconsistence of AB0 group between donor and recipient of hematopoietic stem cells, which is not only fraught with the development of various alloimmune complications, but also fundamentally changes the standards for the selection of blood components for transfusion. A major problem after HSCT is a secondary immunodeficiency, which is important to consider for ensuring prevention of transfusion-transmitted infections (eg, CMV, as well as to carry out activities aimed for the prevention of transfusion- associated graft-versus-host disease. HSCT is a medical technology today, the effectiveness of which is often dependent on the accuracy and integrity of its implementation. So, serious attitude to various supportive therapy, including transfusions of blood components is an important component which determines the success of the treatment.

Virus-Specific T Cells: Broadening Applicability.

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Barrett, A John; Prockop, Susan; Bollard, Catherine M

2018-01-01

Virus infection remains an appreciable cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Although pharmacotherapy and/or antibody therapy may help prevent or treat viral disease, these drugs are expensive, toxic, and often ineffective due to primary or secondary resistance. Further, effective treatments are limited for many infections (eg, adenovirus, BK virus), which are increasingly detected after alternative donor transplants. These deficiencies in conventional therapeutics have increased interest in an immunotherapeutic approach to viral disorders, leading to adoptive transfer of virus-specific cytotoxic T lymphocytes (VSTs), which can rapidly reconstitute antiviral immunity post-transplantation without causing graft-versus-host disease. This review will explore how the VST field has improved outcomes for many patients with life-threatening viral infections after HSCT, and how to broaden applicability beyond the "patient-specific" products, as well as extending to other viral diseases even outside the context of HSCT. Copyright © 2017 The American Society for Blood and Marrow Transplantation. All rights reserved.

Single-centre experience of allogeneic haemopoietic stem cell ...

African Journals Online (AJOL)

Allogeneic haemopoietic stem cell transplant (Allo-HSCT) is used to treat a broad but well-defined range of paediatric conditions, most frequently in paediatric oncology for treatment intensification or salvage therapy for acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL). Allo-HSCT is also indicated in.

Haematopoietic transplants combining a single unrelated cord blood unit and mobilized haematopoietic stem cells from an adult HLA-mismatched third party donor. Comparable results to transplants from HLA-identical related donors in adults with acute leukaemia and myelodysplastic syndromes.

Science.gov (United States)

Sebrango, Ana; Vicuña, Isabel; de Laiglesia, Almudena; Millán, Isabel; Bautista, Guiomar; Martín-Donaire, Trinidad; Regidor, Carmen; Cabrera, Rafael; Fernandez, Manuel N

2010-06-01

We describe results of the strategy, developed by our group, of co-infusion of mobilized haematopoietic stem cells as a support for single-unit unrelated cord blood transplant (dual CB/TPD-MHSC transplants) for treatment of haematological malignancies in adults, and a comparative analysis of results obtained using this strategy and transplants performed with mobilized haematopoietic stem cells from related HLA-identical donors (RTD) for treatment of adults with acute leukaemia and myelodysplastic syndromes. Our data show that the dual CB/TPD-MHSC transplant strategy results in periods of post-transplant neutropenia, final rates of full donor chimerism and transplant-related mortality rates comparable to those of the RTD. Final survival outcomes are comparable in adults transplanted because of acute leukaemia, with different incidences of the complications that most influence these: a higher incidence of infections related to late recovery of protective immunity dependent on T cell functions, and a lower incidence of serious acute graft-versus-host disease and relapses. Recent advances in cord blood transplant techniques allow allogeneic haematopoietic stem cell transplantation (HSCT) to be a viable option for almost every patient who may benefit from this therapeutic approach. Development of innovative strategies to improve the post-transplant recovery of T cells function is currently the main challenge to further improving the possibilities of unrelated cord blood transplantation. Copyright © 2010 Elsevier Ltd. All rights reserved.

Antifungal prophylaxis with fluconazole in allogeneic stem cell transplantation recipients who had prior invasive aspergillosis with subsequent complete resolution by computed tomography.

Science.gov (United States)

Akahoshi, Yu; Kimura, Shun-Ichi; Gomyo, Ayumi; Hayakawa, Jin; Tamaki, Masaharu; Harada, Naonori; Kusuda, Machiko; Kameda, Kazuaki; Ugai, Tomotaka; Wada, Hidenori; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Sato, Miki; Terasako-Saito, Kiriko; Kikuchi, Misato; Nakasone, Hideki; Kako, Shinichi; Kanda, Yoshinobu

2018-04-01

Consensus has yet to be reached regarding secondary prophylaxis in allogeneic hematopoietic stem cell transplantation (HSCT) with a complete resolution of invasive aspergillosis (IA) confirmed by chest computed tomography (CT). We retrospectively evaluated the feasibility of antifungal prophylaxis with fluconazole in allogeneic HSCT recipients who had previously developed IA which showed complete resolution as confirmed by chest CT before HSCT. Consecutive adult patients who underwent allogeneic HSCT at our institution and who had received fluconazole as systemic antifungal prophylaxis from June 2007 to January 2015 were included. We compared the clinical outcomes between patients with a past history of IA who showed a complete resolution of chest CT abnormalities (n = 13) and those without a previous history of IA (n = 137). The cumulative incidence of proven or probable IA was 8.8% in the group without a past history of IA and 0.0% in the group with a past history of IA (p = .268). The cumulative incidence of proven or probable invasive fungal disease (IFD) within 100 days after allogeneic HSCT was 10.9% in the group without a past history of IA and 15.4% in the group with a past history of IA (p = .647). Fluconazole was switched to anti-mould agents in two-thirds of the patients in each group by day 100 after HSCT. Fluconazole was confirmed to be an acceptable prophylactic agent early after allogeneic HSCT in appropriately selected patients.

