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Sample records for allogeneic hematopoietic cell

  1. Allogeneic hematopoietic stem cell transplantation: transfusion issues

    Directory of Open Access Journals (Sweden)

    Akkök ÇA

    2016-05-01

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

  2. Effect of endothelial progenitor cell on hematopoietic reconstitution in allogeneic hematopoietic stem cell transplantation mouse model

    Institute of Scientific and Technical Information of China (English)

    化静

    2013-01-01

    Objective To examine the effects of endothelial progenitor cell (EPC) on hematopoietic reconsititution in allogeneic hematopoietic stem cell transplantation (alloHSCT) mouse model.Methods Allo-HSCT mouse model was established with condition of BU/CY,in which C57BL/6 (H-2b) and BABL/c (H-2d) mice were used

  3. Leukemia in donor cells after allogeneic hematopoietic stem cell transplant

    OpenAIRE

    2002-01-01

    The development of leukemia in donor cells after allogeneic hematopoietic stem cell transplant is an extremely rare event. We report here the case of a patient who developed myelodysplastic syndrome/acute myeloid leukemia, in cells of donor origin 3.5 years after related donor HSCT for refractory chronic lymphocytic leukemia and therapy-induced myelodysplastic syndrome. The origin of the leukemia was determined by analysis of minisatillite polymorphism tested on CD34(+) cells.

  4. 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...

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  6. Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation

    Science.gov (United States)

    2016-04-26

    Thalassemia; Sickle Cell Disease; Glanzmann Thrombasthenia; Wiskott-Aldrich Syndrome; Chronic-granulomatous Disease; Severe Congenital Neutropenia; Leukocyte Adhesion Deficiency; Schwachman-Diamond Syndrome; Diamond-Blackfan Anemia; Fanconi Anemia; Dyskeratosis-congenita; Chediak-Higashi Syndrome; Severe Aplastic Anemia

  7. Financial burden in recipients of allogeneic hematopoietic cell transplantation.

    Science.gov (United States)

    Khera, Nandita; Chang, Yu-hui; Hashmi, Shahrukh; Slack, James; Beebe, Timothy; Roy, Vivek; Noel, Pierre; Fauble, Veena; Sproat, Lisa; Tilburt, Jon; Leis, Jose F; Mikhael, Joseph

    2014-09-01

    Although allogeneic hematopoietic cell transplantation (HCT) is an expensive treatment for hematological disorders, little is known about the financial consequences for the patients who undergo this procedure. We analyzed factors associated with its financial burden and its impact on health behaviors of allogeneic HCT recipients. A questionnaire was retrospectively mailed to 482 patients who underwent allogeneic HCT from January 2006 to June 2012 at the Mayo Clinic, to collect information regarding current financial concerns, household income, employment, insurance, out-of-pocket expenses, and health and functional status. A multivariable logistic regression analysis identified factors associated with financial burden and treatment nonadherence. Of the 268 respondents (56% response rate), 73% reported that their sickness had hurt them financially. All patients for whom the insurance information was available (missing, n = 13) were insured. Forty-seven percent of respondents experienced financial burden, such as household income decreased by >50%, selling/mortgaging home, or withdrawing money from retirement accounts. Three percent declared bankruptcy. Younger age and poor current mental and physical functioning increased the likelihood of financial burden. Thirty-five percent of patients reported deleterious health behaviors because of financial constraints. These patients were likely to be younger, have lower education, and with a longer time since HCT. Being employed decreased the likelihood of experiencing financial burden and treatment nonadherence due to concern about costs. A significant proportion of allogeneic HCT survivors experience financial hardship despite insurance coverage. Future research should investigate potential interventions to help at-risk patients and prevent adverse financial outcomes after this life-saving procedure.

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

    Directory of Open Access Journals (Sweden)

    Francesco Orio

    2014-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    孙于谦

    2013-01-01

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

  10. Alternative donor allogeneic hematopoietic cell transplantation for hemoglobinopathies.

    Science.gov (United States)

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

    2016-04-01

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

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

    Science.gov (United States)

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

    2010-08-26

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

  12. Allogeneic hematopoietic cell transplantation without fluconazole and fluoroquinolone prophylaxis.

    Science.gov (United States)

    Heidenreich, D; Kreil, S; Nolte, F; Reinwald, M; Hofmann, W-K; Klein, S A

    2016-01-01

    Fluoroquinolone (FQ) and fluconazole prophylaxis is recommended for patients undergoing allogeneic hematopoietic cell transplantation (alloHCT). However, due to an uncertain scientific basis and the increasing emergence of resistant germs, this policy should be questioned. Therefore, FQ and fluconazole prophylaxis was omitted in alloHCT at our center. In this retrospective analysis, all consecutive patients (n = 63) who underwent first alloHCT at our institution from September 2010 to September 2013 were included. Patients neither received FQ nor fluconazole prophylaxis. Day 100 mortality, incidence of febrile neutropenia, bacterial infections, and invasive fungal diseases (IFD) were assessed. Sixteen patients who started conditioning under antimicrobial treatment/prophylaxis due to pre-existing neutropenia (3/16), IFD (12/16), or aortic valve replacement (1/16) were excluded from the analysis. Finally, 47 patients were transplanted without prophylaxis as intended. Day 100 mortality was 9 %. Febrile neutropenia occurred in 62 % (29/47); 17/47 patients (36 %) experienced a blood stream infection (BSI) with detection of Gram-positive bacteria in 14 patients, Gram-negative bacteria in five patients, and candida in one patient, respectively. Coagulase-negative staphylococci were the most frequently isolated Gram-positive bacteria; 12/21 isolated Gram-positive and 3/6 Gram-negative bacteria were FQ resistant. In 21 % (10/47) of the patients, IFD (1x proven, 1x probable, and 8x possible) were diagnosed. To conclude, all three criteria, day 100 mortality, the incidence of IFD, and BSI, are in the range of published data for patients transplanted with FQ and fluconazole prophylaxis. These data demonstrate that alloHCT is feasible without FQ and fluconazole prophylaxis.

  13. Long-term outcomes among older patients following nonmyeloablative conditioning and allogeneic hematopoietic cell transplantation for advanced hematologic malignancies

    DEFF Research Database (Denmark)

    Sorror, Mohamed L; Sandmaier, Brenda M; Storer, Barry E;

    2011-01-01

    A minimally toxic nonmyeloablative regimen was developed for allogeneic hematopoietic cell transplantation (HCT) to treat patients with advanced hematologic malignancies who are older or have comorbid conditions.......A minimally toxic nonmyeloablative regimen was developed for allogeneic hematopoietic cell transplantation (HCT) to treat patients with advanced hematologic malignancies who are older or have comorbid conditions....

  14. 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.

  15. Epigenetic therapy in allogeneic hematopoietic stem cell transplantation

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    Qaiser Bashir

    2013-01-01

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

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

    DEFF Research Database (Denmark)

    Koenecke, C; Hertenstein, B; Schetelig, J;

    2010-01-01

    To analyze the outcome of solid organ transplantation (SOT) in patients who had undergone allogeneic hematopoietic stem cell transplantation (HSCT), a questionnaire survey was carried out within 107 European Group of Blood and Marrow Transplantation centers. This study covered HSCT between 1984...

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  18. Association of HMGB1 polymorphisms with outcome after allogeneic hematopoietic cell transplantation

    DEFF Research Database (Denmark)

    Kornblit, Brian Thomas; Masmas, Tania; Petersen, Søren;

    2010-01-01

    Several studies have demonstrated that genetic variation in cytokine genes can modulate the immune reactions after allogeneic hematopoietic cell transplantation (HCT). High mobility group box 1 protein (HMBG1) is a pleiotropic cytokine that functions as a pro-inflammatory signal, important...

  19. Intestinal dysbiosis and allogeneic hematopoietic progenitor cell transplantation

    OpenAIRE

    Raghunathan, Vikram M.; Sheng, Iris; Lim, Seah H.

    2016-01-01

    The intestinal microbiota is a diverse and dynamic ecosystem that is increasingly understood to play a vital role in human health. Hematopoietic stem cell transplant recipients undergo prolonged exposure to antimicrobials, chemotherapeutic agents, and immunosuppressants, resulting in profound shifts in the gut microbiome. A growing body of research has revealed the ways in which these microbiologic shifts shape immune modulation, affecting susceptibility to infections and graft-versus-host di...

  20. Analysis of efficacy and prognosis of allogeneic hematopoietic stem cell transplantation from different donors in treatment of hematologic malignancies

    Institute of Scientific and Technical Information of China (English)

    余正平

    2013-01-01

    Objective To investigate the clinical efficacy of allogeneic hematopoietic stem cell transplantation(allo-HSCT) from unrelated donors and that from related donors in treatment of hematologic malignancies. Methods

  1. Lung function after allogeneic hematopoietic stem cell transplantation in children

    DEFF Research Database (Denmark)

    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...... experienced a decline in lung function of more than 10% during the first 3 to 9 months after HSCT. The decline in forced expiratory volume in 1 second, forced expiratory volume in 1 second/forced vital capacity and diffusion capacity of the lung for carbon monoxide were strongly associated with acute graft...

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

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    Md Ashik eUllah

    2016-04-01

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

  3. Herpesvirus-Associated Central Nervous System Diseases after Allogeneic Hematopoietic Stem Cell Transplantation

    OpenAIRE

    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. Herpesv...

  4. Infections after allogeneic hematopoietic stem cell transplantation with a nonmyeloablative conditioning regimen.

    OpenAIRE

    Frere, Pascale; Baron, Frédéric; Bonnet, Christophe; HAFRAOUI, Kaoutar; Pereira-Martins, Maguy; Willems, Evelyne; Fillet, Georges; Beguin, Yves

    2006-01-01

    Hematopoietic cell transplantation (HCT) following nonmyeloablative conditioning (NMSCT) may be associated with a reduced risk of infection compared to standard allogeneic HCT. We retrospectively analyzed incidence and risk factors of infection in 62 patients undergoing NMSCT with low-dose TBI +/- fludarabine and postgrafting CsA and MMF. The proportion of patients with any infection was 77%, but the majority of infectious events occurred beyond day 30. Donor other than sibling, older age, ea...

  5. Endoscopic diagnosis of cytomegalovirus gastritis after allogeneic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Yasuo; Kakugawa; Masahiro; Kami; Takahisa; Matsuda; Yutaka; Saito; Sung-Won; Kim; Takahiro; Fukuda; Shin-ichiro; Mori; Tadakazu; Shimoda; Ryuji; Tanosaki; Daizo; Saito

    2010-01-01

    AIM:To clarify the endoscopic and clinical findings of cytomegalovirus(CMV) gastritis after allogeneic hematopoietic stem cell transplantation(allo-SCT).METHODS:Between 1999 and 2005,523 patients underwent allo-SCT at our hospital,and 115 of these patients with gastrointestinal symptoms underwent esophagogastroduodenoscopy.RESULTS:CMV gastritis was diagnosed pathologically in seven patients(1.3%) with the other 108 patients serving as controls.Six of the seven patients developed positive CMV antigenemia,and...

  6. A problem-solving education intervention in caregivers and patients during allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Bevans, Margaret; Wehrlen, Leslie; Castro, Kathleen; Prince, Patricia; Shelburne, Nonniekaye; Soeken, Karen; Zabora, James; Wallen, Gwenyth R

    2014-05-01

    The aim of this study was to determine the effect of problem-solving education on self-efficacy and distress in informal caregivers of allogeneic hematopoietic stem cell transplantation patients. Patient/caregiver teams attended three 1-hour problem-solving education sessions to help cope with problems during hematopoietic stem cell transplantation. Primary measures included the Cancer Self-Efficacy Scale-transplant and Brief Symptom Inventory-18. Active caregivers reported improvements in self-efficacy (p caregiver responders also reported better health outcomes such as fatigue. The effect of problem-solving education on self-efficacy and distress in hematopoietic stem cell transplantation caregivers supports its inclusion in future interventions to meet the multifaceted needs of this population.

  7. Eculizumab before and after allogeneic hematopoietic stem cell transplantation in a patient with paroxysmal nocturnal hemoglobinuria

    Directory of Open Access Journals (Sweden)

    Hakan Göker

    2011-09-01

    Full Text Available Paroxysmal nocturnal hemoglobinuria (PNH is characterized by the triad of intravascular hemolysis, venous thrombosis, and cytopenia. Treatment of PNH is generally supportive. Bone marrow transplantation is the only curative therapy for PNH, but is associated with significant morbidity and mortality. Herein, we present a patient with PNH that received eculizumab, a humanized monoclonal antibody that blocks activation of the terminal complement at C5, before and immediately following allogeneic peripheral stem cell transplantation. Prior to hematopoietic stem cell transplantation eculizumab treatment markedly reduced hemolysis and transfusion requirement; however, 1 d post transplantation a hemolytic episode occured, which was successfully stopped with eculizumab re-treatment. Afterwards the patient did not require additional transfusions. The results of this study indicate that early administration of eculizumab may be a safe and effective therapy for hemolytic episodes associated with allogeneic peripheral stem cell transplantation in patients with PNH.

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

    Science.gov (United States)

    Fuji, Shigeo; Kapp, Markus; Einsele, Hermann

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Thissiane L. Gonçalves

    2009-01-01

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

  10. Up-to-date tools for risk assessment before allogeneic hematopoietic cell transplantation.

    Science.gov (United States)

    Elsawy, M; Sorror, M L

    2016-10-01

    Cure of malignant and non-malignant hematological diseases is potentially possible after allogeneic hematopoietic stem cell transplantation (HCT). Accurate evaluation of the risk-benefit ratio for an individual patient could improve the decision-making process about transplant, which ultimately would increase the likelihood of success. Several transplant-related models were designed in an effort to optimize decision-making about suitable candidates for allogeneic HCT. In 1998, The European Society for Blood and Marrow Transplantation (EBMT) developed a five-component pretransplantation risk scoring system for patients with CML. The EBMT score was later tested in patients with various hematological disorders, and it was shown to stratify risks of mortality after allogeneic HCT. More recent research efforts focused on models that assess health status before HCT. A HCT-specific comorbidity index was designed to assign weights to 17 relevant comorbidities that were shown to independently predict non-relapse mortality. Performance status scales and comprehensive geriatric assessment tools might uncover additional overall health limitations that affect long-term survival among older recipients of allogeneic HCT. Other models include the pretransplantation assessment of mortality score that summarizes the impacts of eight different pretransplantation patient- and disease-specific variables into a 50-point model that predicts survival. The disease-risk index captures the impact of primary diagnoses and disease status on relapse and survival following allogeneic HCT. The values and limitations of each model are discussed herein. We also provide insight on how to use these models in the clinic to decide about offering allogeneic HCT with the most suitable conditioning regimen intensity.

  11. Cure for thalassemia major – from allogeneic hematopoietic stem cell transplantation to gene therapy

    Science.gov (United States)

    Srivastava, Alok; Shaji, Ramachandran V.

    2017-01-01

    Allogeneic hematopoietic stem cell transplantation has been well established for several decades as gene replacement therapy for patients with thalassemia major, and now offers very high rates of cure for patients who have access to this therapy. Outcomes have improved tremendously over the last decade, even in high-risk patients. The limited data available suggests that the long-term outcome is also excellent, with a >90% survival rate, but for the best results, hematopoietic stem cell transplantation should be offered early, before any end organ damage occurs. However, access to this therapy is limited in more than half the patients by the lack of suitable donors. Inadequate hematopoietic stem cell transplantation services and the high cost of therapy are other reasons for this limited access, particularly in those parts of the world which have a high prevalence of this condition. As a result, fewer than 10% of eligible patients are actually able to avail of this therapy. Other options for curative therapies are therefore needed. Recently, gene correction of autologous hematopoietic stem cells has been successfully established using lentiviral vectors, and several clinical trials have been initiated. A gene editing approach to correct the β-globin mutation or disrupt the BCL11A gene to increase fetal hemoglobin production has also been reported, and is expected to be introduced in clinical trials soon. Curative possibilities for the major hemoglobin disorders are expanding. Providing access to these therapies around the world will remain a challenge. PMID:27909215

  12. Clinical characteristics of late-onset severe pneumonia after allogeneic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    刘代红

    2013-01-01

    Objective To analyze the clinical characteristics of the late-onset severe pneumonia after allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods A retrospective study was conducted in patients diagnosed as late-onset severe pneumonia after allo-HSCT from March,2009 to January,2013 in People’s Hospital of Peking University.Results Of 1538 patients receiving allo-HSCT,20 developed late-onset severe pneumonia with an incidence rate of 1.3%.Among the 20 patients,17 (85%) had human leukocyte antigen (HLA) identical donors.The other 3 (15%) patients had received haploidentical transplantation.Severe pneumonia occurred at a

  13. Practical Aspects of Allogeneic Hematopoietic Cell Transplantation for Patients with Poor-Risk Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Julio Delgado

    2011-01-01

    Full Text Available Allogeneic hematopoietic cell transplantation has become a viable option for younger patients with poor-risk chronic lymphocytic leukemia. The results obtained with either conventional or reduced-intensity conditioning regimens have been recently evaluated and compared with alternative nontransplant strategies. This manuscript deals with practical aspects of the procedure, including patient and donor selection, conditioning regimen, GVHD prophylaxis, disease monitoring, infectious and noninfectious complications, and timing of the procedure. Finally, we speculate on how we could improve the results obtained with the procedure and new advances currently in clinical trials.

  14. Optimal timing of allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic syndrome.

    Science.gov (United States)

    Alessandrino, Emilio Paolo; Porta, Matteo G Della; Malcovati, Luca; Jackson, Christopher H; Pascutto, Cristiana; Bacigalupo, Andrea; Teresa van Lint, Maria; Falda, Michele; Bernardi, Massimo; Onida, Francesco; Guidi, Stefano; Iori, Anna Paola; Cerretti, Raffaella; Marenco, Paola; Pioltelli, Pietro; Angelucci, Emanuele; Oneto, Rosi; Ripamonti, Francesco; Rambaldi, Alessandro; Bosi, Alberto; Cazzola, Mario

    2013-07-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) represents the only curative treatment for patients with myelodysplastic syndrome (MDS), but involves non-negligible morbidity and mortality. Registry studies have shown that advanced disease stage at transplantation is associated with inferior overall survival. To define the optimal timing of allogeneic HSCT, we carried out a decision analysis by studying 660 patients who received best supportive care and 449 subjects who underwent transplantation. Risk assessment was based on both the International Prognostic Scoring System (IPSS) and the World Health Organization classification-based Prognostic Scoring System (WPSS). We used a continuous-time multistate Markov model to describe the natural history of disease and evaluate the effect of allogeneic HSCT on survival. This model estimated life expectancy from diagnosis according to treatment policy at different risk stages. Relative to supportive care, estimated life expectancy increased when transplantation was delayed from the initial stages until progression to intermediate-1 IPSS-risk or to intermediate WPSS-risk stage, and then decreased for higher risks. Modeling decision analysis on WPSS versus IPSS allowed better estimation of the optimal timing of transplantation. These observations indicate that allogeneic HSCT offers optimal survival benefits when the procedure is performed before MDS patients progress to advanced disease stages.

  15. Relapse of lymphoma after allogeneic hematopoietic cell transplantation: management strategies and outcome.

    Science.gov (United States)

    Wudhikarn, Kitsada; Brunstein, Claudio G; Bachanova, Veronika; Burns, Linda J; Cao, Qing; Weisdorf, Daniel J

    2011-10-01

    The outcome and management of relapsed lymphoma after allogeneic hematopoietic cell transplantation (HCT) is difficult. Therapeutic options may include donor lymphocyte infusion (DLI), reduction of immunosuppression (RIS), chemotherapy, radiation, immunotherapy, second HCT, and experimental treatments, but reported data contrasting the response and efficacy of these salvage treatments are limited. We describe the treatments, response, prognosis, and long-term survival of 72 patients with relapse of lymphoma after allogeneic HCT. Between 1991 and 2007, 227 lymphoma patients underwent allogeneic HCT. Of these, 72 (32%) developed relapse/progression after their HCT at a median of 99 days (0-1898 days); 37 had early (100 days) post-HCT. Three-year survival after HCT was significantly better in late than early relapse (53%; 95% confidence interval [CI] [34%-69%] versus 36%, [20%-52%], P = .02). Of 72 relapsed patients, 29 (40%) survived at a median of 34 (3-148) months posttransplant. The most common cause of death was underlying lymphoma (79%). The overall prognosis of relapsed/progressive lymphoma after allogeneic HCT is disappointing, yet half of patients respond to withdrawal of immunosuppression and additional therapies. Novel treatments can control lymphoma with acceptable morbidity. Particularly for patients with later relapse, ongoing treatment after relapse can yield meaningful benefit and prolonged survival.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2014-12-01

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

  18. Allogeneic hematopoietic stem-cell transplantation for leukocyte adhesion deficiency

    DEFF Research Database (Denmark)

    Qasim, Waseem; Cavazzana-Calvo, Marina; Davies, E Graham

    2009-01-01

    therapeutic option if a suitable HLA-matched stem-cell donation is available. Reduced-intensity conditioning was particularly safe, and mixed-donor chimerism seems sufficient to prevent significant symptoms, although careful long-term monitoring will be required for these patients....... Blood and Marrow Transplant Research. RESULTS: At a median follow-up of 62 months (extending to 14 years), the overall survival rate was 75%. Myeloablative conditioning regimens were used in 28 patients, and reduced-intensity conditioning in 8 patients, with no deaths in this subgroup. Survival rates...

  19. Correlation and Agreement of Handheld Spirometry with Laboratory Spirometry in Allogeneic Hematopoietic Cell Transplant Recipients.

    Science.gov (United States)

    Cheng, Guang-Shing; Campbell, Angela P; Xie, Hu; Stednick, Zach; Callais, Cheryl; Leisenring, Wendy M; Englund, Janet A; Chien, Jason W; Boeckh, Michael

    2016-05-01

    Early detection of subclinical lung function decline may help identify allogeneic hematopoietic cell transplant (HCT) recipients who are at increased risk for late noninfectious pulmonary complications, including bronchiolitis obliterans syndrome. We evaluated the use of handheld spirometry in this population. Allogeneic HCT recipients enrolled in a single-center observational trial performed weekly spirometry with a handheld spirometer for 1 year after transplantation. Participants performed pulmonary function tests in an outpatient laboratory setting at 3 time points: before transplantation, at day 80 after transplantation, and at 1 year after transplantation. Correlation between the 2 methods was assessed by Pearson and Spearman correlations; agreement was assessed using Bland-Altman plots. A total of 437 subjects had evaluable pulmonary function tests. Correlation for forced expiratory volume in 1 second (FEV1) was r = .954 (P spirometry correlated well with laboratory spirometry after allogeneic HCT and may be useful for self-monitoring of patients for early identification of airflow obstruction.

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

    Science.gov (United States)

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

    2005-03-01

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

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

    Directory of Open Access Journals (Sweden)

    Wataru Yamamoto

    2016-08-01

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

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

    Institute of Scientific and Technical Information of China (English)

    燕法红

    2014-01-01

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

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

    Science.gov (United States)

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

    2014-03-01

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

  4. Acute Fibrinous and Organizing Pneumonia Associated With Allogenic Hematopoietic Stem Cell Transplant Successfully Treated With Corticosteroids

    Directory of Open Access Journals (Sweden)

    Lam-Phuong Nguyen DO

    2016-04-01

    Full Text Available Acute fibrinous and organizing pneumonia (AFOP is an extremely rare, relatively new, and distinct histological pattern of acute lung injury characterized predominately by the presence of intra-alveolar fibrin and associated organizing pneumonia. AFOP may be idiopathic or associated with a wide spectrum of clinical conditions. It has a variable clinical presentation from mild respiratory symptoms to that similar to the acute respiratory distress syndrome. Currently there is no consensus on treatment, and corticosteroids previously were of unclear benefit. To date, there are less than 40 cases of AFOP reported in the literature and only one has been linked to hematopoietic stem cell transplantation. Here we report the first case series of 2 patients who developed AFOP following allogenic stem cell transplant that were successfully treated with high-dose corticosteroids.

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

    Science.gov (United States)

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

    2015-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Maria Themeli

    2012-11-01

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

  7. Biopsy-verified bronchiolitis obliterans and other noninfectious lung pathologies after allogeneic hematopoietic stem cell transplantation

    DEFF Research Database (Denmark)

    Uhlving, Hilde Hylland; Andersen, Claus B; Christensen, Ib Jarle

    2015-01-01

    Bronchiolitis obliterans (BO) is a serious complication of allogeneic hematopoietic stem cell transplantation (HSCT). Lung biopsy is the gold standard for diagnosis. This study describes the course of BO and assesses the congruity between biopsy-verified BO and a modified version of the National...... Institutes of Health's consensus criteria for BO syndrome (BOS) based exclusively on noninvasive measures. We included 44 patients transplanted between 2000 and 2010 who underwent lung biopsy for suspected BO. Of those, 23 were diagnosed with BO and 21 presented other noninfectious pulmonary pathologies......, and maximal mid-expiratory flow throughout follow-up, but there was no difference in the change in pulmonary function from the time of lung biopsy. The BO diagnosis was not associated with poorer overall survival. Fifty-two percent of patients with biopsy-verified BO and 24% of patients with other...

  8. YKL-40 in allogeneic hematopoietic cell transplantation after AML and myelodysplastic syndrome

    DEFF Research Database (Denmark)

    Kornblit, B; Wang, T; Lee, S J;

    2016-01-01

    YKL-40, also called chitinase-3-like-1 protein, is an inflammatory biomarker that has been associated with disease severity in inflammatory and malignant diseases, including AML, multiple myeloma and lymphomas. The objective of the current study was to assess the prognostic value of pretransplant......, otherwise equal, donors are available.Bone Marrow Transplantation advance online publication, 18 July 2016; doi:10.1038/bmt.2016.192....... recipient and donor plasma YKL-40 concentrations in patients with AML (n=624) or myelodysplastic syndrome (n=157) treated with allogeneic hematopoietic cell transplantation (HCT). In recipients, the plasma YKL-40 concentrations were increased when the HCT-comorbidity index was ⩾5 (P=0.028). There were...

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

    DEFF Research Database (Denmark)

    Koenecke, C; Hertenstein, B; Schetelig, J

    2010-01-01

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2014-10-01

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

  12. Nephrotic syndrome after allogeneic hematopoietic stem cell transplantation: etiology and pathogenesis.

    Science.gov (United States)

    Luo, Xiao-dan; Liu, Qi-fa; Zhang, Yu; Sun, Jing; Wang, Guo-bao; Fan, Zhi-ping; Yi, Zheng-shan; Ling, Yi-wen; Wei, Yong-qiang; Liu, Xiao-li; Xu, Bing

    2011-02-15

    In this study we investigated the etiology and pathogenesis of nephrotic syndrome (NS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 257 patients with hematopoietic malignancies who survived more than 2 months post allo-HSCT. Associations of NS with the conditioning regimen, graft versus host disease (GVHD), and other variables were analyzed. Pathologic features of the kidney, regulatory T cells (Tregs), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) were studied. NS was identified in 9 patients. The number of Tregs at day+30, 60, 90, and 180 was lower in NS patients than non-NS patients (P=0.001, 0.001, 0.007, 0.003). Serum levels of IFN-γ and TNF-α were higher in NS patients (P=0.032, 0.001, respectively). NS post allo-HSCT was associated with the occurrence of chronic GVHD (P=0.02). NS post-HSCT is an immune disorder that may involve immune complex deposition, Th1 cytokines, and Tregs.

  13. Prognostic Importance of Pretransplant Functional Capacity After Allogeneic Hematopoietic Cell Transplantation

    Science.gov (United States)

    Devlin, Sean M.; Maloy, Molly A.; Wood, William A.; Tuohy, Sharlynn; Espiritu, Noel; Aquino, Jennifer; Kendig, Tiffany; Michalski, Meghan G.; Gyurkocza, Boglarka; Schaffer, Wendy L.; Ali, Benzar; Giralt, Sergio; Jakubowski, Ann A.

    2015-01-01

    Background. The purpose of this study was to investigate the prognostic importance of functional capacity in patients undergoing allogeneic hematopoietic cell transplantation (HCT) for hematological malignancies. Patients and Methods. Using a retrospective design, 407 patients completed a 6-minute walk distance (6MWD) test to assess functional capacity before HCT; 193 (47%) completed a 6MWD test after hospital discharge. Cox proportional hazards regression was used to estimate the risk of nonrelapse mortality (NRM) and overall survival (OS) according to the 6MWD category ( .05 for all). Patients presenting with a pre-HCT 6MWD of <400 m and experiencing a decline in 6MWD had the highest risk of NRM. Conclusion. The 6MWD is a significant univariate predictor of clinical outcomes but did not provide prognostic information beyond that of traditional prognostic markers in HCT. Implications for Practice: The pretransplant 6-minute walk test is a significant univariate predictor of clinical outcomes in hematological patients beyond age but not beyond that of performance status. On this basis, 6-minute walk distance testing should not be considered part of the standard battery of assessments for risk stratification before hematopoietic cell transplantation. PMID:26446235

  14. Immune-related late-onset hemorrhagic cystitis post allogeneic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    HUANG Xiao-jun; LIU Dai-hong; XU Lan-ping; ZHANG Hong-yu; LIU Kai-yan

    2008-01-01

    Background The pathophysiology of late-onset hemorrhagic cystitis (LOHC) is currently not well understood.The aim of this study was to analyze the ailoimmune aetiology in the pathogenesis of LOHC post allogeneic hematopoietic stem cell transplantation (HSCT).Methods A retrospective study was performed on the medical records of 11 patients with immune-related LOHC post allogeneic HSCT. The clinical characteristics, therapy, and outcomes of these patients were analyzed.Results The median time of onset was 42 days after HSCT (range 16-150 days) and the median duration of HC was 43 days (range 29-47 days).All patients presented with prolonged HC for more than 35 days. Nine patients with evidence of cytomegalovirus (CMV) reactivation did not respond to anti-viral therapy even with CMV clearance in the urine post-therapy.Eleven patients with refractory HC received a low dose of corticosteroids and all patients went into complete remission.Conclusion Our data suggest that alloimmune injury is involved in the pathogenesis of HC in at least some patients and that specific therapy might improve the clinical outcome of hemorrhagic cystitis.

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

    Science.gov (United States)

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

    2007-06-01

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

  16. The efficacy and safety of rituximab in treatment of Epstein-Barr virus disease post allogeneic hematopoietic stem-cell transplantation

    Institute of Scientific and Technical Information of China (English)

    许兰平

    2013-01-01

    Objective To investigate the efficacy and safety of rituximab on Epstein-Barr virus(EBV) disease post allogeneic hematopoietic stem-cell transplantation. Methods A retrospective analysis was performed based on clinical

  17. Early Natural Killer Cell Reconstitution Predicts Overall Survival in T Cell-Replete Allogeneic Hematopoietic Stem Cell Transplantation

    DEFF Research Database (Denmark)

    Minculescu, Lia; Marquart, Hanne Vibeke; Friis, Lone Smidstrup

    2016-01-01

    Early immune reconstitution plays a critical role in clinical outcome after allogeneic hematopoietic stem cell transplantation (HSCT). Natural killer (NK) cells are the first lymphocytes to recover after transplantation and are considered powerful effector cells in HSCT. We aimed to evaluate...... the clinical impact of early NK cell recovery in T cell-replete transplant recipients. Immune reconstitution was studied in 298 adult patients undergoing HSCT for acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndrome from 2005 to 2013. In multivariate analysis NK cell numbers...... on day 30 (NK30) > 150 cells/µL were independently associated with superior overall survival (hazard ratio, .79; 95% confidence interval, .66 to .95; P = .01). Cumulative incidence analyses showed that patients with NK30 > 150 cells/µL had significantly less transplant-related mortality (TRM), P = .01...

  18. Acute Myeloid Leukaemia of Donor Cell Origin Developing 17 Years after Allogenic Hematopoietic Cell Transplantation for Acute Promyelocytic Leukaemia

    Science.gov (United States)

    Jiménez, Pilar; Alvarez, J. Carlos; Garrido, Pilar; Lorente, J. Antonio; Palacios, Jorge; Ruiz-Cabello, Francisco

    2012-01-01

    Donor cell leukaemia (DCL) is a rare complication of allogenic hematopoietic cell transplantation (HCT). We report the case of a female patient with acute promyelocytic leukaemia (APL), FAB type M3, who developed acute myeloid leukaemia (AML) type M5 of donor origin 17 years after allogenic bone marrow transplantation (BMT) from her HLA-matched sister. Morphology and immunophenotyping showed differences with the initial leukaemia, and short tandem repeat (STR) analysis confirmed donor-type haematopoiesis. Interphase fluorescence in situ hybridisation (FISH) showed an 11q23 deletion. Given that the latency period between transplant and development of leukaemia was the longest reported to date, we discuss the mechanisms underlying delayed leukaemia onset. PMID:23675279

  19. Reduced-intensity conditioning allogeneic hematopoietic-cell transplantation for older patients with acute myeloid leukemia.

    Science.gov (United States)

    Goyal, Gaurav; Gundabolu, Krishna; Vallabhajosyula, Saraschandra; Silberstein, Peter T; Bhatt, Vijaya Raj

    2016-06-01

    Elderly patients (>60 years) with acute myeloid leukemia have a poor prognosis with a chemotherapy-alone approach. Allogeneic hematopoietic-cell transplantation (HCT) can improve overall survival (OS). However, myeloablative regimens can have unacceptably high transplant-related mortality (TRM) in an unselected group of older patients. Reduced-intensity conditioning (RIC) or nonmyeloablative (NMA) conditioning regimens preserve the graft-versus-leukemia effects but reduce TRM. NMA regimens result in minimal cytopenia and may not require stem cell support for restoring hematopoiesis. RIC regimens, intermediate in intensity between NMA and myeloablative regimens, can cause prolonged myelosuppresion and usually require stem cell support. A few retrospective and prospective studies suggest a possibility of lower risk of relapse with myeloablative HCT in fit older patients with lower HCT comorbidity index; however, RIC and NMA HCTs have an important role in less-fit patients and those with significant comorbidities because of lower TRM. Whether early tapering of immunosuppression, monitoring of minimal residual disease, and post-transplant maintenance therapy can improve the outcomes of RIC and NMA HCT in elderly patients will require prospective trials.

  20. Caspofungin as antifungal prophylaxis in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation: a retrospective analysis

    Directory of Open Access Journals (Sweden)

    Döring Michaela

    2012-07-01

    Full Text Available Abstract Background Pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT often receive intravenous liposomal amphotericin B (L-AmB as antifungal prophylaxis. There are no guidelines for antifungal prophylaxis in children in this situation. Caspofungin (CAS, a broad-spectrum echinocandin, could be an effective alternative with lower nephrotoxicity than L-AmB. Methods We retrospectively analyzed the safety, feasibility, and efficacy of CAS in our center, and compared the results with L-AmB as antifungal monoprophylaxis in pediatric patients undergoing HSCT. 60 pediatric patients received L-AmB (1 or 3 mg/kg bw/day and another 60 patients received CAS (50 mg/m2/day as antifungal monoprophylaxis starting on day one after HSCT. The median ages of patients receiving L-AmB and CAS were 7.5 years and 9.5 years, respectively. Results No proven breakthrough fungal infection occurred in either group during the median treatment period of 23 days in the L-AmB group and 24 days in the CAS group. One patient receiving CAS developed probable invasive aspergillosis. During L-AmB treatment, potassium levels significantly decreased below normal values. Patients treated with L-AmB had more drug-related side effects and an increased need for oral supplementation with potassium, sodium bicarbonate and calcium upon discharge as compared with the CAS group. CAS was well-tolerated and safe in this cohort of immunocompromised pediatric patients, who underwent high-dose chemotherapy and HSCT. Conclusion Prophylactic CAS and L-AmB showed similar efficacy in this biggest cohort of pediatric patients after allogeneic HSCT reported, so far. A prospective randomized trial in children is warranted to allow for standardized guidelines.

  1. Relapse risk in patients with malignant diseases given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning.

    Science.gov (United States)

    Kahl, Christoph; Storer, Barry E; Sandmaier, Brenda M; Mielcarek, Marco; Maris, Michael B; Blume, Karl G; Niederwieser, Dietger; Chauncey, Thomas R; Forman, Stephen J; Agura, Edward; Leis, Jose F; Bruno, Benedetto; Langston, Amelia; Pulsipher, Michael A; McSweeney, Peter A; Wade, James C; Epner, Elliot; Bo Petersen, Finn; Bethge, Wolfgang A; Maloney, David G; Storb, Rainer

    2007-10-01

    Allogeneic hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning for hematologic malignancies depends on graft-versus-tumor effects for eradication of cancer. Here, we estimated relapse risks according to disease characteristics. Between 1997 and 2006, 834 consecutive patients (median age, 55 years; range, 5-74 years) received related (n = 498) or unrelated (n = 336) HCT after 2 Gy total body irradiation alone (n = 171) or combined with fludarabine (90 mg/m(2); n = 663). Relapse rates per patient year (PY) at risk, corrected for follow-up and competing nonrelapse mortality, were calculated for 29 different diseases and stages. The overall relapse rate per PY was 0.36. Patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) in remission (CR), low-grade or mantle cell non-Hodgkin lymphoma (NHL) (CR + partial remission [PR]), and high-grade NHL-CR had the lowest rates (0.00-0.24; low risk). In contrast, patients with advanced myeloid and lymphoid malignancies had rates of more than 0.52 (high risk). Patients with lymphoproliferative diseases not in CR (except Hodgkin lymphoma and high-grade NHL) and myeloid malignancies in CR had rates of 0.26-0.37 (standard risk). In conclusion, patients with low-grade lymphoproliferative disorders experienced the lowest relapse rates, whereas patients with advanced myeloid and lymphoid malignancies had high relapse rates after nonmyeloablative HCT. The latter might benefit from cytoreductive treatment before HCT.

  2. Atovaquone for Prophylaxis of Toxoplasmosis after Allogeneic Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Mendorf, Alexander; Klyuchnikov, Evgeny; Langebrake, Claudia; Rohde, Holger; Ayuk, Francis; Regier, Marc; Christopeit, Maximilian; Zabelina, Tatjana; Bacher, Adelbert; Stübig, Thomas; Wolschke, Christine; Bacher, Ulrike; Kröger, Nicolaus

    2015-01-01

    Toxoplasmosis and infections by other opportunistic agents such as Pneumocystis jirovecii constitute life-threatening risks for patients after allogeneic hematopoietic stem cell transplantation. Trimethoprim/sulfamethoxazole (TMP-SMX) has been well established for post-transplant toxoplasmosis and pneumocystis prophylaxis, but treatment may be limited due to toxicity. We explored atovaquone as an alternative and compared it with TMP-SMX regarding toxicity and efficacy during the first 100 days after transplantation in 155 consecutive adult stem cell recipients. Eight patients with a prior history of TMP-SMX intolerance received atovaquone as first-line prophylaxis. TMP-SMX was used for 141 patients as first-line strategy, but 13 patients (9.2%) were later switched to atovaquone due to TMP-SMX toxicity or gastrointestinal symptoms. No active toxoplasmosis or active P. jirovecii infection developed under continued prophylaxis with either TMP-SMX or atovaquone. However, for reasons of TMP-SMX and/or atovaquone toxicity, 7 patients were unable to tolerate any efficacious toxoplasmosis prophylaxis and therefore obtained inhalative pentamidine as P. jirovecii prophylaxis but no toxoplasmosis prophylaxis. Importantly, 2 of these patients developed severe toxoplasmosis. In summary, atovaquone appears as a valid alternative for at least some post-transplant patients who cannot tolerate TMP-SMX. This should be further confirmed by multicenter trials.

  3. Health-related quality of life after allogeneic hematopoietic stem cell transplantation for sickle cell disease.

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    Bhatia, Monica; Kolva, Elissa; Cimini, Laura; Jin, Zhezhen; Satwani, Prakash; Savone, Mirko; George, Diane; Garvin, James; Paz, Mary Llenell; Briamonte, Courtney; Cruz-Arrieta, Eduvigis; Sands, Stephen

    2015-04-01

    Sickle cell disease (SCD) is a hereditary hemoglobinopathy that affects over 100,000 people in the United States. Patients with SCD are known to experience suboptimal health-related quality of life (HRQoL). In addition to the physical manifestations of SCD, psychological and social stress, along with academic difficulties, secondary to the chronicity of the disease and its complications often affect patients with SCD. Although medical therapy of SCD has improved, allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative therapy. The objective of this study was to measure HRQoL before and after allo-HCT by assessing physical, psychological, and social functioning in patients with SCD who have undergone reduced-toxicity conditioning (busulfan/fludarabine/alemtuzumab) followed by allo-HCT. Patients < 21 years of age undergoing allo-HCT (matched siblings and unrelated donors) for SCD and their primary caregiver were enrolled using either the English or Spanish version of the PedsQoL 4.0. Data were collected at 3 time points: before allo-HCT and on days 180 and 365 after allo-HCT. The change in HRQoL from baseline was assessed with unadjusted and adjusted mixed-effects models in which subjects were treated as random effects, and variance component structure was used. Seventeen patients and 23 primary caregivers were enrolled and reported a mean overall HRQoL of 66.05 (SD, 15.62) and 72.20 (SD, 15.50) at baseline, respectively. In the patient-reported analysis with adjusted mixed-effects models, the estimated improvements in overall HRQoL were 4.45 (SE, 4.98; P = .380) and 16.58 (SE, 5.06; P = .003) at 180 and 365 days, respectively, after allo-HCT. For parent-reported overall HRQoL, the estimated improvements were 1.57 (SE, 4.82; P = .747) and 9.28 (SE, 4.62; P = .053) at 180 and 365 days, respectively, after allo-HCT. Similar results were found across the physical, social, and emotional HRQoL domains with mixed-effects models after adjustment

  4. Serial measurements of cardiac biomarkers in patients after allogeneic hematopoietic stem cell transplantation

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    Roziakova Lubica

    2012-02-01

    Full Text Available Abstract Background Previous therapy with anthracyclines (ANT and conditioning regimen followed by hematopoietic stem cell transplantation (HSCT represents a high risk for development of cardiotoxicity. The aim of this study was to assess subclinical myocardial damage after HSCT using echocardiography and cardiac biomarkers - high sensitive cardiac troponin T (hs-cTnT and N-terminal pro-B-type natriuretic peptide (NT-proBNP and to identify patients at risk of developing clinical cardiotoxicity. Patients and methods Thirty-seven patients who were treated with allogeneic HSCT for hematologic diseases at median age of 28 years at time of HSCT were studied. Conditioning regimen included either chemotherapy without total body irradiation (TBI or combination of chemotherapy with TBI. Twenty-nine (78,3% patients were pretreated with ANT therapy. Cardiac biomarkers were serially measured before conditioning regimen and at days 1, 14 and 30 after HSCT. Cardiac systolic and diastolic functions were assessed before conditioning regimen and 1 month after HSCT by echocardiography. Results The changes in plasma NT-proBNP and hs-cTnT levels during the 30 days following the HSCT were statistically significant (P P Conclusions Elevations in both cardiac biomarkers were found before clinical signs of cardiotoxicity developed. Persistent elevations in NT-pro-BNP and hs-cTnT concentrations simultaneously for a period exceeding 14 days might be used for identification of patients at risk of developing cardiotoxicity and requiring further cardiological follow up.

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

    Science.gov (United States)

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

    2014-10-29

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

  6. Allogeneic hematopoietic stem cell transplantation following reduced-intensity conditioning for mycosis fungoides and Sezary syndrome.

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    Shiratori, Souichi; Fujimoto, Katsuya; Nishimura, Machiko; Hatanaka, Kanako C; Kosugi-Kanaya, Mizuha; Okada, Kohei; Sugita, Junichi; Shigematsu, Akio; Hashimoto, Daigo; Endo, Tomoyuki; Kondo, Takeshi; Abe, Riichiro; Hashino, Satoshi; Matsuno, Yoshihiro; Shimizu, Hiroshi; Teshima, Takanori

    2016-03-01

    Advanced-stage mycosis fungoides and Sezary syndrome (MF/SS) have a poor prognosis. Allogeneic hematopoietic stem cell transplantation (HSCT), particularly using a reduced-intensity conditioning (RIC) regimen, is a promising treatment for advanced-stage MF/SS. We performed RIC-HSCT in nine patients with advanced MF/SS. With a median follow-up period of 954 days after HSCT, the estimated 3-year overall survival was 85.7% (95% confidence interval, 33.4-97.9%) with no non-relapse mortality. Five patients relapsed after RIC-HSCT; however, in four patients whose relapse was detected only from the skin, persistent complete response was achieved in one patient, and the disease was manageable in other three patients by the tapering of immunosuppressants and donor lymphocyte infusion, suggesting that graft-versus-lymphoma effect and 'down-staging' effect from advanced stage to early stage by HSCT improve the prognosis of advanced-stage MF/SS. These results suggest that RIC-HSCT is an effective treatment for advanced MF/SS.

  7. Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics of Immunosuppressants in Allogeneic Hematopoietic Cell Transplantation: Part II.