[Treatment of Gaucher disease with allogeneic hematopoietic stem cell transplantation: report of three cases and review of literatures].

Science.gov (United States)

Tang, Xiangfeng; Luan, Zuo; Wu, Nanhai; Zhang, Bo; Jing, Yuanfang; Du, Hong; Lu, Wei; Xu, Shixia

2015-11-01

To explore the efficacy of unrelated umbilical cord blood transplantation (UCBT) in the treatment of Gaucher disease. The clinical characteristics of three children with Gaucher disease underwent UCBT in our hospital between April 2013 and September 2014 were retrospectively analyzed. Literature on allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of Gaucher disease was searched at Wanfang and Pubmed databases between 1983 and 2015 and was reviewed and summaried. Three children with Gaucher disease, all were female, received UCBT. These patients' age at receiving transplantation was 3.8 years, 7.1 years and 2.6 years, respectively. The second case received the second transplantation. The first and third case received splenectomy before UCBT. The pretreatment regimen was busulfan (Bu)/fludarabine (Flu)/cyclophosphamide (CTX)/antithymocyte globulin (ATG), and for the patient received the second transplantation melphalan was added to the myeloablative conditioning regimen of Bu/Flu/CTX/ATG. Cyclosporine and mycophenolate mofetil (MMF) wee used for prophylaxis of acute graft versus host disease (aGVHD). The dose of cord blood stem cell nucleated cell counts was 9.7 × 10⁷ /kg,11.9 × 10⁷ /kg and 7.6 × 10⁷/kg respectively. The dose of cord blood stem cell CD34⁺ cell counts was 5.4 × 10⁵/kg , 3.5 × 10⁵/kg and 3.2 × 10⁵/kg respectively. The day of granulocytes exceeding 0.5 × 10⁹/L was day 11, 12 and 19 after transplantation, respectively. The day of platelets exceeding 20 × 10⁹/L was day 14, 33 and 74 after transplantation, respectively. At one month after transplantation the rate of chimerism was over 95% and all patients got donor complete chimerism. The level of β-glucocerebrosidase recovered to normal at one month after transplantation. During transplantation, all patients developed cytomegalovirus (CMV) and Epstein-Barr virus (EBV) viremia. In case 1 immune thrombocytopenia occurred at five month after

[A comparative study of unrelated donor and matched-sibling donor allogeneic hematopoietic stem cell transplantation in children and adolescents with acquired severe aplastic anemia].

Science.gov (United States)

Zhou, J; Fu, Y W; Liang, L J; Wang, Q; Han, L J; Zu, Y L; Zhang, Yanli; Zhu, X H; Yu, F K; Fang, B J; Wei, X D; Song, Y P

2016-12-01

Objective: To evaluate the efficacy of unrelated donor allogeneic hematopoietic stem cell transplantation(URD allo-HSCT) for children and adolescents with severe aplastic anemia (SAA). Methods: Clinical data of 34 SAA children and adolescents undergoing allo-HSCT were retrospectively analyzed from October 2001 to October 2015. According to the source of donor, the patients were divided into matched sibling donor allo-HSCT group (MSD group) and unrelated donor group (URD group). The clinical outcome of SAA children and adolescents receiving URD allo-HSCT was assessed, and patients in MSD allo-HSCT group were enrolled as control at the same period. Results: The rate of hematopoietic reconstitution, the time of neutrophil and platelet engraftment, incidence of chimerism and graft rejection between two groups were not statistically different.The incidence of acute graft-versus-host disease (GVHD) in URD group was significantly higher than that in MSD group [42.9%(6/14) vs 10.5%(2/19), P =0.047]. The incidence of grade Ⅱ-Ⅳ acute GVHD and chronic GVHD in URD were higher than those in MSD group [21.4%(3/14) vs 5.3%(1/19), P =0.288; 35.7%(5/14) vs 5.3%(1/19), P =0.062, respectively], yet without significant difference between two groups. Other transplant-related complications including pulmonary complications, hemorrhagic cystitis, incidence of EBV and CMV reactivation and venous occlusive disease were comparable with two regimens. Estimated 5-years overall survival (OS) rate and disease free survival (DFS) rate were not statistically significant between URD group and MSD group [(84.4±6.6)% vs (89.4±7.1)%, (82.5±5.4)% vs (82.1±4.3)%; P =0.766, P =0.884, respectively]. Conclusions: By multivariate analysis, the outcome of URD allo-HSCT in SAA children and adolescent is similar to MSD allo-HSCT. It could be an alternative option as the first-line treatment for SAA children and adolescents without HLA matched sibling donors.

A comparison of the effect of xinruibai versus filgrastim on hematopoietic reconstruction after allogeneic hematopoietic stem cell transplantation.

Science.gov (United States)

Ye, Qixiang; Jiang, Hebi; Jiang, Hua

2018-05-31

To compare the effect of xinruibai (Pegfilgrastim) and filgrastim injections on white blood cell and platelet (PLT) recovery, adverse events, post-operative complications, and cost effectiveness after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Children who underwent allo-HSCT at our hospital from January 2014 to May 2017 due to thalassemia major, aplastic anemia, leukemia, and mucopolysaccharidosis were included. Among the children, 53 received xinruibai injections and 33 received filgrastim injections. There were no significant differences in the average time to neutrophil and platelet recovery, the incidence of post-operative complications after allo-HSCT, the number of red blood cell and PLT infusions, or the incidence of adverse events related to the injection between two groups (P >  0.05). The pain score was 3.06 (SD 0.41) for the xinruibai group and 25.18 (SD 6.22) for the filgrastim group, indicating significant differences between the two groups (P <  0.001). No difference was found in the hospitalization cost. The cost of the granulocyte-colony stimulating factor (G-CSF) was 257.11 ± 61.87 Euro in the xinruibai group and 214.79 ± 0.00 Euro in the filgrastim group, showing significant difference (P <  0.001). Xinruibai injection was more convenient, simple, effective, and safer than filgrastim.