    Science.gov (United States)

    McCune, Jeannine S; Bemer, Meagan J; Long-Boyle, Janel

    2016-05-01

    Part I of this article included a pertinent review of allogeneic hematopoietic cell transplantation (alloHCT), the role of postgraft immunosuppression in alloHCT, and the pharmacokinetics, pharmacodynamics, and pharmacogenomics of the calcineurin inhibitors and methotrexate. In this article (Part II), we review the pharmacokinetics, pharmacodynamics, and pharmacogenomics of mycophenolic acid (MPA), sirolimus, and the antithymocyte globulins (ATG). We then discuss target concentration intervention (TCI) of these postgraft immunosuppressants in alloHCT patients, with a focus on current evidence for TCI and on how TCI may improve clinical management in these patients. Currently, TCI using trough concentrations is conducted for sirolimus in alloHCT patients. Several studies demonstrate that MPA plasma exposure is associated with clinical outcomes, with an increasing number of alloHCT patients needing TCI of MPA. Compared with MPA, there are fewer pharmacokinetic/dynamic studies of rabbit ATG and horse ATG in alloHCT patients. Future pharmacokinetic/dynamic research of postgraft immunosuppressants should include '-omics'-based tools: pharmacogenomics may be used to gain an improved understanding of the covariates influencing pharmacokinetics as well as proteomics and metabolomics as novel methods to elucidate pharmacodynamic responses.

  8. Biopsy-verified bronchiolitis obliterans and other noninfectious lung pathologies after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Uhlving, Hilde Hylland; Andersen, Claus B; Christensen, Ib Jarle; Gormsen, Magdalena; Pedersen, Karen Damgaard; Buchvald, Frederik; Heilmann, Carsten; Nielsen, Kim Gjerum; Mortensen, Jann; Moser, Claus; Sengeløv, Henrik; Müller, Klaus Gottlob

    2015-03-01

    Bronchiolitis obliterans (BO) is a serious complication of allogeneic hematopoietic stem cell transplantation (HSCT). Lung biopsy is the gold standard for diagnosis. This study describes the course of BO and assesses the congruity between biopsy-verified BO and a modified version of the National Institutes of Health's consensus criteria for BO syndrome (BOS) based exclusively on noninvasive measures. We included 44 patients transplanted between 2000 and 2010 who underwent lung biopsy for suspected BO. Of those, 23 were diagnosed with BO and 21 presented other noninfectious pulmonary pathologies, such as cryptogenic organizing pneumonia, diffuse alveolar damage, interstitial pneumonia, and nonspecific interstitial fibrosis. Compared with patients with other noninfectious pulmonary pathologies, BO patients had significantly lower values of forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity, and maximal mid-expiratory flow throughout follow-up, but there was no difference in the change in pulmonary function from the time of lung biopsy. The BO diagnosis was not associated with poorer overall survival. Fifty-two percent of patients with biopsy-verified BO and 24% of patients with other noninfectious pulmonary pathology fulfilled the BOS criteria. Pathological BO diagnosis was not superior to BOS criteria in predicting decrease in pulmonary function beyond the time of biopsy. A lung biopsy may provide a characterization of pathological patterns that can extend our knowledge on the pathophysiology of HSCT-related lung diseases.

  9. Erythropoietin therapy after allogeneic hematopoietic cell transplantation: a prospective, randomized trial.

    Science.gov (United States)

    Jaspers, Aurélie; Baron, Frédéric; Willems, Evelyne; Seidel, Laurence; Hafraoui, Kaoutar; Vanstraelen, Gaetan; Bonnet, Christophe; Beguin, Yves

    2014-07-01

    We conducted a prospective randomized trial to assess hemoglobin (Hb) response to recombinant human erythropoietin (rhEPO) therapy after hematopoietic cell transplantation (HCT). Patients (N = 131) were randomized (1:1) between no treatment (control arm) or erythropoietin at 500 U/kg per week (EPO arm). Patients were also stratified into 3 cohorts: patients undergoing myeloablative HCT with rhEPO to start on day (D)28, patients given nonmyeloablative HCT (NMHCT) with rhEPO to start on D28, and patients also given NMHCT but with rhEPO to start on D0. The proportion of complete correctors (ie, Hb ≥13 g/dL) before D126 posttransplant was 8.1% in the control arm (median not reached) and 63.1% in the EPO arm (median, 90 days) (P < .001). Hb levels were higher and transfusion requirements decreased (P < .001) in the EPO arm, but not during the first month in the nonmyeloablative cohort starting rhEPO on D0. There was no difference in rates of thromboembolic events or other complications between the 2 arms. This is the first randomized trial to demonstrate that rhEPO therapy hastens erythroid recovery and decreases transfusion requirements when started one month after allogeneic HCT. There was no benefit to start rhEPO earlier after NMHCT.

  10. Up-front allogeneic hematopoietic cell transplantation in acute myeloid leukemia arising from the myelodysplastic syndrome.

    Science.gov (United States)

    Choi, Yunsuk; Kim, Sung-Doo; Park, Young-Hoon; Lee, Jae Seok; Kim, Dae-Young; Lee, Jung-Hee; Lee, Kyoo-Hyung; Seol, Miee; Lee, Young-Shin; Kang, Young-Ah; Jeon, Mijin; Jung, Ah Rang; Lee, Je-Hwan

    2015-01-01

    In patients with secondary acute myeloid leukemia (s-AML) arising from the myelodysplastic syndrome (MDS), treatment outcome is unsatisfactory. We compared up-front allogeneic hematopoietic cell transplantation (HCT) to induction chemotherapy (IC) as an initial treatment in patients with s-AML arising from MDS. This retrospective study included 85 patients who were diagnosed with s-AML arising from MDS; 11 patients proceeded to up-front HCT without IC (HCT group) and 74 received IC (IC group) as an initial treatment for s-AML, 28 of whom subsequently underwent HCT. In the IC group, 41.9% achieved complete remission (CR) compared to 81.8% in the HCT group (p = 0.013). The HCT group showed a significantly longer event-free survival (EFS) than the IC group (median 29.2 vs. 5.2 months, p = 0.042). Overall survival of the HCT group was higher than that of the IC group, but the difference was not statistically significant (median 34.6 vs. 7.6 months, p = 0.149). After adjustment for other clinical factors, outcome in the HCT group was significantly better than in the IC group in terms of CR rate (hazard ratio, HR, 11.195; p = 0.007) and EFS (HR, 0.384; p = 0.029). Up-front HCT is a viable option in s-AML arising from MDS if an appropriate donor is available.

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

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    Meiqing Wu

    Full Text Available 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.

  12. Astrovirus Infection in Hospitalized Infants with Severe Combined Immunodeficiency after Allogeneic Hematopoietic Stem Cell Transplantation

    Science.gov (United States)

    Berger, Christoph; Greiner, Oliver; Caduff, Rosmarie; Trkola, Alexandra; Bossart, Walter; Gerlach, Daniel; Schibler, Manuel; Cordey, Samuel; McKee, Thomas Alexander; Van Belle, Sandra; Kaiser, Laurent; Tapparel, Caroline

    2011-01-01

    Infants with severe primary combined immunodeficiency (SCID) and children post-allogeneic hematopoietic stem cell transplantation (HSCT) are extremely susceptible to unusual infections. The lack of generic tools to detect disease-causing viruses among more than 200 potential human viral pathogens represents a major challenge to clinicians and virologists. We investigated retrospectively the causes of a fatal disseminated viral infection with meningoencephalitis in an infant with gamma C-SCID and of chronic gastroenteritis in 2 other infants admitted for HSCT during the same time period. Analysis was undertaken by combining cell culture, electron microscopy and sequence-independent single primer amplification (SISPA) techniques. Caco-2 cells inoculated with fecal samples developed a cytopathic effect and non-enveloped viral particles in infected cells were detected by electron microscopy. SISPA led to the identification of astrovirus as the pathogen. Both sequencing of the capsid gene and the pattern of infection suggested nosocomial transmission from a chronically excreting index case to 2 other patients leading to fatal infection in 1 and to transient disease in the others. Virus-specific, real-time reverse transcription polymerase chain reaction was then performed on different stored samples to assess the extent of infection. Infection was associated with viremia in 2 cases and contributed to death in 1. At autopsy, viral RNA was detected in the brain and different other organs, while immunochemistry confirmed infection of gastrointestinal tissues. This report illustrates the usefulness of the combined use of classical virology procedures and modern molecular tools for the diagnosis of unexpected infections. It illustrates that astrovirus has the potential to cause severe disseminated lethal infection in highly immunocompromised pediatric patients. PMID:22096580

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

    Science.gov (United States)

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

    2013-07-01

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

  14. Astrovirus infection in hospitalized infants with severe combined immunodeficiency after allogeneic hematopoietic stem cell transplantation.

    Directory of Open Access Journals (Sweden)

    Werner Wunderli

    Full Text Available Infants with severe primary combined immunodeficiency (SCID and children post-allogeneic hematopoietic stem cell transplantation (HSCT are extremely susceptible to unusual infections. The lack of generic tools to detect disease-causing viruses among more than 200 potential human viral pathogens represents a major challenge to clinicians and virologists. We investigated retrospectively the causes of a fatal disseminated viral infection with meningoencephalitis in an infant with gamma C-SCID and of chronic gastroenteritis in 2 other infants admitted for HSCT during the same time period. Analysis was undertaken by combining cell culture, electron microscopy and sequence-independent single primer amplification (SISPA techniques. Caco-2 cells inoculated with fecal samples developed a cytopathic effect and non-enveloped viral particles in infected cells were detected by electron microscopy. SISPA led to the identification of astrovirus as the pathogen. Both sequencing of the capsid gene and the pattern of infection suggested nosocomial transmission from a chronically excreting index case to 2 other patients leading to fatal infection in 1 and to transient disease in the others. Virus-specific, real-time reverse transcription polymerase chain reaction was then performed on different stored samples to assess the extent of infection. Infection was associated with viremia in 2 cases and contributed to death in 1. At autopsy, viral RNA was detected in the brain and different other organs, while immunochemistry confirmed infection of gastrointestinal tissues. This report illustrates the usefulness of the combined use of classical virology procedures and modern molecular tools for the diagnosis of unexpected infections. It illustrates that astrovirus has the potential to cause severe disseminated lethal infection in highly immunocompromised pediatric patients.

  15. Isolated central nervous system relapse of chronic myeloid leukemia after allogeneic hematopoietic stem cell transplantation

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    Fuchs Mary

    2012-08-01

    Full Text Available Abstract Background This case report highlights the relevance of quantifying the BCR-ABL gene in cerebrospinal fluid of patients with suspected relapse of chronic myeloid leukemia in the central nervous system. Case presentation We report on a female patient with isolated central nervous system relapse of chronic myeloid leukemia (CML during peripheral remission after allogeneic hematopoietic stem cell transplantation. The patient showed a progressive cognitive decline as the main symptom. MRI revealed a hydrocephalus and an increase in cell count in the cerebrospinal fluid (CSF with around 50% immature blasts in the differential count. A highly elevated BCR-ABL/ ABL ratio was detected in the CSF, whilst the ratio for peripheral blood and bone marrow was not altered. On treatment of the malresorptive hydrocephalus with shunt surgery, the patient showed an initial cognitive improvement, followed by a secondary deterioration. At this time, the cranial MRI showed leukemic infiltration of lateral ventricles walls. Hence, intrathecal administration of cytarabine, methotrexate, and dexamethasone was initiated, which caused a significant decrease of cells in the CSF. Soon after, the patient demonstrated significant cognitive improvement with a good participation in daily activities. At a later time point, after the patient had lost the major molecular response of CML, therapy with dasatinib was initiated. In a further follow-up, the patient was neurologically and hematologically stable. Conclusions In patients with treated CML, the rare case of an isolated CNS blast crisis has to be taken into account if neurological symptoms evolve. The analysis of BCR-ABL in the CSF is a further option for the reliable detection of primary isolated relapse of CML in these patients.

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

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    Shigeo eFuji

    2014-04-01

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

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

    Science.gov (United States)

    Fuji, Shigeo; Kapp, Markus; Einsele, Hermann

    2014-01-01

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

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

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

    2017-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  20. Allogeneic hematopoietic cell transplantation for acute myeloid leukemia in older adults.

    Science.gov (United States)

    Sorror, Mohamed L; Estey, Elihu

    2014-12-01

    Acute myeloid leukemia (AML) is primarily a disease of the elderly and the numbers of these patients are increasing. Patients ≥60 years of age continue to have poor prognosis. Preliminary results suggest benefit from reduced-intensity allogeneic hematopoietic cell transplantation (HCT) in selected patients 60-80 years of age. However, although patients in this age range comprise >50% of those with AML, they currently constitute only 17% of those offered HCT. In the absence of prospective randomized studies comparing HCT and chemotherapy, the decision to recommend HCT rests on retrospective analyses of the risks of relapse and nonrelapse mortality after each approach. There is strong evidence that pre-HCT comorbidities can predict HCT-related morbidity and mortality. Age alone does not appear predictive and, particularly if the risk of relapse with chemotherapy is high, should not be the sole basis for deciding against HCT. Use of geriatric assessment tools, inflammatory biomarkers, and genetic polymorphism data may further aid in predicting nonrelapse mortality after HCT. Disease status and pretreatment cytogenetics with FLT3-TID, NPM-1, and CEBP-α status are the main factors predicting relapse and these are likely to be supplemented by incorporation of other molecular markers and the level of minimal residual disease after chemotherapy. HLA-matched related and unrelated donor grafts seem preferable to those from other donor sources. Donor age is of no clear significance. Models combining comorbidities with AML risk factors are useful in risk assessment before HCT. In this chapter, we integrated information on AML-specific, HCT-specific, and patient-specific risk factors into a risk-adapted approach to guide decisions about HCT versus no HCT.

  1. Clinical and serological characterization of autoimmune hemolytic anemia after allogeneic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Yang Zhen; Wu Bangzhao; Zhou Youning; Wang Wenjuan; Chen Suning; Sun Aining; Wu Depei

    2014-01-01

    Background Autoimmune hemolytic anemia (AIHA) is an uncommon complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) which has only been reported in a few cases.We here aimed to explore its mechanism.Methods We retrospectively analyzed 296 patients who underwent allo-HSCT in our center from July 2010 to July 2012.Clinical manifestations were carefully reviewed and the response to currently available treatment approaches were evaluated.The survival and risk factors of AIHA patients after allo-HSCT were further analyzed.Results Twelve patients were diagnosed with AIHA at a median time of 100 days (15-720 days) after allo-HSCT.The incidence of AIHA after allo-HSCT was 4.1%.IgG antibody were detected in ten patients and IgM antibody in two patients.The two cold antibody AIHA patients had a better response to steroid corticoid only treatment and the ten warm antibody AIHA patients responded to corticosteroid treatment and adjustment of immunosuppressant therapy.Rituximab was shown to be effective for AIHA patients who failed conventional therapy.Survival analysis showed that the combination of AIHA in allo-HSCT patients hinted at poor survival.Cytomegalovirus (CMV) infection,graft-versus-host disease (GVHD) and histocompatibility leukocyte antigen (HLA) mismatch seemed to increase the risk of developing AIHA.Conclusions Patients who develop AIHA after allo-HSCT have poor survival compared to non-AIHA patients.Possible risk factors of AIHA are CMV infection,GVHD,and HLA mismatch.Rituximab is likely to be the effective treatment choice for the refractory patients.

  2. Safety of posaconazole and sirolimus coadministration in allogeneic hematopoietic stem cell transplants.

    Science.gov (United States)

    Kubiak, David W; Koo, Sophia; Hammond, Sarah P; Armand, Philippe; Baden, Lindsey R; Antin, Joseph H; Marty, Francisco M

    2012-09-01

    Sirolimus is used in allogeneic hematopoietic stem cell transplants (HSCTs) for prevention and treatment of graft-versus-host disease (GVHD). Posaconazole is used in this population for invasive fungal disease (IFD) prophylaxis and treatment. As posaconazole strongly inhibits CYP3A4, concurrent administration of sirolimus, a CYP3A4 substrate, and posaconazole has been reported to increase sirolimus drug exposure substantially. Coadministration of posaconazole and sirolimus is contraindicated by the manufacturer of posaconazole. We identified 15 patients who underwent HSCTs at our institution receiving a steady-state dose of sirolimus who subsequently started posaconazole therapy from January 2006 to March 2009. We recorded baseline characteristics, drug administration details, and potential adverse effects related to either drug. All patients underwent HSCTs for treatment of hematologic malignancy. All patients were initially prescribed sirolimus for GVHD prophylaxis and continued therapy after developing GVHD. Twelve patients (80%) received posaconazole for IFD prophylaxis in the setting of GVHD and 3 (20%) for IFD treatment. Patients received sirolimus and posaconazole concurrently for a median of 78 days (interquartile range [IQR] 25-177; range, 6-503). The median daily dose of sirolimus (2 mg/day) before initiation of posaconazole was reduced 50% to a median daily dose of 1 mg/day at steady state. Six patients experienced sirolimus trough levels greater than 12 ng/mL during coadministration, but only 1 patient experienced an adverse event potentially associated with sirolimus exposure during the first month of coadministration. This patient's sirolimus dose was empirically reduced by only 30% on posaconazole initiation. Concurrent sirolimus and posaconazole use seems to be well tolerated with a 33% to 50% empiric sirolimus dose reduction and close monitoring of serum sirolimus trough levels at the time of posaconazole initiation.

  3. Clinicopathological analysis of allogeneic hematopoietic stem cell transplantation-related membranous glomerulonephritis.

    Science.gov (United States)

    Hiramatsu, Rikako; Ubara, Yoshifumi; Sawa, Naoki; Hasegawa, Eiko; Kawada, Masahiro; Imafuku, Aya; Sumida, Keiichi; Mise, Koki; Yamanouchi, Masayuki; Ueno, Toshiharu; Sekine, Akinari; Hayami, Noriko; Suwabe, Tatsuya; Hoshino, Junichi; Takaichi, Kenmei; Ohashi, Kenichi; Fujii, Takeshi; Wake, Atsushi; Taniguchi, Shuichi

    2016-04-01

    Allogeneic hematopoietic stem cell transplantation (HSCT)-related membranous glomerulonephritis (MGN) is poorly understood. A total of 830 patients who underwent HSCT at Toranomon Hospital from 2000 to 2012 were evaluated retrospectively, including 621 patients receiving umbilical cord blood transplantation (UCBT) and 208 patients receiving unrelated bone marrow transplantation. MGN was diagnosed in 5 patients after UCBT (versus none after bone marrow transplantation) and occurred concomitantly with chronic graft-versus-host disease after cessation of immunosuppression. Light microscopy did not show any definite spikes or bubbling of the glomerular basement membrane (GBM) in all 5 patients. In 1 patient (case 5), endocapillary proliferative lesions with fibrin-like deposits were noted in addition to MGN findings. Immunofluorescence demonstrated granular deposits of immunoglobulin G (IgG; IgG1 and IgG4) along the GBM with negativity for C3, C4, and C1q in 4 patients (cases 1-4), whereas case 5 showed positivity for IgG (IgG1, IgG2, IgG3, and IgG4) as well as for C3, C4, and C1q. Electron microscopy revealed electron-dense deposits in the subepithelial space of the GBM in cases 1-4. In case 5, electron-dense deposits were present in the mesangium and the subendothelial space of the GBM, as well as in the subepithelial space. After treatment with immunosuppressants (prednisolone and/or cyclosporin) or angiotensin-converting enzyme inhibitors, complete remission with disappearance of proteinuria was achieved 12.2 months in all 5 patients, but nephrotic-range proteinuria relapsed in 2 patients during follow-up. Serum anti-PLA2R autoantibody was negative in 3 patients. HSCT-related MGN only occurred after UCBT. We believe that there were 2 morphologic patterns: early MGN and membranoproliferative pattern glomerulonephritis.

  4. Risk factor analysis of autoimmune hemolytic anemia after allogeneic hematopoietic stem cell transplantation in children.

    Science.gov (United States)

    Chang, Tsung-Yen; Jaing, Tang-Her; Wen, Yu-Chuan; Huang, I-Anne; Chen, Shih-Hsiang; Tsay, Pei-Kwei

    2016-11-01

    Autoimmune hemolytic anemia (AIHA) is a clinically relevant complication after allogeneic hematopoietic stem cell transplantation (HSCT). Currently, there is no established consensus regarding the optimal therapeutic approach. Whether AIHA contributes to increased mortality is still somewhat controversial.We investigated the incidence, risk factors, and outcome of post-transplant AIHA in 265 consecutive pediatric patients undergoing allo-HSCT over a 17-year period. Onset of AIHA was calculated from the first documented detection of AIHA by either clinical symptoms or positive direct agglutinin test. Resolution of AIHA was defined as normalization of hemoglobin and biochemical markers of hemolysis with sustained transfusion independence.We identified 15 cases of AIHA after allo-HSCT (incidence rate, 6%). Ten (67%) of these patients had a positive direct antiglobulin test. Data were obtained for 9 boys and 6 girls after a median follow-up of 53 months (range 4-102). The median age was 5.1 years (range 0.5-15.4) at the time of HSCT and the median time to emergence was 149 days (range 42-273). No significant risk factor for post-transplant AIHA has emerged from our data to date. In the majority (14 of 15; 93%) of AIHA patients, multiple agents for treatment were required, with 12 of 15 (80%) patients achieving complete resolution of AIHA. No splenectomy was performed in any of our patients.For various reasons, post-transplantation AIHA poses an extraordinary challenge to transplant physicians. Despite the advancements in diagnostic tools, therapeutic challenges remain due to the myriad interacting pathways in AIHA.

  5. Amplification of Surface Antigen P43 Gene and Its Application in Detection of Toxoplasma Gondii in Allogeneic Hematopoietic Stem Cell Transplantation

    Institute of Scientific and Technical Information of China (English)

    ZHOUYongan; YUXinbing; 等

    2002-01-01

    Objective:To establish a rapid,specific and sensitive diagnostic technique for the human Toxoplasma gondii infection in the recipi-ents with allogeneic hematopoietic stem cell transplantation and discuss its clinical significance.Methods:30 patients undergoing allogeneic hematopoietic stem cell transplantation were detected by using ELISA and PCR.Results:Among 30 recipients undergiong allogeneic hematopoietic stem cell transplantation,3 were positive for Toxoplasma gondiii antigen and 5 for surface antigen p43 gene with the positive rate being 13.3% and 16.67% respectively.20 healthy people(negative for anti-Tox antibody)were also tested by using ELISA and PCR.Conclusion:PCR is an accurate,relatively rapid,sensitive and specific method for detecting P43 gene of Toxoplasma gondii.Be-canuse PCR can be applied to a variety of different clinical samples,it can be considered as a valuable additional tool for identification of Toxoplasma gondii infections.

  6. Successful treatment of severe myasthenia gravis developed after allogeneic hematopoietic stem cell transplantation with plasma exchange and rituximab.

    Science.gov (United States)

    Unal, Sule; Sag, Erdal; Kuskonmaz, Baris; Kesici, Selman; Bayrakci, Benan; Ayvaz, Deniz C; Tezcan, Ilhan; Yalnızoglu, Dilek; Uckan, Duygu

    2014-05-01

    Myasthenia gravis is among the rare complications after allogeneic hematopoietic stem cell transplantation and is usually associated with chronic GVHD. Herein, we report a 2-year and 10 months of age female with Griscelli syndrome, who developed severe myasthenia gravis at post-transplant +22nd month and required respiratory support with mechanical ventilation. She was unresponsive to cyclosporine A, methylprednisolone, intravenous immunoglobulin, and mycophenolate mofetil and the symptoms could only be controlled after plasma exchange and subsequent use of rituximab, in addition to cyclosporine A and mycophenolate mofetil maintenance. She is currently asymptomatic on the 6th month of follow-up.

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

    Science.gov (United States)

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

    2017-01-01

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

  8. Efficacy and safety of deferasirox in non-thalassemic patients with elevated ferritin levels after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Jaekel, N; Lieder, K; Albrecht, S; Leismann, O; Hubert, K; Bug, G; Kröger, N; Platzbecker, U; Stadler, M; de Haas, K; Altamura, S; Muckenthaler, M U; Niederwieser, D; Al-Ali, H K

    2016-01-01

    Elevated serum ferritin contributes to treatment-related morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The multicenter DE02 trial assessed the safety, efficacy and impact of deferasirox on iron homeostasis after allogeneic HSCT. Deferasirox was administered at a starting dose of 10 mg/kg per day to 76 recipients of allogeneic HSCT, with subsequent dose adjustments based on efficacy and safety. Deferasirox was initiated at a median of 168 days after HSCT, with 84% of patients still on immunosuppression. Baseline serum ferritin declined from 2045 to 957 ng/mL. Deferasirox induced a negative iron balance in 84% of patients. Hemoglobin increased in the first 3 months, and trough serum cyclosporine levels were stable. Median exposure was 330 days, with a median compliance rate of >80%. The most common investigator-reported drug-related adverse events (AEs) were increased blood creatinine (26.5%), nausea (9.0%) and abdominal discomfort (8.3%). Fifty-four (71.1%) patients experienced drug-related AEs, which occasionally resulted in discontinuation (gastrointestinal (n=6), skin (n=3), elevated transaminases (n=1) and creatinine (n=1)). The incidence of AEs appeared to be dose related, with 7.5 mg/kg per day being the best-tolerated dose. Low-dose deferasirox is an effective chelation therapy after allogeneic HSCT, with a manageable safety profile, even in patients receiving cyclosporine.

  9. [Allogenic hematopoietic stem cell transplantation with unrelated cord blood: report of three cases from the Chilean cord blood bank].

    Science.gov (United States)

    Barriga, Francisco; Wietstruck, Angélica; Rojas, Nicolás; Bertin, Pablo; Pizarro, Isabel; Carmona, Amanda; Guilof, Alejandro; Rojas, Iván; Oyarzún, Enrique

    2013-08-01

    Public cord blood banks are a source of hematopoietic stem cells for patients with hematological diseases who lack a family donor and need allogeneic transplantation. In June 2007 we started a cord blood bank with units donated in three maternity wards in Santiago, Chile. We report the first three transplants done with cord blood units form this bank. Cord blood units were obtained by intrauterine collection at delivery. They were depleted of plasma and red cells and frozen in liquid nitrogen. Tests for total nucleated cells, CD34 cell content, viral serology, bacterial cultures and HLA A, B and DRB1 were done. Six hundred cord blood units were stored by March 2012. Three patients received allogeneic transplant with cord blood from our bank, two with high risk lymphoblastic leukemia and one with severe congenital anemia. They received conditioning regimens according to their disease and usual supportive care for unrelated donor transplantation until full hematopoietic and immune reconstitution was achieved. The three patients had early engraftment of neutrophils and platelets. The child corrected his anemia and the leukemia patients remain in complete remission. The post-transplant course was complicated with Epstein Barr virus, cytomegalovirus and BK virus infection. Two patients are fully functional 24 and 33 months after transplant, the third is still receiving immunosuppression.

  10. Allogeneic hematopoietic stem-cell transplantation for acute myeloid leukemia in remission

    DEFF Research Database (Denmark)

    Nagler, Arnon; Rocha, Vanderson; Labopin, Myriam

    2013-01-01

    Cyclophosphamide (Cy) combined with total-body irradiation (TBI) or with busulfan (Bu) are currently the most common myeloablative regimens used in allogeneic stem-cell transplantation (alloSCT) in adults with acute myelogenous leukemia (AML). Intravenous (IV) Bu has more predictable...

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

    Science.gov (United States)

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

    2014-01-01

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

  12. Quantitative chimerism kinetics in relapsed leukemia patients after allogeneic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    QIN Xiao-ying; WANG Jing-zhi; ZHANG Xiao-hui; LI Jin-lan; LI Ling-di; LIU Kai-yan; HUANG Xiao-jun; LI Guo-xuan; QIN Ya-zhen; WANG Yu; WANG Feng-rong; LIU Dai-hong; XU Lan-ping; CHEN Huan; HAN Wei

    2012-01-01

    Background Chimerism analysis is an important tool for the surveillance of post-transplant engraftment.It offers the possibility of identifying impending graft rejection and recurrence of underlying malignant or non-malignant disease.Here we investigated the quantitative chimerism kinetics of 21 relapsed leukemia patients after allogeneic hematopoietic stem cell transplantation (HSCT).Methods A panel of 29 selected sequence polymorphism (SP) markers was screened by real-time polymerase chain reaction (RT-PCR) to obtain the informative marker for every leukemia patient.Quantitative chimerism analysis of bone marrow (BM) samples of 21 relapsed patients and 20 patients in stable remission was performed longitudinally.The chimerisms of BM and peripheral blood (PB) samples of 14 patients at relapse were compared.Results Twenty-one patients experienced leukemia relapse at a median of 135 days (range,30-720 days) after transplantation.High recipient chimerism in BM was found in all patients at relapse,and increased recipient chimerism in BM samples was observed in 90% (19/21) of patients before relapse.With 0.5% recipient DNA as the cut-off,median time between the detection of increased recipient chimerism and relapse was 45 days (range,0-120 days),with 76% of patients showing increased recipient chimerism at least 1 month prior to relapse.Median percentage of recipient DNA in 20 stable remission patients was 0.28%,0.04%,0.05%,0.05%,0.08%,and 0.05% at 1,2,3,6,9,and 12 months,respectively,after transplantation.This was concordant with other specific fusion transcripts and fluorescent in situ hybridization examination.The recipient chimerisms in BM were significantly higher than those in PB at relapse (P=0.001).Conclusions This SP-based RT-PCR essay is a reliable method for chimerism analysis.Chimerism kinetics in BM can be used as a marker of impending leukemia relapse,especially when no other specific marker is available.Based on our findings

  13. Ceruloplasmin is a potential biomarker for aGvHD following allogeneic hematopoietic stem cell transplantation.

    Directory of Open Access Journals (Sweden)

    Meng Lv

    Full Text Available Acute graft-versus-host-disease (aGvHD is the major cause of non-relapse mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT. Recently, diagnostic biomarkers for aGvHD have been shown to play important roles in evaluating disease status and mortality risk after allo-HSCT. To identify plasma biomarkers for aGvHD with high sensitivity and specificity, a quantitative proteomic approach using 8-plex isobaric tags for relative and absolute quantitation (8-plex iTRAQ was employed to screen differentially expressed proteins in peripheral blood before and after the onset of aGvHD. Four target proteins, ceruloplasmin (CP, myeloperoxidase (MPO, complement factor H (CFH, and alpha-1-acid glycoprotein (AGP, were chosen for preliminary validation with enzyme linked immunosorbent assay (ELISA in 20 paired samples at both the time of diagnosis of aGvHD and the time of complete response. The most promising candidate, ceruloplasmin, was further validated at fixed time points after allo-HSCT and during aGvHD. The plasma ceruloplasmin levels were significantly increased during the period of aGvHD onset and were markedly decreased as aGvHD resolved. The plasma ceruloplasmin levels at different time points post-transplant in the aGvHD (+ group were significantly higher than those in the aGvHD (- group (p<0.001. The elevation of ceruloplasmin level in patients with active aGvHD was independent of infection status. Patients whose ceruloplasmin levels were elevated above 670 μg/ml at 7, 14 and 21 days after allo-HSCT had a remarkably increased probability of subsequently developing aGvHD. In conclusion, our results suggest that plasma ceruloplasmin is a potential plasma biomarker of aGvHD, and it also has prognostic value for risk-adapted prophylaxis during the consecutive time points monitored in the first month after allo-HSCT.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  15. Outcome of allogeneic hematopoietic stem cell transplantation in adult patients with acute myeloid leukemia harboring trisomy 8.

    Science.gov (United States)

    Konuma, Takaaki; Kondo, Tadakazu; Yamashita, Takuya; Uchida, Naoyuki; Fukuda, Takahiro; Ozawa, Yukiyasu; Ohashi, Kazuteru; Ogawa, Hiroyasu; Kato, Chiaki; Takahashi, Satoshi; Kanamori, Heiwa; Eto, Tetsuya; Nakaseko, Chiaki; Kohno, Akio; Ichinohe, Tatsuo; Atsuta, Yoshiko; Takami, Akiyoshi; Yano, Shingo

    2017-03-01

    Trisomy 8 (+8) is one of the most common cytogenetic abnormalities in adult patients with acute myeloid leukemia (AML). However, the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) in adult patients with AML harboring +8 remains unclear. To evaluate, the outcome and prognostic factors in patients with AML harboring +8 as the only chromosomal abnormality or in association with other abnormalities, we retrospectively analyzed the Japanese registration data of 631 adult patients with AML harboring +8 treated with allogeneic HSCT between 1990 and 2013. In total, 388 (61%) patients were not in remission at the time of HSCT. With a median follow-up of 38.5 months, the probability of overall survival and the cumulative incidence of relapse at 3 years were 40 and 34%, respectively. In the multivariate analysis, two or more additional cytogenetic abnormalities and not being in remission at the time of HSCT were significantly associated with a higher overall mortality and relapse. Nevertheless, no significant impact on the outcome was observed in cases with one cytogenetic abnormality in addition to +8. Although more than 60% of the patients received HSCT when not in remission, allogeneic HSCT offered a curative option for adult patients with AML harboring +8.

  16. Clinical and immunological correction of DOCK8 deficiency by allogeneic hematopoietic stem cell transplantation following a reduced toxicity conditioning regimen.

    Science.gov (United States)

    Boztug, Heidrun; Karitnig-Weiß, Cäcilia; Ausserer, Bernd; Renner, Ellen D; Albert, Michael H; Sawalle-Belohradsky, Julie; Belohradsky, Bernd H; Mann, Georg; Horcher, Ernst; Rümmele-Waibel, Alexandra; Geyeregger, Rene; Lakatos, Karoly; Peters, Christina; Lawitschka, Anita; Matthes-Martin, Susanne

    2012-10-01

    Dedicator of cytokinesis 8 protein (DOCK8) deficiency is a combined immunodeficiency disorder characterized by an expanding clinical picture with typical features of recurrent respiratory or gastrointestinal tract infections, atopic eczema, food allergies, chronic viral infections of the skin, and blood eosinophilia often accompanied by elevated serum IgE levels. The only definitive treatment option is allogeneic hematopoietic stem cell transplantation (HSCT). We report a patient with early severe manifestation of DOCK8 deficiency, who underwent unrelated allogeneic HSCT at the age of 3 years following a reduced toxicity conditioning regimen. The transplant course was complicated by pulmonary aspergilloma pretransplantation, adenovirus (ADV) reactivation, and cytomegalovirus (CMV) pneumonitis 4 weeks after transplantation. With antifungal and antiviral treatment the patient recovered. Seven months after transplantation the patient is in excellent clinical condition. Eczematous rash, chronic viral skin infections, and food allergies have subsided, associated with normalization of IgE levels and absolute numbers of eosinophils. Chimerism analysis shows stable full donor chimerism. DOCK8 deficiency can be successfully cured by allogeneic HSCT. This treatment option should be considered early after diagnosis, as opportunistic infections and malignancies that occur more frequently during the natural course of the disease are associated with higher morbidity and mortality.

  17. Surveillance of megakaryocytic function by measurement of CD61-exposing microparticles in allogeneic hematopoietic stem cell recipients.

    Science.gov (United States)

    Rank, Andreas; Nieuwland, Rienk; Delker, Ruth; Pihusch, Verena; Wilkowski, Ralf; Toth, Bettina; Kolb, Hans-Jochem; Pihusch, Rudolf

    2011-01-01

    Increasing evidence suggests that circulating microparticles (MP) exposing CD61 originate predominantly from megakaryocytes. Dramatic changes in megakaryocytic homeostasis are regularly observed following allogeneic hematopoietic stem cell transplantation (HSCT) and associated with transplantation-associated complications. We studied MP plasma levels prospectively in healthy subjects (n = 10) and allogeneic HSCT recipients (n = 19) twice weekly from the start of conditioning therapy up to day 30. A total of 224 measurement points were evaluated. MP were isolated, double-stained with annexin V and anti-CD61, and analyzed by flow cytometry. In uncomplicated HSCT, we found a correlation between platelet and CD61-exposing MP count, which resulted in a constant ratio of MP per platelet. The ratio was increased in patients with active hematological malignancies before transplantation and normalized during conditioning therapy. After take, the MP ratio increased, whereas infections and microangiopathic hemolytic anemia did not affect the ratio. In patients with GvHD, a decreased MP ratio was observed depending on the grade of GvHD, possibly indicating megakaryocytic damage. The MP ratio was able to discriminate between toxic, septic, and GvHD-induced hyperbilirubinemia. We first describe CD61+ MP levels during allogeneic HSCT and postulate that the MP ratio might be a useful biomarker for the surveillance of megakaryocytes during HSCT.

  18. Epidemiology of complementary and alternative medicine therapy use in allogeneic hematopoietic stem cell transplant survivorship patients in Australia.

    Science.gov (United States)

    Lindsay, Julian; Kabir, Masrura; Gilroy, Nicole; Dyer, Gemma; Brice, Lisa; Moore, John; Greenwood, Matthew; Hertzberg, Mark; Gottlieb, David; Larsen, Stephen R; Hogg, Megan; Brown, Louisa; Huang, Gillian; Tan, Jeff; Ward, Christopher; Kerridge, Ian

    2016-12-01

    In addition to prescribed conventional medicines, many allogeneic hematopoietic stem cell transplant (HSCT) survivors also use complementary and alternative medical therapies (CAM), however, the frequency and types of CAMs used by allogeneic HSCT survivors remain unclear. Study participants were adults who had undergone an allogeneic HSCT between 1st January 2000 and 31st December 2012. Participants completed a 402-item questionnaire regarding the use of CAM, medical complications, specialist referrals, medications and therapies, infections, vaccinations, cancer screening, lifestyle, and occupational issues and relationship status following stem cell transplantation. A total of 1475 allogeneic HSCT were performed in the study period. Of the 669 recipients known to be alive at study sampling, 583 were contactable and were sent study packs. Of 432 participants who returned the completed survey (66% of total eligible, 76% of those contacted), 239 (54.1%) HSCT survivors used at least one form of CAM. These included dietary modification (13.6%), vitamin therapy (30%), spiritual or mind-body therapy (17.2%), herbal supplements (13.5%), manipulative and body-based therapies (26%), Chinese medicine (3.5%), reiki (3%), and homeopathy (3%). These results definitively demonstrate that a large proportion of HSCT survivors are using one or more form of CAM therapy. Given the potential benefits demonstrated by small studies of specific CAM therapies in this patient group, as well as clearly documented therapies with no benefit or even toxicity, this result shows there is a large unmet need for additional studies to ascertain efficacy and safety of CAM therapies in this growing population.

  19. 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)

    J.E. Raber-Durlacher; A.M.G.A. Laheij; J.B. Epstein; M. Epstein; G.M. Geerligs; G.N. Wolffe; N.M.A. Blijlevens; J.P. Donnelly

    2013-01-01

    Aim 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).

  20. 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, J.E.; Laheij, A.M.; Epstein, J.B.; Epstein, M.; Geerligs, G.M.; Wolffe, G.N.; Blijlevens, N.M.A.; Donnelly, J.P.

    2013-01-01

    AIM: 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).

  1. The prognostic value of YKL-40 concentrations in nonmyeloablative conditioning allogeneic hematopoietic cell transplantation

    DEFF Research Database (Denmark)

    Mørup, Anne Mette; Kornblit, Brian; Johansen, Julia S;

    2011-01-01

    and plasma YKL-40 concentrations as prognostic biomarkers in a cohort of 149 patients treated with hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning for hematologic malignancies. Recipients with pretransplant YKL-40 concentrations above the age-adjusted 95th percentile (high) had...

  2. Pregnancy after allogeneic hematopoietic stem cell transplantation in a Fanconi anemia patient

    Science.gov (United States)

    Atashkhoei, Simin; Fakhari, Solmaz; Bilehjani, Eissa; Farzin, Haleh

    2017-01-01

    Pregnancy in patients with Fanconi anemia (FA) is rare. However, there are reports of successful pregnancy in Fanconi patients after bone marrow transplantation (BMT, hematopoietic stem cell transplantation). We describe the case of a term pregnant woman with FA who was treated with BMT 2 years earlier. She underwent successful delivery with cesarean section using spinal anesthesia without any complications.

  3. Oral cyclosporine A treatment is feasible after myeloablative conditioning in allogeneic hematopoietic stem cell transplantation

    DEFF Research Database (Denmark)

    Nygaard, M; Hovgaard, D; Schjødt, I M;

    2015-01-01

    underwent myeloablative hematopoietic stem cell transplantation. Twenty-one patients (44%) tolerated CsA orally throughout the transplantation period without increased incidence of acute graft versus host disease(aGVHD). Low concentration of CsA in week 2 was associated with increased incidence of a...

  4. Invasive fungal disease in allogeneic hematopoietic stem cell transplant recipients: an autopsy-driven survey.

    Science.gov (United States)

    Sinkó, J; Csomor, J; Nikolova, R; Lueff, S; Kriván, G; Reményi, P; Bátai, A; Masszi, T

    2008-04-01

    Invasive mycoses are pre-eminent causes of morbidity and mortality in the allogeneic stem cell transplant setting. In spite of novel diagnostic modalities, the timely and specific identification of invasive mycoses still remains challenging. We analyzed the case history of 97 consecutive patients receiving 103 allogeneic stem cell transplants between January 2003 and October 2006 performed by a single team at 2 transplant centers in Budapest, Hungary. All patients with febrile neutropenia not responding to broad-spectrum antibacterial therapy received amphotericin B deoxycholate empirically. In cases of proven or probable invasive aspergillosis, intravenous voriconazole was instituted. Patients who failed to improve on initial therapy were treated with an antifungal combination, while responders were switched to oral voriconazole. A total of 38 patients died following allografting. Both centers had an autopsy rate of 100% due to central health care regulations. An infectious cause of death could be identified in 15 cases, invasive fungal disease being the most prevalent and accounting for 10 fatalities. Six patients died of invasive aspergillosis, while invasive candidiasis and mucormycosis led to a fatal outcome in 2 cases each. Despite the regular use of galactomannan antigen detections and imaging, an ante mortem diagnosis of proven/probable invasive fungal disease could only be established in 4 of 10 autopsy-verified cases (aspergillosis: 3, candidiasis: 1, mucormycosis: 0). In the remaining 6 patients, deep mycoses were missed clinically and were revealed only by postmortem histology. Present diagnostic and therapeutic strategies still seem to be suboptimal for the management of invasive fungal diseases in the high-risk allogeneic stem cell transplant population.

  5. Quality of life, social challenges, and psychosocial support for long-term survivors after allogeneic hematopoietic stem-cell transplantation.

    Science.gov (United States)

    Norkin, Maxim; Hsu, Jack W; Wingard, John R

    2012-01-01

    Over the last two decades quality of life (QoL) and the social challenges of allogeneic hematopoietic stem cell transplant (allo-HSCT) survivors have been emerging as subjects of extensive research and are now considered as very important aspects in the pretransplant evaluation and management of allo-HSCT recipients. Recognition of QoL challenges in allo-HSCT survivors allows timely interventions leading to improvement of post-transplant outcomes. It needs to be recognized that long-lasting life changes associated with survivorship after allo-HSCT also significantly affect QoL of partners of allo-HSCT survivors. Currently, resources should be focused on how research findings can be used by patients, their partners, and physicians to optimize QoL and psychosocial adjustment.

  6. Fulminant Laryngeal-tracheobronchial-pulmonary Aspergillosis: A Rare and Fatal Complication in Allogeneic Hematopoietic Stem Cell Transplantation Recipients

    Science.gov (United States)

    Tao, Tao; Zhang, Ying-Hui; Xue, Sheng-Li; Wu, De-Pei; Chen, Feng

    2017-01-01

    A 23-year-old man who had previously undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT) for severe aplastic anemia was diagnosed with invasive laryngeal-tracheobronchial-pulmonary aspergillosis after presenting with a persistent dry cough at six months post-transplantation based on the findings of laryngoscopy and fiberoptic bronchoscopy. A fiberoptic bronchoscope was used to remove the obstructive material from the patient's airway and posaconazole plus caspofungin were administered to successfully to treat the patient. Our report suggests that laryngoscopy and fiberoptic bronchoscopy should be considered as alternative approaches to the diagnosis and treatment of allo-HSCT recipients with persistent respiratory symptoms when invasive laryngeal aspergillosis and invasive tracheobronchial aspergillosis are suspected. PMID:28154281

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

    Science.gov (United States)

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

    2015-04-01

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

  8. Pregnancy after allogeneic hematopoietic stem cell transplantation in a Fanconi anemia patient

    OpenAIRE

    Atashkhoei S; Fakhari S; Bilehjani E; Farzin H

    2017-01-01

    Simin Atashkhoei, Solmaz Fakhari, Eissa Bilehjani, Haleh Farzin Department of Anesthesiology, Al-Zahra Hospital, Tabriz University of Medical Sciences, Tabriz, Iran Abstract: Pregnancy in patients with Fanconi anemia (FA) is rare. However, there are reports of successful pregnancy in Fanconi patients after bone marrow transplantation (BMT, hematopoietic stem cell transplantation). We describe the case of a term pregnant woman with FA who was treated with BMT 2 years earlie...

  9. Pregnancy after allogeneic hematopoietic stem cell transplantation in a Fanconi anemia patient

    OpenAIRE

    Atashkhoei,Simin; Fakhari,Solmaz; Bilehjani,Eissa; Farzin,Haleh

    2017-01-01

    Simin Atashkhoei, Solmaz Fakhari, Eissa Bilehjani, Haleh Farzin Department of Anesthesiology, Al-Zahra Hospital, Tabriz University of Medical Sciences, Tabriz, Iran Abstract: Pregnancy in patients with Fanconi anemia (FA) is rare. However, there are reports of successful pregnancy in Fanconi patients after bone marrow transplantation (BMT, hematopoietic stem cell transplantation). We describe the case of a term pregnant woman with FA who was treated with BMT 2&n...

  10. Assessing the Influence of Different Comorbidities Indexes on the Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in a Developing Country.

    Directory of Open Access Journals (Sweden)

    Gustavo Machado Teixeira

    Full Text Available Although the application of Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI has enabled better prediction of transplant-related mortality (TRM in allogeneic hematopoietic stem cell transplants (AHSCT, data from developing countries are scarce. This study prospectively evaluated the HCT-CI and the Adult Comorbidity Evaluation (ACE-27, in its original and in a modified version, as predictors of post-transplant complications in adults undergoing a first related or unrelated AHSCT in Brazil. Both bone marrow (BM and peripheral blood stem cells (PBSC as graft sources were included. We analyzed the cumulative incidence of granulocyte and platelet recovery, sinusoidal obstructive syndrome, acute and chronic graft-versus-host disease, relapse and transplant-related mortality, and rates of event-free survival and overall survival. Ninety-nine patients were assessed. Median age was 38 years (18-65 years; HCT-CI ≥ 3 accounted for only 8% of cases; hematologic malignancies comprised 75.8% of the indications for AHSCT. There was no association between the HCT-CI or the original or modified ACE-27 with TRM or any other studied outcomes after AHSCT. These results show that, in the population studied, none of the comorbidity indexes seem to be associated with AHSCT outcomes. A significantly low frequency of high-risk (HCT-CI ≥ 3 in this Brazilian population might justify these results.

  11. Financial impact of allogeneic hematopoietic cell transplantation on patients and families over 2 years: results from a multicenter pilot study.

    Science.gov (United States)

    Denzen, E M; Thao, V; Hahn, T; Lee, S J; McCarthy, P L; Rizzo, J D; Ammi, M; Drexler, R; Flesch, S; James, H; Omondi, N; Murphy, E; Pederson, K; Majhail, N S

    2016-09-01

    Hematopoietic cell transplantation (HCT) is a procedure that can significantly influence the socioeconomic wellbeing of patients, caregivers and their families. Among 30 allogeneic HCT recipients and their caregivers enrolled on a pilot study evaluating the feasibility of studying financial impact of HCT, 16 agreed to participate in the long-term phase, completed a baseline questionnaire and received phone interviews at 6, 12, 18 and 24 months post HCT. Analyses showed that by 2 years post HCT, 54% of patients who previously contributed to household earnings had not returned to work and 80% of patients/caregivers reported transplant as having moderate to great impact on household income. However, patients' levels of confidence in their abilities to meet household financial obligations increased from baseline to 2 years. A relatively large proportion of patients reported inability to pay for medical care through this time period. Case studies demonstrated that patients' individual perceptions of the financial impact of HCT varies considerably, regardless of actual income. We demonstrate the feasibility of conducting a study to evaluate the financial impact of allogeneic HCT through 2 years post transplantation. Some patients/caregivers continue to experience a significant long-term financial burden after this procedure. Our study lays the foundation for a larger evaluation of patient/caregiver financial burden associated with HCT.

  12. Importance of killer immunoglobulin-like receptors in allogeneic hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Danilo Santana Alessio Franceschi

    2011-01-01

    Full Text Available Hematopoietic stem cell transplantation is the treatment of choice for many hematologic diseases, such as multiple myeloma, bone marrow aplasia and leukemia. Human leukocyte antigen (HLA compatibility is an important tool to prevent post-transplant complications such as graft rejection and graft-versus-host disease, but the high rates of relapse limit the survival of transplant patients. Natural Killer cells, a type of lymphocyte that is a key element in the defense against tumor cells, cells infected with viruses and intracellular microbes, have different receptors on their surfaces that regulate their cytotoxicity. Killer immunoglobulin-like receptors are the most important, interacting consistently with human leukocyte antigen class I molecules present in other cells and thus controlling the activation of natural killer cells. Several studies have shown that certain combinations of killer immunoglobulin-like receptors and human leukocyte antigens (in both donors and recipients can affect the chances of survival of transplant patients, particularly in relation to the graft-versusleukemia effect, which may be associated to decreased relapse rates in certain groups. This review aims to shed light on the mechanisms and effects of killer immunoglobulin-like receptors - human leukocyte antigen associations and their implications following hematopoietic stem cell transplantation, and to critically analyze the results obtained by the studies presented herein.

  13. Computed Tomography Findings of Human Polyomavirus BK (BKV)-Associated Cystitis in Allogeneic Hematopoietic Stem Cell Transplant Recipients

    Energy Technology Data Exchange (ETDEWEB)

    Schulze, M.; Beck, R.; Igney, A.; Vogel, M.; Maksimovic, O.; Claussen, C.D.; Faul, C.; Horger, M. [Dept. of Diagnostic Radiology, Dept. of Internal Medicine-Oncology, and Inst. of Medical Virology, Eberhard-Karls Univ., Tbingen (Germany)

    2008-12-15

    Background: Over 70% of the general population worldwide is positive for antibodies against polyomavirus hominis type 1 (BKV). Polyomavirus can be reactivated in immunocompromised patients and thereby induce urogenital tract infection, including cystitis. Purpose: To describe the computed tomography (CT) findings of human polyomavirus-induced cystitis in adult patients after allogeneic hematopoietic stem cell transplantation (allogeneic HCT). Material and Methods: The study population was a retrospective cohort of 11 consecutive adult patients (eight men, three women; age range 22-59 years, mean 42.9 years) who received allogeneic HCT between December 2003 and December 2007 and were tested positive for urinary BKV infection. All CT scans were evaluated with regard to bladder wall thickness, mucosal enhancement, distinct layering of thickened bladder wall, and presence of intravesical clots, perivesical stranding as well as attenuation values of intravesical urine. Clinical data concerning transplant and conditioning regimen variables and laboratory parameters were correlated with degree and extent of imaging findings. Results: All patients had clinical signs of cystitis with different degrees of thickening of the urinary bladder wall. Well-delineated urinary bladder layers were present in six patients. Thickening of the urinary bladder wall was continuous in nine of 11 patients. Increased attenuation of intravesical urine was found in seven patients with hemorrhagic cystitis. Four patients had intraluminal clots. Perivesical stranding was not a major CT finding, occurring in a mild fashion in three of 11 patients. The clinical classification of hemorrhagic cystitis did not correlate with the analyzed imaging parameters. Patient outcome was not influenced by this infectious complication. Conclusion: CT findings in patients with polyomavirus BK cystitis consist of different degrees of bladder wall thickening usually with good delineation of all mural layers and

  14. Computed Tomography Findings of Human Polyomavirus BK (BKV)-Associated Cystitis in Allogeneic Hematopoietic Stem Cell Transplant Recipients

    Energy Technology Data Exchange (ETDEWEB)

    Schulze, M.; Beck, R.; Igney, A.; Vogel, M.; Maksimovic, O.; Claussen, C.D.; Faul, C.; Horger, M. (Dept. of Diagnostic Radiology, Dept. of Internal Medicine-Oncology, and Inst. of Medical Virology, Eberhard-Karls Univ., Tbingen (Germany))

    2008-12-15

    Background: Over 70% of the general population worldwide is positive for antibodies against polyomavirus hominis type 1 (BKV). Polyomavirus can be reactivated in immunocompromised patients and thereby induce urogenital tract infection, including cystitis. Purpose: To describe the computed tomography (CT) findings of human polyomavirus-induced cystitis in adult patients after allogeneic hematopoietic stem cell transplantation (allogeneic HCT). Material and Methods: The study population was a retrospective cohort of 11 consecutive adult patients (eight men, three women; age range 22-59 years, mean 42.9 years) who received allogeneic HCT between December 2003 and December 2007 and were tested positive for urinary BKV infection. All CT scans were evaluated with regard to bladder wall thickness, mucosal enhancement, distinct layering of thickened bladder wall, and presence of intravesical clots, perivesical stranding as well as attenuation values of intravesical urine. Clinical data concerning transplant and conditioning regimen variables and laboratory parameters were correlated with degree and extent of imaging findings. Results: All patients had clinical signs of cystitis with different degrees of thickening of the urinary bladder wall. Well-delineated urinary bladder layers were present in six patients. Thickening of the urinary bladder wall was continuous in nine of 11 patients. Increased attenuation of intravesical urine was found in seven patients with hemorrhagic cystitis. Four patients had intraluminal clots. Perivesical stranding was not a major CT finding, occurring in a mild fashion in three of 11 patients. The clinical classification of hemorrhagic cystitis did not correlate with the analyzed imaging parameters. Patient outcome was not influenced by this infectious complication. Conclusion: CT findings in patients with polyomavirus BK cystitis consist of different degrees of bladder wall thickening usually with good delineation of all mural layers and

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2007-10-01

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

  17. Pregnancy after allogeneic hematopoietic stem cell transplantation in a Fanconi anemia patient

    Directory of Open Access Journals (Sweden)

    Atashkhoei S

    2017-01-01

    Full Text Available Simin Atashkhoei, Solmaz Fakhari, Eissa Bilehjani, Haleh Farzin Department of Anesthesiology, Al-Zahra Hospital, Tabriz University of Medical Sciences, Tabriz, Iran Abstract: Pregnancy in patients with Fanconi anemia (FA is rare. However, there are reports of successful pregnancy in Fanconi patients after bone marrow transplantation (BMT, hematopoietic stem cell transplantation. We describe the case of a term pregnant woman with FA who was treated with BMT 2 years earlier. She underwent successful delivery with cesarean section using spinal anesthesia without any complications. Keywords: Fanconi anemia, bone marrow transplantation, pregnancy, cesarean section, spinal anesthesia

  18. A Comparative Reference Study for the Validation of HLA-Matching Algorithms in the Search for Allogeneic Hematopoietic Stem Cell Donors and Cord Blood Units

    Science.gov (United States)

    2016-08-15

    HLA ISSN 2059-2302 A comparative reference study for the validation of HLA-matching algorithms in the search for allogeneic hematopoietic stem cell...stem cell transplantation; human leukocyte antigen; immunogenetics; matching algorithm ; patient–donor matching Correspondence Werner Bochtler Zentrales...leukocyte antigen (HLA)-matching algorithms is a prerequi- site for the correct and efficient identification of optimal unrelated donors for patients

  19. Late onset of autoimmune hemolytic anemia and pure red cell aplasia after allogeneic hematopoietic stem cell transplantation using in vivo alemtuzumab.

    Science.gov (United States)

    Kako, Shinichi; Kanda, Yoshinobu; Oshima, Kumi; Nishimoto, Nahoko; Sato, Hiroyuki; Watanabe, Takuro; Hosoya, Noriko; Motokura, Toru; Miyakoshi, Shigesaburo; Taniguchi, Shuichi; Kamijo, Aki; Takahashi, Koki; Chiba, Shigeru; Kurokawa, Mineo

    2008-03-01

    Hemolytic anemia and pure red cell aplasia (PRCA) after allogeneic hematopoietic stem cell transplantation (HSCT) have been reported to be mainly related to ABO-incompatibility between donor and recipient. Autoimmune hemolytic anemia (AIHA) without ABO-incompatibility has been also reported after allogeneic HSCT, especially with T-cell depletion. However, optimal management of AIHA or PRCA remains unclear. A 54-year-old male with myelodysplastic syndrome (MDS) underwent haploidentical human leukocyte antigen-mismatched HSCT using in vivo alemtuzumab and developed AIHA and PRCA simultaneously 15 months after transplantation, following the administration of cidofovir and probenecid for persistent cytomegalovirus (CMV) antigenemia and retinitis. AIHA was successfully treated with rituximab, and subsequently PRCA with cyclosporine without relapse of MDS or recurrence of CMV infection. The clinical course suggested that AIHA was mainly caused by humoral immune response, while PRCA was mainly caused by cell-mediated immune response in this patient, although these immune responses might be related to each other.

  20. Roseomonas bacteremia in a recipient of an allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Al-Anazi, K A; AlHashmi, H; Abdalhamid, B; AlSelwi, W; AlSayegh, M; Alzayed, A; Alshibani, Z; AlGarni, A; Al-Ghanem, A; Hassan, H; AlSagheir, A

    2013-08-01

    Roseomonas are pink-pigmented, oxidative, slowly growing, nonfermentative, gram-negative coccobacilli whose identification may require extensive biochemical testing and molecular profiling. Roseomonas infections vary in severity and clinical presentation, and they predominantly occur in immunocompromised and chronically ill patients. The organism is generally susceptible to carbapenems and aminoglycosides, but resistant to most of the cephalosporins and broad-spectrum penicillins. Reported here is a patient with lymphoblastic lymphoma who developed Roseomonas mucosa bacteremia after receiving her hematopoietic stem cell allograft. The bacteremic episode was successfully treated with imipenem and amikacin in addition to removal of the central venous catheter. To our knowledge, this is the first report of Roseomonas bacteremia in a stem cell transplantation recipient.

  1. Cardiac Relapse of Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation

    Science.gov (United States)

    Sánchez-Quintana, Ana; Quijada-Fumero, Alejandro; Laynez-Carnicero, Ana; Breña-Atienza, Joaquín; Poncela-Mireles, Francisco J.; Llanos-Gómez, Juan M.; Cabello-Rodríguez, Ana I.; Ramos-López, María

    2016-01-01

    Secondary or metastatic cardiac tumors are much more common than primary benign or malignant cardiac tumors. Any tumor can cause myocardial or pericardial metastasis, although isolated or combined tumor invasion of the pericardium is more common. Types of neoplasia with the highest rates of cardiac or pericardial involvement are melanoma, lung cancer, and breast and mediastinal carcinomas. Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. Initial treatment involves chemotherapy followed by consolidation treatment to reduce the risk of relapse. In high-risk patients, the treatment of choice for consolidation is hematopoietic stem cell transplantation (HSCT). Relapse of AML is the most common cause of HSCT failure. Extramedullary relapse is rare. The organs most frequently affected, called “sanctuaries,” are the testes, ovaries, and central nervous system. We present a case with extramedullary relapse in the form of a solid cardiac mass. PMID:27642531

  2. Allogeneic hematopoietic stem cell transplantation for inherited bone marrow failure syndromes.

    Science.gov (United States)

    Dalle, Jean-Hugues; Peffault de Latour, Régis

    2016-04-01

    Inherited bone marrow failure (IBMF) syndromes are a heterogeneous group of rare hematological disorders characterized by the impairment of hematopoiesis, which harbor specific clinical presentations and pathogenic mechanisms. Some of these syndromes may progress through clonal evolution, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Most prominent are failures of DNA repair such as Fanconi Anemia and much rarer failure of ribosomal apparatus, e.g., Diamond Blackfan Anemia or of telomere elongation such as dyskeratosis congenita. In these congenital disorders, hematopoietic stem cell transplantation (HSCT) is often a consideration. However, HSCT will not correct the underlying disease and possible co-existing extra-medullary (multi)-organ defects, but will improve BMF. Indications as well as transplantation characteristics are most of the time controversial in this setting because of the rarity of reported cases. The present paper proposes a short overview of current practices.

  3. A 54-Year-Old Woman with Donor Cell Origin of Multiple Myeloma after Allogeneic Hematopoietic Stem Cell Transplantation for the Treatment of CML

    Directory of Open Access Journals (Sweden)

    Erika Maestas

    2016-01-01

    Full Text Available Chronic myeloid leukemia is a myeloproliferative disorder that may be treated with hematopoietic stem cell transplantation (HSCT. While posttransplantation relapse of disease resulting from a failure to eradicate the patient’s original leukemia could occur, patients may also rarely develop a secondary malignancy or myelodysplastic syndrome (MDS of donor origin termed donor cell leukemia (DCL. Cases of donor-derived acute myeloid leukemia (AML or MDS after HSCT or solid tumor transplantation have been published. However, very few cases of donor-derived multiple myeloma (MM exist. We describe a patient who developed a donor-derived MM following allogeneic HSCT from a sibling donor.

  4. Challenges in Determining Genotypes for Pharmacogenetics in Allogeneic Hematopoietic Cell Transplant Recipients.

    Science.gov (United States)

    Langman, Loralie J; Nesher, Lior; Shah, Dimpy P; Azzi, Jacques M; Shpall, Elizabeth J; Rezvani, Katy; Black, John L; Chemaly, Roy F

    2016-09-01

    As part of a pharmacogenetic study, paired blood and oral fluid samples were tested for the IL28B polymorphism (rs12979860) before and after hematopoietic cell transplantation (HCT) to evaluate changes in the genotype and investigate the utility of genotyping in oral fluid in HCT recipients. In 54 patients with leukemia >18 years of age, samples were collected approximately 7 days before HCT and 60 days after HCT. IL28B polymorphism testing was performed using real-time PCR with allele-specific probes. Twenty-four patients had the same genotype as their donors. In 30 patients, the genotype was different from that of the donor. In the oral fluid samples, 4 retained the recipient's genotype, and 18 had a genotype that matched that of the donor. In the remaining 8 patients, the results could not be characterized and appeared to be a combination of both, suggesting mixed proportions of donor and recipient cells. The assumption was that the sloughed epithelial cells of the mouth are of recipient origin. However, oral fluid is a mixture that contains varying numbers of cells of the recipient and immunomodulatory cells from the donor. Therefore, the use of oral fluid after HCT for clinical pharmacogenetics purposes needs further investigation.

  5. Outcome of allogeneic hematopoietic stem cell transplantation for childhood acute lymphoblastic leukemia in second complete remission: a single institution study

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2012-01-01

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

  7. Chest computed tomography of late invasive aspergillosis after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Kojima, Rie; Tateishi, Ukihide; Kami, Masahiro; Murashige, Naoko; Nannya, Yasuhito; Kusumi, Eiji; Sakai, Miwa; Tanaka, Yuji; Kanda, Yoshinobu; Mori, Shin-Ichiro; Chiba, Shigeru; Kusumoto, Masahiko; Miyakoshi, Shigesaburo; Hirai, Hisamaru; Taniguchi, Shuichi; Sakamaki, Hisashi; Takaue, Yoichi

    2005-07-01

    Computed tomography (CT) is a powerful diagnostic tool for invasive aspergillosis (IA) after allogeneic stem cell transplantation (allo-SCT); however, little information is available concerning CT findings of late IA after allo-SCT. To characterize CT findings of late IA, we retrospectively examined medical records and high-resolution CT findings of 27 allo-SCT recipients with late IA. Either acute or chronic GVHD was diagnosed in 24 patients. All 27 patients were given corticosteroids at IA diagnosis. High-resolution CT findings included halo (n=12), centrilobular nodules (n=12), ill-defined consolidation (n=13), ground-glass attenuation (n=8), pleural effusion (n=7), pleural-based consolidation (n=4), and cavitation (n=4). CT findings showing centrilobular nodules and either halo or cavitation were classified into bronchopneumonia type and angioinvasive type, respectively. Angioinvasive-type, bronchopneumonia-type, and combination-type IA were diagnosed in 11, 8, and 4 patients, respectively. CT findings were nonspecific in the other 4 patients. One bronchopneumonia-type case and 2 angioinvasive-type IA cases were subsequently diagnosed as combination type. Although there were no significant differences in patient characteristics between the 2 types of IA, bronchopneumonia-type IA had a poorer prognosis than angioinvasive IA ( P=.022). Halo is a useful diagnostic marker in late IA as well as early IA, and late IA frequently manifests as bronchopneumonia.

  8. [Cold autoimmune hemolytic anemia complicated with relapsed myelodysplastic syndrome after allogeneic hematopoietic cell transplantation].

    Science.gov (United States)

    Okamura, Hiroshi; Nakane, Takahiko; Fujino, Keizo; Koh, Shiro; Yoshimura, Takuro; Nishimoto, Mitsutaka; Hayashi, Yoshiki; Koh, Hideo; Nakao, Yoshitaka; Nakamae, Hirohisa; Hino, Masayuki

    2015-04-01

    Myelodysplastic syndrome (MDS) is known to often be complicated by a range of autoimmune diseases. We herein present a case with MDS complicated by cold autoimmune hemolytic anemia (cold AIHA). The patient was a 51-year-old woman. She was diagnosed with MDS (refractory cytopenia with multilineage dysplasia) in May 2009. In January 2010, she underwent unrelated allogeneic bone marrow transplantation but was re-admitted in October 2010 for treatment of relapsed MDS. Despite daily transfusions of red blood cells, her anemia failed to improve. Her laboratory examinations showed a low haptoglobin level and elevation of indirect bilirubin and LDH. The direct Coombs test was positive at a low and at room temperature and cold agglutinin was negative. After confirming the diagnosis of cold AIHA, all transfusion fluids were warmed but her anemia still failed to improve. In addition to the warmed transfusion fluids, we administered corticosteroids, immunosuppressive agents and high-dose intravenous immunoglobulin infusions. This management strategy ameliorated the patient's hemolytic anemia. To our knowledge, MDS cases complicated by cold AIHA are rare. Our patient thus provides a valuable contribution to medical knowledge.

  9. 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.

  10. Improving Safety of Preemptive Therapy with Oral Valganciclovir for Cytomegalovirus Infection after Allogeneic Hematopoietic Stem Cell Transplantation

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    Corinna Barkam

    2012-01-01

    Full Text Available Valganciclovir (VGC, an oral prodrug of ganciclovir (GCV, has been shown to clear cytomegalovirus (CMV viremia in preemptive treatment of patients after allogeneic hematopoietic stem cell transplantation (alloHSCT, apparently without significant toxicity. Since VGC obviates hospitalization, it is increasingly being adopted, although not approved, in alloHSCT. When we retrospectively evaluated preemptive treatment with VGC versus GCV, foscarnet or cidofovir, in all 312 consecutive CMV viremias of 169 patients allotransplanted at our institution between 1996 and 2006, we found VGC more efficacious (79% than non-VGC therapies (69%. The advantage of outpatient VGC, however, was outbalanced by more profound neutropenias (including two cases of agranulocytosis, one with graft loss requiring subsequent prolonged rehospitalization. Thus, in a second, prospective cohort from 2007 to 2011 (all 202 consecutive CMV viremias of 118 yet older and sicker patients, we implemented twice weekly neutrophil monitoring during outpatient VGC treatment and avoided VGC maintenance therapy. While conserving efficacy (VGC 71%, non-VGC 72%, we could now demonstrate a reduced mean duration of hospitalization with VGC (9 days (0–66 compared to non-VGC (25 days (0–115, without any agranulocytosis episodes. We conclude that safe outpatient VGC therapy is possible in alloHSCT recipients, but requires frequent monitoring to prevent severe myelotoxicity.

  11. A randomized control trial of a psychosocial intervention for caregivers of allogeneic hematopoietic stem cell transplant patients: Effects on distress

    Science.gov (United States)

    Laudenslager, Mark L.; Simoneau, Teri L.; Kilbourn, Kristin; Natvig, Crystal; Philips, Sam; Spradley, Janet; Benitez, Patrick; McSweeney, Peter; Mikulich-Gilbertson, Susan K.

    2015-01-01

    Caregivers of patients receiving allogeneic hematopoietic stem cell transplants (Allo-HSCT) serve a pivotal role in patient care but experience high stress, anxiety, and depression as a result. We theorized that a stress management adapted for Allo-HSCT caregivers would reduce distress compared to treatment as usual (TAU). From 267 consecutive caregivers of Allo-HSCT patients approached, 148 (mean=53.5 years, 75.7% female) were randomized to either psychosocial intervention (n=74) or TAU (n=74). Eight 1-on-1 stress management sessions delivered across the 100 day post-transplant period focused on understanding stress, changing role(s) as caregiver, cognitive behavioral stress management, pacing respiration, and identifying social support. Primary outcomes included perceived stress (psychological) and salivary cortisol awakening response (CAR) (physiological). Randomized groups were not statistically different at baseline. Mixed models analysis of covariance (intent-to-treat) showed that intervention was associated with significantly lower caregiver stress 3 months post-transplant (Mean=20.0, CI95=17.9-22.0) compared to TAU (Mean=23.0, CI95=21.0-25.0) with an effect size (ES) of 0.39 (p=0.039). Secondary psychological outcomes, including depression and anxiety, were significantly reduced with ESs of 0.46 and 0.66 respectively. Caregiver CAR did not differ from non-caregiving controls at baseline and was unchanged by intervention. Despite significant caregiving burden, this psychosocial intervention significantly mitigated distress in Allo-HSCT caregivers. PMID:25961767

  12. β-D-Glucan Screening for Detection of Invasive Fungal Disease in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Koltze, Antonia; Rath, Peter; Schöning, Stefan; Steinmann, Jörg; Wichelhaus, Thomas A; Bader, Peter; Bochennek, Konrad; Lehrnbecher, Thomas

    2015-08-01

    While the assessment of β-D-glucan (BDG) levels in adults improves the early diagnosis of invasive fungal disease (IFD), data on BDG levels in children are limited. We therefore assessed in a prospective cohort study the value of serial BDG screening for early detection of IFD in children undergoing allogeneic hematopoietic stem cell transplantation (HSCT). IFD was defined according to the revised European Organization for Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSG) criteria, with the necessary modification that BDG was not included as a microbiological criterion. For the analysis, a total of 702 serum samples were obtained in 34 pediatric HSCT recipients. Proven IFD occurred in two patients (fusariosis and Candida sepsis, respectively), and probable invasive aspergillosis was diagnosed in four patients. Analyses including different cutoff values for BDG levels and different definitions of the onset of IFD demonstrated that the BDG assay has a relatively high sensitivity and good negative predictive value, whereas the positive predictive value has major limitations (screening in pediatric HSCT recipients has a low positive predictive value and is therefore of limited usefulness.

  13. The clinical impact of cytomegalovirus infection following allogeneic hematopoietic cell transplantation: Why the quest for meaningful prophylaxis still matters.

    Science.gov (United States)

    Chan, Shawna T; Logan, Aaron C

    2017-02-02

    Latent infection with human cytomegalovirus (CMV) is common. Functional immunity effectively contains such latent infections; however, CMV reactivation may cause significant complications in patients undergoing allogeneic hematopoietic cell transplantation (alloHCT). In spite of the universal implementation of post-transplant screening for CMV viremia and the institution of pre-emptive antiviral management, CMV disease still occurs in a small portion of patients. Moreover, interactions between CMV and the immune system have significant implications for the incidence of graft-versus-host disease, the recurrence of malignancy, and non-relapse mortality following alloHCT, even in the era of pre-emptive antiviral management. CMV serostatus thus remains an important consideration for patients undergoing alloHCT. We review the clinical impact of CMV in the setting of alloHCT, interactions between CMV serostatus, viral reactivation, and transplant outcomes, as well as current and evolving strategies for prevention and treatment of CMV-related complications that may have significant impact for alloHCT recipients.

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

    Science.gov (United States)

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

    2010-06-01

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

  15. Posaconazole plasma concentration in pediatric patients receiving antifungal prophylaxis after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Heinz, Werner J; Cabanillas Stanchi, Karin M; Klinker, Hartwig; Blume, Olivia; Feucht, Judith; Hartmann, Ulrike; Feuchtinger, Tobias; Lang, Peter; Handgretinger, Rupert; Döring, Michaela

    2016-02-01

    Posaconazole has been proven to be effective for antifungal prophylaxis in adults after hematopoietic stem cell transplantation (HSCT). Due to low gastrointestinal resorption of posaconazole suspension, bioavailability is impaired. Fatty food improves the uptake of posaconazole, but insufficient data on the pharmacokinetics of posaconazole in pediatric patients are available so far. The single-center analysis investigated 161 posaconazole serum concentrations in 27 pediatric patients after HSCT receiving 12 mg·kg BW(-1)·d(-1) posaconazole suspension depending on age, gender, and intestinal graft-versus-host (iGvHD) disease, and the influence of posaconazole on cyclosporine A plasma concentrations. To improve the uptake of posaconazole, one patient cohort received higher fat nutrition with the drug administration. A comparison of the regular nutrition and higher-fat nutrition groups revealed the following values: 31 (27.4%) versus 8 (16.7%) 2000 ng/ml. The mean posaconazole concentrations in patients with regular nutrition was 1123 ± 811 ng/ml and with higher-fat nutrition was 1191 ± 673 ng/ml. Posaconazole levels in patients with iGvHD were significantly lower (P = 0.0003) than in patients without GvHD. The majority of samples showed a sufficient posaconazole concentration above 700 ng/ml. Posaconazole levels were slightly higher in patients with higher-fat nutrition and significantly lower in patients with iGvHD. Cyclosporine A levels were not significantly higher during posaconazole administration.

  16. Young woman with mild bone marrow dysplasia, GATA2 and ASXL1 mutation treated with allogeneic hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Anna Lübking

    2015-01-01

    We describe a case of symptomatic DCML deficiency and rather discrete bone marrow findings due to GATA2 mutation. Exome sequencing revealed a somatic ASXL1 mutation and the patient underwent allogeneic stem cell transplantation successfully.

  17. A case of systemic mastocytosis associated with acute myeloid leukemia terminating as aleukemic mast cell leukemia after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Bae, Mi Hyun; Kim, Hyun-Ki; Park, Chan-Jeoung; Seo, Eul-Ju; Park, Sang Hyuk; Cho, Young-Uk; Jang, Seongsoo; Chi, Hyun-Sook; Lee, Kyu-Hyung

    2013-03-01

    In up to 40% of systemic mastocytosis (SM) cases, an associated clonal hematological non-mast cell lineage disease such as AML is diagnosed before, simultaneously with, or after the diagnosis of SM. A 40-yr-old man was diagnosed with AML with t(8;21)(q22;q22). Mast cells were not noted at diagnosis, but appeared as immature forms at relapse. After allogeneic hematopoietic stem cell transplantation (HSCT), leukemic myeloblasts were not observed; however, neoplastic metachromatic blasts strikingly proliferated during the state of bone marrow aplasia, and finally, aleukemic mast cell leukemia developed. As the disease progressed, we observed serial morphologic changes from immature mast cells with myeloblasts to only metachromatic blasts and atypical mast cells as mast cell leukemia; FISH analysis showed that the neoplastic mast cells originated from the same clone as the leukemic myeloblasts of AML.

  18. Extramedullary Relapse Following Total Marrow and Lymphoid Irradiation in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation

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    Kim, Ji Hyun [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Stein, Anthony [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Tsai, Nicole [Department of Biostatistics, City of Hope National Medical Center, Duarte, California (United States); Schultheiss, Timothy E. [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Palmer, Joycelynne [Department of Biostatistics, City of Hope National Medical Center, Duarte, California (United States); Liu, An [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Rosenthal, Joseph [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Department of Pediatrics, City of Hope National Medical Center, Duarte, California (United States); Forman, Stephen J. [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Wong, Jeffrey Y.C., E-mail: jwong@coh.org [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States)

    2014-05-01

    Purpose: Approximately 5% to 20% of patients who undergo total body irradiation (TBI) in preparation for hematopoietic cell transplantation (HCT) can develop extramedullary (EM) relapse. Whereas total marrow and lymphoid irradiation (TMLI) provides a more conformally targeted radiation therapy for patients, organ sparing has the potential to place the patient at a higher risk for EM relapse than TBI. This study evaluated EM relapse in patients treated with TMLI at our institution. Methods and Materials: Patients eligible for analysis had been enrolled in 1 of 3 prospective TMLI trials between 2006 and 2012. The TMLI targeted bones, major lymph node chains, liver, spleen, testes, and brain, using image-guided tomotherapy with total dose ranging from 12 to 15 Gy. Results: A total of 101 patients with a median age of 47 years were studied. The median follow-up was 12.8 months. Incidence of EM relapse and bone marrow (BM) relapse were 12.9% and 25.7%, respectively. Of the 13 patients who had EM relapse, 4 also had BM relapse, and 7 had EM disease prior to HCT. There were a total of 19 EM relapse sites as the site of initial recurrence: 11 soft tissue, 6 lymph node, 2 skin. Nine of these sites were within the target region and received ≥12 Gy. Ten initial EM relapse sites were outside of the target region: 5 sites received 10.1 to 11.4 Gy while 5 sites received <10 Gy. Pretransplantation EM was the only significant predictor of subsequent EM relapse. The cumulative incidence of EM relapse was 4% at 1 year and 11.4% at 2 years. Conclusions: EM relapse incidence was as frequent in regions receiving ≥10 Gy as those receiving <10 Gy. EM relapse rates following TMLI that included HCT regimens were comparable to published results with regimens including TBI and suggest that TMLI is not associated with an increased EM relapse risk.

  19. HLA-C incompatibilities in allogeneic unrelated hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

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

    2011-01-15

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

  1. Cidofovir in the Treatment of BK Virus-Associated Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Philippe, Michael; Ranchon, Florence; Gilis, Lila; Schwiertz, Vérane; Vantard, Nicolas; Ader, Florence; Labussiere-Wallet, Hélène; Thomas, Xavier; Nicolini, Franck-Emmanuel; Wattel, Eric; Ducastelle-Leprêtre, Sophie; Barraco, Fiorenza; Lebras, Laure; Salles, Gilles; Michallet, Mauricette; Rioufol, Catherine

    2016-04-01

    After allogeneic hematopoietic stem cell transplantation (HSCT), BK virus-associated hemorrhagic cystitis (BKV-HC) is a common complication. Although supportive measures have been the standard of care for many years, several studies suggested the efficacy of cidofovir. The aim of this study was to assess the safety profile and efficacy of cidofovir. A retrospective study was conducted on all patients treated with cidofovir in our HSCT unit between March 2011 and May 2013. Data for efficacy (partial [PR] or complete response [CR]), prescription (dose, frequency, number of doses, and administration route), and toxicity were collected from published reports and medical files. Renal toxicity was evaluated using creatinine clearance calculated with the Cockcroft and Gault formula. A parallel literature search using PubMed (last search, May 2015) was performed. From March 2011 to June 2013, 27 of 181 patients undergoing allogeneic HSCT in our department received cidofovir for BKV-HC: 24 (88.9%) intravenously, 1 intravesically, and 2 via both routes. Mean dose was 5 mg/kg per administration, for a median of 4 injections (range, 1 to 11), from twice a week to once every 2 weeks. CR was achieved in 22 patients (81.5%), PR in 2, and no response in 2 patients. Eight patients presented renal failure (29.6%): 6 moderate (creatinine clearance cidofovir was 27% (35 mL/min; range, 2 to 159). In 3 cases renal insufficiency and hematologic toxicity led to discontinuation of treatment or switch to intravesical instillation. For 3 patients cidofovir dose was reduced because of nephrotoxicity. Thirteen studies have reported on the use of cidofovir for BKV-HC (204 patients) since 2005. Intravenous cidofovir was used for 91.3% of patients, with doses ranging from .5 to 5 mg/kg. The main toxicity reported was renal failure (9% to 50% in 9 studies). Between 60% and 100% of CRs were observed independently of cidofovir dose or administration route. Cidofovir is an effective therapy for

  2. Numerical impairment of nestin(+) bone marrow niches in acute GvHD after allogeneic hematopoietic stem cell transplantation for AML.

    Science.gov (United States)

    Medinger, M; Krenger, W; Jakab, A; Halter, J; Buser, A; Bucher, C; Passweg, J; Tzankov, A

    2015-11-01

    The nestin(+) perivascular bone marrow (BM) stem cell niche (N(+)SCN) may be involved in GvHD. To investigate whether acute GvHD (aGvHD) reduces the number of N(+)SCN, we examined patients with AML who had undergone allogeneic hematopoietic stem cell transplantation. In the test cohort (n=8), the number of N(+)SCN per mm(2) in BM biopsies was significantly reduced in aGvHD patients at the time of aGvHD compared with patients who did not have aGvHD (1.2±0.78 versus 2.6±0.93, P=0.04). In the validation cohort (n=40), the number of N(+)SCN was reduced (1.9±0.99 versus 2.6±0.90 N(+)SCN/mm(2), P=0.05) in aGvHD patients. Receiver operating curves suggested that the cutoff score that best discriminated between patients with and without aGvHD was 2.29 N(+)SCN/mm(2). Applying this cutoff score, 9/11 patients with clinically relevant aGvHD (⩾grade 2) and 13/20 with any type of GvHD had decreased N(+)SCN numbers compared with only 10/29 patients without clinically relevant aGvHD (P=0.007) and 6/20 patients without any type of GvHD (P=0.028). In patients tracked over time, N(+)SCN density returned to normal after aGvHD resolved or remained stable in patients who did not have aGvHD. Our results show a decrease in the number of N(+)SCN in aGvHD.

  3. IL-18 single nucleotide polymorphisms in hematologic malignancies with HLA matched sibling donor allogeneic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    蔡小矜

    2014-01-01

    Objective To explore the impact of interleukin-18(IL-18)single nucleotide polymorphisms on outcomes of hematologic malignancies with HLA-matched sibling donor hematopoietic stem cell transplantation(allo-HSCT).Methods Single-nucleotide polymorphisms in IL-18 promoter was detected by PCR-sequence-specific primer analysis(PCR-SSP)in 93 recipients and their HLA matched sibling donors.Hematopoietic reconstitution,

  4. Long-term ultra-low-dose acyclovir against varicella-zoster virus reactivation after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Asano-Mori, Yuki; Kanda, Yoshinobu; Oshima, Kumi; Kako, Shinichi; Shinohara, Akihito; Nakasone, Hideki; Sato, Hiroyuki; Watanabe, Takuro; Hosoya, Noriko; Izutsu, Koji; Asai, Takashi; Hangaishi, Akira; Motokura, Toru; Chiba, Shigeru; Kurokawa, Mineo

    2008-06-01

    To evaluate the efficacy of long-term prophylaxis with ultra-low-dose acyclovir against varicella-zoster virus (VZV) reactivation, we analyzed the records of 242 Japanese adult patients who underwent allogeneic hematopoietic stem cell transplantation for the first time from 1995 to 2006 at our hospital. We started long-term oral acyclovir at 200 mg/day in July 2001. Acyclovir was continued until the end of immunosuppressive therapy and at least 1 year after transplantation. Sixty-six patients developed VZV reactivation at a median of 248 days after HSCT, with a cumulative incidence of 34.7%. Only one breakthrough reactivation occurred during long-term acyclovir, which responded well to therapeutic dose of valacyclovir. The use of long-term acyclovir was the only independent determinant that significantly decreased the overall incidence of VZV reactivation (20% vs. 50%, P < 0.0001). With this prophylaxis, visceral dissemination and serious complications other than post-herpetic neuralgia was completely eliminated, and thereby need for hospitalization was significantly reduced (21% vs. 71%, P = 0.0034). Fifteen of the 57 patients who discontinued acyclovir developed VZV reactivation, with a cumulative incidence of 32.1%. VZV reactivation following discontinuation tended to occur in patients who were receiving immunosuppressive therapy at the cessation of acyclovir. These findings suggested that long-term prophylaxis of ultra-low-dose acyclovir resulted in a successful prevention of severe VZV-related symptoms and death, with a significantly decreased overall incidence of VZV reactivation. Prolongation of prophylactic acyclovir on profound immunosuppression might be important for thorough suppression of VZV reactivation.

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

    Directory of Open Access Journals (Sweden)

    Nadjanara Dorna Bueno

    2011-06-01

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

  6. Epstein-Barr Virus Lymphoproliferative Disease Following Allogeneic Hematopoietic Stem Cell Transplantation: Prediction and Early Intervention

    NARCIS (Netherlands)

    J.W.J. van Esser (Joost)

    2003-01-01

    textabstractEpstein-Barr virus (EBV) has been associated with a variety of both infectious and malignant human diseases. These viruses are characterized by (B-cell) lymphotropism, their ability to establish latent infection in host cells and to induce proliferation of these latently infected cells.

  7. Acinetobacter baumannii Septicemia in a Recipient of an Allogeneic Hematopoietic Stem Cell Transplantation

    Science.gov (United States)

    Al-Anazi, Khalid Ahmed; Abdalhamid, Baha; Alshibani, Zeyad; Awad, Khalid; Alzayed, Abdullah; Hassan, Hoda; Alsayiegh, Mohammed

    2012-01-01

    Acinetobacter baumannii is a gram-negative, nonfermentative coccobacillus that causes infections in immunocompromised and chronically ill patients and is associated with multidrug resistance. Two days before receiving her nonmyeloablative stem cell allograft, a patient with acute myeloid leukemia developed Acinetobacter baumannii bacteremia that caused septic shock which was successfully treated with imipenem and removal of the central venous catheter. To our knowledge, this is the first report of Acinetobacter baumannii septicemia in a hematopietic stem cell transplantation recipient. PMID:23259136

  8. Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies

    Science.gov (United States)

    2016-08-15

    SCID; Omenn's Syndrome; Reticular Dysgenesis; Wiskott-Aldrich Syndrome; Bare Lymphocyte Syndrome; Common Variable Immunodeficiency; Chronic Granulomatous Disease; CD40 Ligand Deficiency; Hyper IgM Syndrome; X-linked Lymphoproliferative Disease; Hemophagocytic Lymphohistiocytosis; Griscelli Syndrome; Chediak-Higashi Syndrome; Langerhan's Cell Histiocytosis

  9. 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.

  10. Neurological complications after allogeneic hematopoietic stem cell transplantation in children, a single center experience.

    Science.gov (United States)

    Azik, Fatih; Yazal Erdem, Arzu; Tavil, Betül; Bayram, Cengiz; Tunç, Bahattin; Uçkan, Duygu

    2014-06-01

    In this study, we retrospectively examined the data of children who underwent allo-HSCT from HLA-matched family donors. We analyzed the incidence, etiological factors, clinical characteristics, possible reasons, risk factors, and follow-up of neurologic complications. BU-based conditioning regimens were used in most of the cases (n = 62). The median duration of follow-up for the 89 patients was 20 months (range 1-41 months). Eleven percent of transplanted children developed one or more neurological symptoms after HSCT with a median observation time of two months (range -6 days to 18 months). The median age of the four girls and six boys with neurological complication was 13 yr (range 5.3-17.6 yr). Cylosporine A neurotoxicity was diagnosed in five children, four of them were PRES. The rest of complications were BU and lorazepam toxicity, an intracranial hemorrhage, a sinovenous thrombosis, and a transient ischemic attack during extracorpereal photopheresis. No difference was found between groups of neurological complication according to age, gender, diagnosis, hospitalization time, neutrophil and platelet engraftment time, stem cell source, and conditioning regimen, acute and chronic GVHD or VOD. Neurological complication was the cause of death in one patient (1.1%).

  11. Polymorphism in the interleukin-7 receptor-alpha and outcome after allogeneic hematopoietic cell transplantation with matched unrelated donor

    DEFF Research Database (Denmark)

    Shamim, Z; Spellman, S; Haagenson, M;

    2013-01-01

    and increased treatment-related mortality (TRM) (rs1494555G) and acute graft versus host disease (aGvHD) (rs1494555G and rs1494558T) after hematopoietic cell transplantation (HCT). Some studies have confirmed an association between rs6897932C and multiple sclerosis. In this study, we evaluated the prognostic...

  12. Transmission of an expanding donor-derived del(20q) clone through allogeneic hematopoietic stem cell transplantation without the development of a hematologic neoplasm.

    Science.gov (United States)

    Aikawa, Vania; Porter, David; Luskin, Marlise R; Bagg, Adam; Morrissette, Jennifer J D

    2015-12-01

    Donor cell leukemia is a rare complication of allogeneic hematopoietic stem cell transplantation (HSCT), which may result from the development of a new malignancy in previously healthy donor cells after transplant into the recipient, or it may derive from the transmission of an occult leukemia from donor to recipient. We report a case of donor derived 20q11.2 deletion in a male patient who received an allogeneic HSCT from his HLA-identical sister for the treatment of his chronic lymphocytic leukemia. Bone marrow cells from the donor were found to contain the 20q deletion that expanded over time, but which was absent in her peripheral blood cells. Although cases of donor cell leukemia after HSCT have been reported, in this case there has been no evidence of an associated hematologic neoplasm in either the donor or recipient. Pre-transplant donor bone marrow evaluations are not practical or warranted, however the finding of new cytogenetic abnormalities after transplant mandates a thorough evaluation of the donor.

  13. Allogeneic hematopoietic stem cell transplantation in patients with diffuse large B cell lymphoma relapsed after autologous stem cell transplantation: a GITMO study.

    Science.gov (United States)

    Rigacci, Luigi; Puccini, Bendetta; Dodero, Anna; Iacopino, Pasquale; Castagna, Luca; Bramanti, Stefania; Ciceri, Fabio; Fanin, Renato; Rambaldi, Alessandro; Falda, Michele; Milone, Giuseppe; Guidi, Stefano; Martelli, Massimo Fabrizio; Mazza, Patrizio; Oneto, Rosi; Bosi, Alberto

    2012-06-01

    Patients who relapse after an autologous hematopoietic stem cell transplantation (SCT) have a very poor prognosis. We have retrospectively analyzed diffuse large B cell lymphoma patients who underwent an allo-SCT after an auto-SCT relapse reported in the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) database. From 1995 to 2008, 3449 autologous transplants were reported in the GITMO database. Eight hundred eighty-four patients relapsed or progressed after transplant; 165 patients, 19% of the relapsed patients, were treated with allo-transplant. The stem cell donor was related to the patient in 108 cases. A reduced intensity conditioning regimen was used in 116. After allo-SCT, 72 patients (43%) obtained a complete response and 9 obtained a partial response with an overall response rate of 49%; 84 patients (51%) experienced rapid progression of disease. Ninety-one patients died, 45 due to disease and 46 due to treatment-related mortality. Acute graft-versus-host disease was recorded in 57 patients and a chronic GvHD in 38 patients. With a median follow-up of 24 months (2-144) after allo, overall survival (OS) was 39%, and after a median of 21 months (2-138) after allo, progression-free survival (PFS) was 32%. Multivariate analysis indicated that the only factors affecting OS were status at allo-SCT, and those affecting PFS were status at allo-SCT and stem cell donor. This retrospective analysis shows that about one-fifth of patients with diffuse large B cell lymphoma who experience relapse after autologous transplantation may be treated with allogeneic transplantation. Moreover, the only parameter affecting either OS or PFS was the response status at the time of allo-SCT.