A cost-utility and budget impact analysis of allogeneic hematopoietic stem cell transplantation for severe thalassemic patients in Thailand.

Science.gov (United States)

Leelahavarong, Pattara; Chaikledkaew, Usa; Hongeng, Suradej; Kasemsup, Vijj; Lubell, Yoel; Teerawattananon, Yot

2010-07-16

Hematopoietic stem cell transplantation (HSCT) is the only curative treatment available to severe thalassemic patients. The treatment, however, is very costly, particularly in the context of low and middle income countries, and no studies have been carried out to explore its economic justifiability. This study aimed to estimate the cost-utility of HSCT compared with blood transfusions combined with iron chelating therapy (BT-ICT) for severe thalassemia in Thailand, and to investigate the affordability of HSCT using a budget impact analysis. A Markov model was used to estimate the relevant costs and health outcomes over the patients' lifetimes taking a societal perspective as recommended by Thailand's health technology assessment guidelines. All future costs and outcomes were discounted at a rate of 3% per annum. Primary outcomes of interest were lifetime costs, quality adjusted life years (QALYs) gained, and the incremental cost-effectiveness ratio (ICER) in Thai baht (THB) per QALY gained. Compared to BT-ICT, the incremental cost-effectiveness ratio increased with patient age from 80,700 to 183,000 THB per QALY gained for related HSCT and 209,000 to 953,000 THB per QALY gained for unrelated HSCT among patients aged 1 to 15 years (US$1= 34 THB). The governmental budget impact analysis showed that providing 200 related HSCT to patients aged 1 to 10 years, in accordance with the current infrastructure limitations, would initially require approximately 90 million additional THB per year. At a societal willingness to pay of 100,000 THB per QALY gained, related HSCT was likely to be a cost-effective and affordable treatment for young children with severe thalassemia in Thailand.

Physical activity reduces fatigue in patients with cancer and hematopoietic stem cell transplant recipients: A systematic review and meta-analysis of randomized trials.

Science.gov (United States)

Oberoi, Sapna; Robinson, Paula D; Cataudella, Danielle; Culos-Reed, S Nicole; Davis, Hailey; Duong, Nathan; Gibson, Faith; Götte, Miriam; Hinds, Pamela; Nijhof, Sanne L; Tomlinson, Deborah; van der Torre, Patrick; Cabral, Sandra; Dupuis, L Lee; Sung, Lillian

2018-02-01

Objective was to determine whether physical activity reduces the severity of fatigue in patients with cancer or hematopoietic stem cell transplant (HSCT) recipients. We conducted a meta-analysis of randomized trials comparing physical activity with control interventions for the management of fatigue in patients with cancer or HSCT recipients. There were 170 trials included. Physical activity reduced the severity of fatigue when compared to all control groups (standardized mean difference -0.49, 95% confidence interval -0.60 to -0.37; P fatigue although smaller effects were observed with resistance exercises (P interaction = 0.01). Other intervention and patient characteristics did not influence the effect of physical activity on the severity of fatigue. Physical activity was effective at reducing fatigue in patients with cancer and HSCT recipients across patient sub-groups. Determining the best approaches for safe implementation should be a priority. Copyright © 2017 Elsevier B.V. All rights reserved.

Earlier defibrotide initiation post-diagnosis of veno-occlusive disease/sinusoidal obstruction syndrome improves Day +100 survival following haematopoietic stem cell transplantation.

Science.gov (United States)

Richardson, Paul G; Smith, Angela R; Triplett, Brandon M; Kernan, Nancy A; Grupp, Stephan A; Antin, Joseph H; Lehmann, Leslie; Miloslavsky, Maja; Hume, Robin; Hannah, Alison L; Nejadnik, Bijan; Soiffer, Robert J

2017-07-01

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a progressive, potentially fatal complication of conditioning for haematopoietic stem cell transplant (HSCT). The VOD/SOS pathophysiological cascade involves endothelial-cell activation and damage, and a prothrombotic-hypofibrinolytic state. Severe VOD/SOS (typically characterized by multi-organ dysfunction) may be associated with >80% mortality. Defibrotide is approved for treating severe hepatic VOD/SOS post-HSCT in the European Union, and for hepatic VOD/SOS with renal or pulmonary dysfunction post-HSCT in the United States. Previously, defibrotide (25 mg/kg/day in 4 divided doses for a recommended ≥21 days) was available through an expanded-access treatment protocol for patients with VOD/SOS. Data from this study were examined post-hoc to determine if the timing of defibrotide initiation post-VOD/SOS diagnosis affected Day +100 survival post-HSCT. Among 573 patients, defibrotide was started on the day of VOD/SOS diagnosis in approximately 30%, and within 7 days in >90%. The relationship between Day +100 survival and treatment initiation before/after specific days post-diagnosis showed superior survival when treatment was initiated closer to VOD/SOS diagnosis with a statistically significant trend over time for better outcomes with earlier treatment initiation (P defibrotide should not be delayed after diagnosis of VOD/SOS. © 2017 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

[Combination of busulfan with increased-dose of fludarabine as conditioning regimen for MDS and MDS-AML patients with allo-HSCT].