  14. Osteonecrosis in children after allogeneic hematopoietic cell transplantation: study of prevalence, risk factors and longitudinal changes using MR imaging.

    Science.gov (United States)

    Sharma, S; Leung, W-H; Deqing, P; Yang, J; Rochester, R; Britton, L; Neel, M D; Ness, K K; Kaste, S C

    2012-08-01

    Osteonecrosis after hematopoietic SCT (HCT) has seldom been addressed in pediatric populations. At our institution, since January 2002, children undergoing allogeneic HCT (alloHCT) receive yearly follow-up magnetic resonance imaging (MR) of hips and knees. To estimate the prevalence, longitudinal changes and associated risk factors for osteonecrosis after alloHCT, we reviewed MRs for children who underwent single alloHCT during the study period. We analyzed 149 of 344 patients who had post-HCT MR imaging performed (84 males; median age 11 years (range, 0.5-21 years)), median follow-up time was 32.6 months (range, 2.8-97.2 months). In all, 44 (29.5%) developed osteonecrosis of hips and/or knees; of those, 20 (45%) had at least 30% epiphyseal involvement. In 23 (52%), osteonecrosis lesions were identified in the first and in 43 (98%) by the third yearly scan. Knees were more frequently involved than hips; severity of osteonecrosis was greater in hips. Those who had pre-alloHCT osteonecrosis, two patients' hips and six patients' knees resolved completely; three patients' osteonecrosis lesions regressed after alloHCT. On risk factor analysis, age at time of alloHCT (P=0.051) and osteonecrosis identified by MRs before alloHCT (P=0.001) were the primary risk factors. This analysis shows that preventive strategies for osteonecrosis in this population should focus on measures to minimize risk factors before alloHCT.

  15. Successful clearance of cutaneous acyclovir-resistant, foscarnet-refractory herpes virus lesions with topical cidofovir in an allogeneic hematopoietic stem cell transplant patient.

    Science.gov (United States)

    Muluneh, B; Dean, A; Armistead, P; Khan, T

    2013-06-01

    Cidofovir is a deoxycytidine monophosphate analog with broad spectrum activity against various deoxyribonucleic acid viruses. Cidofovir is marketed as an injectable for intravenous use; however, there is a topical cidofovir formulation utilized for viral dermatologic infections. Here, we present a case of a successful clearance of a perianal acyclovir resistant and foscarnet refractory herpes simplex virus (HSV1) ulcer in a 34 year-old woman who had undergone allogeneic hematopoietic stem cell transplantation. After 1 week of therapy with cidofovir gel, the patient's ulcer was clinically improved, and the lesion was negative for herpes simplex virus transcripts by real-time polymerase chain reaction testing. The wound remained herpes simplex virus negative by real-time polymerase chain reaction on repeat testing 1 week later. Based on this and other reports in HIV/AIDS patients, we believe that cidofovir gel has utility in the management of cutaneous, acyclovir-resistant HSV infections.

  16. EFFECTS OF INTERLEUKIN-4 ON GRANULOCYTE-MACROPHAGE-COLONY FORMATION FROM MURINE BONE MARROW CELLS AND HEMATOPOIETIC RECONSTITUTION FOLLOWING MURINE ALLOGENEIC BONE MARROW TRANSPLANTATION

    Institute of Scientific and Technical Information of China (English)

    朱康儿; KerryAtkinson

    1994-01-01

    We investigated the effects of mouse recombinant IL-4 on hematopoiesis in vitro and in vivo.IL-4 alone was found to be incapable of stimulating colony formation,but it inhibited both IL-3-and GM-CSF-induced colony for-mation by murine hematopoietic progenitor cells.In contrast,colony formation induced by G-CSF was enhanced in the presence of IL-4.We also studied the influence of IL-4 on hematopoietie reconstiution after allogeneic bone marrow transplantation in a murine model,and found that IL-4 and G-CSF was significantly suppressed by IL-4.The combination of IL-4 and GM-CSF caused a significant decrease in the absolute mumber of meutrophils.

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

    Science.gov (United States)

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

    2014-09-01

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

  18. Pharmacokinetic targeting of intravenous busulfan reduces conditioning regimen related toxicity following allogeneic hematopoietic cell transplantation for acute myelogenous leukemia

    Directory of Open Access Journals (Sweden)

    Nishihori Taiga

    2010-10-01

    Full Text Available Abstract Optimal conditioning therapy for hematopoietic cell transplantation (HCT in acute myelogenous leukemia (AML remains undefined. We retrospectively compared outcomes of a consecutive series of 51 AML patients treated with oral busulfan (1 mg/kg every 6 hours for 4 days and cyclophosphamide (60 mg/kg IV × 2 days - (Bu/Cy with 100 consecutive AML patients treated with pharmacokinetic targeted IV busulfan (AUC

  19. ACTIVATION OF T. GONDII INFECTION AFTER ALLOGENEIC TRANSPLANTATION OF HEMATOPOIETIC STEM CELLS: DEPENDENCE ON TIME OF TRANSPLANTATION AND SEROLOGICAL STATUS OF THE PATIENTS

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2009-09-01

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

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

    Science.gov (United States)

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

    2017-03-01

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

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

    Science.gov (United States)

    Dvorak, Christopher C; Horn, Biljana N; Puck, Jennifer M; Czechowicz, Agnieszka; Shizuru, Judy A; Ko, Rose M; Cowan, Morton J

    2014-09-01

    For infants with SCID, the ideal conditioning regimen before allogeneic HCT would omit cytotoxic chemotherapy to minimize short- and long-term complications. We performed a prospective pilot trial with G-CSF plus plerixafor given to the host to mobilize HSC from their niches. We enrolled six patients who received CD34-selected haploidentical cells and one who received T-replete matched unrelated BM. All patients receiving G-CSF and plerixafor had generally poor CD34(+) cell and Lin(-) CD34(+) CD38(-) CD90(+) CD45RA(-) HSC mobilization, and developed donor T cells, but no donor myeloid or B-cell engraftment. Although well tolerated, G-CSF plus plerixafor alone failed to overcome physical barriers to donor engraftment.

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

    Science.gov (United States)

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

    2016-09-20

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

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

    Science.gov (United States)

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

    2016-07-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  6. Effect of c-mpl ligands after total body irradiation (TBI) with and without allogeneic hematopoietic stem cell transplantation: low-dose TBI does not prevent sensitization.

    Science.gov (United States)

    Nash, Richard A; Takatu, Alessandra; Feng, Ziding; Slichter, Sherrill; Abrams, Kraig; Espino, German; Gass, M John; Georges, George E; McSweeney, Peter A; Shulman, Howard M; Storb, Rainer

    2002-01-01

    This study investigates the potential role of the recombinant c-mpl ligands (recombinant human thrombopoietin [rhTPO] and pegylated recombinant human megakaryocyte growth and development factor [PEG-rhMGDF]) on the recovery of platelet counts after TBI with and without allogeneic hematopoietic stem cell transplantation (HSCT) in an established canine model. Initially, 3 cohorts, each with 2 nonirradiated dogs, received increasing doses of rhTPO (5 microg/kg per day; 10 microg/kg per day; 20 microg/kg per day) for 7 days to determine the optimal dose. The dose of 10 microg/kg per day of rhTPO was selected for subsequent studies. Ten dogs then received either rhTPO or placebo for 28 days after 200 cGy TBI without HSCT. The rhTPO group had fewer days with platelet counts RhTPO-specific antibodies developed in 2 dogs, which caused a significant but transient decrease of the platelet counts. Retreatment of these sensitized dogs with rhTPO resulted in profound transient decreases in platelet counts. In the next study, 20 dogs received either PEG-rhMGDF or placebo for 21 days after 920 cGy TBI and allogeneic HSCT. The median time to platelet recovery (>20,000/microL) for the PEG-rhMGDF group (n = 10) was 14.0 days compared to 15.5 days for the control group (n = 10; log rank, P = .35). There were no significant differences in the total time to platelet counts 500/microL. The effects of rhTPO on recovery of platelet and granulocyte counts after sublethal TBI were modest, and no effects of PEG-rhMGDF were observed on hematopoietic recovery after high-dose TBI and allogeneic HSCT. The significant effect that rhTPO-specific antibodies had on the platelet counts may limit the clinical role of recombinant c-mpl ligands unless sensitization can be prevented.

  7. Impact of Pretransplantation 18F-fluorodeoxy Glucose—Positron Emission Tomography Status on Outcomes after Allogeneic Hematopoietic Cell Transplantation for Non-Hodgkin Lymphoma

    Science.gov (United States)

    Bachanova, Veronika; Burns, Linda J.; Ahn, Kwang Woo; Laport, Ginna G.; Akpek, Görgün; Kharfan-Dabaja, Mohamed A.; Nishihori, Taiga; Agura, Edward; Armand, Philippe; Jaglowski, Samantha M.; Cairo, Mitchell S.; Cashen, Amanda F.; Cohen, Jonathon B.; D'Souza, Anita; Freytes, César O.; Gale, Robert Peter; Ganguly, Siddhartha; Ghosh, Nilanjan; Holmberg, Leona A.; Inward, David J.; Kanate, Abraham S.; Lazarus, Hillard M.; Malone, Adriana K.; Munker, Reinhold; Mussetti, Alberto; Norkin, Maxim; Prestidge, Tim D.; Rowe, Jacob M.; Satwani, Prakash; Siddiqi, Tanya; Stiff, Patrick J.; William, Basem M.; Wirk, Baldeep; Maloney, David G.; Smith, Sonali M.; Sureda, Anna M.; Carreras, Jeanette; Hamadani, Mehdi

    2015-01-01

    Assessment with 18F-fluorodeoxy glucose (FDG)—positron emission tomography (PET) before hematopoietic cell transplantation (HCT) for lymphoma may be prognostic for outcomes. Patients with chemotherapy-sensitive non—Hodgkin lymphoma (NHL) undergoing allogeneic HCT reported to the Center of International Blood and Marrow Transplantation Registry between 2007 and 2012 were included. Pre-HCT PET status (positive versus negative) was determined by the reporting transplantation centers. We analyzed 336 patients; median age was 55 years and 60% were males. Follicular lymphoma (n = 104) was more common than large cell (n = 85), mantle cell (n = 69), and mature natural killer or T cell lymphoma (n = 78); two thirds of the cohort received reduced-intensity conditioning; one half had unrelated donor grafts. Patients underwent PET scanning a median of 1 month (range, .07 to 2.83 months) before HCT; 159 were PET positive and 177 were PET negative. At 3 years, relapse/progression, progression-free survival (PFS), and overall survival (OS) in PET-positive versus PET-negative groups were 40% versus 26%; P = .007; 43% versus 47%; P = .47; and 58% versus 60%; P = .73, respectively. On multivariate analysis, a positive pretransplantation PET was associated with an increased risk of relapse/progression (risk ratio [RR], 1.86; P = .001) but was not associated with worse OS (RR, 1.29, 95% confidence interval [CI], .96 to 1.7; P = .08), PFS (RR, 1.32; 95% CI, .95 to 1.84; P = .10), or nonrelapse mortality (RR, .75; 95% CI, .48 to 1.18; P = .22). PET status conferred no influence on graft-versus-host disease. A positive PET scan before HCT is associated with increased relapse risk but should not be interpreted as a barrier to a successful allograft. PET status does not appear to predict survival after allogeneic HCT for NHL. PMID:25983043

  8. Impact of Pretransplantation (18)F-fluorodeoxy Glucose-Positron Emission Tomography Status on Outcomes after Allogeneic Hematopoietic Cell Transplantation for Non-Hodgkin Lymphoma.

    Science.gov (United States)

    Bachanova, Veronika; Burns, Linda J; Ahn, Kwang Woo; Laport, Ginna G; Akpek, Görgün; Kharfan-Dabaja, Mohamed A; Nishihori, Taiga; Agura, Edward; Armand, Philippe; Jaglowski, Samantha M; Cairo, Mitchell S; Cashen, Amanda F; Cohen, Jonathon B; D'Souza, Anita; Freytes, César O; Gale, Robert Peter; Ganguly, Siddhartha; Ghosh, Nilanjan; Holmberg, Leona A; Inwards, David J; Kanate, Abraham S; Lazarus, Hillard M; Malone, Adriana K; Munker, Reinhold; Mussetti, Alberto; Norkin, Maxim; Prestidge, Tim D; Rowe, Jacob M; Satwani, Prakash; Siddiqi, Tanya; Stiff, Patrick J; William, Basem M; Wirk, Baldeep; Maloney, David G; Smith, Sonali M; Sureda, Anna M; Carreras, Jeanette; Hamadani, Mehdi

    2015-09-01

    Assessment with (18)F-fluorodeoxy glucose (FDG)-positron emission tomography (PET) before hematopoietic cell transplantation (HCT) for lymphoma may be prognostic for outcomes. Patients with chemotherapy-sensitive non-Hodgkin lymphoma (NHL) undergoing allogeneic HCT reported to the Center of International Blood and Marrow Transplantation Registry between 2007 and 2012 were included. Pre-HCT PET status (positive versus negative) was determined by the reporting transplantation centers. We analyzed 336 patients; median age was 55 years and 60% were males. Follicular lymphoma (n = 104) was more common than large cell (n = 85), mantle cell (n = 69), and mature natural killer or T cell lymphoma (n = 78); two thirds of the cohort received reduced-intensity conditioning; one half had unrelated donor grafts. Patients underwent PET scanning a median of 1 month (range, .07 to 2.83 months) before HCT; 159 were PET positive and 177 were PET negative. At 3 years, relapse/progression, progression-free survival (PFS), and overall survival (OS) in PET-positive versus PET-negative groups were 40% versus 26%; P = .007; 43% versus 47%; P = .47; and 58% versus 60%; P = .73, respectively. On multivariate analysis, a positive pretransplantation PET was associated with an increased risk of relapse/progression (risk ratio [RR], 1.86; P = .001) but was not associated with increased mortality (RR, 1.29, 95% confidence interval [CI], .96 to 1.7; P = .08), therapy failure (RR, 1.32; 95% CI, .95 to 1.84; P = .10), or nonrelapse mortality (RR, .75; 95% CI, .48 to 1.18; P = .22). PET status conferred no influence on graft-versus-host disease. A positive PET scan before HCT is associated with increased relapse risk but should not be interpreted as a barrier to a successful allograft. PET status does not appear to predict survival after allogeneic HCT for NHL.

  9. Recipient HLA-C Haplotypes and microRNA 148a/b Binding Sites Have No Impact on Allogeneic Hematopoietic Cell Transplantation Outcomes.

    Science.gov (United States)

    Hoff, Gretchen A; Fischer, Johannes C; Hsu, Katharine; Cooley, Sarah; Miller, Jeffrey S; Wang, Tao; Haagenson, Michael; Spellman, Stephen; Lee, Stephanie J; Uhrberg, Markus; Venstrom, Jeffrey M; Verneris, Michael R

    2017-01-01

    Natural killer cells are important in graft-versus-leukemia responses after hematopoietic cell transplantation (HCT). A variety of surface receptors dictates natural killer cell function, including killer cell immunoglobulin-like receptor recognition of HLA-C. Previous single-center studies show that HLA-C epitopes, designated C1 and C2, were associated with allogeneic HCT outcomes; specifically, recipients homozygous for the C1 epitope (C1/C1) experienced a survival benefit. Additionally, mismatching at HLA-C was beneficial in recipients possessing at least 1 C2 allele, whereas the opposite was true for homozygous C1 (C1/C1) recipients where HLA-C mismatching resulted in worse outcomes. In this analysis we aimed to validate these findings in a large multicenter study. We also set out to determine whether surface expression of recipient HLA-C, determined by polymorphism in a microRNA (miR-148a/b) binding site within the 3'-region of the HLA-C transcript, was associated with transplant outcomes. In this large registry cohort, we were unable to confirm the prior findings regarding recipient HLA-C epitope status and outcome. Additionally, HLA-C surface expression (ie, surface density), as predicted by the miR-148a/b binding single nucleotide polymorphism, was also not with associated transplant outcomes. Collectively, neither HLA-C surface expression, as determined by miR-148a/b, nor recipient HLA-C epitopes (C1, C2) are associated with allogeneic HCT outcomes.

  10. Allogeneic Hematopoietic Cell Transplantation for Children with Sickle Cell Disease Is Beneficial and Cost-Effective: A Single-Center Analysis.

    Science.gov (United States)

    Arnold, Staci D; Jin, Zhezhen; Sands, Stephen; Bhatia, Monica; Kung, Andrew L; Satwani, Prakash

    2015-07-01

    Limited data exist regarding health care utilization (HCU) in patients receiving allogeneic hematopoietic cell transplantation (alloHCT) for sickle cell disease. Financial data from 2002 to 2011 were analyzed for 26 alloHCT patients and 48 control subjects (referred but without alloHCT). HCU of alloHCT was determined over 3 time periods: pre-alloHCT, during alloHCT (day 0 to day +365), and post-alloHCT. The median total cost per patient during the alloHCT year was $413,000 inpatient and $18,000 outpatient. Post-alloHCT HCU decreased when compared with pre-alloHCT and control subjects. The median cost of post-alloHCT outpatient visits per patient was significantly less when compared with pre-alloHCT (P = .044). The median cost of post-alloHCT inpatient visits per patient approached significance when compared with those pre-alloHCT (P = .079). Sixteen post-alloHCT patients, 19 control subjects, and 14 unaffected siblings were surveyed using Pediatric Quality of Life Inventory and EuroQOL questionnaires; however, the questionnaire scores across all 3 patient groups were not statistically significant (P = .2638). When adjusted for health-related quality of life, the analysis suggested alloHCT has a positive impact on health-related quality of life over control subjects. These pilot data support our hypothesis that alloHCT in children with sickle cell disease reduces HCU compared with control subjects without alloHCT.

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

    Science.gov (United States)

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

    2008-03-01

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

  12. Safety and efficacy of total body irradiation, cyclophosphamide, and cytarabine as a conditioning regimen for allogeneic hematopoietic stem cell transplantation in patients with acute lymphoblastic leukemia.

    Science.gov (United States)

    Mori, Takehiko; Aisa, Yoshinobu; Kato, Jun; Yamane, Akiko; Nakazato, Tomonori; Shigematsu, Naoyuki; Okamoto, Shinichiro

    2012-04-01

    Disease relapse still greatly interferes with the success of allogeneic hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia (ALL). This study retrospectively evaluated the long-term safety and efficacy of a conditioning regimen consisting of total body irradiation (TBI; 12 Gy), cyclophosphamide (CY; 60 mg kg(-1) , two doses), and high-dose cytarabine (Ara-C; 2 g m(-2) ; four doses) for patients with ALL. Fifty-five patients (median age: 31-years old) were evaluated. Stem cells were from human leukocyte antigen-identical siblings in 22 patients and from alternative donors in 33. There were no cases of early death before engraftment, and 100-day transplant-related mortality was 7.3%. With a median follow-up period of 9.6 years, 5-year overall and disease-free survival were 63.2% (95% CI: 46.5-79.9%) and 63.6% (95% CI: 47.1-80.1%) in patients with complete remission, respectively, both of which were significantly higher than the values of 27.3% (95% CI: 8.7-46.0%) and 22.7% (95% CI: 5.3-40.1%) for patients in advanced stages (P < 0.01). These results suggest that TBI and CY (TBI-CY) plus Ara-C could be a feasible and effective conditioning regimen for adult patients with ALL both in remission and in advanced stages, and a future study to compare this combination therapy with TBI-CY is required.

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

    Science.gov (United States)

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

    2015-05-01

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

  14. 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.

  15. Sirolimus for Refractory Autoimmune Hemolytic Anemia after Allogeneic Hematopoietic Stem Cell Transplantation: A Case Report and Literature Review of the Treatment of Post-Transplant Autoimmune Hemolytic Anemia.

    Science.gov (United States)

    Park, Jeong A; Lee, Hyun-Hee; Kwon, Hyun-Seop; Baik, Chung-Ryul; Song, Sae-Am; Lee, Jung Nye

    2016-01-01

    Autoimmune hemolytic anemia (AIHA) may occur after any type of allogeneic hematopoietic stem cell transplantation (HCT), even ABO-matched transplantation. It tends to be refractory to standard corticosteroid treatment and requires multiple transfusions. Though, there is no consensus regarding the optimal treatment for post-transplant severe AIHA. We present a pediatric patient with refractory AIHA after umbilical cord blood transplantation. She developed severe AIHA at 3months after transplantation and was unresponsive to multiple treatment modalities, including corticosteroids, intravenous immunoglobulin, plasma exchange and rituximab, resulting in persistent transfusion dependency. Sirolimus, a mammalian target of rapamycin inhibitor, was started on day 67 after the onset of AIHA, and this patient was successfully rescued without any complications. Sirolimus induces apoptosis in autoreactive lymphocytes, increases regulatory T cells and has been reported to have a positive effect on AIHA following solid organ transplantation (SOT). We reviewed the literature regarding post-transplant AIHA in the PubMed database and evaluated the treatment outcome of sirolimus in AIHA after SOT.

  16. Long-term Survival and Late Effects among 1-year Survivors of Second Allogeneic Hematopoietic Cell Transplantation for Relapsed Acute Leukemia and Myelodysplastic Syndromes

    Science.gov (United States)

    Duncan, Christine N.; Majhail, Navneet S.; Brazauskas, Ruta; Wang, Zhiwei; Cahn, Jean-Yves; Frangoul, Haydar A.; Hayashi, Robert J.; Hsu, Jack W.; Kamble, Rammurti T.; Kasow, Kimberly A.; Khera, Nandita; Lazarus, Hillard M.; Loren, Alison W.; Marks, David I.; Maziarz, Richard T.; Mehta, Paulette; Myers, Kasiani C.; Norkin, Maxim; Pidala, Joseph A.; Porter, David L.; Reddy, Vijay; Saber, Wael; Savani, Bipin N.; Schouten, Harry C.; Steinberg, Amir; Wall, Donna A.; Warwick, Anne B.; Wood, William A.; Yu, Lolie C.; Jacobsohn, David A.; Sorror, Mohamed L.

    2014-01-01

    We analyzed the outcomes of patients who survived disease-free for 1-year or more following second allogeneic hematopoietic cell transplantation (HCT) for relapsed acute leukemia or myelodysplastic syndromes between 1980 and 2009. A total of 1285 patients received a second allogeneic transplant following disease relapse; among these 325 survived relapse-free at 1-year after the second HCT. The median time from first to second HCT was 17 and 24 months for children and adults, respectively. A myeloablative preparative regimen was used in the second transplant in 62% of children and 45% of adult patients. The overall 10-year conditional survival rates after second transplantation in this cohort of patients who had survived disease-free for at least one year were 55% in children and 39% in adults. Relapse was the leading cause of mortality (77% and 54% of deaths in children and adults, respectively). In multivariate analyses, only disease status prior to second HCT was significantly associated with higher risk for overall mortality (HR 1.71 for patients with disease not in complete remission prior to second HCT, P<0.01). Chronic graft-versus-host disease (GVHD) developed in 43% and 75% of children and adults following second transplant. Chronic GVHD was the leading cause of non-relapse mortality followed by organ failure and infection. The cumulative incidence of developing at least one of the studied late effects at 10-years after second HCT was 63% in children and 55% in adults. The most frequent late effects in children were growth disturbance (10-year cumulative incidence 22%) and cataracts (20%), and in adults were cataracts (20%) and avascular necrosis (13%). Among patients with acute leukemia and myelodysplastic syndromes who receive a second allogeneic HCT for relapse and survive disease-free for at least 1-year, many can be expected to survive long term. However, they continue to be at risk for relapse and non-relapse morbidity and mortality. Novel approaches

  17. Long-term survival and late effects among one-year survivors of second allogeneic hematopoietic cell transplantation for relapsed acute leukemia and myelodysplastic syndromes.

    Science.gov (United States)

    Duncan, Christine N; Majhail, Navneet S; Brazauskas, Ruta; Wang, Zhiwei; Cahn, Jean-Yves; Frangoul, Haydar A; Hayashi, Robert J; Hsu, Jack W; Kamble, Rammurti T; Kasow, Kimberly A; Khera, Nandita; Lazarus, Hillard M; Loren, Alison W; Marks, David I; Maziarz, Richard T; Mehta, Paulette; Myers, Kasiani C; Norkin, Maxim; Pidala, Joseph A; Porter, David L; Reddy, Vijay; Saber, Wael; Savani, Bipin N; Schouten, Harry C; Steinberg, Amir; Wall, Donna A; Warwick, Anne B; Wood, William A; Yu, Lolie C; Jacobsohn, David A; Sorror, Mohamed L

    2015-01-01

    We analyzed the outcomes of patients who survived disease-free for 1 year or more after a second allogeneic hematopoietic cell transplantation (HCT) for relapsed acute leukemia or myelodysplastic syndromes between 1980 and 2009. A total of 1285 patients received a second allogeneic transplant after disease relapse; among these, 325 were relapse free at 1 year after the second HCT. The median time from first to second HCT was 17 and 24 months for children and adults, respectively. A myeloablative preparative regimen was used in the second transplantation in 62% of children and 45% of adult patients. The overall 10-year conditional survival rates after second transplantation in this cohort of patients who had survived disease-free for at least 1 year was 55% in children and 39% in adults. Relapse was the leading cause of mortality (77% and 54% of deaths in children and adults, respectively). In multivariate analyses, only disease status before second HCT was significantly associated with higher risk for overall mortality (hazard ratio, 1.71 for patients with disease not in complete remission before second HCT, P < .01). Chronic graft-versus-host disease (GVHD) developed in 43% and 75% of children and adults after second transplantation. Chronic GVHD was the leading cause of nonrelapse mortality, followed by organ failure and infection. The cumulative incidence of developing at least 1 of the studied late effects within 10 years after second HCT was 63% in children and 55% in adults. The most frequent late effects in children were growth disturbance (10-year cumulative incidence, 22%) and cataracts (20%); in adults they were cataracts (20%) and avascular necrosis (13%). Among patients with acute leukemia and myelodysplastic syndromes who receive a second allogeneic HCT for relapse and survive disease free for at least 1 year, many can be expected to survive long term. However, they continue to be at risk for relapse and nonrelapse morbidity and mortality. Novel

  18. Successful treatment with intravesical cidofovir for virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation: A case report and a review of the literature.

    Science.gov (United States)

    Sakurada, Maki; Kondo, Tadakazu; Umeda, Masayuki; Kawabata, Hiroshi; Yamashita, Kouhei; Takaori-Kondo, Akifum

    2016-07-01

    Virus-associated hemorrhagic cystitis (VAHC) is a formidable complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The standard management of severe VAHC after allo-HSCT has not been established. Intravenous administration of cidofovir (CDV), an acyclic nucleoside analogue with broad-spectrum activity against DNA viruses, has been reported to be effective for VAHC, but it can cause severe renal toxicity. Here we report four cases who achieved clinical responses with intravesical instillation of CDV for severe VAHC after allo-HSCT. Median age was 57 years (40-63), and all were male. The underlying diseases were hematological malignancies. Three had received bone marrow transplantation, and one received cord blood transplantation twice. Conditioning regimen was myeloablative for one, and reduced-intensity for three. The viral types were BK virus and/or adenovirus. Two patients had received CDV intravenously prior to the intravesical therapy. A dose of intravesical CDV was 2-5 mg/kg. In all cases, symptoms of cystitis improved dramatically within a few days without showing any systemic adverse effects. The virological response was observed in two cases. This local therapy was effective even in the cases refractory to the intravenous CDV and a case with severe renal failure. Along with the review of literature, we propose that the intravesical instillation of CDV can be a therapeutic option for severe VAHC after allo-HSCT.

  19. High Incidence of Afebrile Bloodstream Infection Detected by Surveillance Blood Culture in Patients on Corticosteroid Therapy after Allogeneic Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Kameda, Kazuaki; Kimura, Shun-Ichi; Akahoshi, Yu; Nakano, Hirofumi; Harada, Naonori; 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; Kanda, Junya; Kako, Shinichi; Tanihara, Aki; Nishida, Junji; Kanda, Yoshinobu

    2016-02-01

    Bloodstream infections (BSI) are still important complications after allogeneic hematopoietic stem cell transplantation (allo-SCT). Patients who are receiving corticosteroid therapy can develop BSI without fever. The utility of surveillance blood cultures in these situations is controversial. We retrospectively analyzed 74 patients who received a corticosteroid consisting of ≥.5 mg/kg prednisolone or equivalent after allo-SCT. In principle, we performed surveillance blood culture weekly for these patients. Sixteen patients (21.6%) developed definite BSI. In a multivariate analysis, a myeloablative conditioning regimen, high-risk disease status at allo-SCT, and the presence of a central venous catheter at the initiation of corticosteroid therapy were identified as independent significant risk factors for the development of definite BSI. At the first definite BSI episode, 7 patients (46.7%) were afebrile and diagnosed by surveillance blood culture. However, 6 of these 7 afebrile patients showed various signs that could be attributed to infection at the time of positive blood culture. In conclusion, patients receiving corticosteroid therapy after allo-SCT frequently develop afebrile BSI. Although surveillance blood culture might be beneficial in these situations, it also seems important to not miss the signs of BSI, even when patients are afebrile.

  20. The Presence of Anti-HLA Antibodies before and after Allogeneic Hematopoietic Stem Cells Transplantation from HLA-Mismatched Unrelated Donors

    Directory of Open Access Journals (Sweden)

    Anna Koclega

    2012-01-01

    Full Text Available Although anti-human leukocyte antigen antibodies (anti-HLA Abs are important factors responsible for graft rejection in solid organ transplantation and play a role in post-transfusion complications, their role in allogeneic hematopoietic stem cell transplantation (allo-HSCT has not been finally defined. Enormous polymorphism of HLA-genes, their immunogenicity and heterogeneity of antibodies, as well as the growing number of allo-HSCTs from partially HLA-mismatched donors, increase the probability that anti-HLA antibodies could be important factors responsible for the treatment outcomes. We have examined the incidence of anti-HLA antibodies in a group of 30 allo-HSCT recipients from HLA-mismatched unrelated donors. Anti-HLA Abs were identified in sera collected before and after allo-HSCT. We have used automated DynaChip assay utilizing microchips bearing purified class I and II HLA antigens for detection of anti-HLA Abs. We have detected anit-HLA antibodies against HLA-A, B, C, DR, DQ and DP, but no donor or recipient-specific anti-HLA Abs were detected in the studied group. The preliminary results indicate that anti-HLA antibodies are present before and after allo-HSCT in HLA-mismatched recipients.

  1. Spontaneous thoracic air-leakage syndrome in patients following allogeneic hematopoietic stem cell transplantation: Causes, CT-follow up and patient outcome

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    Vogel, Monika [Department of Diagnostic Radiology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, 72076 Tuebingen (Germany)]. E-mail: monika.vogel@med.uni-tuebingen.de; Brodoefel, Harald [Department of Diagnostic Radiology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, 72076 Tuebingen (Germany); Bethge, Wolfgang [Department of Internal Medicine-Oncology, Eberhard-Karls-University, Ottfried-Mueller-Str. 5, 72070 Tuebingen (Germany); Faul, Christoph [Department of Internal Medicine-Oncology, Eberhard-Karls-University, Ottfried-Mueller-Str. 5, 72070 Tuebingen (Germany); Hartmann, Joerg [Department of Internal Medicine-Oncology, Eberhard-Karls-University, Ottfried-Mueller-Str. 5, 72070 Tuebingen (Germany); Schimmel, Heiko [Department of Pathology, Eberhard-Karls-University, Liebermeisterstrasse 8, 72076 Tuebingen (Germany); Wehrmann, Manfred [Department of Pathology, Eberhard-Karls-University, Liebermeisterstrasse 8, 72076 Tuebingen (Germany); Claussen, Claus D. [Department of Diagnostic Radiology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, 72076 Tuebingen (Germany); Horger, Marius [Department of Diagnostic Radiology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, 72076 Tuebingen (Germany)

    2006-12-15

    Objective: The purpose of this article is to describe and illustrate the acute and follow-up imaging features, clinical constellation and outcome of patients with thoracic air-leakage syndrome following allogeneic hematopoietic stem cell transplantation (allo-HCT). Methods: Patients with evidence of thoracic air-leakage, i.e. spontaneous pneumomediastinum, spontaneous pneumothorax or interstitial emphysema after allo-HCT were retrospectively identified by a chart review. Acute and follow-up morphology, duration and patient outcome were analyzed on CT (HRCT or MSCT with HR-reconstructions). Correlation was made with histological results of transbronchial biopsy. Results: The 6 patients included (3 male and 3 female, 14-64 years old) with thoracic air-leakage after allo-HCT all had histologically proven bronchiolitis obliterans (BO) or bronchiolitis obliterans organizing pneumonia (BOOP). Thoracic air-leakage consisted of spontaneous pneumomediastinum associated with active invasive pulmonary aspergillosis (IPA) in 4/6 and spontaneous pneumothorax or interstitial emphysema each in 1/6 patients. Duration of thoracic air-leakage was 7-135 days. Of the patients with spontaneous pneumomediastinum, 3/4 died of IPA. One patient survived until complete regression of spontaneous pneumomediastinum. One patient died 7 days after spontaneous pneumothorax and one survived developing chronic interstitial emphysema. Conclusion: In all cases, thoracic air-leakage was associated to BO or BOOP. In the majority of cases with additional IPA, thoracic air-leakage is more indicative for severity of pulmonary disease than a life-threatening entity itself.

  2. Efficacy and safety of oral deferasirox treatment in the posttransplant period for patients who have undergone allogeneic hematopoietic stem cell transplantation (alloHSCT).

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    Sivgin, Serdar; Eser, Bulent; Bahcebasi, Sami; Kaynar, Leylagul; Kurnaz, Fatih; Uzer, Elmas; Pala, Cigdem; Deniz, Kemal; Ozturk, Ahmet; Cetin, Mustafa; Unal, Ali

    2012-05-01

    Iron overload is considered to be associated with various complications in patients who undergo both allogeneic (allo) and autologous hematopoietic stem cell transplantation (HSCT). A total of 23 alloHSCT recipients who started deferasirox treatment due to hyperferritinemia (ferritin ≥1,000 ng/mL) were analyzed retrospectively. The demographic characteristics, data about deferasirox treatment, and history of phlebotomy were obtained from the patients' files. The reduction in posttreatment ferritin levels was found statistically significant compared with pretreatment ferritin levels in both def+phlebotomy and def+nonphlebotomy groups (p = 0.025 and 0.017, respectively). The liver enzymes, especially ALT and bilirubins, were significantly reduced after the treatment (p deferasirox treatment reduced pretreatment ferritin levels below the level of 1,000 ng/mL in a median period of 94 days, and these data were found to be statistically significant (p deferasirox was 94 days (72-122). The most common adverse effects were nausea and vomiting, which occurred in three of the patients (13%). In conclusion, our data suggest that oral deferasirox treatment may be used as a safe and effective alternative method for reducing iron overload in alloHSCT recipients, whether combined with or without phlebotomy.

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

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    Grazyna Kaminska-Winciorek

    2016-01-01

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

  4. Value of surveillance blood culture for early diagnosis of occult bacteremia in patients on corticosteroid therapy following allogeneic hematopoietic stem cell transplantation.

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    Chizuka, A; Kami, M; Kanda, Y; Murashige, N; Kishi, Y; Hamaki, T; Kim, S-W; Hori, A; Kojima, R; Mori, S-I; Tanosaki, R; Gomi, H; Takaue, Y

    2005-03-01

    Bloodstream infection (BSI) is a significant complication following allogeneic hematopoietic stem cell transplantation (allo-SCT). Corticosteroids mask inflammatory responses, delaying the initiation of antibiotics. We reviewed medical records of 69 allo-SCT patients who had been on >0.5 mg/kg prednisolone to investigate the efficacy of weekly surveillance blood cultures. A total of 36 patients (52%) had positive cultures, 25 definitive BSI and 11 probable BSI. Pathogens in definitive BSI were Staphylococcus epidermidis (n=7), S. aureus (n=4), Entrococcus faecalis (n=3), Pseudomonas aeruginosa (n=5), Acenitobacter lwoffii (n=4), and others (n=10). The median interval from the initiation of corticosteroids to the first positive cultures was 24 days (range, 1-70). At the first positive cultures, 15 patients with definitive BSI were afebrile. Four of them remained afebrile throughout the period of positive surveillance cultures. Patients with afebrile BSI tended to be older (P=0.063), and had in-dwelling central venous catheters less frequently than febrile patients (P<0.0001). Bloodstream pathogens were directly responsible for death in two patients with afebrile BSI. This study demonstrates that cortisosteroid frequently masks inflammatory reactions in allo-SCT recipients given conrticosteroids, and that surveillance blood culture is only diagnostic clue for 'occult' BSI.

  5. Autoimmune hemolytic anemia after allogeneic hematopoietic stem cell transplantation: analysis of 533 adult patients who underwent transplantation at King's College Hospital.

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    Wang, Meng; Wang, Wenjia; Abeywardane, Ayesha; Adikarama, Malinthi; McLornan, Donal; Raj, Kavita; de Lavallade, Hugues; Devereux, Stephen; Mufti, Ghulam J; Pagliuca, Antonio; Potter, Victoria T; Mijovic, Aleksandar

    2015-01-01

    Autoimmune hemolytic anemia (AIHA) is a recognized complication of hematopoietic stem cell transplantation (HSCT); it is often refractory to treatment and carries a high mortality. To improve understanding of the incidence, risk factors, and clinical outcome of post-transplantation AIHA, we analyzed 533 patients who received allogeneic HSCT, and we identified 19 cases of AIHA after HSCT (overall incidence, 3.6%). The median time to onset, from HSCT to AIHA, was 202 days. AIHA was associated with HSCT from unrelated donors (hazard ratio [HR], 5.28; 95% confidence interval [CI], 1.22 to 22.9; P = .026). In the majority (14 of 19; 74%) of AIHA patients, multiple agents for treatment were required, with only 9 of 19 (47%) patients achieving complete resolution of AIHA. Patients with post-transplantation AIHA had a higher overall mortality (HR, 2.48; 95% CI, 1.33 to 4.63; P = .004), with 36% (4 of 11 cases) of deaths attributable to AIHA.

  6. Mixed T Cell Chimerism After Allogeneic Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia Using an Alemtuzumab-Containing Regimen Is Shaped by Persistence of Recipient CD8 T Cells.

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    Grimaldi, Francesco; Potter, Victoria; Perez-Abellan, Pilar; Veluchamy, John P; Atif, Muhammad; Grain, Rosemary; Sen, Monica; Best, Steven; Lea, Nicholas; Rice, Carmel; Pagliuca, Antonio; Mufti, Ghulam J; Marsh, Judith C W; Barber, Linda D

    2017-02-01

    Prevention of graft-versus-host disease (GVHD) is paramount for allogeneic hematopoietic stem cell transplantation (HSCT) to treat nonmalignant diseases. We previously reported that allogeneic HSCT for severe aplastic anemia (SAA) using the fludarabine, cyclophosphamide, and alemtuzumab (Campath-1H) (FCC) regimen is associated with a very low risk of GVHD and excellent clinical outcomes. We now report a single-center study of 45 patients with longer follow-up and investigation of lymphocyte recovery. Overall survival (OS) was 93%, and event-free survival (EFS) was 90.7%. Acute and chronic GVHD each occurred in 6 patients (13.3%), and only 1 case was severe. Mixed T cell chimerism was frequent and persisted after cessation of immunosuppression. T cells were extensively depleted, representing only 11.3% of lymphocytes at day 30 and rising to 43.8% by 1 year, but still significantly below normal levels (67.2%; P = .018), and deficiency persisted after immunosuppressive therapy (IST) withdrawal. Depletion of CD4 T cells was particularly profound, causing inversion of the normal CD4:CD8 T cell ratio. T cell subset composition was also abnormal, with memory and effector T cells predominating for at least 6 months after FCC HSCT. Analysis of T cell subset chimerism showed that CD4 T cells were predominantly donor-derived at 1 year, whereas recipient-derived CD8 T cells shaped mixed chimerism with a notable contribution of recipient effector CD8 T cells. The prolonged mixed T cell chimerism after IST withdrawal and low incidence of GVHD indicates the establishment of mutual tolerance, but the low incidence of viral disease suggests maintenance of antiviral immunity. Our study shows that despite the abnormal T cell profile after allogeneic HSCT for SAA using the FCC regimen, this regimen is conducive to an excellent clinical outcome.

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

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    Krumlauf Michael

    2011-04-01

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

  8. Dose Escalation of Total Marrow Irradiation With Concurrent Chemotherapy in Patients With Advanced Acute Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

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    Wong, Jeffrey Y.C., E-mail: jwong@coh.org [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Forman, Stephen; Somlo, George [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Rosenthal, Joseph [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Department of Pediatrics, City of Hope National Medical Center, Duarte, California (United States); Liu An; Schultheiss, Timothy; Radany, Eric [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Palmer, Joycelynne [Department of Biostatistics, City of Hope National Medical Center, Duarte, California (United States); Stein, Anthony [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States)

    2013-01-01

    Purpose: We have demonstrated that toxicities are acceptable with total marrow irradiation (TMI) at 16 Gy without chemotherapy or TMI at 12 Gy and the reduced intensity regimen of fludarabine/melphalan in patients undergoing hematopoietic cell transplantation (HCT). This article reports results of a study of TMI combined with higher intensity chemotherapy regimens in 2 phase I trials in patients with advanced acute myelogenous leukemia or acute lymphoblastic leukemia (AML/ALL) who would do poorly on standard intent-to-cure HCT regimens. Methods and Materials: Trial 1 consisted of TMI on Days -10 to -6, etoposide (VP16) on Day -5 (60 mg/kg), and cyclophosphamide (CY) on Day -3 (100 mg/kg). TMI dose was 12 (n=3 patients), 13.5 (n=3 patients), and 15 (n=6 patients) Gy at 1.5 Gy twice daily. Trial 2 consisted of busulfan (BU) on Days -12 to -8 (800 {mu}M min), TMI on Days -8 to -4, and VP16 on Day -3 (30 mg/kg). TMI dose was 12 (n=18) and 13.5 (n=2) Gy at 1.5 Gy twice daily. Results: Trial 1 had 12 patients with a median age of 33 years. Six patients had induction failures (IF), and 6 had first relapses (1RL), 9 with leukemia blast involvement of bone marrow ranging from 10%-98%, 5 with circulating blasts (24%-85%), and 2 with chloromas. No dose-limiting toxicities were observed. Eleven patients achieved complete remission at Day 30. With a median follow-up of 14.75 months, 5 patients remained in complete remission from 13.5-37.7 months. Trial 2 had 20 patients with a median age of 41 years. Thirteen patients had IF, and 5 had 1RL, 2 in second relapse, 19 with marrow blasts (3%-100%) and 13 with peripheral blasts (6%-63%). Grade 4 dose-limiting toxicities were seen at 13.5 Gy (stomatitis and hepatotoxicity). Stomatitis was the most frequent toxicity in both trials. Conclusions: TMI dose escalation to 15 Gy is possible when combined with CY/VP16 and is associated with acceptable toxicities and encouraging outcomes. TMI dose escalation is not possible with BU/VP16 due to

  9. 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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    Jacewicz, R; Lewandowski, K; Rupa-Matysek, J; Jędrzejczyk, M; Berent, J

    2015-01-01

    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.

  10. 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.

  11. Frequency analysis of TRBV subfamily sjTRECs to characterize T-cell reconstitution in acute leukemia patients after allogeneic hematopoietic stem cell transplantation

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    Yang Lijian

    2011-04-01

    Full Text Available Abstract Background Allogeneic hematopoietic stem cell transplantation (allo-HSCT leads to a prolonged state of immunodeficiency and requires reconstitution of normal T-cell immunity. Signal joint T-cell receptor excision DNA circles (sjTRECs are markers of developmental proximity to the thymus that have been used to evaluate thymic function related to T-cell immune reconstitution after HSCT. To assess the proliferative history in different T-cell receptor beta variable region (TRBV subfamilies of T cells after HSCT, expansion of TRBV subfamily-naive T cells was determined by analysis of a series of TRBV-BD1 sjTRECs. Methods sjTRECs levels were detected by real-time quantitative polymerase chain reaction (PCR in peripheral blood mononuclear cells (PBMCs from 43 Chinese acute leukemia patients who underwent allo-HSCT. Twenty-three TRBV-BD1 sjTRECs were amplified by semi-nested PCR. Sixteen age-matched healthy volunteers served as normal controls. Results sjTRECs levels were low or undetectable in the first 6 weeks after allo-HSCT and increased after 8 weeks post HSCT; however, sjTRECs levels at week 20 post-HSCT were still less than normal controls. Frequencies of TRBV subfamily sjTRECs in PBMCs from recipients at week 8 post-HSCT (29.17 ± 20.97% or at week 16 post-HSCT (38.33 ± 9.03% were significantly lower than those in donors (47.92 ± 13.82% or recipients at pre-HSCT (45.83 ± 14.03%. However, frequencies of TRBV subfamily sjTRECs in recipients at week 30 post-HSCT (42.71 ± 21.62% were similar to those in donors and recipients at pre-HSCT. sjTRECs levels in donors had a positive linear correlation with sjTRECs levels in recipients within 8-12 weeks post-HSCT. Patients with acute graft-versus-host disease (GVHD or chronic GVHD had profoundly reduced TRECs levels during the first year post-HSCT. Frequencies of BV22-BD1 sjTRECs and BV23-BD1 sjTRECs in patients with GVHD were significantly lower than those in recipients at pre-HSCT, and the

  12. A HIGHER INCIDENCE OF RELAPSE FOR ACUTE LYMPHOCYTIC LEUKEMIA TREATED WITH ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION CONDITIONED WITH BU-CY2 REGIMEN

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    朱康儿; 钟隽; 张涛; 曾慧兰

    2003-01-01

    Objective: To analyze long-term outcome in sixty leukemia patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) following busulfan and cyclophosphamide (BU-CY2) between 1994 and 2000. Methods: BU-CY2 was used as the conditioning regimen and allo-HSCT was performed for all patients. All the patients were followed-up until August 2001 or death. The leukemia-free survival, relapse and transplant-related mortality were discussed. Results: All 60 patients had sustained engraftment. Acute GVHD occurred in 22 out of 60 patients (36.7%), and the incidence of acute GVHD was 48% in the patients with CML, 30% in AML and 26.7% in ALL. 38 patients are still alive in continuous remission with a median follow-up of 30 months (range 12-84) and 22 patients have died. The main causes of death were acute GVHD in 3 patients, CMV-IP in 7 patients and relapse in 11 patients, the remaining one died of pulmonary infection. Among 11 patients who died of relapse, 8 patients with ALL relapsed in the early stage post transplant (8/15, 53.3%), relapse was observed in the remaining 3 patients with AML, and however, no relapse was observed in CML. The probability of disease-free survival at 3 years for CML. AML and ALL patients was 80%, 70% and 26.7%, respectively. Conclusion: This results suggests that BU-CY2 is an effective conditioning regimen in patients with AML and CML, resulting in a low relapse rate and high long-term survival rate, but not as effective in patients with ALL, with a higher incidence of relapse and therefore, not recommended for ALL patients.

  13. Allogeneic Hematopoietic Stem Cell Transplantation after Conditioning Regimens with Fludarabine/melphalan or Fludarabine/busulfan for Patients with Hematological Malignancies: A Single-center Analysis.

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    Yamamoto, Wataru; Andou, Taiki; Itabashi, Megumi; Koyama, Satoshi; Ishii, Yoshimi; Numata, Ayumi; Motohashi, Kenji; Hagihara, Maki; Matsumoto, Kenji; Fujisawa, Shin

    2016-01-01

    Objective Fludarabine plus melphalan (FM) and fludarabine plus busulfan (FB) are two major conditioning regimens for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods We retrospectively analyzed patients who underwent allo-HSCT after a conditioning regimen consisting of FM or FB with/without total body irradiation for hematological malignancies between 2005 and 2014. Results There were 41 patients who met the criteria. The median follow-up time for the survivors was 3 years. Thirty-two patients received allo-HSCT after the FM regimen and nine patients received allo-HSCT after the FB regimen. Patients who received FB were older than those who received FM (p=0.041). There was no significant difference in the 3-year overall survival between patients who had received FB and those who had received FM (29.6% vs. 56.5%, p=0.267). The 3-year cumulative incidence of relapse was significantly higher in patients who had received FB than that in patients who had received FM (66.7% vs. 17.8%, p=0.004), and FB was an independent prognostic factor for relapse by a multivariate analysis (hazard ratio, 9.8; 95% confidential interval, 2.5-39.3; p=0.001). When we restricted the evaluation to patients with acute myeloid leukemia and myelodysplastic syndrome, the 3-year cumulative incidence of relapse was also significantly higher in patients who had received FB than that in patients who had received FM (75.0% vs. 16.1%, p=0.004). Conclusion The results suggest that FM may provide better disease control than FB.

  14. Rituximab, fludarabine, and total body irradiation as conditioning regimen before allogeneic hematopoietic stem cell transplantation for advanced chronic lymphocytic leukemia: long-term prospective multicenter study.

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    Michallet, Mauricette; Socié, Gerard; Mohty, Mohamad; Sobh, Mohamad; Bay, Jacques-O; Morisset, Stéphane; Labussière-Wallet, Hélène; Tabrizi, Reza; Milpied, Noel; Bordigoni, Pierre; El-Cheikh, Jean; Blaise, Didier

    2013-02-01

    To evaluate the efficacy and toxicity of reduced-intensity conditioning (RIC) combining fludarabine, low-dose total body irradiation (TBI) and rituximab before allogeneic hematopoietic stem cell transplantation (allo-HSCT) from human leucocyte antigen (HLA) identical siblings, we conducted a prospective study in patients ≤65 years old with advanced chronic lymphocytic leukemia (CLL) stage B or C in response after a salvage treatment. Conditioning included rituximab (375 mg/m² on day 5), fludarabine (30 mg/m² from day 4 to day 2), TBI (2 Gy on day 0), and rituximab (500 mg/m² on days 1 and 8). Forty patients were included, 34 (85%) were male with a median age of 54 years (range, 35-65 years), 38 (95%) were in B stage, and 2 were in stage C; only 7 patients (17%) were in complete response. Seven (17%) patients did not receive rituximab. Thirty-nine (98%) patients engrafted, 17 patients developed acute graft-versus-host disease (GVHD) grade ≥II with a cumulative incidence at 3 months of 44% (36-52) with a significant protective effect of rituximab (p = 0.02). The cumulative incidence of chronic GVHD was 29% (21-36) at 12 months for both limited and extensive forms. The median overall survival was not reached with 5-years probability of 55% (41-74). The multivariate analysis showed a positive effect of rituximab on overall survival and event-free survival (hazard ratio [HR] = 0.1 [0-0.6], p = 0.02; and HR = 0.1 [0-0.4], p = 0.035, respectively). The association of fludarabine, TBI, and rituximab is feasible, well tolerated, and allows better outcomes in advanced CLL.

  15. Prognostic implication of gene mutations on overall survival in the adult acute myeloid leukemia patients receiving or not receiving allogeneic hematopoietic stem cell transplantations.

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    Chou, Sheng-Chieh; Tang, Jih-Luh; Hou, Hsin-An; Chou, Wen-Chien; Hu, Fu-Chang; Chen, Chien-Yuan; Yao, Ming; Ko, Bor-Sheng; Huang, Shang-Yi; Tsay, Woei; Chen, Yao-Chang; Tien, Hwei-Fang

    2014-11-01

    Several gene mutations have been shown to provide clinical implications in patients with acute myeloid leukemia (AML). However, the prognostic impact of gene mutations in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. We retrospectively evaluated the clinical implications of 8 gene mutations in 325 adult AML patients; 100 of them received allo-HSCT and 225 did not. The genetic alterations analyzed included NPM1, FLT3-ITD, FLT3-TKD, CEBPA, RUNX1, RAS, MLL-PTD, and WT1. In patients who did not receive allo-HSCT, older age, higher WBC count, higher lactate dehydrogenase level, unfavorable karyotype, and RUNX1 mutation were significantly associated with poor overall survival (OS), while CEBPA double mutation (CEBPA(double-mut)) and NPM1(mut)/FLT3-ITD(neg) were associated with good outcome. However, in patients who received allo-HSCT, only refractory disease status at the time of HSCT and unfavorable karyotype were independent poor prognostic factors. Surprisingly, RUNX1 mutation was an independent good prognostic factor for OS in multivariate analysis. The prognostic impact of FLT3-ITD or NPM1(mut)/FLT3-ITD(neg) was lost in this group of patients receiving allo-HSCT, while CEBPA(double-mut) showed a trend to be a good prognostic factor. In conclusion, allo-HSCT can ameliorate the unfavorable influence of some poor-risk gene mutations in AML patients. Unexpectedly, the RUNX1 mutation showed a favorable prognostic impact in the context of allo-HSCT. These results need to be confirmed by further studies with more AML patients.

  16. Caspofungin first-line therapy for invasive aspergillosis in allogeneic hematopoietic stem cell transplant patients: an European Organisation for Research and Treatment of Cancer study.

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    Herbrecht, R; Maertens, J; Baila, L; Aoun, M; Heinz, W; Martino, R; Schwartz, S; Ullmann, A J; Meert, L; Paesmans, M; Marchetti, O; Akan, H; Ameye, L; Shivaprakash, M; Viscoli, C

    2010-07-01

    Caspofungin at standard dose was evaluated as first-line monotherapy of mycologically documented probable/proven invasive aspergillosis (IA) (unmodified European Organisation for Research and Treatment of Cancer/Mycosis Study Group criteria) in allogeneic hematopoietic SCT patients. The primary efficacy end point was complete or partial response at end of caspofungin treatment. Response at week 12, survival and safety were additional end points. Enrollment was stopped prematurely because of low accrual, with 42 enrolled and 24 eligible, giving the study a power of 85%. Transplant was from unrelated donors in 16 patients; acute or chronic GVHD was present in 15. In all, 12 patients were neutropenic (<500/microl) at baseline, 10 received steroids and 16 calcineurin inhibitors or sirolimus. Median duration of caspofungin treatment was 24 days. At the end of caspofungin therapy, 10 (42%) patients had complete or partial response (95% confidence interval: 22-63%); 1 (4%) and 12 (50%) had stable and progressing disease, respectively; one was not evaluable. At week 12, eight patients (33%) had complete or partial response. Survival rates at week 6 and 12 were 79 and 50%, respectively. No patient had a drug-related serious adverse event or discontinued because of toxicity. Caspofungin first-line therapy was effective and well tolerated in allogeneic hematopoietic SCT patients with mycologically documented IA.

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

    Science.gov (United States)

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

    2013-03-01

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

  18. Degree of Predicted Minor Histocompatibility Antigen Mismatch Correlates with Poorer Clinical Outcomes of Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation

    DEFF Research Database (Denmark)

    Larsen, Malene Erup; Kornblit, B; Larsen, Mette Voldby;

    2010-01-01

    population as well as all the possible nsSNP differences between any two individuals, it is likely that many miHAs have yet to be discovered. The objective of the current study was to predict novel HLA-A and HLA-B restricted miHAs in a cohort of patients treated with non-myeloablative conditioning allogeneic...... binding to any of the HLA-A or -B molecules expressed by the patient and donor. Patients with more than the median of three predicted miHAs had a significantly lower five-year overall survival (42% vs 70%, P=0.0060, adjusted hazard ratio (HR) 2.6, P=0.0047) and significantly higher treatment related......-restricted presentation and recognition of peptides encompassing these. Our data also suggest that 6 of the 11 proteins included in the current study could contain more miHAs yet to be identified, and that the presence of multiple miHAs confers a higher risk of mortality after non-myeloablative conditioning HCT...

  19. Production of good manufacturing practice-grade cytotoxic T lymphocytes specific for Epstein-Barr virus, cytomegalovirus and adenovirus to prevent or treat viral infections post-allogeneic hematopoietic stem cell transplant.

    Science.gov (United States)

    Sili, Uluhan; Leen, Ann M; Vera, Juan F; Gee, Adrian P; Huls, Helen; Heslop, Helen E; Bollard, Catherine M; Rooney, Cliona M

    2012-01-01

    Infections with a range of common community viruses remain a major cause of mortality and morbidity after allogeneic hematopoietic stem cell transplantation. T cells specific for cytomegalovirus (CMV), Epstein-Barr virus (EBV) and adenoviruses can safely prevent and infections with these three most common culprits, but the manufacture of individual T cell lines for each virus would be prohibitive in terms of time and cost. We have demonstrated that T cells specific for all three viruses can be manufactured in a single culture using monocytes and EBV-transformed B lymphoblastoid cell lines (LCLs), both transduced with an adenovirus vector expressing pp65 of CMV, as antigen-presenting cells. Trivirus-specific T cell lines produced from healthy stem cell donors could prevent and treat infections with all three viruses, not only in the designated recipient, but in unrelated, partially-HLA-matched third party recipients. We now provide the details and logistics of T cell manufacture.

  20. Hematopoietic reconstitution on the prognosis of hematological malignancies after allogenceic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    张燕

    2012-01-01

    Objective To analyze the impact of the time to hematopoietic reconstitution on the prognosis of hematological malignancies after allogeneic hematopoietic stem cell transplantation(allo-HSCT) . Methods 173 patients with hematological malignancies treated with allo-HSCT (excluding umbilical cord blood transplantation)

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

    Science.gov (United States)

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

    2015-10-01

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

  2. PARASITIC INFECTIONS IN HEMATOPOIETIC STEM CELL TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    Isidro Jarque

    2016-07-01

    Full Text Available Parasitic infections are rarely documented in hematopoietic stem cell transplant recipients. However, they may be responsible for fatal complications that are only diagnosed at autopsy. Increased awareness of the possibility of parasitic diseases both in autologous and allogeneic stem cell transplant patients is relevant not only for implementing preventive measures but also for performing an early diagnosis and starting appropriate therapy for these unrecognized but fatal infectious complications in hematopoietic transplant recipients. In this review, we will focus on parasitic diseases occurring in this population especially those with major clinical relevance including toxoplasmosis, American trypanosomiasis, leishmaniasis, malaria, and strongyloidiasis, among others, highlighting the diagnosis and management in hematopoietic transplant recipients.

  3. Allogeneic Hematopoietic Cell Transplantation in Multiple Myeloma: Focus on Longitudinal Assessment of Donor Chimerism, Extramedullary Disease, and High-Risk Cytogenetic Features.

    Science.gov (United States)

    Rasche, Leo; Röllig, Christoph; Stuhler, Gernot; Danhof, Sophia; Mielke, Stephan; Grigoleit, Goetz Ulrich; Dissen, Lea; Schemmel, Lea; Middeke, Jan Moritz; Rücker, Viktoria; Schreder, Martin; Schetelig, Johannes; Bornhäuser, Martin; Einsele, Hermann; Thiede, Christian; Knop, Stefan

    2016-11-01

    Although generally not applied as first-line treatment of multiple myeloma, allogeneic hematopoietic cell transplantation (allo-SCT) can still be chosen as ultimate escalation approach in high-risk patients, preferentially within the framework of clinical trials. In this study, we investigated whether decreasing donor chimerism (DC) is predictive for relapse. In addition, we comprehensively determined the impact of several other disease- and treatment-related factors on outcome. One hundred fifty-five multiple myeloma patients whose DC status was followed serially by the short tandem repeat-based techniques at a single lab were included in this retrospective study. Outcome variables were studied in univariate and multivariable analyses. Available were 2.324 DC samples (median, 12 per patient). Loss of full DC was associated with shorter progression-free survival (PFS) (HR, 1.7; 95% CI, 1.1 to 2.6) but did not impact overall survival. Two-thirds of patients with International Myeloma Working Group-defined relapses still displayed a full DC in peripheral blood or bone marrow. Extramedullary manifestations were observed in 33% of patients, accounting for the discrepancy between DC analysis and the actual disease status. In multivariable analysis, the 2 most relevant variables for an unfavorable PFS were progressive disease before allo-SCT (HR, 3.0; 95% CI, 1.5 to 5.9) and allo-SCT at least the second relapse (HR, 2.8; 95% CI, 1.5 to 4.9), whereas for overall survival progressive disease or partial response before allo-SCT had the strongest negative effects (HR, 4.2; 95% CI, 1.9 to 9, and HR, 2.0; 95% CI, 1.0 to 3.8, respectively). Adverse cytogenetics such as del17p, t(4,14) or amp(1q21) were not associated with shorter survival after allo-SCT. Extensive DC sampling beyond robust engraftment does not appear to provide additional information helpful for disease management in most patients and is challenged by a significant incidence of extramedullary disease. In our

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

    Institute of Scientific and Technical Information of China (English)

    朱康儿; 张涛; 陈盛亭; 钟隽; 曾慧兰

    2004-01-01

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

  5. A randomized trial of the effect of a walking regimen on the functional status of 100 adult allogeneic donor hematopoietic cell transplant patients.

    Science.gov (United States)

    DeFor, Todd E; Burns, Linda J; Gold, Eva-Maria A; Weisdorf, Daniel J

    2007-08-01

    To investigate the impact of exercise on adult allogeneic hematopoietic cell transplant recipients, we randomized 100 patients to either a structured walking regimen or to a control group with no formal exercise program. Starting on the day of admission for transplant, patients in the exercise arm were asked to walk on a treadmill twice a day for 15 minutes while in the hospital. After discharge, they were asked to walk once a day for 30 minutes. The effect of the exercise program was primarily measured by the change in the Karnofsky score (KPS) from transplant admission to day 100 posttransplant, which was scored by the attending physician who was blinded to the assigned exercise regimen. The decline in KPS was smaller in the exercise group than in the control group: 10 points versus 20 points. This difference was not statistically significant in the total study population (P=.21) but was statistically significant among the subset of older and less fit patients receiving nonmyeloablative pretransplant conditioning (P=.04). Sixty-four percent of patients on the exercise arm who had a baseline KPSor=90 by day 100 compared to 18% of the control arm (P=.03). Thirty-two percent of patients with a baseline score>or=90 had a score>or=90 by day 100 in both groups (P=.99). Analyses of patients' self reported scores at the time of discharge for physical and emotional well-being showed that the exercise arm had better scores for physical well-being (Ppatients, scores for physical and emotional well-being were both higher in the exercise arm (P=.02). Length of hospitalization and survival were not different between the 2 study arms. We conclude that assignment of a structured walking regimen to patients can lead to better physical performance during the recovery period and by patient assessment, a better perceived physical and emotional state. In addition, exercise has a greater impact among patients who are less fit coming into transplant. Structured exercise may have a

  6. The influence of interleukin-7 receptor α-chain haplotypes on outcome after allogeneic hematopoietic cell transplantation

    DEFF Research Database (Denmark)

    Broux, B; Shamim, Z; Wang, T;

    2014-01-01

    We investigated the influence of IL-7 receptor α-chain (IL-7Rα) gene haplotypes in donors on the outcome of haematopoietic cell transplantation (HCT). Unlike the association between single donor SNPs and HCT outcome found previously, only trends towards association were found here, due to 'diluti...

  7. Fatal deep vein thrombosis after allogeneic reduced intensity hematopoietic stem cell transplantation for the treatment of metastatic gastric cancer.

    Science.gov (United States)

    Kamitsuji, Yuri; Mori, Shin-Ichiro; Kami, Masahiro; Yamada, Hirofumi; Shirakawa, Kazuo; Kishi, Yukiko; Murashige, Naoko; Kim, Sung-Won; Heike, Yuji; Takaue, Yoichi

    2004-08-01

    A 61-year-old man received reduced intensity stem cell transplantation (RIST) for the treatment of metastatic gastric cancer. The cytoreductive course of RIST was uneventful until day 0, when fever suddenly developed and his performance status deteriorated. Edema developed in the bilateral lower extremities by day 7, which was diagnosed by Doppler ultrasonography as deep vein thrombosis (DVT) involving the femoral veins to the inferior vena cava. While the edema improved with anticoagulation treatment, gastrointestinal graft-versus-host disease (GVHD) followed on day 13. Diarrhea subsided spontaneously, but hypoalbuminemia persisted, with the subsequent development of oliguria and jaundice on day 18. He died of sepsis on day 30, without any evidence of cancer progression. This case demonstrates that DVT is a potentially significant problem following RIST for solid tumors.

  8. Present and future of allogeneic natural killer cell therapy

    Directory of Open Access Journals (Sweden)

    Okjae eLim

    2015-06-01

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

  9. Hematopoietic System

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    2011370 The efficacy and safety of second allogeneic hematopoietic stem cell transplantation for post-transplant hematologic malignancies relapse. CHEN Yuhong(陳育紅),et al.Instit Hematol,People’s Hosp,Peking Univ,Beijing 100044. Abstract:Objective To investigate the safety and efficacy of second allogeneic hematopoietic stem cell transplantation for the relapsed hematologic malignancies.Methods The data of 25 relapsed patients received the second allogeneic transplantation as a salvage therapy

  10. ABO血型不合异基因造血干细胞移植治疗恶性血液病%ABO-incompatible allogeneic hematopoietic stem cell transplantation for treating malignant hematologic diseases

    Institute of Scientific and Technical Information of China (English)

    邵晓雁; 欧阳建; 陈兵; 许景艳; 杨永公; 周敏

    2008-01-01

    合患者移植后成分输血过程未出现溶血反应,移植后也均未发生迟发性溶血反应.结论:ABO血型不合不影响造血干细胞移植的效果,且较为安全.%BACKGROUND:ABO-incompatibility between donor and recipient is not a barrier for Successful allogeneic hematopoietic stem cell transplantation even though it is well established that major ABO incompatibility may lead to prolonged destruction of donor-derived erythrocytos and prolonged transfusioil requirements.OBJECTIVE:To explore the effect of ABO.incompatible on clinical characteristics in allogeneic-hematopoietic stem cell transplantation.DESIGN:A retrospective observation.SETTING:Department of Hematology.the Affiliated Drum Tower Hospital of Nanjing University Medical School.PARTICIPANTS:Fourteen patients(11 males and 3 feiliales,aged 15-60 years old)with malignant hematologic diseases who received ABO-incompatible allogeneic hematopoietic stem cell transplantation in the Affiliated Drum Tower Hospital of Nanjing University Medical School from May 2002 to September 2007 Were recruited for this study.Of the 14 patients,7 were human leukocyte antigen(HLA).matched,and the other 7 were HLA-half-matched.Controls were 11 patients who received ABO-compatibility bone marrow transplantation during the same period.Written informed consents for receiving allogeneic hematopoietic stem cell transplantation were obtained from each reciplent.The donors were sibling sister,sibling brother.son and mother,and they all agreed to provide marrow for transplantation.T1lis experiment was given an approval by the Ethics Committees of the hospital.METHODS:Regimen conditioning:HLA-matched transplantation regimen conditioning consisted of busulfan(Bu)and cyclophosphamide(Cy).HLA-half-matched transplantation regimen conditioning adopted GIAC program from Beijing People's Hospital.The GIAC program consisted of 4 parts:G:granulocyte colony-stimulating factors used for donors;I:stronger immunosuppressive regimen

  11. Allogeneic hematopoietic stem cell transplantation from an alternative stem cell source in Fanconi anemia patients: analysis of 47 patients from a single institution

    Directory of Open Access Journals (Sweden)

    C.R. de Medeiros

    2006-10-01

    Full Text Available We transplanted 47 patients with Fanconi anemia using an alternative source of hematopoietic cells. The patients were assigned to the following groups: group 1, unrelated bone marrow (N = 15; group 2, unrelated cord blood (N = 17, and group 3, related non-sibling bone marrow (N = 15. Twenty-four patients (51% had complete engraftment, which was not influenced by gender (P = 0.87, age (P = 0.45, dose of cyclophosphamide (P = 0.80, nucleated cell dose infused (P = 0.60, or use of anti-T serotherapy (P = 0.20. Favorable factors for superior engraftment were full HLA compatibility (independent of the source of cells; P = 0.007 and use of a fludarabine-based conditioning regimen (P = 0.046. Unfavorable factors were > or = 25 transfusions pre-transplant (P = 0.011 and degree of HLA disparity (P = 0.007. Intensity of mucositis (P = 0.50 and use of androgen prior to transplant had no influence on survival (P = 0.80. Acute graft-versus-host disease (GVHD grade II-IV and chronic GVHD were diagnosed in 47 and 23% of available patients, respectively, and infections prevailed as the main cause of death, associated or not with GVHD. Eighteen patients are alive, the Kaplan-Meyer overall survival is 38% at ~8 years, and the best results were obtained with related non-sibling bone marrow patients. Three recommendations emerged from the present study: fludarabine as part of conditioning, transplant in patients with <25 transfusions and avoidance of HLA disparity. In addition, an extended family search (even when consanguinity is not present seeking for a related non-sibling donor is highly recommended.

  12. DNMT3A R882 Mutation with FLT3-ITD Positivity Is an Extremely Poor Prognostic Factor in Patients with Normal-Karyotype Acute Myeloid Leukemia after Allogeneic Hematopoietic Cell Transplantation.

    Science.gov (United States)

    Ahn, Jae-Sook; Kim, Hyeoung-Joon; Kim, Yeo-Kyeoung; Lee, Seun-Shin; Jung, Sung-Hoon; Yang, Deok-Hwan; Lee, Je-Jung; Kim, Nan Young; Choi, Seung Hyun; Jung, Chul Won; Jang, Jun-Ho; Kim, Hee Je; Moon, Joon Ho; Sohn, Sang Kyun; Won, Jong-Ho; Kim, Sung-Hyun; Kim, Dennis Dong Hwan

    2016-01-01

    The prognostic relevance of epigenetic modifying genes (DNMT3A, TET2, and IDH1/2) in patients with acute myeloid leukemia (AML) has been investigated extensively. However, the prognostic implications of these mutations after allogeneic hematopoietic cell transplantation (HCT) have not been evaluated comprehensively in patients with normal-karyotype (NK)-AML. A total of 115 patients who received allogeneic HCT for NK-AML were retrospectively evaluated for the FLT3-ITD, NPM1, CEBPA, DNMT3A, TET2, IDH1/2, WT1, NRAS, ASXL2, FAT1, DNAH11, and GATA2 mutations in diagnostic samples and analyzed for long-term outcomes after allogeneic HCT. The prevalence rates for the mutations were as follows: FLT3-ITD positivity (FLT3-ITD(pos)) (32.2%), NPM1 mutation (43.5%), CEBPA mutation (double) (24.6%), DNMT3A mutation (DNMT3A(mut)) (31.3%), DNMT3A R882(mut) (18.3%), TET2 mutation (8.7%), and IDH1/2 mutation (16.5%). The 5-year overall survival (OS) and event-free survival (EFS) rates were 57.3% and 58.1%, respectively. A multivariate analysis revealed that FLT3-ITD(pos) (hazard ratio, [HR], 2.23; P = .006) and DNMT3A R882(mut) (HR, 2.74; P = .002) were unfavorable prognostic factors for OS. In addition, both mutations were significant risk factors for EFS and relapse. People with DNMT3A R882(mut) accompanied by FLT3-ITD(pos) had worse OS and EFS, and higher relapse rates than those with the other mutations, which were confirmed in a propensity score 1:2 matching analysis. These results suggest that DNMT3A R882(mut), particularly when accompanied by FLT3-ITD(pos), is a significant prognostic factor for inferior transplantation survival outcome by increasing relapse risk, even after allogeneic HCT.

  13. 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.

    Directory of Open Access Journals (Sweden)

    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.

  14. Emerging uses for pediatric hematopoietic stem cells.

    Science.gov (United States)

    Domen, Jos; Gandy, Kimberly; Dalal, Jignesh

    2012-04-01

    Many new therapies are emerging that use hematopoietic stem and progenitor cells. In this review, we focus on five promising emerging trends that are altering stem cell usage in pediatrics: (i) The use of hematopoietic stem cell (HSC) transplantation, autologous or allogeneic, in the treatment of autoimmune disorders is one. (ii) The use of cord blood transplantation in patients with inherited metabolic disorders such as Hurler syndrome shows great benefit, even more so than replacement enzyme therapy. (iii) Experience with the delivery of gene therapy through stem cells is increasing, redefining the potential and limitations of this therapy. (iv) It has recently been shown that human immunodeficiency virus (HIV) infection can be cured by the use of selected stem cells. (v) Finally, it has long been postulated that HSC-transplantation can be used to induce tolerance in solid-organ transplant recipients. A new approach to tolerance induction using myeloid progenitor cells will be described.

  15. Conventional allogeneic hematopoietic stem cell transplantation for lymphoma may overcome the poor prognosis associated with a positive FDG-PET scan before transplantation.

    Science.gov (United States)

    Yoshimi, Akihide; Izutsu, Koji; Takahashi, Miwako; Kako, Shinichi; Oshima, Kumi; Kanda, Yoshinobu; Motokura, Toru; Chiba, Shigeru; Momose, Toshimitsu; Ohtomo, Kuni; Kurokawa, Mineo

    2008-06-01

    A positive scan in pretransplantation fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has been shown to be associated with a poor prognosis in patients with lymphoma undergoing high-dose chemotherapy followed by autologous stem cell transplantation (ASCT). For those with a positive FDG-PET scan, treatment that includes allogeneic stem cell transplantation (allo-SCT) may be an alternative. However, it is uncertain whether allo-SCT can overcome a poor prognosis. Therefore, we conducted a retrospective analysis of 14 patients with lymphoma who had undergone FDG-PET scan within one month before allo-SCT at our institution. Eleven patients were FDG-PET-positive and three were negative. With a median follow-up of 17 months (range: 6-44) after allo-SCT, the cumulative incidence of progression was 29.3% in FDG-PET-positive patients and 0% in the FDG-PET-negative patients. Four of the 11 patients who had post-transplantation FDG-PET showed FDG-avid lesions on the first post-transplantation scan. In two of the four, regression of the lesions was observed during the scheduled reduction of immunosuppressant without donor lymphocyte infusion and remained without progression at the last follow-up (34 and 8 months). Durable responses after allo-SCT, at least with conventional conditioning regimens, can be expected in patients with FDG-PET-positive lesions before transplantation. Thus, conventional allo-SCT could be an attractive modality compared to ASCT for patients with positive FDG-PET after the completion of conventional salvage chemotherapy, and particularly for patients with T and NK-cell lymphomas.

  16. Allogeneic hematopoietic cell transplantation after conditioning with I-131-anti-CD45 antibody plus fludarabine and low-dose total body irradiation for elderly patients with advanced acute myeloid leukemia or high-risk myelodysplastic syndrome.

    Energy Technology Data Exchange (ETDEWEB)

    Pagel, John M.; Gooley, T. A.; Rajendran, Joseph G.; Fisher, Darrell R.; Wilson, Wendy A.; Sandmaier, B. M.; Matthews, D. C.; Deeg, H. Joachim; Gopal, Ajay K.; Martin, P. J.; Storb, R.; Press, Oliver W.; Appelbaum, Frederick R.

    2009-12-24

    We conducted a study to estimate the maximum tolerated dose (MTD) of I-131-anti-CD45 antibody (Ab; BC8) that can be combined with a standard reduced-intensity conditioning regimen before allogeneic hematopoietic cell transplantation. Fifty-eight patients older than 50 years with advanced acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) were treated with (131)I-BC8 Ab and fludarabine plus 2 Gy total body irradiation. Eighty-six percent of patients had AML or MDS with greater than 5% marrow blasts at the time of transplantation. Treatment produced a complete remission in all patients, and all had 100% donor-derived CD3(+) and CD33(+) cells in the blood by day 28 after the transplantation. The MTD of I-131-BC8 Ab delivered to liver was estimated to be 24 Gy. Seven patients (12%) died of nonrelapse causes by day 100. The estimated probability of recurrent malignancy at 1 year is 40%, and the 1-year survival estimate is 41%. These results show that CD45-targeted radiotherapy can be safely combined with a reduced-intensity conditioning regimen to yield encouraging overall survival for older, high-risk patients with AML or MDS. This study was registered at www.clinicaltrials.gov as #NCT00008177.

  17. Allogeneic hematopoietic cell transplantation after conditioning with 131I-anti-CD45 antibody plus fludarabine and low-dose total body irradiation for elderly patients with advanced acute myeloid leukemia or high-risk myelodysplastic syndrome.

    Science.gov (United States)

    Pagel, John M; Gooley, Theodore A; Rajendran, Joseph; Fisher, Darrell R; Wilson, Wendy A; Sandmaier, Brenda M; Matthews, Dana C; Deeg, H Joachim; Gopal, Ajay K; Martin, Paul J; Storb, Rainer F; Press, Oliver W; Appelbaum, Frederick R

    2009-12-24

    We conducted a study to estimate the maximum tolerated dose (MTD) of (131)I-anti-CD45 antibody (Ab; BC8) that can be combined with a standard reduced-intensity conditioning regimen before allogeneic hematopoietic cell transplantation. Fifty-eight patients older than 50 years with advanced acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) were treated with (131)I-BC8 Ab and fludarabine plus 2 Gy total body irradiation. Eighty-six percent of patients had AML or MDS with greater than 5% marrow blasts at the time of transplantation. Treatment produced a complete remission in all patients, and all had 100% donor-derived CD3(+) and CD33(+) cells in the blood by day 28 after the transplantation. The MTD of (131)I-BC8 Ab delivered to liver was estimated to be 24 Gy. Seven patients (12%) died of nonrelapse causes by day 100. The estimated probability of recurrent malignancy at 1 year is 40%, and the 1-year survival estimate is 41%. These results show that CD45-targeted radiotherapy can be safely combined with a reduced-intensity conditioning regimen to yield encouraging overall survival for older, high-risk patients with AML or MDS. This study was registered at www.clinicaltrials.gov as #NCT00008177.

  18. Higher proportions of peripheral CD19+CD5+ B cells predict the effect of corticosteroid in patients with late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    FU Hai-xia; WANG Jing-zhi; ZHAO Ting; ZHANG Yuan-yuan; CHEN Yao; HUANG Xiao-jun; XU Lan-ping; LIU Dai-hong; LIU Kai-yan; CHEN Huan; HAN Wei; ZHANG Xiao-hui; WANG Yu; WANG Feng-rong

    2011-01-01

    Background The cause of late-onset hemorrhagic cystitis (LOHC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains obscure. In clinical practice, some LOHC patients respond to immunosuppression.The aim of this study was to determine the immune pathogenesis of LOHC post allo-HSCT.Methods With the diagnosis of LOHC, patients were given initial treatment consisting of fluid hydration, alkalization and forced diuresis, and empirical anti-viral therapy for 10-14 days or until a week after the virus became negative. The nonresponders were applied corticosteroid. Seven to ten days later, patients' response was evaluated. Along with treatment, CD19+ B lymphocyte subsets were measured at various study points.Results From October 2009 to March 2010, we found 28 cases of LOHC occurred in 25 patients who underwent allo-HSCT in our hospital. Except that three cases were not treated according to the protocol, the other 25 cases were divided into three groups: anti-virus responders (Group A, n=6), corticosteroid responders (Group B1, n=16),corticosteroid and anti-virus nonresponders (Group C, n=3) according to their clinical response. Percentages of CD19+CD5+ B lymphocytes were not significantly different among three groups at onset of LOCH. However, in Group B1after the first anti-virus phase, percentages of CD19+CD5+ lymphocytes significantly increased comparing with those at onset (P=0.022), and then significantly decreased at PR (P=0.003) and CR (P=0.002) with corticosteroid treatment. But significant change was not observed in Groups A and C.Conclusion The immune etiology seems to be involved in the development of LOHC and the proportion of CD19+CD5+lymphocytes may serve as a cellular biomarker to predict the response to corticosteroid in LOHC.

  19. Myositis in Griscelli syndrome type 2 treated with hematopoietic cell transplantation

    DEFF Research Database (Denmark)

    Born, Alfred Peter; Müller, Klaus; Marquart, Hanne Vibeke;

    2010-01-01

    and elevated plasma creatine kinase. Muscle biopsy showed massive inflammatory changes in some fascicles, while other fascicles were relatively spared. Clinical symptoms and biopsy changes resolved after immunosuppression and allogeneic hematopoietic cell transplantation. Our results suggest that muscle...

  20. A reappraisal of ICU and long-term outcome of allogeneic hematopoietic stem cell transplantation patients and reassessment of prognosis factors: results of a 5-year cohort study (2009-2013).

    Science.gov (United States)

    Platon, L; Amigues, L; Ceballos, P; Fegueux, N; Daubin, D; Besnard, N; Larcher, R; Landreau, L; Agostini, C; Machado, S; Jonquet, O; Klouche, K

    2016-02-01

    Epidemiology and prognosis of complications related to allogeneic hematopoietic stem cell transplant (HSCT) recipients requiring admission to intensive care unit (ICU) have not been reassessed precisely in the past few years. We performed a retrospective single-center study on 318 consecutive HSCT patients (2009-2013), analyzing outcome and factors prognostic of ICU admission. Among these patients, 73 were admitted to the ICU. In all, 32 patients (40.3%) died in ICU, 46 at hospital discharge (63%) and 61 (83.6%) 1 year later. Survivors had a significantly lower sequential organ failure assessment (SOFA) score, serum lactate and bilirubin upon ICU admission. Catecholamine support, mechanical ventilation (MV) and/or renal replacement therapy during ICU stay, a delayed organ support and an active graft versus host disease (GvHD) significantly worsen the outcome. By multivariate analysis, the worsening of SOFA score from days 1 to 3, the need for MV and the occurrence of an active GvHD were predictive of mortality. In conclusion, the incidence of HSCT-related complications requiring an admission to an ICU was at 22%, with an ICU mortality rate of 44%, and 84% 1 year later. A degradation of SOFA score at day 3 of ICU, need of MV and occurrence of an active GvHD are main predictive factors of mortality.

  1. [A medical-pharmaceutical partnership model as a contributor to the success in conditioning regimen for allogenic hematopoietic stem cell transplantation in adults: a cross-reflection on our organizations].

    Science.gov (United States)

    Bourget, Philippe; Falaschi, Ludivine; Suarez, Felipe; Galland, Valérie; Blot, Dominique; Trompette, Caroline; Sibon, David; Fontbrune, Flore Sicre de; Merlette, Christophe; Vidal, Fabrice; Corriol, Odile; Giraud, Bérénice; Broissand, Christine; Clement, Rozenn; Hermine, Olivier

    2012-06-01

    Allogeneic hematopoietic stem-cell transplant (allo-SCT) remains the only cure for many hematological malignancies and some benign and congenital diseases. Busulfan, proposed in its injectable form, has quickly become a mainstay of pharmacological and myeloablative (or non-myeloablative) conditioning. This is following the outbreak in 2010 of a multicenter international clinical phase II trial, we tested the robustness and reliability of our organization in a complex model of organization and multifactorial partnership. In this type "BuCy2" protocol based on a classical treatment duration of 4 consecutive days, the administration of IV busulfan is given in one single daily infusion instead of the conventional 16 infusions, while keeping the same total dose. Under these conditions, the treatment is totally secured using a therapeutic drug monitoring of busulfan, applied in real-time. The process is technically complex and requires the very close cooperation of the teams involved. A strength, weakness, opportunity and threat (SWOT) analysis has been constructed; it fully supports continuous quality improvement to the triple benefit of the nursing chain, the patients and their environment. Several critical points were identified and corrected. The experiment strongly contributes to the safety and security of the medication circuit at the hospital and, improves the performance of allo-SCT. It also contributes to the protection of all actors in the health field and their working environment via a well-functioning quality management system.

  2. Hyperglycemia as a possible risk factor for mold infections-the potential preventative role of intensified glucose control in allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Fuji, S; Löffler, J; Savani, B N; Einsele, H; Kapp, M

    2016-12-12

    Diabetes mellitus (DM) is well-known as a disorder that increases the risk of infectious diseases. Various reports have shown that innate immunity is impaired in patients with DM, which is considered to be a major cause of increased risk of infectious diseases. However, there is a paucity of data about the actual risk of mold infections in patients with DM. Several treatment procedures, such as solid organ transplantation and hematopoietic stem cell transplantation (HSCT), are intrinsically associated with a high risk of mold infections and also correlated with an increased risk of post-transplant DM. Therefore, we could assume that organ transplant recipients or HSCT recipients with DM are at quite high risk of mold infections. Here, we aim to summarize the information about the increased risk of mold infections in patients with DM, and propose possible interventions such as intensive glucose control to reduce this risk in patients with DM.Bone Marrow Transplantation advance online publication, 12 December 2016; doi:10.1038/bmt.2016.306.

  3. Busulfan plus fludarabine as a myeloablative conditioning regimen compared with busulfan plus cyclophosphamide for acute myeloid leukemia in first complete remission undergoing allogeneic hematopoietic stem cell transplantation: a prospective and multicenter study

    Directory of Open Access Journals (Sweden)

    Liu Hui

    2013-02-01

    Full Text Available Abstract Objective We conducted a prospective, randomized, open-label, multicenter study to compare busulfan plus fludarabine (BuFlu with busulfan plus cyclophosphamide (BuCy as the conditioning regimen in allogeneic hematopoietic stem cell transplantation (allo-HSCT for acute myeloid leukemia (AML in first complete remission (CR1. Methods Totally 108 AML-CR1 patients undergoing allo-HSCT were randomized into BuCy (busulfan 1.6 mg/kg, q12 hours, -7 ~ -4d; cyclophosphamide 60 mg/kg.d, -3 ~ -2d or BuFlu (busulfan 1.6 mg/kg, q12 hours, -5 ~ -2d; fludarabine 30 mg/m2.d, -6 ~ -2d group. Hematopoietic engraftment, regimen-related toxicity (RRT, graft-versus-host disease (GVHD, transplant related mortality (TRM, and overall survival were compared between the two groups. Results All patients achieved hematopoietic reconstitution except for two patients who died of RRT during conditioning. All patients obtained complete donor chimerism by day +30 post-transplantation. The incidence of total and III-IV RRT were 94.4% and 81.5% (P = 0.038, and 16.7% and 0.0% (P = 0.002, respectively, in BuCy and BuFlu group. With a median follow up of 609 (range, 3–2130 days after transplantation, the 5-year cumulative incidence of TRM were 18.8 ± 6.9% and 9.9 ± 6.3% (P = 0.104; the 5-year cumulative incidence of leukemia relapse were 16.5 ± 5.8% and 16.2 ± 5.3% (P = 0.943; the 5-year disease-free survival and overall survival were 67.4 ± 7.6% and 75.3 ± 7.2% (P = 0.315, and 72.3 ± 7.5% and 81.9 ± 7.0% (P = 0.177, respectively in BuCy and BuFlu group. Conclusion Compared with BuCy, BuFlu as a myeloablative condition regimen was associated with lower toxicities and comparable anti-leukemic activity in AML-CR1 patients undergoing allo-HSCT.

  4. THE TIME IS NOW: MOVING TOWARDS VIRUS-SPECIFIC T CELLS AFTER ALLOGENIC HEMATOPOIETIC STEM CELL TRANSPLANTATION AS THE STANDARD OF CARE

    OpenAIRE

    2014-01-01

    Adoptive immunotherapy—in particulary T cell therapy—has recently emerged as a useful strategy with the potential to overcome many of the limitations of antiviral drugs for the treatment of viral complications after hematopietic stem cell transplantation (HSCT). In this review we briefly summarize the current methods for virus- specific T cell isolation or selection and we report results from clinical trials employing these techniques, focusing specifically on the strategies aimed to broaden ...

  5. THE TIME IS NOW: MOVING TOWARDS VIRUS-SPECIFIC T CELLS AFTER ALLOGENIC HEMATOPOIETIC STEM CELL TRANSPLANTATION AS THE STANDARD OF CARE

    Science.gov (United States)

    Saglio, Francesco; Hanley, Patrick J; Bollard, Catherine M

    2014-01-01

    Adoptive immunotherapy—in particulary T cell therapy—has recently emerged as a useful strategy with the potential to overcome many of the limitations of antiviral drugs for the treatment of viral complications after hematopietic stem cell transplantation (HSCT). In this review we briefly summarize the current methods for virus- specific T cell isolation or selection and we report results from clinical trials employing these techniques, focusing specifically on the strategies aimed to broaden the application of this technology. PMID:24438896

  6. Improvement of Thymopoiesis after Hematopoietic Stem Cell Transplantation by Cytokines: Translational studies in experimental animal models

    NARCIS (Netherlands)

    E-J. Wils (Evert-Jan)

    2011-01-01

    textabstractAllogeneic hematopoietic stem cell transplantation (AlloHSCT) is a powerful treatment modality that is frequently applied as part of treatment of hematological malignancies, aplastic anemia and inborn errors of hematopoietic progenitor cells. A major drawback of alloHSCT is the treatment

  7. The time is now: moving toward virus-specific T cells after allogeneic hematopoietic stem cell transplantation as the standard of care.

    Science.gov (United States)

    Saglio, Francesco; Hanley, Patrick J; Bollard, Catherine M

    2014-02-01

    Adoptive immunotherapy-in particular, T-cell therapy-has recently emerged as a useful strategy with the potential to overcome many of the limitations of antiviral drugs for the treatment of viral complications after hematopietic stem cell transplantation. In this review, we briefly summarize the current methods for virus-specific T-cell isolation or selection and we report results from clinical trials that have used these techniques, focusing specifically on the strategies aimed to broaden the application of this technology.

  8. Clinical and In Vitro Studies on Impact of High-Dose Etoposide Pharmacokinetics Prior Allogeneic Hematopoietic Stem Cell Transplantation for Childhood Acute Lymphoblastic Leukemia on the Risk of Post-Transplant Leukemia Relapse.