Science.gov (United States)

Yuan, Jing; Ren, Hanyun; Qiu, Zhixiang; Li, Yuan; Wang, Mangju; Liu, Wei; Xu, Weilin; Sun, Yuhua; Wang, Lihong; Liang, Zeyin; Dong, Yujun; Ou, Jinping; Wang, Wensheng; Yin, Yue; Cen, Xinan; Wang, Qian

2015-06-01

To investigate the safety and efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndrome (MDS) and secondary acute myelogenous leukemia (MDS-AML) using conditioning regimen with busulfan (Bu) and increased-dose of fludarabine (ID-Flu). A total of 49 patients with MDS or MDS-AML were treated by allo-HSCT, the clinical data was analyzed retrospectively. All patients achieved hematopoietic reconstitution. Neutrophil engraftment was at 10 - 22 days (median 13 days), and platelet engraftment was at 8 - 66 days (median 16 days). The cumulative incidences of Ⅱ-Ⅳ degree acute graft-versus-host disease (GVHD), hemorrhagic cystitis (HC), and hepatic venous occlusive disease (VOD) were 28.6%, 14.3% and 2.0%, respectively. The transplant-related mortality (TRM) was only 4.1% at 100d and 8.2% at 1-92 months of followed-up (median 14 months) period. Overall survival (OS) and disease free survival (DFS) was 75.5%, 73.5%, respectively. Kaplan-Meier curve showed that 3-year OS and 3-year DFS was (71.1 ± 7.8)%, (66.7 ± 8.3)%, respectively, with a relapse incidence (RI) 16.3%. OS for MDS and MDS-AML was 81.5% and 68.2%, and RI in two settings was 3.7%, 31.8%, respectively. OS for MDS-AML at complete remission (CR) and non-CR subgroup was 83.3% and 50.0%, respectively, while cumulative RR was 16.7% and 50.0%, respectively. OS and RI except for non-CR subgroup were 82.1% and 7.7%. Univariate analysis showed that pre-HSCT disease status had correlation with OS (P=0.031), but age, decitabine in conditioning regimen, stem cell source, HLA matching, patient-donor gender, dose of mononuclear cells and GVHD had no correlation with OS. Bu/ID-Flu conditioning regimen for MDS and MDS-AML has high efficiency, fewer complications, lower toxicity and TRM. The OS and DFS were higher and RI was lower except for refractory MDS-AML patients. The regimen is valuable for clinical application.

Treatment of radiation exposure and regeneration medicine. Regeneration treatment of blood vessels by transplantation of autologous marrow monocytes

International Nuclear Information System (INIS)

Nagai, Kazuhiro; Kamihira, Shimeru; Matsumaru, Ichiro; Fukushima, Takuya; Yamaguchi, Hakuichiro; Miyazaki, Yasushi; Yamachika, Shiro; Eishi, Kiyoyuki; Tomonaga, Masao

2007-01-01

Described are usefulness and future view of regenerative medicine in the treatment of radiation exposure as exemplified by the vascular regeneration by autologous marrow cell transplantation. Vascular endothelial cells (VEC), possessing a high ability to divide, are known sensitive to radiation, which gives damage of blood vessel to alter its permeability leading to apoptosis of VEC, organ/tissue injuries and final damages in the cerebral blood vessels, central nervous system and skin, the acute radiation syndrome (ARS). Authors present successful cases of patients with chronic limb ischemia in the Therapeutic Angiogenesis using Cell Transplantation Trial (TACT), to whom the treatment is conducted with transplantation of autologous marrow monocyte fraction containing endothelial progenitor cells that differentiate to VEC. As well, they touch on a case of the patient encountered in a nuclear accident, mentioning that VEC are found partly derived from the donor after heamatopoietic stem cell transplantation (HSCT). Efficacy of HSCT in a literature is reviewed and commented to be an only limited one in 31 patients of various radiation accidents. However, treatment of ARS where stem cells are target, with regenerative medicine will become more useful in future, as basic and clinical researches will provide requisite findings. (T.I.)

Effects of hematopoietic stem cell transplantation on acyl-CoA oxidase deficiency: a sibling comparison study

Science.gov (United States)

Monuki, Edwin S.; Powers, James; Schwartz, Phillip H.; Watkins, Paul A.; Shi, Yang; Moser, Ann; Shrier, David A.; Waterham, Hans R.; Nugent, Diane J.; Abdenur, Jose E.

2015-01-01

Objective Acyl-CoA oxidase (ACOX1) deficiency is a rare disorder of peroxisomal very-long chain fatty acid oxidation. No reports detailing attempted treatment, longitudinal imaging, or neuropathology exist. We describe the natural history of clinical symptoms and brain imaging in two siblings with ACOX1 deficiency, including the younger sibling's response to allogeneic unrelated donor hematopoietic stem cell transplantation (HSCT). Methods We conducted retrospective chart review to obtain clinical history, neuro-imaging, and neuropathology data. ACOX1 genotyping were performed to confirm the disease. In vitro fibroblast and neural stem cell fatty acid oxidation assays were also performed. Results Both patients experienced a fatal neurodegenerative course, with late-stage cerebellar and cerebral gray matter atrophy. Serial brain magnetic resonance imaging in the younger sibling indicated demyelination began in the medulla and progressed rostrally to include the white matter of the cerebellum, pons, midbrain, and eventually subcortical white matter. The successfully engrafted younger sibling had less brain inflammation, cortical atrophy, and neuronal loss on neuroimaging and neuropathology compared to the untreated older sister. Fibroblasts and stem cells demonstrated deficient very long chain fatty acid oxidation. Interpretation Although HSCT did not halt the course of ACOX1 deficiency, it reduced the extent of white matter inflammation in the brain. Demyelination continued because of ongoing neuronal loss, which may be due to inability of transplant to prevent progression of gray matter disease, adverse effects of chronic corticosteroid use to control graft-versus-host disease, or intervention occurring beyond a critical point for therapeutic efficacy. PMID:24619150

Associations between levels of insulin-like growth factor 1 and sinusoidal obstruction syndrome after allogeneic haematopoietic stem cell transplantation

DEFF Research Database (Denmark)

Weischendorff, Sarah; Kielsen, Katrine; Sengeløv, H

2017-01-01

. We hypothesised that insulin-like growth factor-1 (IGF-1), a mediator of growth and proliferation of various tissues, may attenuate chemotherapy-induced tissue damage after HSCT. We prospectively measured plasma levels of IGF-1 and its binding protein 3 (IGFBP-3) in 41 patients undergoing...... myeloablative HSCT. IGF-1 and IGFBP-3 levels were inversely correlated with C-reactive protein and interleukin-6 levels post HSCT. In multivariate analyses, low levels of IGF-1 and IGFBP-3 before conditioning were associated with increased risk of developing sinusoidal obstruction syndrome (SOS; OR=5.00 per 1...... SDS decrease in IGF-1 (95% CI: 1.45-16.67), P=0.011 and OR=5.00 (1.37-20.00), P=0.015, respectively). Furthermore, low pre-transplant levels of IGF-1 and IGFBP-3 were associated with increased fluid retention during the first 21 days post transplant (OR=7.69 (95% CI: 1.59-33.33), P=0.012, and OR=2...

'Crazy-Paving' Patterns on High-Resolution CT Scans in Patients with Pulmonary Complications after Hematopoietic Stem Cell Transplantation

Energy Technology Data Exchange (ETDEWEB)

Marchiori, Edson; Escuissato, Dante L.; Gasparetto, Taisa Davaus; Considera, Daniela Peixoto [Federal University, Sao Paulo (Brazil); Franquet, Tomas [Hospital de Sant Pau, Universitat Autonoma de Barcelona, Barcelona (Spain)

2009-02-15

To describe the pulmonary complications following hematopoietic stem cell transplantation (HSCT) that can present with a 'crazy-paving' pattern in high-resolution CT scans. Retrospective review of medical records from 2,537 patients who underwent HSCT. The 'crazy-paving' pattern consists of interlobular and intralobular septal thickening superimposed on an area of ground-glass attenuation on high-resolution CT scans. The CT scans were retrospectively reviewed by two radiologists, who reached final decisions by consensus. We identified 10 cases (2.02%), seven male and three female, with pulmonary complications following HSCT that presented with the 'crazy-paving' pattern. Seven (70%) patients had infectious pneumonia (adenovirus, herpes simplex, influenza virus, cytomegalovirus, respiratory syncytial virus, and toxoplasmosis), and three patients presented with non-infectious complications (idiopathic pneumonia syndrome and acute pulmonary edema). The 'crazy-paving' pattern was bilateral in all cases, with diffuse distribution in nine patients (90%), predominantly in the middle and inferior lung regions in seven patients (70%), and involving the anterior and posterior regions of the lungs in nine patients (90%). The 'crazy-paving' pattern is rare in HSCT recipients with pulmonary complications and is associated with infectious complications more commonly than non-infectious conditions.

Mind and body practices for fatigue reduction in patients with cancer and hematopoietic stem cell transplant recipients: A systematic review and meta-analysis.

Science.gov (United States)

Duong, Nathan; Davis, Hailey; Robinson, Paula D; Oberoi, Sapna; Cataudella, Danielle; Culos-Reed, S Nicole; Gibson, Faith; Götte, Miriam; Hinds, Pamela; Nijhof, Sanne L; Tomlinson, Deborah; van der Torre, Patrick; Ladas, Elena; Cabral, Sandra; Dupuis, L Lee; Sung, Lillian

2017-12-01

To determine whether non-physical activity mind and body practices reduce the severity of fatigue in patients with cancer or hematopoietic stem cell transplant (HSCT) recipients compared to control interventions. We included randomized trials which compared non-physical activity mind and body practices compared with control interventions for the management of fatigue in cancer and HSCT patients. Among 55 trials (4975 patients), interventions were acupuncture or acupressure (n=12), mindfulness (n=11), relaxation techniques (n=10), massage (n=6), energy therapy (n=5), energizing yogic breathing (n=3) and others (n=8). When combined, all interventions significantly reduced fatigue severity compared to all controls (standardized mean difference -0.51, 95% confidence interval -0.73 to -0.29). More specifically, mindfulness and relaxation significantly reduced fatigue severity. Mindfulness and relaxation were effective at reducing fatigue severity in patients with cancer and HSCT recipients. Future studies should evaluate how to translate these findings into clinical practice across different patient groups. Copyright © 2017 Elsevier B.V. All rights reserved.