    Science.gov (United States)

    Sobiak, Joanna; Kazimierczak, Urszula; Kowalczyk, Dariusz W; Chrzanowska, Maria; Styczyński, Jan; Wysocki, Mariusz; Szpecht, Dawid; Wachowiak, Jacek

    2015-10-01

    The impact of etoposide (VP-16) plasma concentrations on the day of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on leukemia-free survival in children with acute lymphoblastic leukemia (ALL) was studied. In addition, the in vitro effects of VP-16 on the lymphocytes proliferation, cytotoxic activity and on Th1/Th2 cytokine responses were assessed. In 31 children undergoing allo-HSCT, VP-16 plasma concentrations were determined up to 120 h after the infusion using the HPLC-UV method. For mentioned in vitro studies, VP-16 plasma concentrations observed on allo-HSCT day were used. In 84 % of children, VP-16 plasma concentrations (0.1-1.5 μg/mL) were quantifiable 72 h after the end of the drug infusion, i.e. when allo-HSCT should be performed. In 20 (65 %) children allo-HSCT was performed 4 days after the end of the drug infusion, and VP-16 was still detectable (0.1-0.9 μg/mL) in plasma of 12 (39 %) of them. Post-transplant ALL relapse occurred in four children, in all of them VP-16 was detectable in plasma (0.1-0.8 μg/mL) on allo-HSCT day, while there was no relapse in children with undetectable VP-16. In in vitro studies, VP-16 demonstrated impact on the proliferation activity of stimulated lymphocytes depending on its concentration and exposition time. The presence of VP-16 in plasma on allo-HSCT day may demonstrate an adverse effect on graft-versus-leukemia (GvL) reaction and increase the risk of post-transplant ALL relapse. Therefore, if 72 h after VP-16 administration its plasma concentration is still above 0.1 μg/mL then the postponement of transplantation for next 24 h should be considered to protect GvL effector cells from transplant material.

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

    Institute of Scientific and Technical Information of China (English)

    ZHANG Lan-fang; XIA Chang-qing

    2013-01-01

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

  10. Efficacy of Allogeneic Hematopoietic Stem Cell Transplantation in Treatment of Severe Aplastic Anemia%异基因造血干细胞移植治疗重型再生障碍性贫血的疗效研究

    Institute of Scientific and Technical Information of China (English)

    朱玲; 薛梅; 王志东; 闫洪敏; 刘静; 丁丽; 王恒湘

    2011-01-01

    Objective To explore the effectiveness of Allogeneic hematopoietic stem cell transplantation ( allo -HSCT ) in treating severe aplastic anemia ( SAA ).Methods Among the 8 patients, 1 patient received allogeneic peripheral stem cell transplantation from an HLA matched sibling, 4 patients received allogeneic bone marrow and peripheral stem cell transplantation from haploidentical donors ( parents ), 3 patients received unrelated allogeneic peripheral stem cell transplantation.Conditioning regimens included: fludarabine, Cyeclophosphamide, anti - themocyte globulin ( for unrelated and HLA matched sibling donors ); fludarabine, Cyeclophosphamide, busulphan and anti - lymphocyte globulin ( ALG ) /anti - themocyte globulin ( ATG ) ( for haploidentical donors ).For prevention of graft versus host disease ( GVHD ) the patient with HLA matched sibling donor was administered with a combination of immunosuppressive drugs including CSA, short - course MTX while for the patients with haploidentical or unrelated donors, MMF, anti - CD25 monoclonal antibody and ATG were, also employed.Results All the 8 patients achieved hematopoietic reconstitution after transplantation.It took 10 ~ 17 days ( : median: 12.5 days ) for the level of neutrophils to reach 0.5 × 10 /L and 9-25 days ( median: 13.8 days ) for platelets to reach 20 × 10 /L.All the 8 patients became donor chimerism.As for the complications, CMV - related sepsis was found in 5 cases, hemorrhagic cystitis in 3 cases, Grade Ⅰ ~ Ⅲ graf - versus - host disease ( GVHD ) and chronic local GVHD in 2 patients, and central nervous system infection accompanied with pure red aplastic anemia in 1 case.All the patients survived during the follow - up ( range: 9 ~ 38 months; median: 20 months).Conclusion Allo - HSCT is an effective approach for treating patients with SAA.It may be helpful to prolong the survivals of these patients.%目的 探讨异基因造血干细胞移植(allo-HSCT)治疗重型再生障

  11. Allogeneic hematopoietic stem cell transplantation for chronic lymphocytic leukemia%慢性淋巴细胞白血病的造血干细胞移植治疗

    Institute of Scientific and Technical Information of China (English)

    杨申淼; 江倩; 许兰平

    2013-01-01

      慢性淋巴细胞白血病(CLL)存在很大的临床异质性。尽管免疫化疗方案的进步带来了显著的疗效,部分患者仍可在短期内发生疾病进展,或处于疾病难治耐药的状态。由于移植物抗CLL效应的存在,异基因造血干细胞移植的根治性意义获得肯定。年轻CLL患者如具有高危因素,包括:嘌呤类似物耐药或治疗后早期复发,以及具有17p(TP53位点)缺失和TP53突变,异基因造血干细胞移植是合理的治疗选择。减低强度的预处理方案有效降低了患者的治疗相关死亡率。%Chronic lymphocytic leukemia(CLL) is an indolent lymphoproliferative disorder with great clinical heterogeneity. The immunochemotherapeutic regimens have improved the outcome of majority of the patients. Nonetheless, in some patients, the disease progresses shortly after the immunochemotherapy, while in others, it becomes refractory and drug resistant. Allogeneic hematopoietic stem cell transplantation(allo-SCT) potentially cures CLL due to the graft versus CLL effect. It has been wildly accepted that allo-SCT is a good option for young CLL patients with high risk factors, including purine analogue resistance, early relapse after purine analogue-based treatment, and 17p deletion and TP53 mutation. Reduced-intensity conditioning regimens effectively decrease the treatment-related mortality.

  12. Proven Epstein-Barr encephalitis with negative EBV-DNA load in cerebrospinal fluid after allogeneic hematopoietic stem cell transplantation in a child with acute lymphoblastic leukemia.

    Science.gov (United States)

    Barberi, Walter; Perrone, Salvatore; Iori, Anna Paola; Torelli, Giovanni Fernando; Testi, Anna Maria; Moleti, Maria Luisa; Ceglie, Teresa; Papoff, Paola; Caresta, Elena; Antonelli, Manila; Gianno, Francesca; Melone, Antonio; Badiali, Manuela; Giangaspero, Felice; Foà, Robin; Gentile, Giuseppe

    2015-02-01

    We report a case of EBV encephalitis in a seven-yr-old child with Ph+ ALL. Two months after an allogeneic HSCT from his HLA mismatched mother, the patient showed an altered sensorium, generalized seizures, and a left hemiparesis. Brain MRI demonstrated multiple lesions highly suggestive for viral encephalitis. Blood and CSF PCR analyses were negative for the most common viruses involved in immunocompromised patients including EBV. A cerebral biopsy was performed, which showed intense gliosis and perivascular lymphocytic cuffing. PCR analysis performed on brain tissue was positive only for the EBV genome, while extensive investigations for other viral infections were negative. The patient's neurological symptoms rapidly worsened and he died two months later. This case report suggests that in patients presenting neurological and radiological signs of encephalitis after an HSCT, an EBV involvement should be considered, even in the absence of CSF and blood PCR virus detection.

  13. 同胞相合异基因造血干细胞移植治疗恶性血液病的疗效%Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantation for Malignant Hematopathy

    Institute of Scientific and Technical Information of China (English)

    邱大发; 黄贵年; 许晓军; 郭子文; 何慧清; 任志娟; 林淑华; 宋奎; 牛晓敏; 黎伟超

    2011-01-01

    目的 探讨同胞相合异基因造血干细胞移植治疗恶性血液病的临床疗效.方法 将26例恶性血液病患者按移植前疾病状态分为2组:高危组11例和标危组15例.2组患者均采用外周血同胞相合异基因造血干细胞移植.预处理方案:高危组采用全身照射+环磷酰胺,标危组采用白消安+环磷酰胺;移植物抗宿主病的预防:2组均采用环孢素A+短程甲氨蝶呤,或加霉酚酸脂.观察2组患者造血重建和急、慢性移植物抗宿主病、巨细胞病毒活动性感染/巨细胞病毒病、移植复发及移植相关死亡及无病生存等情况.结果 2组患者移植后均获得造血重建,均为完全供体嵌合型.2组患者移植后14例发生急性移植物抗宿主病(aGVHD),累积发病率为53.8%(14/26).9例发生慢性移植物抗宿主病(cGVHD),累积发病率为45.0%(9/20).2组患者移植后有20例(76.9%)出现巨细胞病毒血症,无一例患者发生巨细胞病毒病.标危组复发率与高危组比较差异无统计学意义(6.7%vs 18.2%,P>0.05).标危组移植相关病死率与高危组比较差异有统计学意义(13.3%vs 54.5%,P<0.05).高危组和标危组患者1、3年累积无病生存率分别为30.3%、85.1%和15.2%、68.1%(均P<0.05).结论 移植前疾病状态是影响移植疗效的重要因素,移植物抗宿主病的发生对移植后疾病的复发及生活质量有重要的影响.%Objective To explore the clinical curative effect of matched sibling allogeneic hematopoietic stem cell transplantation(HSCT) on malignant hematopathy. Methods Twenty-six patients with malignant hematopathy were divided into two groups according to primary disease situation before transplantation: high-risk group (11 cases) and standard-risk group (15 cases). Matched sibling allogeneic HSCT were performed in all patients. Total body irradiation plus cyclophosphamide were used as conditioning therapy in high-risk group and busulphan plus cyclophosphamide were used in

  14. Cryopreservation of hematopoietic stem/progenitor cells for therapeutic use.

    Science.gov (United States)

    Watt, Suzanne M; Austin, Eric; Armitage, Sue

    2007-01-01

    To date, more than 25,000 hematopoietic transplants have been carried out across Europe for hematological disorders, the majority being for hematological malignancies. At least 70% of these are autologous transplants, the remaining 30% being allogeneic, which are sourced from related (70% of the allogeneic) or unrelated donors. Peripheral blood mobilized with granulocyte colony stimulating factor is the major source of stem cells for transplantation, being used in approx 95% of autologous transplants and in approx 65% of allogeneic transplants. Other cell sources used for transplantation are bone marrow and umbilical cord blood. One crucial advance in the treatment of these disorders has been the development of the ability to cryopreserve hematopoietic stem cells for future transplantation. For bone marrow and mobilized peripheral blood, the majority of cryopreserved harvests come from autologous collections that are stored prior to a planned infusion following further treatment of the patient or at the time of a subsequent relapse. Other autologous harvests are stored as backup or "rainy day" harvests, the former specifically being intended to rescue patients who develop graft failure following an allogeneic transplant or who may require this transplant at a later date. Allogeneic bone marrow and mobilized peripheral blood are less often cryopreserved than autologous harvests. This is in contrast to umbilical cord blood that may be banked for directed or sibling (related) hematopoietic stem cell transplants, for allogeneic unrelated donations, and for autologous donations. Allogeneic unrelated donations are of particular use for providing a source of hematopoietic stem cells for ethnic minorities, patients with rare human leukocyte antigen types, or where the patient urgently requires a transplant and cannot wait for the weeks to months required to prepare a bone marrow donor. There are currently more than 200,000 banked umbilical cord blood units registered with

  15. Hematopoietic Stem-Cell Transplantation for Sickle Cell Disease

    Directory of Open Access Journals (Sweden)

    Atila Tanyeli

    2014-02-01

    Full Text Available Sickle cell anemia is one of the most common hemoglobinopathies in the worldwide. Sickle cell anemia characterized by crises and organ failure develops over time. Myeloablative stem cell transplantation is curative but it has been performed in children younger than 16 years of age. Modest modifications in the conditioning regimen and supportive care have improved outcome such that the majority of children with a suitable HLA-matched sibling donor can expect a cure from this approach. But nonmyeloablative protocols are crucial for the future of Hematopoietic Stem-Cell Transplantation for older sickle cell anemia patients with organ failure. A protocol for nonmyeloablative allogeneic hematopoietic stem-cell transplantation that includes total-body irradiation and treatment with alemtuzumab and sirolimus can achieve stable, mixed donor–recipient chimerism. Stem cell transplantation is recommended in the presence of HLA-matched siblings in patients at risk.

  16. Comparison of Outcomes for Pediatric Patients With Acute Myeloid Leukemia in Remission and Undergoing Allogeneic Hematopoietic Cell Transplantation With Myeloablative Conditioning Regimens Based on Either Intravenous Busulfan or Total Body Irradiation: A Report From the Japanese Society for Hematopoietic Cell Transplantation.

    Science.gov (United States)

    Ishida, Hiroyuki; Kato, Motohiro; Kudo, Kazuko; Taga, Takashi; Tomizawa, Daisuke; Miyamura, Takako; Goto, Hiroaki; Inagaki, Jiro; Koh, Katsuyoshi; Terui, Kiminori; Ogawa, Atsushi; Kawano, Yoshifumi; Inoue, Masami; Sawada, Akihisa; Kato, Koji; Atsuta, Yoshiko; Yamashita, Takuya; Adachi, Souichi

    2015-12-01

    Pediatric patients with acute myeloid leukemia (AML) mainly receive myeloablative conditioning regimens based on busulfan (BU) or total body irradiation (TBI) before allogeneic hematopoietic cell transplantation (allo-HCT); however, the optimal conditioning regimen remains unclear. To identify which of these regimens is better for pediatric patients, we performed a retrospective analysis of nationwide registration data collected in Japan between 2006 and 2011 to assess the outcomes of patients receiving these regimens before a first allo-HCT. Myeloablative conditioning regimens based on i.v. BU (i.v. BU-MAC) (n = 69) or TBI (TBI-MAC) (n = 151) were compared in pediatric AML patients in first or second complete remission (CR1/CR2). The incidences of sinusoid obstruction syndrome, acute and chronic graft-versus-host disease, and early nonrelapse mortality (NRM) before day 100 were similar for both conditioning groups; however, the incidence of bacterial infection during the acute period was higher in the TBI-MAC group (P = .008). Both groups showed a similar incidence of NRM, and there was no significant difference in the incidence of relapse between the groups. Univariate and multivariate analyses revealed no significant differences in the 2-year relapse-free survival rates for the i.v. BU-MAC and TBI-MAC groups in the CR1/CR2 setting (71% versus 67%, P = .36; hazard ratio, .73; 95% CI, .43 to 1.24, respectively). TBI-MAC was no better than i.v. BU-MAC for pediatric AML patients in remission. Although this retrospective registry-based analysis has several limitations, i.v. BU-MAC warrants further evaluation in a prospective trial.

  17. 异基因造血干细胞移植治疗急性髓系白血病的现状%Allogeneic hematopoietic stem cell transplantation in treatment of acute myeloid leukemia

    Institute of Scientific and Technical Information of China (English)

    符粤文; 王倩; 宋永平

    2013-01-01

    异基因造血干细胞移植(allo-HSCT)是治疗急性髓系白血病(AML)的有效方法之一.allo-HSCT的治疗作用来自于预处理中的放疗和(或)化疗,以及供者免疫系统的移植物抗白血病(GVL)效应.近十年来,随着对白血病细胞生物学特性研究的不断深入,根据细胞遗传学和分子标志对AML进行危险程度分级,使我们能够挑选出哪些AML患者可以从allo-HSCT中获益.allo-HSCT治疗AML的临床疗效已有明显提高,并且适用范围也较前扩大,但在AML中的应用还存在一定差异.现对allo-HSCT治疗AML的机制、时机、疗效、供者选择及预处理方案进行讨论.%Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective way to acute myeloid leukemia (AML).The therapy effect of allo-HSCT comes from the preconditioning of the radiation and/or chemotherapy,as well as the graft versus leukemia (GVL) effect of the donor' s immune system.In nearly a decade,with the deepening research on biological characteristics of leukemia cells,according to the cytogenetic and molecular markers to dangerous degree classification of AML,which enables us to pick out AML patients can benefit from allo-HSCT.The clinical curative effect of allo-HSCT for AML has obviously improved,and applicable scope has also extended,but there are some differences in the application of AML.The mechanism,opportunity,curative effects,donor selection and preconditioning of allo-HSCT for AML are discussed.

  18. Cytomegalovirus Reactivation after Allogeneic Hematopoietic Stem Cell Transplantation is Associated with a Reduced Risk of Relapse in Patients with Acute Myeloid Leukemia Who Survived to Day 100 after Transplantation: The Japan Society for Hematopoietic Cell Transplantation Transplantation-related Complication Working Group.

    Science.gov (United States)

    Takenaka, Katsuto; Nishida, Tetsuya; Asano-Mori, Yuki; Oshima, Kumi; Ohashi, Kazuteru; Mori, Takehiko; Kanamori, Heiwa; Miyamura, Koichi; Kato, Chiaki; Kobayashi, Naoki; Uchida, Naoyuki; Nakamae, Hirohisa; Ichinohe, Tatsuo; Morishima, Yasuo; Suzuki, Ritsuro; Yamaguchi, Takuhiro; Fukuda, Takahiro

    2015-11-01

    Cytomegalovirus (CMV) infection is a major infectious complication after allogeneic hematopoietic cell transplantation (allo-HSCT). Recently, it was reported that CMV reactivation is associated with a decreased risk of relapse in patients with acute myeloid leukemia (AML). The aim of this study was to evaluate the impact of early CMV reactivation on the incidence of disease relapse after allo-HSCT in a large cohort of patients. The Japan Society for Hematopoietic Cell Transplantation's Transplantation-Related Complication Working Group retrospectively surveyed the database of the Transplant Registry Unified Management Program at the Japan Society for Hematopoietic Cell Transplantation. Patients with AML (n = 1836), acute lymphoblastic leukemia (ALL, n = 911), chronic myeloid leukemia (CML, n = 223), and myelodysplastic syndrome (MDS, n = 569) who underwent their first allo-HSCT from HLA-matched related or unrelated donors between 2000 and 2009 and who survived without disease relapse until day 100 after transplantation were analyzed. Patients who received umbilical cord blood transplantation were not included. Patients underwent surveillance by pp65 antigenemia from the time of engraftment, and the beginning of preemptive therapy was defined as CMV reactivation. Cox proportional hazards models were used to evaluate the risk factors of relapse, nonrelapse, and overall mortality. CMV reactivation and acute/chronic graft-versus-host disease (GVHD) were evaluated as time-dependent covariates. CMV reactivation was associated with a decreased incidence of relapse in patients with AML (20.3% versus 26.4%, P = .027), but not in patients with ALL, CML, or MDS. Among 1836 patients with AML, CMV reactivation occurred in 795 patients (43.3%) at a median of 42 days, and 436 patients (23.7%) relapsed at a median of 221 days after allo-HSCT. Acute GVHD grades II to IV developed in 630 patients (34.3%). By multivariate analysis considering competing risk factors, 3

  19. 异基因造血干细胞移植治疗骨髓增生异常综合征临床疗效分析%Clinical efficacy of allogeneic hematopoietic stem cell transplantation on myelodysplastic syndrome

    Institute of Scientific and Technical Information of China (English)

    皖湘; 孙自敏; 刘会兰; 耿良权; 王兴兵; 丁凯阳; 童娟; 汤宝林; 王祖贻

    2012-01-01

    The aim of the study was to analyze retrospectively the indication and timing of transplantation, choice of hematopoietic stem cell source, preparative regimens for treating myelodysplastic syndrome ( MDS ) by allogeneic hematopoietic stem cell transplantation ( Allo-HSCT ) and its efficacy. Details of myeloid recovery were available from 21 patients, only one adult patient failed to have engraftment in the first transplantation with unrelated cord blood, but obtained hematopoiesis recovery by 4/6 HLA-matched related peripheral blood stem cell transplantation ( PBSCT ) combined with bone marrow transplantation ( BMT ) from her mother in thirty-eight days. Three patients died at median time of 13 months after transplantation, but none of 22 patients relapsed. When to proceed HSCT for MDS patients is dependent on international prognostic scoring system( IPSS ), patients at high risk group shall transplant as soon as possible after the disease diagnosed, and low-risk group shall be transplanted after treated with other drugs while the effect is not well. Patients without a matched family donor or unrelated donor are referred to HLA-haploidentical unrelated cord blood transplantation ( UCBT ). Preparative regimens include myeloablative or reduced intensity conditioning ( RIC ), and the outcome of transplantation is comparable.%回顾性分析异基因造血干细胞移植(Allo-HSCT)治疗骨髓增生异常综合征(MDS)的适应证、治疗时机、移植物的选择、移植预处理方案的选择和移植疗效.22例患者中21例获得造血重建,1例非血缘脐血移植(UCBT)未获得植入的成人患者,于非血缘脐血移植(UCBT)后38 d进行母亲HLA4/6相合的外周血联合骨髓造血干细胞移植解救治疗获得植入.22例中死亡3例,无1例复发.MDS患者何时进行Allo-HSCT需依据国际预后积分系统(IPSS )对患者分组,评分属于高危组的患者宜在疾病确诊后尽早进行移植,而低危组的患者可在其他药物治

  20. Comparative efficacy of tandem autologous versus autologous followed by allogeneic hematopoietic cell transplantation in patients with newly diagnosed multiple myeloma: a systematic review and meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Kharfan-Dabaja Mohamed A

    2013-01-01

    Full Text Available Abstract Background Despite advances in understanding of clinical, genetic, and molecular aspects of multiple myeloma (MM and availability of more effective therapies, MM remains incurable. The autologous-allogeneic (auto-allo hematopoietic cell transplantation (HCT strategy is based on combining cytoreduction from high-dose (chemo- or chemoradio-therapy with adoptive immunotherapy. However, conflicting results have been reported when an auto-allo HCT approach is compared to tandem autologous (auto-auto HCT. A previously published meta-analysis has been reported; however, it suffers from serious methodological flaws. Methods A systematic search identified 152 publications, of which five studies (enrolling 1538 patients met inclusion criteria. All studies eligible for inclusion utilized biologic randomization. Results Assessing response rates by achievement of at least a very good partial response did not differ among the treatment arms [risk ratio (RR (95% CI = 0.97 (0.87-1.09, p = 0.66]; but complete remission was higher in the auto-allo HCT arm [RR = 1.65 (1.25-2.19, p = 0.0005]. Event-free survival did not differ between auto-allo HCT group versus auto-auto HCT group using per-protocol analysis [hazard ratio (HR = 0.78 (0.58-1.05, p = 0.11] or using intention-to-treat analysis [HR = 0.83 (0.60-1.15, p = 0.26]. Overall survival (OS did not differ among these treatment arms whether analyzed on per-protocol [HR = 0.88 (0.33-2.35, p = 0.79], or by intention-to-treat [HR = 0.80 (0.48-1.32, p = 0.39] analysis. Non-relapse mortality (NRM was significantly worse with auto-allo HCT [RR (95%CI = 3.55 (2.17-5.80, p  Conclusion Despite higher complete remission rates, there is no improvement in OS with auto-allo HCT; but this approach results in higher NRM in patients with newly diagnosed MM. At present, totality of evidence suggests that an auto-allo HCT approach for patients with newly diagnosed

  1. 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

    DEFF Research Database (Denmark)

    Michallet, M; Sobh, M; Milligan, D;

    2010-01-01

    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...

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

    Science.gov (United States)

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

    2016-02-01

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

  3. Impact of Inflammatory Cytokine Gene Polymorphisms on Developing Acute Graft-versus-Host Disease in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Riccardo Masetti

    2015-01-01

    Full Text Available Single nucleotide polymorphisms (SNPs in gene encoding pro- and anti-inflammatory factors have been associated with the occurrence of aGvHD. We retrospectively tested a wide panel of 38 polymorphisms in 19 immunoregulatory genes, aiming to first establish, in a pediatric HSCT setting, which SNPs were significantly associated with the development of aGvHD. A significant association was found between aGvHD grades II–IV and SNPs of donor IL10-1082GG, and Fas-670CC + CT and recipient IL18-607 TT + TG genotype. aGvHD grades III-IV resulted associated with donor IL10-1082GG, Fas-670CC + CT, and TLR4-3612TT as well as the use of peripheral CD34+ cells as stem cell source. The multivariate analysis confirmed the association between donor IL10-1082GG and Fas-670CC + CT and aGvHD grades II–IV and between donor IL10-1082GG and TLR4-3612TT and aGvHD grades III-IV. In conclusion we found an association between IL10, FAS, and TLR4 in the donor and IL18 in the recipient and an increased risk of developing aGvHD in transplanted children. Knowledge of the SNPs of cytokine genes associated with aGvHD represents a useful tool for an integrated pretransplantation risk assessment and could guide the physicians to an optimal and more accurate HSCT planning.

  4. Allogeneic hematopoietic stem cell transplantation for primary myelodysplastic syndrome Transplante alogênico de células progenitoras hematopoiéticas para síndrome mielodisplásica primária

    Directory of Open Access Journals (Sweden)

    Carlos R. Medeiros

    2004-01-01

    Full Text Available Characteristics and outcomes of 52 patients with myelodysplastic syndrome (MDS who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT were analyzed. Median age was 30 years (range 2-61 years and median time from diagnosis to allo-HSCT was 10 months (range 1-161 months. Thirty-six patients had advanced MDS or acute myeloid leukemia following MDS at transplant. Conditioning with busulfan and cyclophosphamide was administered to 73% of patients, and the median value of graft dose was 2.595 x 10(8 of total nucleated cells/kg. Overall survival and disease free survival at 4 years were 36% and 33%, respectively. Nineteen patients were alive, with a median follow-up of 3.8 years. Twelve patients relapsed and only one is alive, after donor lymphocyte infusion. Interval II occurred in 19 patients. Donor type (identical related versus non-related/partially matched related influenced the incidence of acute GVHD (P = 0.03. Eleven patients developed chronic GVHD and previous acute GVHD was a risk factor (P = 0.03. Thirty-three patients died, 22 (67% secondary to transplant-related complications. Patients with MDS should undergo allo-HSCT earlier, mainly if they have a compatible donor and are young.Características e resultados de 52 pacientes com síndrome mielodisplásica (MDS submetidos a transplante alogênico de células progenitoras hematopoiéticas (TCPH foram analisados. A idade mediana foi de 30 anos (variação de 2-61 anos e o tempo mediano entre o diagnóstico e transplante foi de dez meses (variação de 1-161 meses. Trinta e seis pacientes tinham MDS avançada ou leucemia mielóide aguda secundária a MDS ao transplante. O condicionamento com busulfano e ciclo­fosfamida foi recebido por 73% dos pacientes, e a dose celular mediana do enxerto foi de 2.56 x 10(8 células nucleadas/kg. A sobrevida global e a sobrevida livre de doença aos quatro anos foi de 36% e 33%, respectivamente. Dezenove pacientes estavam vivos, com um

  5. 异基因造血干细胞移植后肠球菌相关性腹泻的临床分析%Clinical analysis of enterococcus associated diarrhea in patients received allogeneic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    万鼎铭; 周雪芳; 谢新生; 孙玲; 孙慧; 曹伟杰; 边志磊; 李丽

    2014-01-01

    Aim:To explore clinical characteristics of enterococcus associated diarrhea ( EAD) in patients received allo-geneic hematopoietic stem cell transplantation (allo-HSCT), analyze the corresponding causes and seek effective prevention and treatment measures .Methods:Retrospective analysis was performed in 36 EAD patients who had received allo-HSCT. And 36 healthy individuals with normal intestinal microflora were chosen as control group .The change of intestinal microflora in EAD patients was observed .Another 70 patients received allo-HSCT,among whom,40 were HLA all-matched transplanta-tion,and 30 were HLA haploidentical transplantation .Results:There was significant reduction in the counting of the intesti-nal flora such as Lactobacillus, Bifidobacterium, Bacteroides, and Enterobacter, etc(P<0.001).The EAD positive rate was 40.0%in HLA all-matched transplantation, and 66.7%in HLA haploidentical transplantation(χ2 =4.878,P=0.027).Oral administration of teicoplanin supplemented with probiotics could cure those patients with EAD .Conclusion: There is high occurrence of EAD for patients received allo-HSCT.Once that happens , patients should receive active treatment .%目的:探讨异基因造血干细胞移植( allo-HSCT)后肠球菌相关性腹泻( EAD)的临床特点,分析原因,寻求有效的防治措施。方法:对36例allo-HSCT后EAD患者的临床资料进行回顾性分析,同时以36例健康人群作为对照组,观察EAD患者肠道菌群变化。同期行allo-HSCT者共70例,其中全相合移植40例,单倍体移植30例。结果:allo-HSCT后EAD患者肠道菌群中乳酸杆菌、双歧杆菌、类杆菌、肠杆菌等细菌数量明显下降,差异有统计学意义(P均<0.001)。全相合移植EAD发生率为40.0%,单倍体移植发生率为66.7%,差异有统计学意义(χ2=4.878,P=0.027)。 EAD患者口服替考拉宁并辅助益生菌治疗均治愈。结论:EAD常见于allo-HSCT后,

  6. Caspofungin for treatment of invasive fungal infections after allogeneic hematopoietic stem cell transplantation%卡泊芬净治疗异基因造血干细胞移植术后侵袭性真菌感染

    Institute of Scientific and Technical Information of China (English)

    白海涛; 王椿; 万理萍; 姜杰玲; 杨隽; 蔡宇

    2013-01-01

    Objective To investigate the efficacy and safety of Caspofungin for the treatment of invasive fungal infections after allogeneic hematopoietic stem cell transplantation ( allo-HSCT). Methods Thirty-nine cases of invasive fungal infections after allo-HSCT were selected, stratified diagnosis was made according to the standard of European Organization for Research on Treatment of Cancer ( EORTC), and treatment with intravenous Caspofungin was performed. The initial dosage and maintenance dosage were 70 mg/d and 50 mg/d respectively, with time of infusion more than 1 h and course of treatment ranging from 14 d to 42 d. Imaging and microbiological examinations were carried out weekly before treatment and in the course of treatment. Side effects were assessed after treatment. Results The overall favorable response to Caspofungin was 76.9% (30/39). The response rates of confirmed cases, clinically diagnosed cases and suspected cases were 100% (3/3), 73.7% (14/19) and 76.5% (13/17) respectively. There was no significant difference in the response rates between clinically diagnosed cases and suspected cases (P > 0. 05). Three cases had mild liver function abnormalities, and hypokalemia occurred in 4 cases. Conclusion Caspofungin is an effective agent with minimal adverse effects for treatment of invasive fungal infections after allo-HSCT.%目的 观察卡泊芬净治疗异基因造血干细胞移植(allo-HSCT)术后患者深部真菌感染的疗效和安全性.方法 收集39例诊断为深部真菌感染的allo-HSCT术后患者,按照欧洲癌症治疗研究组织(EORTC)的诊断标准分层诊断,给予静脉卡泊芬净治疗.卡泊芬净首日负荷剂量70 mg/d,维持剂量50 mg/d,输注时间≥1h,疗程14~42 d.患者治疗前和治疗期间每周进行影像学检查和微生物学检验;治疗后进行药物不良反应评价.结果 39例allo-HSCT术后侵袭性真菌感染患者经卡泊芬净治疗后,总有效率为76.9% (30/39);3例

  7. Hemorrhagic cystitis after hematopoietic stem cell trans-plantation: much progress and many remaining issues

    Institute of Scientific and Technical Information of China (English)

    Edmund K. Waller

    2007-01-01

    @@ The manuscript by Xu et al1 addresses an important question in the field of allogeneic hematopoietic progenitor cell transplantation (HPCT): how to identify those patients at risk for hemmoraghic cystitis. The authors performed a retrospective analysis of 250 patients undergoing allogeneic HPCT following myeloablative conditioning with busulfan and cyclophosphamide using a standard post-transplant immunoprophylaxis with cyclosporine, short-course methotrexate and mycophenylate.

  8. Hematopoietic cell transplantation for Crohn's disease; is it time?

    Institute of Scientific and Technical Information of China (English)

    Y Leung; M Geddes; J Storek; R Panaccione; PL Beck

    2006-01-01

    AIM: To review all studies in the literature that have assessed Hematopoietic cell transplantation (HCT)and Crohn's disease (CD) with the ultimate aims of determining if this is a viable treatment option for those with CD. A secondary aim was to review the above literature and determine if the studies shed further light on the mechanisms involved in the pathogenesis of CD.METHODS: An extensive Medline search was performed on all articles from 1970 to 2005 using the keywords;bone marrow transplant, stem cell, hematopoietic cell,Crohn's disease and inflammatory bowel disease.RESULTS: We identified one case in which a patient developed CD following an allogeneic HCT from a sibling suffering with CD. Evidence for transfer of the genetic predisposition to develop CD was also identified with report of a patient that developed severe CD following an allogeneic HCT. Following HCT it was found that the donor (that had no signs or symptoms of CD) and the recipient had several haplotype mismatches in HLA class Ⅲ genes in the IBD3 locus including a polymorphism of NOD2/CARD15 that has been associated with CD.Thirty three published cases of patients with CD who underwent either autologous or allogeneic HCT were identified. At the time of publication 29 of these 33patients were considered to be in remission. The median follow-up time was seven years, and twenty months for allogeneic and autologous HCT respectively. For patients who underwent HCT primarily for treatment of their CD there have been no mortalities related to transplant complications.CONCLUSION: Overall these preliminary data suggest that both allogeneic and autologous HCT may be effective in inducing remission in refractory CD. This supports the hypothesis that the hematolymphatic cells play a key role in CD and that resetting of the immune system may be a critical approach in the management or cure of CD.

  9. Regeneration of adenovirus specific T-cells after allogeneic, hematopietic stem cell transplantation in children and adolescents

    OpenAIRE

    2010-01-01

    Adenovirus is a significant cause of morbidity and mortality in pediatric allogeneic hematopoietic stem cell transplant recipients, and control of infection seems to require antigen-specific T cells. Aim of this Work was to estimate the Regeneration of Adenovirus-specific T-cells In 26 children (Age 8 months -25 years) over 6 months after HSCT and to investigate the effects of the transplantations parameter, Virus reactivation and the Transplantations complications on the adv-specific cell...

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

    Directory of Open Access Journals (Sweden)

    Hamilton Betty K

    2013-01-01

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

  11. Hematopoietic stem cells and the aging hematopoietic system.

    Science.gov (United States)

    Gazit, Roi; Weissman, Irving L; Rossi, Derrick J

    2008-10-01

    The etiology of the age-associated pathophysiological changes of the hematopoietic system including the onset of anemia, diminished adaptive immune competence, and myelogenous disease development are underwritten by the loss of normal homeostatic control. As tissue and organ homeostasis in adults is primarily mediated by the activity of stem and progenitor cells, it has been suggested that the imbalances accompanying aging of the hematopoietic system may stem from alterations in the prevalence and/or functional capacity of hematopoietic stem cells (HSCs) and progenitors. In this review, we examine evidence implicating a role for stem cells in the aging of the hematopoietic system, and focus on the mechanisms suggested to contribute to stem cell aging.

  12. The risk factors of post-transplant lymphoproliferative disorders following haploidentical hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    张春丽

    2014-01-01

    Objective Post-transplant lymphoproliferative disorder(PTLD)occurring after allogeneic hematopoietic stem cell transplantation(allo-HSCT)is rare but severe.Risk factors including pre-HSCT exposure variables,conditioning regimens,transplant-related complications,and post-HSCT immune reconstitution were investigated in the development of PTLD after allo-HSCT.Methods A

  13. Recommendations on hematopoietic stem cell transplantation for inherited bone marrow failure syndromes

    NARCIS (Netherlands)

    de Latour, R. Peffault; Peters, C.; Gibsons, B.; Strahm, B.; Lankester, A.; de Heredia, C. D.; Longoni, D.; Fioredda, F.; Locatelli, F.; Yaniv, I.; Wachowiak, J.; Donadieu, J.; Lawitschka, A.; Bierings, M.; Wlodarski, M.; Corbacioglu, S.; Bonanomi, S.; Samarasinghe, S.; Leblanc, T.; Dufour, C.; Dalle, J-H

    2015-01-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) offers the potential to cure patients with an inherited bone marrow failure syndrome (IBMFS). However, the procedure involves the risk of treatment-related mortality and may be associated with significant early and late morbidity. For these r

  14. Rhizomucor and Scedosporium Infection Post Hematopoietic Stem-Cell Transplant

    Directory of Open Access Journals (Sweden)

    Dânia Sofia Marques

    2011-01-01

    Full Text Available Hematopoietic stem-cell transplant recipients are at increased risk of developing invasive fungal infections. This is a major cause of morbidity and mortality. We report a case of a 17-year-old male patient diagnosed with severe idiopathic acquired aplastic anemia who developed fungal pneumonitis due to Rhizomucor sp. and rhinoencephalitis due to Scedosporium apiospermum 6 and 8 months after undergoing allogeneic hematopoietic stem-cell transplant from an HLA-matched unrelated donor. Discussion highlights risk factors for invasive fungal infections (i.e., mucormycosis and scedosporiosis, its clinical features, and the factors that must be taken into account to successfully treat them (early diagnosis, correction of predisposing factors, aggressive surgical debridement, and antifungal and adjunctive therapies.

  15. Stem cells and the aging hematopoietic system.

    Science.gov (United States)

    Beerman, Isabel; Maloney, William J; Weissmann, Irving L; Rossi, Derrick J

    2010-08-01

    Advancing age is accompanied by a number of clinically significant conditions arising in the hematopoietic system that include: diminution and decreased competence of the adaptive immune system, elevated incidence of certain autoimmune diseases, increased hematological malignancies, and elevated incidence of age-associated anemia. As with most tissues, the aged hematopoietic system also exhibits a reduced capacity to regenerate and return to normal homeostasis after injury or stress. Evidence suggests age-dependent functional alterations within the hematopoietic stem cell compartment significantly contribute to many of these pathophysiologies. Recent developments have shed light on how aging of the hematopoietic stem cell compartment contributes to hematopoietic decline through diverse mechanisms.

  16. ROLE AND TIMING OF HEMATOPOIETIC CELL TRANSPLANTATION FOR MYELODYSPLASTIC SYNDROME

    Directory of Open Access Journals (Sweden)

    Teresa L Field

    2010-07-01

    Full Text Available Allogeneic hematopoietic cell transplantation (HCT is the only curative treatment for patients with myelodysplastic syndromes (MDS.  Most patients with MDS are older than 60 years and age-associated morbidities limit the patients’ options for curative transplant therapy.  Since the development of conditioning regimens with reduced toxicity, the age limitations for HCT have waned for those patients with good performance status. This review will discuss the role of HCT for MDS based on prognostic features, the optimal timing of HCT, and outcomes based on patient age.

  17. Hematopoietic Stem-Cell Transplantation in the Developing World: Experience from a Center in Western India

    Directory of Open Access Journals (Sweden)

    Chirag A. Shah

    2015-01-01

    Full Text Available We describe our experience of first 50 consecutive hematopoietic stem-cell transplants (HSCT done between 2007 and 2012 at the Apollo Hospital, Gandhinagar, 35 autologous HSCT and 15 allogeneic HSCT. Indications for autologous transplant were multiple myeloma, non-Hodgkin lymphoma, Hodgkin lymphoma, and acute myeloid leukemia, and indications for allogeneic transplants were thalassemia major, aplastic anaemia, chronic myeloid leukemia, and acute lymphoblastic and myeloid leukaemia. The median age of autologous and allogeneic patient’s cohort was 50 years and 21 years, respectively. Median follow-up period for all patients was 39 months. Major early complications were infections, mucositis, acute graft versus host disease, and venoocclusive disease. All of our allogeneic and autologous transplant patients survived during the first month of transplant. Transplant related mortality (TRM was 20% (N = 3 in our allogeneic and 3% (N = 1 in autologous patients. Causes of these deaths were disease relapse, sepsis, hemorrhagic complications, and GVHD. 46% of our autologous and 47% of our allogeneic patients are in complete remission phase after a median follow-up of 39 months. 34% of our autologous patients and 13% of our allogeneic patients had disease relapse. Overall survival rate in our autologous and allogeneic patients is 65.7% and 57.1%, respectively. Our results are comparable to many national and international published reports.

  18. 异体造血干细胞移植患者移植期照顾者身心状态的质性研究%Qualitative research of caregiver's physical and mental health for allogeneic hematopoietic stem cell transplant patients

    Institute of Scientific and Technical Information of China (English)

    武全莹

    2014-01-01

    Objective To investigate caregiver's physical and mental status for allogeneic hematopoietic stem cell transplantation patients during the transplant , explore their physical and psychological problems , analyze the reasons and propose related countermeasures .Methods Phenomenological method in the qualitative research was used to collect the data of 12 caregivers by direct interviewing , and records as well as phenomenological analysis was used for analysis .Results Caregivers endured great physical and psychological pressure, whose quality of life was affected and economic burden was too heavy .They had a strong sense of confusion due to the heavy responsibility of caring patients .Conclusions Except for the allogeneic hematopoietic stem cell transplantation patients , doctors and nurse should pay more attention to the pressure of caregivers, try to reduce their psychological burden and call for more love and caring from medical institutions and community .%目的:了解异体造血干细胞移植患者移植期间照顾者的身心真实感受,探讨照顾者在此期间存在的身体和心理问题,分析相关原因,并提出相应对策。方法运用质性研究中现象学研究的方法,采用直接访谈方式收集12例照顾者的资料,应用分析记录和现象分析法进行分析。结果照顾者身心承受巨大压力,生活质量受到影响,经济负担过重,对患者的照顾工作负担沉重,有强烈困惑感。结论医护在照顾异体造血干细胞移植患者的同时,更要关注照顾者的身心压力,设法减轻他们的心理负担,并呼吁医疗机构和社会给予异体造血干细胞移植患者照顾者应有的关爱和照顾。

  19. Application of human amniotic mesenchymal cells as an allogeneic transplantation cell source in bone regenerative therapy

    Energy Technology Data Exchange (ETDEWEB)

    Tsuno, Hiroaki [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Yoshida, Toshiko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Nogami, Makiko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Orthopedic Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Koike, Chika; Okabe, Motonori [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Noto, Zenko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Arai, Naoya; Noguchi, Makoto [Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Nikaido, Toshio, E-mail: tnikaido@med.u-toyama.ac.jp [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan)

    2012-12-01

    Autogenous mesenchymal stem cells (MSCs) have therapeutic applications in bone regenerative therapy due to their pluripotency. However, the ability of MSCs to proliferate and differentiate varies between donors. Furthermore, alternative sources of MSCs are required for patients with contraindications to autogenous cell therapy. The aim of this study was to evaluate the potential of mesenchymal cells from the human amniotic membrane (HAM) as a source of cells for allogeneic transplantation in bone regenerative therapy. Cells that retained a proliferative capacity of more than 50 population doubling level were distinguished from other HAM cells as HAM{alpha} cells and induced to osteogenic status-their in vivo osteogenesis was subsequently investigated in rats. It was found that HAM{alpha} cells were spindle shaped and were positive for MSC markers and negative for hematopoietic stem cell markers. Alkaline phosphatase activity and calcium deposition increased with osteogenic status of HAM{alpha} cells. The expression of osteocalcin mRNA was increased in HAM{alpha} cells cultured on calcium phosphate scaffolds. Moreover, xenografted HAM{alpha} cells remained viable and produced extracellular matrix for several weeks. Thus, this study suggests that human amniotic mesenchymal cells possess osteogenic differentiation potential and could be applied to allogeneic transplantation in bone regenerative therapy. - Highlights: Black-Right-Pointing-Pointer Human amniotic mesenchymal cells include cells (HAM{alpha} cells) that have the properties of MSCs. Black-Right-Pointing-Pointer HAM{alpha} cells have excellent osteogenic differentiation potential. Black-Right-Pointing-Pointer Osteogenic differentiation ability of HAM{alpha} was amplified by calcium phosphate scaffolds. Black-Right-Pointing-Pointer HAM{alpha} cells can be applicable to allogeneic cell transplantation in bone regenerative therapy.

  20. Hematopoietic stem cell transplantation in Europe 2014: more than 40 000 transplants annually.

    Science.gov (United States)

    Passweg, J R; Baldomero, H; Bader, P; Bonini, C; Cesaro, S; Dreger, P; Duarte, R F; Dufour, C; Kuball, J; Farge-Bancel, D; Gennery, A; Kröger, N; Lanza, F; Nagler, A; Sureda, A; Mohty, M

    2016-06-01

    A record number of 40 829 hematopoietic stem cell transplantation (HSCT) in 36 469 patients (15 765 allogeneic (43%), 20 704 autologous (57%)) were reported by 656 centers in 47 countries to the 2014 survey. Trends include: continued growth in transplant activity, more so in Eastern European countries than in the west; a continued increase in the use of haploidentical family donors (by 25%) and slower growth for unrelated donor HSCT. The use of cord blood as a stem cell source has decreased again in 2014. Main indications for HSCT were leukemias: 11 853 (33%; 96% allogeneic); lymphoid neoplasias; 20 802 (57%; 11% allogeneic); solid tumors; 1458 (4%; 3% allogeneic) and non-malignant disorders; 2203 (6%; 88% allogeneic). Changes in transplant activity include more allogeneic HSCT for AML in CR1, myeloproliferative neoplasm (MPN) and aplastic anemia and decreasing use in CLL; and more autologous HSCT for plasma cell disorders and in particular for amyloidosis. In addition, data on numbers of teams doing alternative donor transplants, allogeneic after autologous HSCT, autologous cord blood transplants are presented.