Mitigation of Late Renal and Pulmonary Injury After Hematopoietic Stem Cell Transplantation

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Cohen, Eric P., E-mail: Eric.Cohen2@va.gov [Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Bedi, Manpreet; Irving, Amy A. [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Jacobs, Elizabeth; Tomic, Rade [Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Klein, John [Department of Biostatistics, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Lawton, Colleen A.; Moulder, John E. [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States)

2012-05-01

Purpose: To update the results of a clinical trial that assessed whether the angiotensin-converting enzyme inhibitor captopril was effective in mitigating chronic renal failure and pulmonary-related mortality in subjects undergoing total body irradiation (TBI) in preparation for hematopoietic stem cell transplantation (HSCT). Methods and Materials: Updated records of the 55 subjects who were enrolled in this randomized controlled trial were analyzed. Twenty-eight patients received captopril, and 27 patients received placebo. Definitions of TBI-HSCT-related chronic renal failure (and relapse) were the same as those in the 2007 analysis. Pulmonary-related mortality was based on clinical or autopsy findings of pulmonary failure or infection as the primary cause of death. Follow-up data for overall and pulmonary-related mortality were supplemented by use of the National Death Index. Results: The risk of TBI-HSCT-related chronic renal failure was lower in the captopril group (11% at 4 years) than in the placebo group (17% at 4 years), but this was not statistically significant (p > 0.2). Analysis of mortality was greatly extended by use of the National Death Index, and no patients were lost to follow-up for reasons other than death prior to 67 months. Patient survival was higher in the captopril group than in the placebo group, but this was not statistically significant (p > 0.2). The improvement in survival was influenced more by a decrease in pulmonary mortality (11% risk at 4 years in the captopril group vs. 26% in the placebo group, p = 0.15) than by a decrease in chronic renal failure. There was no adverse effect on relapse risk (p = 0.4). Conclusions: Captopril therapy produces no detectable adverse effects when given after TBI. Captopril therapy reduces overall and pulmonary-related mortality after radiation-based HSCT, and there is a trend toward mitigation of chronic renal failure.

Mitigation of Late Renal and Pulmonary Injury After Hematopoietic Stem Cell Transplantation

International Nuclear Information System (INIS)

Cohen, Eric P.; Bedi, Manpreet; Irving, Amy A.; Jacobs, Elizabeth; Tomic, Rade; Klein, John; Lawton, Colleen A.; Moulder, John E.

2012-01-01

Purpose: To update the results of a clinical trial that assessed whether the angiotensin-converting enzyme inhibitor captopril was effective in mitigating chronic renal failure and pulmonary-related mortality in subjects undergoing total body irradiation (TBI) in preparation for hematopoietic stem cell transplantation (HSCT). Methods and Materials: Updated records of the 55 subjects who were enrolled in this randomized controlled trial were analyzed. Twenty-eight patients received captopril, and 27 patients received placebo. Definitions of TBI-HSCT-related chronic renal failure (and relapse) were the same as those in the 2007 analysis. Pulmonary-related mortality was based on clinical or autopsy findings of pulmonary failure or infection as the primary cause of death. Follow-up data for overall and pulmonary-related mortality were supplemented by use of the National Death Index. Results: The risk of TBI-HSCT-related chronic renal failure was lower in the captopril group (11% at 4 years) than in the placebo group (17% at 4 years), but this was not statistically significant (p > 0.2). Analysis of mortality was greatly extended by use of the National Death Index, and no patients were lost to follow-up for reasons other than death prior to 67 months. Patient survival was higher in the captopril group than in the placebo group, but this was not statistically significant (p > 0.2). The improvement in survival was influenced more by a decrease in pulmonary mortality (11% risk at 4 years in the captopril group vs. 26% in the placebo group, p = 0.15) than by a decrease in chronic renal failure. There was no adverse effect on relapse risk (p = 0.4). Conclusions: Captopril therapy produces no detectable adverse effects when given after TBI. Captopril therapy reduces overall and pulmonary-related mortality after radiation-based HSCT, and there is a trend toward mitigation of chronic renal failure.

MAPK Signal Transduction Pathway Regulation: A Novel Mechanism of Rat HSC-T6 Cell Apoptosis Induced by FUZHENGHUAYU Tablet

Directory of Open Access Journals (Sweden)

Qi Wang

2013-01-01

Full Text Available FUZHENGHUAYU Tablets have been widely used in the treatment of liver fibrosis in China. Here, we investigate the apoptotic effect of FUZHENGHUAYU Tablet in rat liver stellate cell line HSC-T6. HSC-T6 cells were incubated with control serum or drug serum from rats fed with 0.9% NaCl or FUZHENGHUAYU Tablet, respectively. Cells exposed to drug serum showed higher proportions of early and late apoptotic cells than controls. The mRNA levels of collagens I and III, TGF-β1 and α-SMA were reduced by drug serum compared to control serum. Differentially expressed mRNAs and miRNAs were analyzed by microarray and sequencing, respectively. We identified 334 differentially expressed mRNAs and also 60 GOs and two pathways related to the mRNAs. Seventy-five differentially expressed miRNAs were down-regulated by drug serum and 1963 target genes were predicted. 134 GOs up-regulated in drug serum group were linked to miRNA targets, and drug serum also regulated 43 miRNA signal transduction pathways. Protein levels were evaluated by Western blot. Drug serum down-regulated (phospho-SAPK/JNK/(SAPK/JNK and up-regulated phospho-p38/p38 ratios. The study showed that FUZHENGHUAYU Tablet induced apoptosis in rat HSC-T6 cells possibly in part by activating p38 and inhibiting SAPK/JNK.

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.

HIGH BODY MASS INDEX AMONG PATIENTS UNDERGOING HEMATOPOIETIC STEM CELL TRANSPLANTATION: RESULTS OF A CROSS-SECTIONAL EVALUATION OF NUTRITIONAL STATUS IN A PRIVATE HOSPITAL.

Science.gov (United States)

Pereira, Andrea Z; Victor, Elivane S; Vidal Campregher, Paulo; Piovacari, Silvia M F; Bernardo Barban, Juliana S; Pedreira, Wilson L; Hamerschlak, Nelson

2015-12-01

nutritional status before hematopoietic stem cell transplantation (HSCT) affects prognosis: better nourished patients have shorter time to engraftment, while malnutrition is associated with increase of mortality rates, complications, medical costs, poor quality of life and hospitalization stay. Furthermore, underweight patients have increased risk of death in the early post- HSCT period, and non-relapse mortality is greater for those who are extremely underweight, overweight and obese. Obesity is associated with treatment-related toxicity, higher incidence of grade II-IV acute graft-versus- host disease (GVHD), infections and mortality. The objective of this study was to investigate the nutritional status of patients undergoing HSCT between 2007-2013 in a private hospital, by calculating the body mass index (BMI), to verify the prevalence of any nutritional imbalances, especially obesity. in this retrospective study, based on medical records, we analyzed data from all patients with malignant and nonmalignant diseases who underwent HSCT from January 2007 to February 2014 in the Hematology- Oncology and Bone Marrow Transplantation Center at a large, tertiary referral center in Brazil. a total of 257 cases were treated in the period and analyzed, of which 79% were aged up to 65 years old. Among these, 56% were overweight or obese. We observed a higher prevalence of obesity in elderly patients (P < 0.001). The mean BMI of the total sample was 26.4 kg/m2. BMI was significantly different between genders, with higher prevalence of overweight among men (P < 0.001). differently from other studies, our investigation has shown low rates of underweight and more overweight and obesity rates in men and elderly patients undergoing HSCT. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Antibiotic prophylaxis in hematopoietic stem cell transplantation. A meta-analysis of randomized controlled trials.

Science.gov (United States)

Kimura, Shun-ichi; Akahoshi, Yu; Nakano, Hirofumi; Ugai, Tomotaka; Wada, Hidenori; Yamasaki, Ryoko; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Ashizawa, Masahiro; Sato, Miki; Terasako-Saito, Kiriko; Nakasone, Hideki; Kikuchi, Misato; Yamazaki, Rie; Kako, Shinichi; Kanda, Junya; Tanihara, Aki; Nishida, Junji; Kanda, Yoshinobu

2014-07-01

We performed a meta-analysis to evaluate the impact of systemic antibiotic prophylaxis in hematopoietic stem cell transplantation (HSCT) recipients. We collected reports from PubMed, the Cochrane Library, EMBASE, CINAHL, and Web of Science, along with references cited therein. We included prospective, randomized studies on systemic antibiotic prophylaxis in HSCT recipients. Seventeen trials with 1453 autologous and allogeneic HSCT recipients were included. Systemic antibiotic prophylaxis was compared with placebo or no prophylaxis in 10 trials and with non-absorbable antibiotics in two trials. Systemic antibiotics other than fluoroquinolones were evaluated in five of these 12 trials. Four trials evaluated the effect of the addition of antibiotics for gram-positive bacteria to fluoroquinolones. One trial compared two different systemic antibiotic regimens: fluoroquinolones versus trimethoprim-sulfamethoxazole. As a result, systemic antibiotic prophylaxis reduced the incidence of febrile episodes (OR 0.16; 95%CI 0.09-0.30), clinically or microbiologically documented infection (OR 0.38; 95%CI 0.22-0.63) and bacteremia (OR 0.31; 95%CI 0.16-0.59) without significantly affecting all-cause mortality or infection-related mortality. Systemic antibiotic prophylaxis successfully reduced the incidence of infection. However, there was no significant impact on mortality. The clinical benefits of prophylaxis with fluoroquinolones were inconclusive because of the small number of clinical trials evaluated. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

[Pretreatment doses of antithymocyte globubin-fresenius for allogeneic hematopoietic stem cell transplantation for beta-thalassemia major].

Science.gov (United States)

Li, Chunfu; Wang, Yanhua; Wu, Xuedong; Pei, Fuyu; He, Yuelin; Feng, Xiaoqin; Liu, Huaying

2012-05-01

To investigate the effects of different doses of antithymocyte globubin-fresenius (ATG-F) for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with beta-thalassemia Major. Sixty-four children with beta-thalassemia major undergoing allo-HSCT were divided into two equal groups to receive ATG-F pretreatments at high (30 mg/kg) or low (15 mg/kg) doses as part of the conditioning regimen including mainly cyclophosphamide, busulfan, fludarabine, and thiotepa. The outcomes of the patients were compared between the two groups. No obvious difference were noted in the time to leukocyte and platelet engraftment between the two groups. The incidence of grade II-IV acute graft-versus-host disease (aGVHD) appeared to be higher in the low-dose group than in the high-dose group (12.5% vs 9.4%). The incidence of grade III-IV aGVHD was also higher in the low dose group (12.5% vs 6.3%), but the difference was not statistically significant. Application of high-dose ATG-F was associated with a higher rate of probable and possible fungal infection (P<0.05). The two doses of ATG-F is feasible as a part of the conditioning regimen for allo-HSCT in children with beta-thalassemia major.

Universal Mask Usage for Reduction of Respiratory Viral Infections After Stem Cell Transplant: A Prospective Trial.