  1. Management of Epstein-Barr Virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines.

    Science.gov (United States)

    Styczynski, Jan; van der Velden, Walter; Fox, Christopher P; Engelhard, Dan; de la Camara, Rafael; Cordonnier, Catherine; Ljungman, Per

    2016-07-01

    Epstein-Barr virus-related post-transplant lymphoproliferative disorders are recognized as a significant cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation. To better define current understanding of post-transplant lymphoproliferative disorders in stem cell transplant patients, and to improve its diagnosis and management, a working group of the Sixth European Conference on Infections in Leukemia 2015 reviewed the literature, graded the available quality of evidence, and developed evidence-based recommendations for diagnosis, prevention, prophylaxis and therapy of post-transplant lymphoproliferative disorders exclusively in the stem cell transplant setting. The key elements in diagnosis include non-invasive and invasive methods. The former are based on quantitative viral load measurement and imaging with positron emission tomography; the latter with tissue biopsy for histopathology and detection of Epstein-Barr virus. The diagnosis of post-transplant lymphoproliferative disorder can be established on a proven or probable level. Therapeutic strategies include prophylaxis, preemptive therapy and targeted therapy. Rituximab, reduction of immunosuppression and Epstein-Barr virus-specific cytotoxic T-cell therapy are recommended as first-line therapy, whilst unselected donor lymphocyte infusions or chemotherapy are options as second-line therapy; other methods including antiviral drugs are discouraged.

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

    Science.gov (United States)

    Mihăilă, R-G

    2016-01-01

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

  3. Therapy-related acute myeloid leukemia and myelodysplastic syndrome after hematopoietic cell transplantation for lymphoma.

    Science.gov (United States)

    Yamasaki, S; Suzuki, R; Hatano, K; Fukushima, K; Iida, H; Morishima, S; Suehiro, Y; Fukuda, T; Uchida, N; Uchiyama, H; Ikeda, H; Yokota, A; Tsukasaki, K; Yamaguchi, H; Kuroda, J; Nakamae, H; Adachi, Y; Matsuoka, K-I; Nakamura, Y; Atsuta, Y; Suzumiya, J

    2017-04-03

    Therapy-related acute myeloid leukemia and myelodysplastic syndrome (t-AML/MDS) represent severe late effects in patients receiving hematopoietic cell transplantation (HCT) for lymphoma. The choice between high-dose therapy with autologous HCT and allogeneic HCT with reduced-intensity conditioning remains controversial in patients with relapsed lymphoma. We retrospectively analyzed incidence and risk factors for the development of t-AML/MDS in lymphoma patients treated with autologous or allogeneic HCT. A total of 13 810 lymphoma patients who received autologous (n=9963) or allogeneic (n=3847) HCT between 1985 and 2012 were considered. At a median overall survival (OS) of 52 and 46 months in autologous and allogeneic HCT groups, respectively, lymphoma patients receiving autologous HCT (1.38% at 3 years after autologous HCT) had a significant risk for developing t-AML/MDS compared to allogeneic HCT (0.37% at 3 years after allogeneic HCT, Pafter autologous and allogeneic HCT were high-stage risk at HCT (P=0.04) or secondary malignancies (P<0.001) and receiving cord blood stem cell (P=0.03) or involved field radiotherapy (P=0.002), respectively. Strategies that carefully select lymphoma patients for autologous HCT, by excluding lymphoma patients with high-stage risk at HCT, may allow the identification of individual lymphoma patients at particular high risk for t-AML/MDS.Bone Marrow Transplantation advance online publication, 3 April 2017; doi:10.1038/bmt.2017.52.

  4. Research progress of hypomethylating agents in myelodysplastic syndrome patients with allogeneic hematopoietic stem cell transplantation%去甲基化药物在骨髓增生异常综合征患者异基因造血干细胞移植中应用的研究进展

    Institute of Scientific and Technical Information of China (English)

    王钊

    2015-01-01

    去甲基化药物(HMA)在骨髓增生异常综合征(MDS)患者中具有良好的抗肿瘤作用.目前,MDS患者于接受异基因造血干细胞移植(allo-HSCT)前,应用HMA作为桥接治疗是减少该病患者肿瘤负荷的重要治疗方法之一.同时,研究显示,MDS患者于接受allo-H SCT后应用HMA,对于预防及延缓疾病复发具有一定作用.笔者拟就MDS患者在接受allo-HSCT前、后应用HMA的研究进展进行综述如下.%Hypomethylating agents (HMA) have shown good antitumor effects in myelodysplastic syndrome (MDS) patients.At present,before allogeneic hematopoietic stem cell transplantation (alloHSCT),the application of HMA is an important bridge treatment method to reduce the tumor load of MDS patients.At the same time,some studies show that the application of HMA after allo-HSCT plays a certain role in preventing or delaying the recurrence of disease.The author will review the application of HMA in MDS patients with allo-HSCT from the aspect of before and after allo-HSCT.

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

    Directory of Open Access Journals (Sweden)

    Paulo José Lorenzoni

    2007-09-01

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

  6. Hematopoietic Stem Cell Transplantation—50 Years of Evolution and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Israel Henig

    2014-10-01

    Full Text Available Hematopoietic stem cell transplantation is a highly specialized and unique medical procedure. Autologous transplantation allows the administration of high-dose chemotherapy without prolonged bone marrow aplasia. In allogeneic transplantation, donor-derived stem cells provide alloimmunity that enables a graft-versus-tumor effect to eradicate residual disease and prevent relapse. The first allogeneic transplantation was performed by E. Donnall Thomas in 1957. Since then the field has evolved and expanded worldwide. New indications beside acute leukemia and aplastic anemia have been constantly explored and now include congenital disorders of the hematopoietic system, metabolic disorders, and autoimmune disease. The use of matched unrelated donors, umbilical cord blood units, and partially matched related donors has dramatically extended the availability of allogeneic transplantation. Transplant-related mortality has decreased due to improved supportive care, including better strategies to prevent severe infections and with the incorporation of reduced-intensity conditioning protocols that lowered the toxicity and allowed for transplantation in older patients. However, disease relapse and graft-versus-host disease remain the two major causes of mortality with unsatisfactory progress. Intense research aiming to improve adoptive immunotherapy and increase graft-versus-leukemia response while decreasing graft-versus-host response might bring the next breakthrough in allogeneic transplantation. Strategies of graft manipulation, tumor-associated antigen vaccinations, monoclonal antibodies, and adoptive cellular immunotherapy have already proved clinically efficient. In the following years, allogeneic transplantation is likely to become more complex, more individualized, and more efficient.

  7. Matched unrelated donor allogeneic transplantation provides comparable long-term outcome to HLA-identical sibling transplantation in relapsed diffuse large B-cell lymphoma

    NARCIS (Netherlands)

    Avivi, I.; Canals, C.; Vernant, J.P.; Wulf, G.; Nagler, A.; Hermine, O.; Petersen, E.; Yakoub-Agha, I.; Craddock, C.; Schattenberg, A.V.; Niederwieser, D.; Thomson, K.; Blaise, D.; Attal, M.; Pfreundschuh, M.; Passweg, J.; Russell, N.; Dreger, P.; Sureda, A.

    2014-01-01

    The objective of this retrospective analysis was to compare outcomes of patients with diffuse large B-cell lymphoma (DLBCL) who received either a matched sibling (sib) or an unrelated donor (URD) allogeneic hematopoietic cell transplantation (allo-HCT). Long-term outcome of 172 DLBCL patients receiv

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

    Science.gov (United States)

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

    2016-06-23

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

  9. Successful hematopoietic cell transplantation in a patient with X-linked agammaglobulinemia and acute myeloid leukemia.

    Science.gov (United States)

    Abu-Arja, Rolla F; Chernin, Leah R; Abusin, Ghada; Auletta, Jeffery; Cabral, Linda; Egler, Rachel; Ochs, Hans D; Torgerson, Troy R; Lopez-Guisa, Jesus; Hostoffer, Robert W; Tcheurekdjian, Haig; Cooke, Kenneth R

    2015-09-01

    X-linked agammaglobulinemia (XLA) is a primary immunodeficiency characterized by marked reduction in all classes of serum immunoglobulins and the near absence of mature CD19(+) B-cells. Although malignancy has been observed in patients with XLA, we present the first reported case of acute myeloid leukemia (AML) in a patient with XLA. We also demonstrate the complete correction of the XLA phenotype following allogeneic hematopoietic cell transplantation for treatment of the patient's leukemia.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1986-10-01

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

  11. Fecal microbiota transplantation for fulminant Clostridium difficile infection in an allogeneic stem cell transplant patient.

    Science.gov (United States)

    Neemann, K; Eichele, D D; Smith, P W; Bociek, R; Akhtari, M; Freifeld, A

    2012-12-01

    We present a case of severe Clostridium difficile infection (CDI) in a non-neutropenic allogeneic hematopoietic stem cell transplant recipient who was treated successfully with fecal microbiota therapy after standard pharmacologic therapy had failed. Following naso-jejunal instillation of donor stool, the patient's symptoms resolved within 48 h. Bowel resection was averted. This is the first case in the literature, to our knowledge, to describe fecal microbiota therapy in a profoundly immunocompromised host with severe CDI. We propose that fecal microbiota therapy be considered as a therapeutic option in immunosuppressed patients with refractory severe CDI.

  12. How Does Influenza A (H1N1 Infection Proceed in Allogeneic Stem Cell Transplantation Recipients?

    Directory of Open Access Journals (Sweden)

    Sinem Civriz Bozdağ

    2012-03-01

    Full Text Available Clinical course of H1N1 infection in Allogeneic Hematopoietic Stem Cell Transplantation (AHSCT patients is contraversial. We report three AHSCT patients who were infected with Influenza A/H1N1 infection. All of the patients were diagnosed with different hematological diagnosis and were at different stages of transplantation.All of them were treated with oseltamivir,zanamivir was switched with oseltamivir in one patient. All of the three patients were survived without any complication. Swine flu, can display with different courses and progress with bacterial or other viral infections in immunsupressed patients.

  13. Administration of G-CSF from day +6 post-allogeneic hematopoietic stem cell transplantation in children and adolescents accelerates neutrophil engraftment but does not appear to have an impact on cost savings.

    Science.gov (United States)

    O'Rafferty, Ciara; O'Brien, Mairead; Smyth, Elaine; Keane, Sinead; Robinson, Hillary; Lynam, Paul; O'Marcaigh, Aengus; Smith, Owen P

    2016-05-01

    G-CSF post-allogeneic HSCT accelerates neutrophil engraftment, but evidence that it impacts on cost-related outcomes is lacking. We performed a retrospective child and adolescent single-center cohort study examining G-CSF administration from Day +6 of allogeneic HSCT vs. ad hoc G-CSF use where clinically indicated. Forty consecutive children and adolescents undergoing allogeneic HSCT were included. End-points were as follows: time to engraftment; incidence of acute and chronic GvHD; number of patients alive at Day +100; 180-day TRM; post-transplant days in hospital; and cost of antimicrobials, TPN, and G-CSF usage. Neutrophil engraftment occurred earlier in the group that received G-CSF from Day +6. There was no difference between groups in any of the other end-points with the following exception: the cost of GCSF was significantly higher in the D + 6 G-CSF group. However, median G-CSF cost in this group amounted to only €280. There was a trend towards reduced cost of antimicrobials in the D + 6 G-CSF group, although this did not reach significance (p = 0.13). The median cost per patient of antimicrobial agents between groups differed by €1116. This study demonstrated the administration of G-CSF on Day +6 in pediatric HSCT to be safe. A further study using a larger cohort of patients is warranted to ascertain its true clinico-economic value.

  14. Impact of genomic risk factors on outcome after hematopoietic stem cell transplantation for patients with chronic myeloid leukemia.

    NARCIS (Netherlands)

    Dickinson, A.M.; Pearce, K.F.; Norden, J.; O'Brien, S.G.; Holler, E.; Bickeboller, H.; Balavarca, Y.; Rocha, V.; Kolb, H.J.; Hromadnikova, I.; Sedlacek, P.; Niederwieser, D.; Brand, R.; Ruutu, T.; Apperley, J.; Szydlo, R.; Goulmy, E.; Siegert, W.; Witte, T.J.M. de; Gratwohl, A.

    2010-01-01

    BACKGROUND: Non-HLA gene polymorphisms have been shown to influence outcome after allogeneic hematopoietic stem cell transplantation. Results were derived from heterogeneous, small populations and their value remains a matter of debate. DESIGN AND METHODS: In this study, we assessed the effect of si

  15. Impact of genomic risk factors on outcome after hematopoietic stem cell transplantation for patients with chronic myeloid leukemia

    NARCIS (Netherlands)

    Dickinson, Anne M.; Pearce, Kim F.; Norden, Jean; O'Brien, Stephen G.; Holler, Ernst; Bickeboeller, Heike; Balavarca, Yesilda; Rocha, Vanderson; Kolb, Hans-Jochem; Hromadnikova, Ilona; Sedlacek, Petr; Niederwieser, Dietger; Brand, Ronald; Ruutu, Tapatti; Apperleyy, Jane; Szydlo, Richard; Goulmy, Els; Siegert, Wolfgang; de Witte, Theo; Gratwohl, Alois

    2010-01-01

    Background Non-HLA gene polymorphisms have been shown to influence outcome after allogeneic hematopoietic stem cell transplantation. Results were derived from heterogeneous, small populations and their value remains a matter of debate. Design and Methods In this study, we assessed the effect of sing

  16. HLA-mismatched/haploidentical hematopoietic stem cell transplantation:a field in which Chinese doctors are making great contributions

    Institute of Scientific and Technical Information of China (English)

    HUANG Xiao-jun

    2010-01-01

    @@ Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the best, or even the only,option for the cure of leukemia, especially for patients with high risk factors.1 However, it is limited by the shortage of suitable donors, because only 25%-30% patients can find a human leukocyte antigen (HLA)-identical sibling donor.

  17. Cerebral Rhizomucor Infection Treated by Posaconazole Delayed-Release Tablets in an Allogeneic Stem Cell Transplant Recipient

    Directory of Open Access Journals (Sweden)

    Diego O. Andrey

    2017-02-01

    Full Text Available Mucormycosis (zygomycosis is an emerging fungal disease in allogeneic hematopoietic stem cell transplant (allo-HSCT recipients. A 30-year-old woman diagnosed with acute myelomonocytic leukemia and needing allo-HSCT presented pulmonary and cerebral infection due to Rhizomucor pusillus. This fungal infection was treated with surgical treatment and posaconazole delayed-release tablets. This strategy allowed reaching high drug levels that could not be obtained with the posaconazole solution.

  18. Undifferentiated spondyloarthritis following allogeneic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Espinoza Luis R

    2010-06-01

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

  19. The impact of center experience on results of reduced intensity:allogeneic hematopoietic SCT for AML. An analysis from the Acute Leukemia Working Party of the EBMT

    DEFF Research Database (Denmark)

    Giebel, S; Labopin, M; Mohty, M

    2013-01-01

    Allogeneic hematopoietic SCT with reduced-intensity conditioning (RIC-HSCT) is increasingly adopted for the treatment of older adults with AML. Our goal was to verify for the first time, if center experience influences outcome of RIC-HSCT. Results of 1413 transplantations from HLA-matched related...

  20. The impact of center experience on results of reduced intensity : allogeneic hematopoietic SCT for AML. An analysis from the Acute Leukemia Working Party of the EBMT

    NARCIS (Netherlands)

    Giebel, S.; Labopin, M.; Mohty, M.; Mufti, G. J.; Niederwieser, D.; Cornelissen, J. J.; Janssen, J. J. W. M.; Milpied, N.; Vindelov, L.; Petersen, E.; Arnold, R.; Bacigalupo, A.; Blaise, D.; Craddock, C.; Nagler, A.; Frassoni, F.; Sadus-Wojciechowska, M.; Rocha, V.

    2013-01-01

    Allogeneic hematopoietic SCT with reduced-intensity conditioning (RIC-HSCT) is increasingly adopted for the treatment of older adults with AML. Our goal was to verify for the first time, if center experience influences outcome of RIC-HSCT. Results of 1413 transplantations from HLA-matched related or

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

    Science.gov (United States)

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

    2016-01-01

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

  2. Myositis in Griscelli syndrome type 2 treated with hematopoietic cell transplantation

    DEFF Research Database (Denmark)

    Born, Alfred Peter; Müller, Klaus; Marquart, Hanne Vibeke;

    2010-01-01

    Griscelli syndrome is an autosomal recessive disorder characterized by pigmentary dilution and is occasionally associated with a hemophagocytic syndrome (type 2). We present a 13-year-old girl with Griscelli syndrome type 2, who developed a hemophagocytic syndrome along with marked muscle weakness...... and elevated plasma creatine kinase. Muscle biopsy showed massive inflammatory changes in some fascicles, while other fascicles were relatively spared. Clinical symptoms and biopsy changes resolved after immunosuppression and allogeneic hematopoietic cell transplantation. Our results suggest that muscle...

  3. Survival Advantage and Comparable Toxicity in Reduced-Toxicity Treosulfan-Based versus Reduced-Intensity Busulfan-Based Conditioning Regimen in Myelodysplastic Syndrome and Acute Myeloid Leukemia Patients after Allogeneic Hematopoietic Cell Transplantation.

    Science.gov (United States)

    Sakellari, Ioanna; Mallouri, Despina; Gavriilaki, Eleni; Batsis, Ioannis; Kaliou, Maria; Constantinou, Varnavas; Papalexandri, Apostolia; Lalayanni, Chrysavgi; Vadikolia, Chrysanthi; Athanasiadou, Anastasia; Yannaki, Evangelia; Sotiropoulos, Damianos; Smias, Christos; Anagnostopoulos, Achilles

    2017-03-01

    Treosulfan has been incorporated in conditioning regimens for sustained remission without substantial toxicity and treatment-related mortality (TRM). We aimed to analyze the safety and efficacy of a fludarabine 150 mg/m(2) and treosulfan 42 g/m(2) (FluTreo) conditioning regimen in medically infirm patients. Outcomes were compared with those of a similar historical group treated with fludarabine 150 mg/m(2) to 180 mg/m(2), busulfan 6.4 mg/kg, and antithymocyte globulin (ATG) 5 mg/kg to 7.5 mg/kg (FluBuATG). Thirty-one consecutive patients with acute myeloid leukemia (AML; n = 21), myelodysplastic syndrome (MDS; n = 6), or treatment-related AML (n = 4) received FluTreo conditioning. The historical group consisted of 26 consecutive patients treated with FluBuATG. In the FluTreo group, engraftment was prompt in all patients and 74% achieved >99% donor chimerism by day +30. No grades III or IV organ toxicities were noted. One-year cumulative incidences (CI) of acute and chronic graft-versus-host disease (GVHD) were 19.4% and 58.4%. The groups were similar for age, disease risk, lines of treatment, hematopoietic cell transplantation-specific comorbidity index, and acute or chronic GVHD incidence, except that there were more matched unrelated donor recipients in the FluTreo group (P < .001). With 20 (range, 2 to 36) months follow-up for FluTreo and 14 (range, 2 to 136) for FluBuATG, the 1-year cumulative overall survival (OS) probability was 76% versus 57%, respectively (P = .026); 1-year disease-free survival (DFS) was 79% versus 38% (P < .001). In multivariate analysis, the only significantly favorable factor for OS and DFS was FluTreo (P = .010 and P = .012). The CI of relapse mortality was markedly decreased in FluTreo versus FluBuATG (7.4% versus 42.3%, P < .001). In conclusion, the treosulfan-based regimen resulted in favorable OS and DFS with acceptable toxicity and low relapse rates compared with busulfan-based conditioning.

  4. Hematopoietic Stem Cells Expansionin Rotating Wall Vessel

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    1 IntroductionClinical trials have demonstrated that ex vivo expanded hematopoietic stem cells (HSCs) and progenitors offer great promise in reconstituting in vivo hematopoiesis in patients who have undergone intensive chemotherapy. It is therefore necessary to develop a clinical-scale culture system to provide the expanded HSCs and progenitors. Static culture systems such as T-flasks and gas-permeable blood bags are the most widely used culture devices for expanding hematopoietic cells. But they reveal sev...

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

    Science.gov (United States)

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

    2016-01-01

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

  6. Intra-hematopoietic cell fusion as a source of somatic variation in the hematopoietic system.

    Science.gov (United States)

    Skinner, Amy M; Grompe, Markus; Kurre, Peter

    2012-06-15

    Cell fusion plays a well-recognized, physiological role during development. Bone-marrow-derived hematopoietic cells have been shown to fuse with non-hematopoietic cells in a wide variety of tissues. Some organs appear to resolve the changes in ploidy status, generating functional and mitotically-competent events. However, cell fusion exclusively involving hematopoietic cells has not been reported. Indeed, genomic copy number variation in highly replicative hematopoietic cells is widely considered a hallmark of malignant transformation. Here we show that cell fusion occurs between cells of the hematopoietic system under injury as well as non-injury conditions. Experiments reveal the acquisition of genetic markers in fusion products, their tractable maintenance during hematopoietic differentiation and long-term persistence after serial transplantation. Fusion events were identified in clonogenic progenitors as well as differentiated myeloid and lymphoid cells. These observations provide a new experimental model for the study of non-pathogenic somatic diversity in the hematopoietic system.

  7. 异基因造血干细胞移植后纯红细胞再生障碍性贫血发生的影响因素分析%Analysis of influencing factors on occurrence of posttransplant pure red cell aplastic anemia following allogeneic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    马威; 张定宇; 尹建平; 张义成; 江梦天; 肖毅; 余谨; 姚立

    2013-01-01

    目的 分析异基因造血干细胞移植后纯红细胞再生障碍性贫血(PRCA)发生的危险因素.方法 收集完成全部观察的225名与供者HLA匹配的异基因造血干细胞移植患者,其中21例(9.33%)发生移植后PRCA.用SPSS统计分析软件对移植红细胞生长延缓期时间(d)、免疫溶血病发生、ABO血型相容性、aGVHD分级、原发病、血浆sHLA-G1和G5含量以及年龄、性别等作单因素Logistic回归分析,然后对有明显差异的观察指标作多因素Logistic回归分析.结果 单因素Logistic回归分析显示:ABO血型相容性、aGVHD分级、原发病、sHLA-G5含量、患者年龄及性别等因素OR值分别为0.596、0.553、1.079、1.007、1.023和2.961(P值分别为0.129、0.720、0.173、0.227、0.334和0.110),移植后红细胞生长延缓期时间、sHLA-G1含量以及溶血病发生对累积Logic模型的OR值分别0.983、0.033、12.799(P值分别为0.001、0.033、0.003),多因素Loostic回归分析结果显示移植后红细胞生长延缓期时间、sHLA-G1含量以及溶血病发生对Logistic模型有统计学意义(OR值为1.017、0.964、0.110,P值分别为0.001、0.045、0.006).结论 移植红细胞生长延缓期时间、血浆sHLA-G1含量以及溶血病发生是移植后PRCA发生的主要影响因素.%Objective To analysis the influencing factors on occurrence of posttransplant pure red cell aplasia (PRCA)following allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods HLA-matched with donors,225 patients after allogeneic hematopoietic stem cell transplantation were investigated,21 patients (9.33%) developed pure red cell aplasia among them.On occurrence of posttransplant PRCA,the multiple influencing factors were analysed in the logistic model regression,consisting of the lag phase time (days) on engrafted red cell growth,occurrence of immunohemolytic disease,compatibility of ABO blood type,classification of aGVHD,primary diseases,sHLA-G1 and G5 contents

  8. Impact of conditioning with TBI in adult patients with T-cell ALL who receive a myeloablative allogeneic stem cell transplantation

    DEFF Research Database (Denmark)

    Cahu, X; Labopin, M; Giebel, S;

    2016-01-01

    Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a therapeutic option for adult patients with T-cell ALL (T-ALL). Meanwhile, few allo-SCT data specific to adult T-ALL have been described thus far. Specifically, the optimal myeloablative conditioning regimen is unknown. In this ret...... patients with T-ALL entitled to receive a myeloablative allo-SCT may benefit from TBI-based regimens.Bone Marrow Transplantation advance online publication, 30 November 2015; doi:10.1038/bmt.2015.278.......Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a therapeutic option for adult patients with T-cell ALL (T-ALL). Meanwhile, few allo-SCT data specific to adult T-ALL have been described thus far. Specifically, the optimal myeloablative conditioning regimen is unknown...

  9. A case report on the nutrition support of an allogenic hematopoietic stem cell transplant patient%异基因造血干细胞移植白血病患者的营养支持1例报告

    Institute of Scientific and Technical Information of China (English)

    姚卓贤; 张京晶; 冯凯

    2015-01-01

    Objective:To investigate the effect of parenteral nutrition (PN) support on a leukemia patient following allogenic hematopoietic stem cell transplantation (HSCT).Methods:The nutrition plan was made by the clinical pharmacist through active participation in pharmaceutical care following HSCT of the leukemia patient.Results:After adopting the nutrition support plan, the nutrition status of the patient recovered quickly, and the chance for the occurrence of complications was reduced. Conclusion: PN support is crucial for HSCT patients during pretreatment period and stress response period after radiotherapy and chemotherapy, and plays an important role for the recovery of hematopoiesis.%目的:探讨肠外营养支持对白血病病人造血干细胞移植期间营养状态的影响。方法:临床药师通过参与白血病患者造血干细胞移植期间的药学监护,提出制定营养支持方案。结果:临床医生采取了药师的营养支持方案,患者的营养状况得以尽快地恢复,减少了并发症发生的机会。结论:肠外营养支持对造血干细胞移植病人平稳度过预处理期、放疗、化疗后应激反应期与促进造血功能的恢复有重要的意义。

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

    Institute of Scientific and Technical Information of China (English)

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

    2016-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    许金华; 李晓丰

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Sook Kyung Yum

    2013-11-01

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

  13. Autonomous behavior of hematopoietic stem cells

    NARCIS (Netherlands)

    Kamminga, LM; Akkerman, [No Value; Weersing, E; Ausema, A; Dontje, B; Van Zant, G; de Haan, G

    2000-01-01

    Objective. Mechanisms that affect the function of primitive hematopoietic stem cells with long-term proliferative potential remain largely unknown. Here we assessed whether properties of stem cells are cell-extrinsically or cell-autonomously regulated. Materials and Methods. We developed a model in

  14. Oral changes in individuals undergoing hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Regina Haddad Barrach

    2015-04-01

    Full Text Available INTRODUCTION: Patients undergoing hematopoietic stem cell transplantation receive high doses of chemotherapy and radiotherapy, which cause severe immunosuppression.OBJECTIVE: To report an oral disease management protocol before and after hematopoietic stem cell transplantation.METHODS: A prospective study was carried out with 65 patients aged > 18 years, with hematological diseases, who were allocated into two groups: A (allogeneic transplant, 34 patients; B (autologous transplant, 31 patients. A total of three dental status assessments were performed: in the pre-transplantation period (moment 1, one week after stem cell infusion (moment 2, and 100 days after transplantation (moment 3. In each moment, oral changes were assigned scores and classified as mild, moderate, and severe risks.RESULTS: The most frequent pathological conditions were gingivitis, pericoronitis in the third molar region, and ulcers at the third moment assessments. However, at moments 2 and 3, the most common disease was mucositis associated with toxicity from the drugs used in the immunosuppression.CONCLUSION: Mucositis accounted for the increased score and potential risk of clinical complications. Gingivitis, ulcers, and pericoronitis were other changes identified as potential risk factors for clinical complications.

  15. High-grade cytomegalovirus antigenemia after hematopoietic stem cell transplantation.

    Science.gov (United States)

    Asano-Mori, Y; Oshima, K; Sakata-Yanagimoto, M; Nakagawa, M; Kandabashi, K; Izutsu, K; Hangaishi, A; Motokura, T; Chiba, S; Kurokawa, M; Hirai, H; Kanda, Y

    2005-11-01

    Clinical impact of high-grade (HG) cytomegalovirus (CMV) antigenemia after hematopoietic stem cell transplantation has not been clarified. Therefore, in order to investigate the risk factors and outcome for HG-CMV antigenemia, we retrospectively analyzed the records of 154 Japanese adult patients who underwent allogeneic hematopoietic stem cell transplantation for the first time from 1995 to 2002 at the University of Tokyo Hospital. Among 107 patients who developed positive CMV antigenemia at any level, 74 received risk-adapted preemptive therapy with ganciclovir (GCV), and 17 of these developed HG-antigenemia defined as > or = 50 positive cells per two slides. The use of systemic corticosteroids at > or = 0.5 mg/kg/day at the initiation of GCV was identified as an independent significant risk factor for HG-antigenemia. Seven of the 17 HG-antigenemia patients developed CMV disease, with a cumulative incidence of 49.5%, which was significantly higher than that in the low-grade antigenemia patients (4%, P<0.001). However, overall survival was almost equivalent in the two groups. In conclusion, the development of HG-antigenemia appeared to depend on the profound immune suppression of the recipient. Although CMV disease frequently developed in HG-antigenemia patients, antiviral therapy could prevent a fatal outcome.

  16. Reduced-Intensity Conditioning Combined with (188)Rhenium Radioimmunotherapy before Allogeneic Hematopoietic Stem Cell Transplantation in Elderly Patients with Acute Myeloid Leukemia: The Role of In Vivo T Cell Depletion.

    Science.gov (United States)

    Schneider, Sebastian; Strumpf, Annette; Schetelig, Johannes; Wunderlich, Gerd; Ehninger, Gerhard; Kotzerke, Jörg; Bornhäuser, Martin

    2015-10-01

    The combination of reduced-intensity conditioning, (188)rhenium anti-CD66 radioimmunotherapy, and in vivo T cell depletion was successfully applied in elderly patients with acute myeloid leukemia or myelodysplastic syndrome. Within a prospective phase II protocol, we investigated whether a dose reduction of alemtuzumab (from 75 mg to 50 mg MabCampath) would improve leukemia-free survival by reducing the incidence of relapse. Fifty-eight patients (median age, 67 years; range, 54 to 76) received radioimmunotherapy followed by fludarabine 150 mg/m(2) and busulfan 8 mg/kg combined with either 75 mg (n = 26) or 50 mg (n = 32) alemtuzumab. Although we observed a trend towards a shorter duration of neutropenia in the 50 mg group (median, 19 versus 21 days; P = .07), the time from transplantation to neutrophil and platelet engraftment as well as the overall incidence of engraftment did not differ. The incidence of severe acute graft-versus-host disease tended to be higher after the lower alemtuzumab dose (17% versus 4%; P = .15). No significant differences in the cumulative incidences of relapse (38% versus 35%; P = .81) or nonrelapse mortality (46% versus 27%; P = .31) were observed. Accordingly, disease-free and overall survival were not significantly different between groups. Although the feasibility of radioimmunotherapy plus reduced-intensity conditioning could be demonstrated in elderly patients, the dose reduction of alemtuzumab had no positive impact on overall outcome.

  17. Bacterial foodborne infections after hematopoietic cell transplantation.

    Science.gov (United States)

    Boyle, Nicole M; Podczervinski, Sara; Jordan, Kim; Stednick, Zach; Butler-Wu, Susan; McMillen, Kerry; Pergam, Steven A

    2014-11-01

    Diarrhea, abdominal pain, and fever are common among patients undergoing hematopoietic cell transplantation (HCT), but such symptoms are also typical with foodborne infections. The burden of disease caused by foodborne infections in patients undergoing HCT is unknown. We sought to describe bacterial foodborne infection incidence after transplantation within a single-center population of HCT recipients. All HCT recipients who underwent transplantation from 2001 through 2011 at the Fred Hutchinson Cancer Research Center in Seattle, Washington were followed for 1 year after transplantation. Data were collected retrospectively using center databases, which include information from transplantation, on-site examinations, outside records, and collected laboratory data. Patients were considered to have a bacterial foodborne infection if Campylobacter jejuni/coli, Listeria monocytogenes, E. coli O157:H7, Salmonella species, Shigella species, Vibrio species, or Yersinia species were isolated in culture within 1 year after transplantation. Nonfoodborne infections with these agents and patients with pre-existing bacterial foodborne infection (within 30 days of transplantation) were excluded from analyses. A total of 12 of 4069 (.3%) patients developed a bacterial foodborne infection within 1 year after transplantation. Patients with infections had a median age at transplantation of 50.5 years (interquartile range [IQR], 35 to 57), and the majority were adults ≥18 years of age (9 of 12 [75%]), male gender (8 of 12 [67%]) and had allogeneic transplantation (8 of 12 [67%]). Infectious episodes occurred at an incidence rate of 1.0 per 100,000 patient-days (95% confidence interval, .5 to 1.7) and at a median of 50.5 days after transplantation (IQR, 26 to 58.5). The most frequent pathogen detected was C. jejuni/coli (5 of 12 [42%]) followed by Yersinia (3 of 12 [25%]), although Salmonella (2 of 12 [17%]) and Listeria (2 of 12 [17%]) showed equal frequencies; no cases of Shigella

  18. Ex vivo Expansion of Hematopoietic Stem Cells

    NARCIS (Netherlands)

    E. Farahbakhshian (Elnaz)

    2013-01-01

    textabstractHematopoiesis is a complex cellular differentiation process resulting in the formation of all blood cell types. In this process, hematopoietic stem cells (HSCs) reside at the top of the hematopoiesis hierarchy and have the capacity to differentiate into all blood cell lineages (multipote

  19. Human hematopoietic cell culture, transduction, and analyses

    DEFF Research Database (Denmark)

    Bonde, Jesper; Wirthlin, Louisa; Kohn, Donald B;

    2008-01-01

    This unit provides methods for introducing genes into human hematopoietic progenitor cells. The Basic Protocol describes isolation of CD34(+) cells, transduction of these cells with a retroviral vector on fibronectin-coated plates, assaying the efficiency of transduction, and establishing long...

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    ). Allogeneic skin grafts are known to be acutely rejected. Successful allogeneic STSG has only been reported in sporadic cases of identical twins (isotransplantation). This case is the first to demonstrate what works in theory: the immune system of a stem cell transplanted patient with 100% or mixed stable......SUMMARY: We present a unique case of a bone marrow stem cell transplanted (BMT) patient with cutaneous chronic Graft versus Host Disease (cGvHD) who underwent successful allogeneic split-thickness skin graft (STSG) transplantation. BMT had previously been carried out due to myelodysplasia and non...... donor chimaerism will not recognise skin from the stem cell donor as foreign. Due to advances in haematology, the number of BMT patients and their long-term survival is expected to increase. cGvHD, predisposing to skin problems and ulcerations, complicates up to 70% of cases of BMT. In BMT patients...

  1. Advance in hematopoietic stem cells transplantation for leukemia

    Institute of Scientific and Technical Information of China (English)

    HUANG Xiao-jun

    2008-01-01

    @@ During the past 50 years, intensive studies into the characteristics of hematopoietic stem cell transplantation immunology and the emergence of new immunosuppressant and anti-infective drugs have significantly improved the clinical result of hematopoietic stem cell transplantation (HSCT).

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

    Science.gov (United States)

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

    2006-01-01

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

  3. Differential requirements for hematopoietic commitment between human and rhesus embryonic stem cells.

    Science.gov (United States)

    Rajesh, Deepika; Chinnasamy, Nachimuthu; Mitalipov, Shoukhrat M; Wolf, Don P; Slukvin, Igor; Thomson, James A; Shaaban, Aimen F

    2007-02-01

    Progress toward clinical application of ESC-derived hematopoietic cellular transplantation will require rigorous evaluation in a large animal allogeneic model. However, in contrast to human ESCs (hESCs), efforts to induce conclusive hematopoietic differentiation from rhesus macaque ESCs (rESCs) have been unsuccessful. Characterizing these poorly understood functional differences will facilitate progress in this area and likely clarify the critical steps involved in the hematopoietic differentiation of ESCs. To accomplish this goal, we compared the hematopoietic differentiation of hESCs with that of rESCs in both EB culture and stroma coculture. Initially, undifferentiated rESCs and hESCs were adapted to growth on Matrigel without a change in their phenotype or karyotype. Subsequent differentiation of rESCs in OP9 stroma led to the development of CD34(+)CD45(-) cells that gave rise to endothelial cell networks in methylcellulose culture. In the same conditions, hESCs exhibited convincing hematopoietic differentiation. In cytokine-supplemented EB culture, rESCs demonstrated improved hematopoietic differentiation with higher levels of CD34(+) and detectable levels of CD45(+) cells. However, these levels remained dramatically lower than those for hESCs in identical culture conditions. Subsequent plating of cytokine-supplemented rhesus EBs in methylcellulose culture led to the formation of mixed colonies of erythroid, myeloid, and endothelial cells, confirming the existence of bipotential hematoendothelial progenitors in the cytokine-supplemented EB cultures. Evaluation of four different rESC lines confirmed the validity of these disparities. Although rESCs have the potential for hematopoietic differentiation, they exhibit a pause at the hemangioblast stage of hematopoietic development in culture conditions developed for hESCs.

  4. Results of hematopoietic stem cell transplantation after treatment with different high-dose total-body irradiation regimens in five Dutch centers

    NARCIS (Netherlands)

    van Kempen-Harteveld, M. Loes; Brand, Ronald; Kal, Henk B.; Verdonck, Leo F.; Hofman, Pieter; Schattenberg, Anton V.; van der Maazen, Richard W.; Cornelissen, Jan J.; Eijkenboom, Wil M. H.; van der Lelie, Johannes P.; Oldenburger, Foppe; Barge, Renee M.; van Biezen, Anja; Vossen, Jaak M. J. J.; Noordijk, Evert M.; Struikmans, Henk

    2008-01-01

    Purpose: To evaluate results of high-dose total-body irradiation (TBI) regimens for hematopoietic stem cell transplantation. Methods and Materials: A total of 1,032 patients underwent TBI in one or two fractions before autologous or allogeneic hematologic stem cell transplantation for acute leukemia

  5. Results of hematopoietic stem cell transplantation after treatment with different high-dose total-body irradiation regimens in five Dutch centers.

    NARCIS (Netherlands)

    Kempen-Harteveld, ML van; Brand, R.; Kal, H.B.; Verdonck, L.F.; Hofman, P.; Schattenberg, A.V.M.B.; Maazen, R.W.M. van der; Cornelissen, J.J.L.M.; Eijkenboom, W.M.H.; Lelie, JP van der; Oldenburger, F.; Barge, R.M.; Biezen, A. van; Vossen, J.M.J.J.; Noordijk, E.M.; Struikmans, H.

    2008-01-01

    PURPOSE: To evaluate results of high-dose total-body irradiation (TBI) regimens for hematopoietic stem cell transplantation. METHODS AND MATERIALS: A total of 1,032 patients underwent TBI in one or two fractions before autologous or allogeneic hematologic stem cell transplantation for acute leukemia

  6. Recent advances in hematopoietic stem cell biology

    DEFF Research Database (Denmark)

    Bonde, Jesper; Hess, David A; Nolta, Jan A

    2004-01-01

    PURPOSE OF REVIEW: Exciting advances have been made in the field of hematopoietic stem cell biology during the past year. This review summarizes recent progress in the identification, culture, and in vivo tracking of hematopoietic stem cells. RECENT FINDINGS: The roles of Wnt and Notch proteins...... in regulating stem cell renewal in the microenvironment, and how these molecules can be exploited in ex vivo stem cell culture, are reviewed. The importance of identification of stem cells using functional as well as phenotypic markers is discussed. The novel field of nanotechnology is then discussed...... in the context of stem cell tracking in vivo. This review concludes with a section on the unexpected potential of bone marrow-derived stem cells to contribute to the repair of damaged tissues. The contribution of cell fusion to explain the latter phenomenon is discussed. SUMMARY: Because of exciting discoveries...

  7. Induction of embryonic stem cells to hematopoietic cells in vitro

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    In order to get hematopoietic cells from embryonic stem (ES) cells and to study development mechanisms of hematopoietic cells, the method of inducing embryonic stem cells to hematopoietic cells was explored by differenciating mouse ES cells and human embryonic cells in three stages. The differentiated cells were identified by flow cytometry, immunohistochemistry and Wright's staining. The results showed that embryoid bodies (EBs) could form when ES cells were cultured in the medium with 2-mercaptoethanol (2-ME). However, cytokines, such as stem cell factor (SCF), thrombopoietin (TPO), interleukin-3 (IL-3), interleukin-6 (IL-6), erythropoietin (EPO) and granular colony stimulating factor (G-CSF), were not helpful for forming EBs. SCF, TPO and embryonic cell conditional medium were useful for the differentiation of mouse EBs to hematopoietic progenitors. Eighty-six percent of these cells were CD34+ after 6-d culture. Hematopoietic progenitors differentiated to B lymphocytes when they were cocultured with primary bone marrow stroma cells in the DMEM medium with SCF and IL-6. 14 d later, most of the cells were CD34-CD38+. Wright's staining and immunohistochemistry showed that 80% of these cells were plasma-like morphologically and immunoglubolin positive. The study of hematopoietic cells from human embryonic cells showed that human embryonic cell differentiation was very similar to that of mouse ES cells. They could form EBs in the first stage and the CD34 positive cells account for about 48.5% in the second stage.

  8. Activated allogeneic NK cells preferentially kill poor prognosis B-cell chronic lymphocytic leukemia cells

    OpenAIRE

    2016-01-01

    Mutational status of TP53 together with expression of wild type (wt) IGHV represents the most widely accepted biomarkers, establishing a very poor prognosis in B-cell chronic lymphocytic leukemia (B-CLL) patients. Adoptive cell therapy using allogeneic HLA mismatched Natural Killer (NK) cells has emerged as an effective and safe alternative in the treatment of acute myeloid and lymphoid leukemias that do not respond to traditional therapies. We have described that allogeneic activated NK cell...

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  10. Genomic Editing of the HIV-1 Coreceptor CCR5 in Adult Hematopoietic Stem and Progenitor Cells Using Zinc Finger Nucleases

    OpenAIRE

    2013-01-01

    The HIV-1 coreceptor CCR5 is a validated target for HIV/AIDS therapy. The apparent elimination of HIV-1 in a patient treated with an allogeneic stem cell transplant homozygous for a naturally occurring CCR5 deletion mutation (CCR5Δ32/Δ32) supports the concept that a single dose of HIV-resistant hematopoietic stem cells can provide disease protection. Given the low frequency of naturally occurring CCR5Δ32/Δ32 donors, we reasoned that engineered autologous CD34+ hematopoietic stem/progenitor ce...

  11. Hematopoietic stem cell transplantation in multiple sclerosis

    DEFF Research Database (Denmark)

    Rogojan, C; Frederiksen, J L

    2009-01-01

    Intensive immunosuppresion followed by hematopoietic stem cell transplantation (HSCT) has been suggested as potential treatment in severe forms of multiple sclerosis (MS). Since 1995 ca. 400 patients have been treated with HSCT. Stabilization or improvement occurred in almost 70% of cases at least...

  12. Hyperthyroidism after allogeneic hematopoietic stem cell transplantation:a case report and literature review%异基因造血干细胞移植术后发生甲状腺功能亢进1例报告并文献复习

    Institute of Scientific and Technical Information of China (English)

    郭芳; 郑永江

    2015-01-01

    Objective To investigate the characteristics of diagnosis and treatment on hyperthyroidism after allogeneic hematopoietic stem cell transplantation (AHSCT).Methods The clinical data of a female patient who suffered from hyperthyroidism after AHSCT at Department of Hematology of the Third Affiliated Hospital,Sun Yat-sen University at December 2008 were analyzed retrospectively.The clinical manifestation,laboratory examination,diagnosis and treatment of the patient were summarized and analyzed, and the relevant literatures were reviewed.Results The patient developed the symptoms of hyperthyroidism at 39 months after AHSCT,and had the clinical manifestation and laboratory examination results specific to hyperthyroidism.The patient was diagnosed as diffuse toxic goiter (Graves’disease)and had good prognosis after drug therapy.Conclusions It is rare to develop hyperthyroidism after AHSCT that has specific clinical manifestation and can be confirmed by laboratory examination.Graves'disease has good prognosis with early diagnosis and treatment.%目的:探讨异基因造血干细胞移植术后发生甲状腺功能亢进(甲亢)的诊治特点。方法回顾性分析2008年12月在中山大学附属第三医院血液科行异基因造血干细胞移植术后发生甲亢的1例女性患者的临床资料,总结分析该例患者的临床表现、实验室检查以及诊治经过,并复习相关文献。结果该患者异基因造血干细胞移植术后39个月出现甲亢症状,患者有甲亢特异性临床表现和实验室检查结果,诊断为弥漫性毒性甲状腺肿(Graves 病),给予药物治疗后效果良好。结论异基因造血干细胞移植术后发生甲亢临床少见,有特异性临床表现,确诊主要依靠实验室检查。该病如早期诊断和治疗,疗效良好。

  13. Disseminated toxoplasmosis after allogeneic stem cell transplantation in a seronegative recipient.

    Science.gov (United States)

    Osthoff, M; Chew, E; Bajel, A; Kelsey, G; Panek-Hudson, Y; Mason, K; Szer, J; Ritchie, D; Slavin, M

    2013-02-01

    Toxoplasmosis is increasingly diagnosed after hematopoietic stem cell transplantation (HSCT) and is associated with considerable morbidity and mortality. In the majority of cases, reactivation of latent disease secondary to impaired cellular and humoral immunity after HSCT is believed to be the main pathogenetic mechanism. Hence, primary toxoplasmosis is rarely considered in the differential diagnosis of infections after HSCT in a recipient who is seronegative for Toxoplasma gondii pre-transplant. We herein report a seronegative patient with acute T-cell lymphoblastic leukemia, who developed primary disseminated toxoplasmosis 5 months after HSCT from a seronegative unrelated donor. A review of all reported cases of primary toxoplasmosis after HSCT revealed significantly increased morbidity and mortality. Patients with negative pre-transplant Toxoplasma serology should therefore be considered at risk for toxoplasmosis after allogeneic HSCT. Possible prevention and monitoring strategies for seronegative recipients are reviewed and discussed in detail.