Science.gov (United States)

Sung, Anthony D; Sung, Julia A M; Thomas, Samantha; Hyslop, Terry; Gasparetto, Cristina; Long, Gwynn; Rizzieri, David; Sullivan, Keith M; Corbet, Kelly; Broadwater, Gloria; Chao, Nelson J; Horwitz, Mitchell E

2016-10-15

Respiratory viral infections (RVIs) are frequent complications of hematopoietic stem cell transplant (HSCT). Surgical masks are a simple and inexpensive intervention that may reduce nosocomial spread. In this prospective single-center study, we instituted a universal surgical mask policy requiring all individuals with direct contact with HSCT patients to wear a surgical mask, regardless of symptoms or season. The primary endpoint was the incidence of RVIs in the mask period (2010-2014) compared with the premask period (2003-2009). RVIs decreased from 10.3% (95/920 patients) in the premask period to 4.4% (40/911) in the mask period (P mask group compared with the premask group (0.19-0.85, P = .02). In contrast, no decrease was observed during this same period in an adjacent hematologic malignancy unit, which followed the same infection control practices except for the mask policy. The majority of this decrease was in parainfluenza virus 3 (PIV3) (8.3% to 2.2%, P mask is associated with a reduction in RVIs, particularly PIV3, during the most vulnerable period following HSCT. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Magnetic resonance detection of CD34+ cells from umbilical cord blood using a 19F label

NARCIS (Netherlands)

L.E. Duinhouwer (Lucia); Van Rossum, B.J.M. (Bernard J. M.); S.T. van Tiel (Sandra); R.M. van der Werf (Ramon); R.Q. Doeswijk (Ronald); J.C. Haeck (Joost); Rombouts, E.W.J.C. (Elwin W. J. C.); M.N.D. Ter Borg (Mariëtte N. D.); G. Kotek (Gyula); E. Braakman (Eric); J.J. Cornelissen (Jan); M.R. Bernsen (Monique)

2015-01-01

textabstractImpaired homing and delayed recovery upon hematopoietic stem cell transplantation (HSCT) with hematopoietic stem cells (HSC) derived from umbilical cord blood (UCB) is a major problem. Tracking transplanted cells in vivo will be helpful to detect impaired homing at an early stage and

Intravital imaging of donor allogeneic effector and regulatory T cells with host dendritic cells during GVHD.

Science.gov (United States)

Lin, Kaifeng Lisa; Fulton, LeShara M; Berginski, Matthew; West, Michelle L; Taylor, Nicholas A; Moran, Timothy P; Coghill, James M; Blazar, Bruce R; Bear, James E; Serody, Jonathan S

2014-03-06

Graft-versus-host disease (GVHD) is a systemic inflammatory response due to the recognition of major histocompatibility complex disparity between donor and recipient after hematopoietic stem cell transplantation (HSCT). T-cell activation is critical to the induction of GVHD, and data from our group and others have shown that regulatory T cells (Tregs) prevent GVHD when given at the time of HSCT. Using multiphoton laser scanning microscopy, we examined the single cell dynamics of donor T cells and dendritic cells (DCs) with or without Tregs postallogeneic transplantation. We found that donor conventional T cells (Tcons) spent very little time screening host DCs. Tcons formed stable contacts with DCs very early after transplantation and only increased velocity in the lymph node at 20 hours after transplant. We also observed that Tregs reduced the interaction time between Tcons and DCs, which was dependent on the generation of interleukin 10 by Tregs. Imaging using inducible Tregs showed similar disruption of Tcon-DC contact. Additionally, we found that donor Tregs induce host DC death and down-regulate surface proteins required for donor T-cell activation. These data indicate that Tregs use multiple mechanisms that affect host DC numbers and function to mitigate acute GVHD.

Umbilical Cord Blood Banking for Transplantation in Morocco: Problems and opportunities

Directory of Open Access Journals (Sweden)

Mazini L

2014-11-01

Full Text Available Since the success of the first umbilical cord blood (UCB transplantation in a child with Fanconi anaemia in 1989, great interests have emerged for this source of stem cells. UCB provides an unlimited source of ethnically diverse stem cells and is an alternative for bone marrow (BM and peripheral blood (PB heamatopoietic stem cell transplantation (HSCT. Thus, UCB and manipulated stem cells are now collected and banked according to international accreditation standards for listing on registries allowing rapid search and accessibility worldwide. This work aims to identify problems limiting the creation of a Moroccan cord blood bank and to highlight opportunities and issues of a new legislation promoting additional applications of cell therapy.

Antiviral T Cells for Adenovirus in the Pretransplant Period: A Bridge Therapy for Severe Combined Immunodeficiency.

Science.gov (United States)

Miller, Holly K; Hanley, Patrick J; Lang, Haili; Lazarski, Christopher A; Chorvinsky, Elizabeth A; McCormack, Sarah; Roesch, Lauren; Albihani, Shuroug; Dean, Marcus; Hoq, Fahmida; Adams, Roberta H; Bollard, Catherine M; Keller, Michael D

2018-05-09

Viral infections can be life threatening in patients with severe combined immunodeficiency (SCID) and other forms of profound primary immunodeficiency disorders both before and after hematopoietic stem cell transplantation (HSCT). Adoptive immunotherapy with virus-specific T cells (VSTs) has been utilized in many patients in the setting of HSCT, but has very rarely been attempted for treatment of viral infections before HSCT. Here we describe the use of VSTs in an infant with RAG1 SCID who had developed disseminated adenovirus which failed to improve on cidofovir. Adenovirus cleared following 2 doses of VSTs and marrow infusion from a matched unrelated donor, without incidence of graft versus host disease. T cell receptor-b sequencing demonstrated expansion of adenovirus-specific T cell fraction of the VSTs, suggesting that infusion facilitated viral clearance. This report suggests that VSTs are likely safe in the pre-HSCT period, and may be a useful bridge therapy for infants with SCID and persistent viral infections. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

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.

Knowledge, attitude and control practices of sickle cell disease ...

African Journals Online (AJOL)

Knowledge, attitude and control practices of sickle cell disease among youth corps members ... PROMOTING ACCESS TO AFRICAN RESEARCH ... access to haemopoeitic stem cell transplantation (HSCT) in our environment, stronger efforts ...

Efficacy of cryotherapy associated with laser therapy for decreasing severity of melphalan-induced oral mucositis during hematological stem-cell transplantation: a prospective clinical study.