  14. Donor-Derived Smoldering Multiple Myeloma following a Hematopoietic Cell Transplantation for AML

    Science.gov (United States)

    Fiala, Mark; Slade, Michael; Westervelt, Peter

    2017-01-01

    Posttransplant Lymphoproliferative Disorder (PTLD) is one of the most common malignancies complicating solid organ transplantation. In contrast, PTLD accounts for a minority of secondary cancers following allogeneic hematopoietic cell transplantation (HCT). Here we report on a 61-year-old woman who received an ABO-mismatched, HLA-matched unrelated donor hematopoietic cell transplantation from a presumably healthy donor for a diagnosis of acute myeloid leukemia (AML). Eighteen months following her transplant, she developed a monoclonal gammopathy. Bone marrow studies revealed 10% plasma cells, but the patient lacked clinical defining features of multiple myeloma (MM); thus a diagnosis of smoldering multiple myeloma (SMM) was established. Cytogenetic and molecular studies of the bone marrow confirmed the plasma cells were donor-derived. The donor lacks a diagnosis of monoclonal gammopathy of undetermined significance, SMM, or MM. PMID:28316846

  15. Donor-Derived Smoldering Multiple Myeloma following a Hematopoietic Cell Transplantation for AML

    Directory of Open Access Journals (Sweden)

    Bita Fakhri

    2017-01-01

    Full Text Available Posttransplant Lymphoproliferative Disorder (PTLD is one of the most common malignancies complicating solid organ transplantation. In contrast, PTLD accounts for a minority of secondary cancers following allogeneic hematopoietic cell transplantation (HCT. Here we report on a 61-year-old woman who received an ABO-mismatched, HLA-matched unrelated donor hematopoietic cell transplantation from a presumably healthy donor for a diagnosis of acute myeloid leukemia (AML. Eighteen months following her transplant, she developed a monoclonal gammopathy. Bone marrow studies revealed 10% plasma cells, but the patient lacked clinical defining features of multiple myeloma (MM; thus a diagnosis of smoldering multiple myeloma (SMM was established. Cytogenetic and molecular studies of the bone marrow confirmed the plasma cells were donor-derived. The donor lacks a diagnosis of monoclonal gammopathy of undetermined significance, SMM, or MM.

  16. RESULTS OF HEMATOPOIETIC CELL TRANSPLANTATION IN PEDIATRIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    A. Mousavi

    2008-05-01

    Full Text Available Hematopoietic cell transplantation (HCT is an accepted treatment for acute myeloid leukemia (AML in first remission, the treatment of choice for chronic myeloid leukemia (CML and high risk groups of ALL who relapse with conventional chemotherapy. We assessed results of HCT for pediatric leukemia in our center. A total of 92 children, 63 with diagnose of AML, 23 with ALL and 6 with CML received allogeneic transplantation from HLA full matched siblings (57.6% and autologous transplantation (42.4%. Source of hematopoietic cells were peripheral blood 83.7%, bone marrow 15.2% and cord blood 1.6%. The median transplanted nucleated cells were 6.4 ± 4.7 ×108 /Kg (body weight of patients and mononuclear cells were 5.5 ± 2.9×108/Kg. The most common conditioning regimens were cyclophosphamide + busulfan. Prophylaxis regimen for GVHD was cyclosporin ± methotrexate. GVHD occurred in 50 (54.3% patients. Eighty five of children had engraftment, 26 (28.6% relapsed and 57 (62% are alive. The most common cause of death was relapse (68.6%. Five years overall survival of patients with AML and ALL were 49% and 44% respectively and disease free survival of them were 52% and 49%. One year overall survival and disease free survival of CML was 57%. Overall survival increased with increasing age of patients at transplantation time (P = 0.06. Longer survival significantly related to earlier WBC and platelet recovery (P < 0.0001 and P = 0.006 respectively. Considering acceptable overall and disease free survival of patients after HCT, we concluded that is a good modality in treatment of leukemia of children.

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

    Science.gov (United States)

    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.

  18. The effect of a multimodal intervention on treatment-related symptoms in patients undergoing hematopoietic stem cell transplantation: a randomized controlled trial

    DEFF Research Database (Denmark)

    Jarden, Mary; Nelausen, Knud; Hovgaard, Doris;

    2009-01-01

    in patients undergoing myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT). Forty-two patients (18-65 years) were randomized either to an intervention or a control group. The intervention group received standard treatment and care, and a supervised four- to six-week structured...

  19. Genetic Modification of Hematopoietic Stem Cells as a Therapy for HIV/AIDS

    Directory of Open Access Journals (Sweden)

    Patrick Younan

    2013-11-01

    Full Text Available The combination of genetic modification and hematopoietic stem cell (HSC transplantation may provide the necessary means to develop an alternative treatment option to conventional antiretroviral therapy. As HSCs give rise to all hematopoietic cell types susceptible to HIV infection, modification of HSCs is an ideal strategy for the development of infection-resistant immune cell populations. Although promising results have been obtained in multiple animal models, additional evidence is needed to convincingly demonstrate the feasibility of this approach as a treatment of HIV-1 infected patients. Here, we review the potential of HSC transplantation and the recently identified limitations of this approach. Using the Berlin Patient as a model for a functional cure, we contrast the confines of autologous versus allogeneic transplantation. Finally, we suggest that although autologous, gene-modified HSC-transplantation may significantly reduce plasma viremia, reaching the lower detection limits currently obtainable through daily HAART will remain a challenging endeavor that will require innovative combinatorial therapies.

  20. Genetic modification of hematopoietic stem cells as a therapy for HIV/AIDS.

    Science.gov (United States)

    Younan, Patrick; Kowalski, John; Kiem, Hans-Peter

    2013-11-28

    The combination of genetic modification and hematopoietic stem cell (HSC) transplantation may provide the necessary means to develop an alternative treatment option to conventional antiretroviral therapy. As HSCs give rise to all hematopoietic cell types susceptible to HIV infection, modification of HSCs is an ideal strategy for the development of infection-resistant immune cell populations. Although promising results have been obtained in multiple animal models, additional evidence is needed to convincingly demonstrate the feasibility of this approach as a treatment of HIV-1 infected patients. Here, we review the potential of HSC transplantation and the recently identified limitations of this approach. Using the Berlin Patient as a model for a functional cure, we contrast the confines of autologous versus allogeneic transplantation. Finally, we suggest that although autologous, gene-modified HSC-transplantation may significantly reduce plasma viremia, reaching the lower detection limits currently obtainable through daily HAART will remain a challenging endeavor that will require innovative combinatorial therapies.

  1. Microsatellite instability confounds engraftment analysis of hematopoietic stem-cell transplantation.

    Science.gov (United States)

    Tseng, Li-Hui; Tang, Jih-Luh; Haley, Lisa; Beierl, Katie; Gocke, Christopher D; Eshleman, James R; Lin, Ming-Tseh

    2014-07-01

    Polymorphic short tandem-repeat, or microsatellite, loci have been widely used to analyze chimerism status after allogeneic hematopoietic stem-cell transplantation. In molecular diagnostic laboratories, it is recommended to calculate mixed chimerism for at least 2 informative loci and to avoid microsatellite loci on chromosomes with copy number changes. In this report, we show that microsatellite instability observed in 2 patients with acute leukemia may confound chimerism analysis. Interpretation errors may occur even if 2 to 3 loci are analyzed because of length variation in multiple microsatellite loci. Although microsatellite loci with length variation should not be selected for chimerism analysis, the presence of microsatellite instability, like copy number alteration because of aberrant chromosomes, provides evidence of recurrent or residual cancer cells after hematopoietic stem-cell transplantation.

  2. Hematopoietic stem cell origin of connective tissues.

    Science.gov (United States)

    Ogawa, Makio; Larue, Amanda C; Watson, Patricia M; Watson, Dennis K

    2010-07-01

    Connective tissue consists of "connective tissue proper," which is further divided into loose and dense (fibrous) connective tissues and "specialized connective tissues." Specialized connective tissues consist of blood, adipose tissue, cartilage, and bone. In both loose and dense connective tissues, the principal cellular element is fibroblasts. It has been generally believed that all cellular elements of connective tissue, including fibroblasts, adipocytes, chondrocytes, and bone cells, are generated solely by mesenchymal stem cells. Recently, a number of studies, including those from our laboratory based on transplantation of single hematopoietic stem cells, strongly suggested a hematopoietic stem cell origin of these adult mesenchymal tissues. This review summarizes the experimental evidence for this new paradigm and discusses its translational implications.

  3. Proteomic cornerstones of hematopoietic stem cell differentiation

    DEFF Research Database (Denmark)

    Klimmeck, Daniel; Hansson, Jenny; Raffel, Simon

    2012-01-01

    Regenerative tissues such as the skin epidermis, the intestinal mucosa or the hematopoietic system are organized in a hierarchical manner with stem cells building the top of this hierarchy. Somatic stem cells harbor the highest self-renewal activity and generate a series of multipotent progenitors...... which differentiate into lineage committed progenitors and subsequently mature cells. In this report, we applied an in-depth quantitative proteomic approach to analyze and compare the full proteomes of ex vivo isolated and FACS-sorted populations highly enriched for either multipotent hematopoietic stem....../progenitor cells (HSPCs, Lin(neg)Sca-1(+)c-Kit(+)) or myeloid committed precursors (Lin(neg)Sca-1(-)c-Kit(+)). By employing stable isotope dimethyl labeling and high-resolution mass spectrometry, more than 5,000 proteins were quantified. From biological triplicate experiments subjected to rigorous statistical...

  4. Proven/Probable Invasive Fungal Infection in hematologic patients with Acute Myeloid Leukaemia and/or in Allogeneic Hematopoietic Stem Cell Transplant recipients. | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available ni fungine invasive certe/probabilili in pazienti ematologici con leucemia mieloide acuta e/o in pazienti co... settimane come terapia di mantenimento per infezioni fungine invasive certe/probabilili in pazienti ematologici con leucemia...oietic Stem Cell Transplant recipients. infezioni fungine invasive certe/probabilili in pazienti ematologici con leucemia... recipients. infezioni fungine invasive certe/probabilili in pazienti ematologici con leucemia mieloide acut...ndard con L-AMB 3 mg / kg una volta al giorno nei pazienti ematologici in trattamento per leucemia

  5. Clinical observation of allogeneic hematopoietic stem cell transplantation for 20 patients with hematologic malignancies%异基因造血干细胞移植治疗恶性血液病20例临床疗效观察

    Institute of Scientific and Technical Information of China (English)

    潘鹏吉; 王季石; 孙志强; 卢英豪; 李梦醒; 赵鹏; 龙正美

    2012-01-01

    Objective To evaluate the efficacy of allogeneic stem cell transplantation (allo-HSCT) in treatment of hematologic malignancies and observe hematopoietic reconstitution, graft versus host disease (GVHD) occurrence,transplant-related complications and the outcome of disease.Methods 20 patients with hematologic malignancies cured by allo-HSCT were analyzed retrospectively. 15 males and 5 females patients were enrolled, and the median age was 39 (8-59) years. Mobilization of donor’ s stem cells using rhG-CSF program 3 days before transplantation.Conditioning regimen:the patients with HLA-matched used modified Bu/Cy programs,the patients with HLA-mismatched (with 1 to 3 loci mismatched) used the modified Bu/Cy+ ATG program; the patient with T-ALL and the patient with MM used Flu+Bu/Cy program. GVHD prevention programs: mycophenolate mofetil + cyclosporine + short course methotrexate. Results 20 patients were successfully engrafted,the median time of absolute neutrophil count (ANC) > 0.5×109/L was 13 (12-17) days,the median time of Plt > 20×109/L was 16 (12-23) days, and the hematopoietic reconstitution was rapid in those patients who were transplanted by the donors with the collected amount of CDh cells > 2.5× 106/kg (recipient body weigh) or the collected amount of mononuclear cell > 5.0×10s/kg (recipient body weigh).No severe hemolytic reaction occurred in 11 cases of blood group incompatibility between donor and recipient after transplantation,11 cases (55 %) developed acute GVHD (aGVHD):4 cases Ⅰ degree aGVHD,4 cases Ⅱ degree aGVHD,2 cases Ⅲ degree aGVHD,1 case Ⅳ degree aGVHD,all patients were improved after treatment.All patients attained complete remission (CR) after transplantation.Follow-up 6 (2-14) months,1 patient died in 5 months after transplantation because of leukemia relapse, 1 case died in 4 months after transplantation because of self-disabling autoimmune hemolytic cyclosporine, chronic GVHD (cGVHD) and multiple organ failure

  6. 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.

  7. The clinical study of the haploidentical allogeneic hematopoietic stem cell transplantation with paternal donors in high-risk leukemia%父供子单倍体异基因造血干细胞移植治疗高危白血病2例临床分析

    Institute of Scientific and Technical Information of China (English)

    孙巍; 王晓华

    2013-01-01

    Objective To analyze the clinical features and therapeutic effect of haploidentical allogeneic hematopoietic stem cell transplantation (Allo-HSCT) with paternal donors in treating high-risk leukemia.Methods Clinical data of 2 cases with high-risk leukemia treated with haploidentical Allo-HSCT from paternal donors were analyzed.Results The transfusion cell number for these 2 cases were 17.7 × 108/kg and 8.3 × 108/kg,respectively; the graft survival time of white cells were +7 d and + 16 d,respectively; the graft survival time of platelet were + 18 d and +8 d,respectively; all 2 cases turned to full-donor type ultimately.Among them,1 case occurred acute intestinal tract GVHD (Ⅳ°),the other was complicated with skin Ⅱ ° GVHD.One case died of infection after transplantation at + 146 d,and the other remained survival without relapse.Conclusions Non-T-depleted HLA haploidentical Allo-HSCT is becoming a safe and effective alternative method in treating high-risk leukemia without HLA-matched related and unrelated donors.Besides,paternal antigen donor could be considered as a source of hemopoietic stem cell.%目的 探讨父供子单倍型造血干细胞移植治疗高危白血病的临床特点及疗效.方法 对2例高危白血病接受父供子单倍型造血干细胞移植患儿的临床资料进行回顾性分析.结果 2例患儿回输有核细胞数分别为17.7×108/kg、8.3×108/kg,白细胞植活时间分别为+7d和+16 d,血小板植活时间分别为+18 d和+8 d;2例均转为完全供者型;1例出现急性肠道GVHD(Ⅳ度),1例出现皮肤Ⅱ度GVHD;1例因移植后感染于+146 d死亡,1例存活,均无白血病复发倾向.结论 非去T细胞性单倍型异基因造血干细胞移植正逐渐成为一种安全有效的治疗方法,为缺乏HLA完全相合相关或无关供者的高危难治性白血病患者提供了新的治疗选择.同时也提示父亲或父系抗原供者同样可以作为异基因造血干细胞来源.

  8. 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...

  9. DNA methylation profiling of hematopoietic stem cells.

    Science.gov (United States)

    Begtrup, Amber Hogart

    2014-01-01

    DNA methylation is a key epigenetic mark that is essential for properly functioning hematopoietic stem cells. Determining where functionally relevant DNA methylation marks exist in the genome is crucial to understanding the role that methylation plays in hematopoiesis. This chapter describes a method to profile DNA methylation by selectively enriching methylated DNA sequences that are bound in vitro by methyl-binding domain (MBD) proteins. The MBD-pulldown approach selects for DNA sequences that have the potential to be "read" by the endogenous machinery involved in epigenetic regulation. Furthermore, this approach is feasible with very small quantities of DNA, and is compatible with the use of any downstream high-throughput sequencing approach. This technique offers a reliable, simple, and powerful tool for exploration of the role of DNA methylation in hematopoietic stem cells.

  10. Allogeneic stem cell transplantation in acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Natasha Ali

    2012-11-01

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

  11. Consideration of strategies for hematopoietic cell transplantation.

    Science.gov (United States)

    Yaniv, Isaac; Ash, Shifra; Farkas, Daniel L; Askenasy, Nadir; Stein, Jerry

    2009-01-01

    Bone marrow transplantation has been adoptively transferred from oncology to the treatment of autoimmune disorders. Along with extension of prevalent transplant-related concepts, the assumed mechanism that arrests autoimmunity involves elimination of pathogenic cells and resetting of immune homeostasis. Similar to graft versus tumor (GVT) reactivity, allogeneic transplants are considered to provide a better platform of immunomodulation to induce a graft versus autoimmunity reaction (GVA). It is yet unclear whether recurrence of autoimmunity in both autologous and allogeneic settings reflects relapse of the disease, transplant-associated immune dysfunction or insufficient immune modulation. Possible causes of disease recurrence include reactivation of residual host pathogenic cells and persistence of memory cells, genetic predisposition to autoimmunity and pro-inflammatory characteristics of the target tissues. Most important, there is little evidence that autoimmune disorders are indeed abrogated by current transplant procedures, despite reinstitution of both peripheral and thymic immune homeostasis. It is postulated that non-specific immunosuppressive therapy that precedes and accompanies current bone marrow transplant strategies is detrimental to the active immune process that restores self-tolerance. This proposition refocuses the need to develop strategies of immunomodulation without immunosuppression.

  12. Haploidentical Natural Killer Cells Infused before Allogeneic Stem Cell Transplantation for Myeloid Malignancies: A Phase I Trial.

    Science.gov (United States)

    Lee, Dean A; Denman, Cecele J; Rondon, Gabriela; Woodworth, Glenda; Chen, Julianne; Fisher, Tobi; Kaur, Indreshpal; Fernandez-Vina, Marcelo; Cao, Kai; Ciurea, Stefan; Shpall, Elizabeth J; Champlin, Richard E

    2016-07-01

    Allogeneic stem cell transplantation is an effective treatment for high-risk myeloid malignancies, but relapse remains the major post-transplantation cause of treatment failure. Alloreactive natural killer (NK) cells mediate a potent antileukemic effect and may also enhance engraftment and reduce graft-versus-host disease (GVHD). Haploidentical transplantations provide a setting in which NK cell alloreactivity can be manipulated, but they are associated with high rates of GVHD. We performed a phase I study infusing escalating doses of NK cells from an HLA haploidentical-related donor-selected for alloreactivity when possible-as a component of the preparative regimen for allotransplantation from a separate HLA-identical donor. The goal of infusing third-party alloreactive NK cells was to augment the antileukemic effect of the transplantation without worsening GVHD and, thus, improve the overall outcome of hematopoietic transplantation. Twenty-one patients with high-risk acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelogenous leukemia refractory or beyond first remission received a preparative regimen with busulfan and fludarabine followed by infusion of apheresis-derived, antibody-selected, and IL-2-activated NK cells. Doses were initially based on total nucleated cell (TNC) content and later based on CD56(+) cells to reduce variability. CD56(+) content ranged from .02 to 8.32 × 10(6)/kg. IL-2, .5 × 10(6) units/m(2) subcutaneously was administered daily for 5 days in the final cohort (n = 10). CD3(+) cells in the NK cell product were required to be transplantation-related causes, and 11 patients died of relapse. Despite the small sample size, survival was highly associated with CD56(+) cells delivered (P = .022) and development of ≥ grade 3 GVHD (P = .006). There were nonsignificant trends toward higher survival rates in those receiving NK cells from KIR ligand-mismatched donors and KIR-B haplotype donors. There was no

  13. Inhaled corticosteroids stabilize constrictive bronchiolitis after hematopoietic stem cell transplantation.

    Science.gov (United States)

    Bashoura, L; Gupta, S; Jain, A; Couriel, D R; Komanduri, K V; Eapen, G A; Safdar, A; Broglio, K R; Adachi, R; Dickey, B F

    2008-01-01

    Post transplantation constrictive bronchiolitis (PTCB) is the most common pulmonary complication among long-term survivors of allogeneic hematopoietic stem cell transplantation (HSCT). It is a late manifestation of GVHD. Its treatment with high-dose systemic corticosteroids and other immunosuppressive regimens is associated with multiple side effects. Topical corticosteroids are used for the treatment of other manifestations of GVHD to minimize these side effects. We conducted a retrospective analysis of a series of adult patients to evaluate the efficacy of high-dose inhaled corticosteroids in the treatment of PTCB. Seventeen patients with new-onset airflow obstruction were diagnosed with PTCB. Their forced expiratory volume in 1 s (FEV1) declined from a median of 84% (range, 56-119) before HSCT to 53% (26-82) after HSCT. All patients received inhaled fluticasone propionate 500-940 microg two times daily. Symptoms of airway obstruction improved and FEV1 stabilized 3-6 months after treatment. We conclude that high-dose inhaled corticosteroids may be effective in the treatment of PTCB and propose a plausible mechanism of its action. A prospective evaluation of its efficacy is warranted.

  14. Hematopoietic specification from human pluripotent stem cells: current advances and challenges toward de novo generation of hematopoietic stem cells.

    Science.gov (United States)

    Slukvin, Igor I

    2013-12-12

    Significant advances in cellular reprogramming technologies and hematopoietic differentiation from human pluripotent stem cells (hPSCs) have already enabled the routine production of multiple lineages of blood cells in vitro and opened novel opportunities to study hematopoietic development, model genetic blood diseases, and manufacture immunologically matched cells for transfusion and cancer immunotherapy. However, the generation of hematopoietic cells with robust and sustained multilineage engraftment has not been achieved. Here, we highlight the recent advances in understanding the molecular and cellular pathways leading to blood development from hPSCs and discuss potential approaches that can be taken to facilitate the development of technologies for de novo production of hematopoietic stem cells.

  15. Preliminary Analysis of Therapeutic Efficacy and Prognosis of Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Advanced Chronic Myeloid Leukemia%异基因造血干细胞移植治疗进展期慢性髓系白血病疗效及预后的初步分析

    Institute of Scientific and Technical Information of China (English)

    宋阿霞; 翟卫华; 张荣莉; 冯四洲; 韩明哲; 杨栋林; 魏嘉鳞; 闫嶂松; 王玫; 姜尔烈; 黄勇; 马巧玲; 何袆

    2011-01-01

    加速期和急变期慢性髓系白血病(CML)患者预后较差,异基因造血干细胞移植(allo-HSCT)是这一类患者唯一具有治愈可能的治疗方法.本研究探讨allo-HSCT治疗进展期CML的疗效及预后.对1998年9月至2008年1月28例接受allo-HSCT的患者从疗效、移植前基础特点与预后、移植前治疗策略与预后、移植后事件与预后等方面进行了回顾性分析.结果表明:28例患者中10例活存并持续缓解,3年总活存率和无病活存率分别34.9%和35.7%;18例死亡.单因素分析发现,克隆演进和原始细胞比例是预后不良的基线危险因素,二者结合可以预测预后.移植前应用伊马替尼并取得完全血液学缓解并不能改善预后.对移植后事件的预后分析发现,并发重度移植物抗宿主病是预后不良的危险因素.结论:对于接受allo-HSCT治疗的进展期CML病例,克隆演进和原始细胞比例是具有预后意义,移植前应用伊马替尼并不能改善预后.%Chronic myeloid leukemia (CML) at advanced and blastic phase is a disease with poor prognosis, for which allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only treatment choice with curative potential. This study was purposed to investigate the therapeutic efficacy of allo-HSCT and prognosis of advanced CML patients. The 28 cases of CML in accelerated phase or blast crisis received allo-HSCT were analysed retrospectively in terms curative efficacy, basic characteristics before transplant and prognosis, therapeutic strategy before transplant and prognosis, events after transplant and prognosis. The results indicated that 10 out of 28 patients were in complete remission, showing a 3-year overall survival and disease-free survaval rate of 34.9% and 35.7% respectively; 18 patients died. Univariate analysis revealed that the clonal evolution and blast amount are baseline risk factor of poor prognosis, and combination of them can be used to predict the outcome

  16. Clinical analysis of allogeneic hematopoietic stem cells transplantation for treatment of 15 children with malignant hematological diseases%异基因造血干细胞移植治疗儿童恶性血液病15例临床分析

    Institute of Scientific and Technical Information of China (English)

    王娴静; 董秀娟; 陈蕾; 马红霞; 焦雪丽; 吴书一; 刘文刚; 赵晓武

    2014-01-01

    目的 观察异基因造血干细胞移植(allo-HSCT)治疗儿童恶性血液病的疗效和相关并发症,探讨allo-HSCT治疗儿童恶性血液病的适应证.方法 回顾性分析15例接受allo-HSCT治疗的儿童恶性血液病患者的临床资料,其中13例为急性白血病,1例为慢性粒细胞白血病(加速期),1例为骨髓增生异常综合征(MDS-REBT);8例为亲缘供者,7例为非亲缘供者;11例行外周血造血干细胞移植治疗,4例行脐血造血干细胞移植治疗;6例为HLA配型全相合,9例为HLA配型不全相合.结果 15例患儿中生存7例,生存期为5个月~6年;5例因复发或重症感染放弃治疗;3例死亡.6例发生急性移植物抗宿主病(GVHD),包括Ⅰ度3例,Ⅱ、Ⅲ、Ⅳ度各1例,其中发生Ⅳ度急性GVHD患儿死亡.2例发生广泛性慢性GVHD,其中1例死亡,另1例生活质量严重受影响.结论 allo-HSCT是治疗儿童恶性血液病的重要方法,其并发症多、风险大,在防治并发症的同时,应严格把握allo-HSCT治疗儿童恶性血液病的适应证.%Objective To observe the therapeutic efficiency and associated complications of allogeneic hematopoietic stem cells transplantation (allo-HSCT) for treatment of children with malignant hematological disease.Methods Fifteen children with malignant hematological disease were subjected to allo-HSCT from Jan 2007 to Jan 2013.Among those 15 patients,13 cases were diagnosed as acute leukemia (AL),1 case as chronic myeloid leukemia (CML),and 1 case as myelodysplastic syndrome (MDS-RAEB).The clinical characters of all cases after transplantation were analyzed retrospectively.Results Seven cases survived from 5 months to 6 years after transplantation.Five cases abandoned treatment because of relapse or severe infections.Three cases developed grade Ⅰ acute graft-versus-host disease (aGVHD),three cases developed grade Ⅱ,Ⅲ and Ⅳ aGVHD respectively,and one case died of Ⅳ aGVHD.Two patients experienced extensive chronic graft

  17. 异基因造血干细胞移植后慢性炎症性脱髓鞘性多发神经病变一例并文献复习%Chronic inflammatory demyelinating polyneuropathy after allogeneic hematopoietic stem cell transplantation: a case report and review of the literature

    Institute of Scientific and Technical Information of China (English)

    胡凯; 王继军; 万伟; 克晓燕

    2011-01-01

    目的 提高对异基因造血干细胞移植( allo-HSCT)后并发慢性炎症性脱髓鞘性多发神经病变( CIDP)的认识,探讨其临床特点、诊断及治疗.方法 报道1例慢性粒细胞白血病患者allo-HSCT 后发生CIDP的临床和实验室检查特征及治疗经过.结果 患者在移植后发生急性及慢性移植物抗宿主病(GVHD),在第+105天起出现慢性迁延反复的多发部位神经系统症状,以面瘫、四肢肌力减退、排尿困难为主,经多次腰椎穿刺脑脊液检查以及神经电生理检查,除外其他神经系统疾病后诊断为CIDP.经静脉丙种球蛋白、糖皮质激素、免疫抑制剂治疗及功能锻炼,GVHD及CIDP有所改善,但终因长期免疫抑制继发感染而死亡.结论 allo-HSCT后CIDP是一种罕见的、诊治困难的神经系统并发症,为移植相关的多种因素所致,GVHD及免疫系统紊乱是主要原因,应及时诊断,合理治疗.%Objective To study chronic inflammatory demyelinating polyneuropathy (CIDP) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and the clinical manifestation,diagnosis and treatment.Methods The clinical manifestation,laboratory examination,treatment and outcome of a patient with chronic myeloid leukemia after allo-HSCT were studied.Results Acute and chronic graft-versus-host disease(GVHD) were occurred in the patient followed by chronic multiple nervous system symptoms from +105 day including facioplegia,decreased muscle strength and dysuria.According to clinical manifestation,results of cerebrospinal fluid exam and electroneurophysiology exam,CIDP was diagnosed.The clinical condition was improved after treatment with intravenous immunoglobulin,glucocorticoid, immunosuppressive agents and functional exercises,but the patient died of secondary infection finally.Conclusion CIDP after allo-HSCT is a rare complication of nervous system and difficult to diagnose and treat.Numerous transplant-related causes are probably

  18. Hematopoietic stem cell transplantation for infantile osteopetrosis.

    Science.gov (United States)

    Orchard, Paul J; Fasth, Anders L; Le Rademacher, Jennifer; He, Wensheng; Boelens, Jaap Jan; Horwitz, Edwin M; Al-Seraihy, Amal; Ayas, Mouhab; Bonfim, Carmem M; Boulad, Farid; Lund, Troy; Buchbinder, David K; Kapoor, Neena; O'Brien, Tracey A; Perez, Miguel A Diaz; Veys, Paul A; Eapen, Mary

    2015-07-01

    We report the international experience in outcomes after related and unrelated hematopoietic transplantation for infantile osteopetrosis in 193 patients. Thirty-four percent of transplants used grafts from HLA-matched siblings, 13% from HLA-mismatched relatives, 12% from HLA-matched, and 41% from HLA-mismatched unrelated donors. The median age at transplantation was 12 months. Busulfan and cyclophosphamide was the most common conditioning regimen. Long-term survival was higher after HLA-matched sibling compared to alternative donor transplantation. There were no differences in survival after HLA-mismatched related, HLA-matched unrelated, or mismatched unrelated donor transplantation. The 5- and 10-year probabilities of survival were 62% and 62% after HLA-matched sibling and 42% and 39% after alternative donor transplantation (P = .01 and P = .002, respectively). Graft failure was the most common cause of death, accounting for 50% of deaths after HLA-matched sibling and 43% of deaths after alternative donor transplantation. The day-28 incidence of neutrophil recovery was 66% after HLA-matched sibling and 61% after alternative donor transplantation (P = .49). The median age of surviving patients is 7 years. Of evaluable surviving patients, 70% are visually impaired; 10% have impaired hearing and gross motor delay. Nevertheless, 65% reported performance scores of 90 or 100, and in 17%, a score of 80 at last contact. Most survivors >5 years are attending mainstream or specialized schools. Rates of veno-occlusive disease and interstitial pneumonitis were high at 20%. Though allogeneic transplantation results in long-term survival with acceptable social function, strategies to lower graft failure and hepatic and pulmonary toxicity are urgently needed.

  19. Exogenous endothelial cells as accelerators of hematopoietic reconstitution

    Directory of Open Access Journals (Sweden)

    Mizer J

    2012-11-01

    Full Text Available Abstract Despite the successes of recombinant hematopoietic-stimulatory factors at accelerating bone marrow reconstitution and shortening the neutropenic period post-transplantation, significant challenges remain such as cost, inability to reconstitute thrombocytic lineages, and lack of efficacy in conditions such as aplastic anemia. A possible means of accelerating hematopoietic reconstitution would be administration of cells capable of secreting hematopoietic growth factors. Advantages of this approach would include: a ability to regulate secretion of cytokines based on biological need; b long term, localized production of growth factors, alleviating need for systemic administration of factors that possess unintended adverse effects; and c potential to actively repair the hematopoietic stem cell niche. Here we overview the field of hematopoietic growth factors, discuss previous experiences with mesenchymal stem cells (MSC in accelerating hematopoiesis, and conclude by putting forth the rationale of utilizing exogenous endothelial cells as a novel cellular therapy for acceleration of hematopoietic recovery.

  20. Ex Vivo Expanded Allogeneic Mesenchymal Stem Cells With Bone Marrow Transplantation Improved Osteogenesis in Infants With Severe Hypophosphatasia.

    Science.gov (United States)

    Taketani, Takeshi; Oyama, Chigusa; Mihara, Aya; Tanabe, Yuka; Abe, Mariko; Hirade, Tomohiro; Yamamoto, Satoshi; Bo, Ryosuke; Kanai, Rie; Tadenuma, Taku; Michibata, Yuko; Yamamoto, Soichiro; Hattori, Miho; Katsube, Yoshihiro; Ohnishi, Hiroe; Sasao, Mari; Oda, Yasuaki; Hattori, Koji; Yuba, Shunsuke; Ohgushi, Hajime; Yamaguchi, Seiji

    2015-01-01

    Patients with severe hypophosphatasia (HPP) develop osteogenic impairment with extremely low alkaline phosphatase (ALP) activity, resulting in a fatal course during infancy. Mesenchymal stem cells (MSCs) differentiate into various mesenchymal lineages, including bone and cartilage. The efficacy of allogeneic hematopoietic stem cell transplantation for congenital skeletal and storage disorders is limited, and therefore we focused on MSCs for the treatment of HPP. To determine the effect of MSCs on osteogenesis, we performed multiple infusions of ex vivo expanded allogeneic MSCs for two patients with severe HPP who had undergone bone marrow transplantation (BMT) from asymptomatic relatives harboring the heterozygous mutation. There were improvements in not only bone mineralization but also muscle mass, respiratory function, and mental development, resulting in the patients being alive at the age of 3. After the infusion of MSCs, chimerism analysis of the mesenchymal cell fraction isolated from bone marrow in the patients demonstrated that donor-derived DNA sequences existed. Adverse events of BMT were tolerated, whereas those of MSC infusion did not occur. However, restoration of ALP activity was limited, and normal bony architecture could not be achieved. Our data suggest that multiple MSC infusions, following BMT, were effective and brought about clinical benefits for patients with lethal HPP. Allogeneic MSC-based therapy would be useful for patients with other congenital bone diseases and tissue disorders if the curative strategy to restore clinically normal features, including bony architecture, can be established.

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    Lifescience Database Archive (English)

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  5. The Use of Statins in Hematopoietic Stem Cell Transplantation and Solid Organ Transplantation.

    Science.gov (United States)

    Shimabukuro-Vornhagen, Alexander; Schlösser, Hans; Kisner, Tulay; Stippel, Dirk L; von Bergwelt-Baildon, Michael

    2013-01-14

    Allogeneic hematopoietic stem cell transplantation and solid organ transplantation have become established treatments offered to patients for whom there are otherwise no curative treatment options. Unfortunately, these therapeutic modalities are associated with severe complications that limit its applicability. Alloimmunity is an important cause of morbidity and mortality after both organ transplantation and allogeneic hematopoietic stem cell transplantation and represents a major barrier to the more wide-spread use of these treatment modalities. Statins are a class of lipid-lowering drugs, which also posses immunomodulatory effects. Results from preclinial research and early-stage clinical studies indicate that treatment with statins could be beneficial for the prevention and treatment of graft-versus-host disease and transplant rejection. In addition to preventing graft-versus-host disease or graft rejection statins possess several other effects that might prove beneficial in the setting of transplantation, such as cardiovascular protection and antineoplastic activity. Here we summarize the current knowledge about the immunomodulatory effects of statins and discuss the clinical implications for their use in patients undergoing stem cell transplantation or solid organ transplantation.

  6. Allogeneic Mesenchymal Stem Cell Treatment Induces Specific Alloantibodies in Horses

    Directory of Open Access Journals (Sweden)

    Sean D. Owens

    2016-01-01

    Full Text Available Background. It is unknown whether horses that receive allogeneic mesenchymal stem cells (MSCs injections develop specific humoral immune response. Our goal was to develop and validate a flow cytometric MSC crossmatch procedure and to determine if horses that received allogeneic MSCs in a clinical setting developed measurable antibodies following MSC administration. Methods. Serum was collected from a total of 19 horses enrolled in 3 different research projects. Horses in the 3 studies all received unmatched allogeneic MSCs. Bone marrow (BM or adipose tissue derived MSCs (ad-MSCs were administered via intravenous, intra-arterial, intratendon, or intraocular routes. Anti-MSCs and anti-bovine serum albumin antibodies were detected via flow cytometry and ELISA, respectively. Results. Overall, anti-MSC antibodies were detected in 37% of the horses. The majority of horses (89% were positive for anti-bovine serum albumin (BSA antibodies prior to and after MSC injection. Finally, there was no correlation between the amount of anti-BSA antibody and the development of anti-MSC antibodies. Conclusion. Anti allo-MSC antibody development was common; however, the significance of these antibodies is unknown. There was no correlation between either the presence or absence of antibodies and the percent antibody binding to MSCs and any adverse reaction to a MSC injection.

  7. Hematopoietic Stem Cell Transplantation in Adult Sickle Cell Disease: Problems and Solutions

    Directory of Open Access Journals (Sweden)

    Hakan Özdoğu

    2015-09-01

    Full Text Available Sickle cell disease-related organ injuries cannot be prevented despite hydroxyurea use, infection prophylaxis, and supportive therapies. As a consequence, disease-related mortality reaches 14% in adolescents and young adults. Hematopoietic stem cell transplantation is a unique curative therapeutic approach for sickle cell disease. Myeloablative allogeneic hematopoietic stem cell transplantation is curative for children with sickle cell disease. Current data indicate that long-term disease-free survival is about 90% and overall survival about 95% after transplantation. However, it is toxic in adults due to organ injuries. In addition, this curative treatment approach has several limitations, such as difficulties to find donors, transplant-related mortality, graft loss, graft-versus-host disease (GVHD, and infertility. Engraftment effectivity and toxicity for transplantations performed with nonmyeloablative reduced-intensity regimens in adults are being investigated in phase 1/2 trials at many centers. Preliminary data indicate that GVHD could be prevented with transplantations performed using reduced-intensity regimens. It is necessary to develop novel regimens to prevent graft loss and reduce the risk of GVHD.

  8. Eradication of Pulmonary Aspergillosis in an Adolescent Patient Undergoing Three Allogeneic Stem Cell Transplantations for Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Michaela Döring

    2012-01-01

    Full Text Available Systemic fungal infections are a major cause of infection-related mortality in patients with hematologic malignancies. This report addresses the case of an adolescent patient with acute lymphoblastic leukemia who underwent three allogeneic hematopoietic stem cell transplantations and developed pulmonary aspergillosis. Combination therapy with liposomal amphotericin B (L-AmB, 3 mg/kg bw/day and caspofungin (CAS, 50 mg/day during the first allogeneic hematopoietic stem cell transplantation (HSCT improved the pulmonary situation. After shifting the antifungal combination therapy to oral voriconazole (2 × 200 mg/day and CAS, a new pulmonal lesion occurred alongside the improvements in the existing pulmonary aspergillosis. An antifungal combination during a second HSCT with L-AmB (3 mg/kg bw/day and CAS showed an improvement in the pulmonary aspergillosis. A combination therapy with CAS and L-AmB (1 mg/kg bw/day during the third HSCT led once again to progress the pulmonary aspergillosis, after increasing the L-AMB to 3 mg/kg bw/day for recovery. The presented case provides an example of how, despite severe immunosuppression, a combination of antifungal drugs administered intravenously at therapeutic dosages may be more efficient than either intravenous monotherapy or combinations of intravenous and oral antifungals in selecting pediatric and adolescent patients with proven fungal infections.

  9. Epigenetic regulation of hematopoietic stem cell aging

    Energy Technology Data Exchange (ETDEWEB)

    Beerman, Isabel, E-mail: isabel.beerman@childrens.harvard.edu [Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138 (United States); Department of Pediatrics, Harvard Medical School, Boston, MA 02115 (United States); Program in Cellular and Molecular Medicine, Division of Hematology/Oncology, Boston Children' s Hospital, MA 02116 (United States); Rossi, Derrick J. [Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138 (United States); Department of Pediatrics, Harvard Medical School, Boston, MA 02115 (United States); Program in Cellular and Molecular Medicine, Division of Hematology/Oncology, Boston Children' s Hospital, MA 02116 (United States)

    2014-12-10

    Aging is invariably associated with alterations of the hematopoietic stem cell (HSC) compartment, including loss of functional capacity, altered clonal composition, and changes in lineage contribution. Although accumulation of DNA damage occurs during HSC aging, it is unlikely such consistent aging phenotypes could be solely attributed to changes in DNA integrity. Another mechanism by which heritable traits could contribute to the changes in the functional potential of aged HSCs is through alterations in the epigenetic landscape of adult stem cells. Indeed, recent studies on hematopoietic stem cells have suggested that altered epigenetic profiles are associated with HSC aging and play a key role in modulating the functional potential of HSCs at different stages during ontogeny. Even small changes of the epigenetic landscape can lead to robustly altered expression patterns, either directly by loss of regulatory control or through indirect, additive effects, ultimately leading to transcriptional changes of the stem cells. Potential drivers of such changes in the epigenetic landscape of aged HSCs include proliferative history, DNA damage, and deregulation of key epigenetic enzymes and complexes. This review will focus largely on the two most characterized epigenetic marks – DNA methylation and histone modifications – but will also discuss the potential role of non-coding RNAs in regulating HSC function during aging.

  10. Nutritional assessment as predictor of complications after hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Marcela Espinoza

    2016-02-01

    Full Text Available ABSTRACT Introduction: Nutritional support is pivotal in patients submitted to hematopoietic stem cell transplantation. Nutritional status has been associated with time of engraftment and infection rates. In order to evaluate the association between nutritional parameters and clinical outcomes after transplantation a cohort of transplant patients was retrospectively evaluated. Methods: All 50 patients transplanted between 2011 and 2014 were included. The nutritional status before transplantation, ten days after transplantation and before discharge was assessed including anthropometry, body mass index, albumin, prealbumin and total urinary nitrogen. Results: The median follow-up time was 41 months and the median age of patients was 41 years. Thirty-two underwent allogeneic and 18 autologous transplants. Diagnoses included acute leukemias (n = 27, lymphoma (n = 7, multiple myeloma (n = 13, and aplastic anemia (n = 3. Thirty-seven patients developed mucositis (three Grade 1, 15 Grade 2, 18 Grade 3 and one Grade 4, and twenty-two allogeneic, and five autologous transplant patients required total parenteral nutrition. Albumin and total urinary nitrogen were associated with length of hospital stay and platelet and neutrophil engraftment. None of the nutritional parameters evaluated were associated with overall survival. Non-relapse mortality was 14% and overall survival was 79% at 41 months of follow-up. Conclusions: After hematopoietic stem cell transplantation, high catabolism was associated with longer length of hospital stay, the need of total parenteral nutrition and platelet and neutrophil engraftment times. Nutritional parameters were not associated with overall survival.

  11. Myelodysplastic syndrome evolving from aplastic anemia treated with immunosuppressive therapy: efficacy of hematopoietic stem cell transplantation.

    Science.gov (United States)

    Kim, Sung-Yong; Le Rademacher, Jennifer; Antin, Joseph H; Anderlini, Paolo; Ayas, Mouhab; Battiwalla, Minoo; Carreras, Jeanette; Kurtzberg, Joanne; Nakamura, Ryotaro; Eapen, Mary; Deeg, H Joachim

    2014-12-01

    A proportion of patients with aplastic anemia who are treated with immunosuppressive therapy develop clonal hematologic disorders, including post-aplastic anemia myelodysplastic syndrome. Many will proceed to allogeneic hematopoietic stem cell transplantation. We identified 123 patients with post-aplastic anemia myelodysplastic syndrome who from 1991 through 2011 underwent allogeneic hematopoietic stem cell transplantation, and in a matched-pair analysis compared outcome to that in 393 patients with de novo myelodysplastic syndrome. There was no difference in overall survival. There were no significant differences with regard to 5-year probabilities of relapse, non-relapse mortality, relapse-free survival and overall survival; these were 14%, 40%, 46% and 49% for post-aplastic anemia myelodysplastic syndrome, and 20%, 33%, 47% and 49% for de novo myelodysplastic syndrome, respectively. In multivariate analysis, relapse (hazard ratio 0.71; P=0.18), non-relapse mortality (hazard ratio 1.28; P=0.18), relapse-free survival (hazard ratio 0.97; P=0.80) and overall survival (hazard ratio 1.02; P=0.88) of post-aplastic anemia myelodysplastic syndrome were similar to those of patients with de novo myelodysplastic syndrome. Cytogenetic risk was independently associated with overall survival in both groups. Thus, transplant success in patients with post-aplastic anemia myelodysplastic syndrome was similar to that in patients with de novo myelodysplastic syndrome, and cytogenetics was the only significant prognostic factor for post-aplastic anemia myelodysplastic syndrome patients.

  12. Tuberculosis in Hematopoietic Stem Cell Transplant Recipients

    OpenAIRE

    Ramos, Jéssica Fernandes; Batista, Marjorie Vieira; Costa, Silvia Figueiredo

    2013-01-01

    Literature on tuberculosis (TB) occurring in recipients of Hematopoietic Stem Cell Transplant (HSCT) is scanty even in countries where TB is common. Most reports of TB in HSCT patients were from ASIA, in fact the TB incidence ranging from 0.0014 (USA) to 16% (Pakistan). There are few reports of TB diagnosis during the first two weeks after HSCT; most of cases described in the literature occurred after 90 days of HSCT, and the lung was the organ most involved. The mortality ranged from 0 to 50...

  13. Hematopoietic potential cells in skeletal muscle

    Institute of Scientific and Technical Information of China (English)

    Atsushi Asakura

    2007-01-01

    @@ During mouse embryogenesis,the formation of primi-tive hematopoiesis begins in the yolk sac on embryonic day 7.5(E7.5).Thereafter,definitive hematopoietic stem cell(HSC)activity is first detectable in the aorta-gonad-mesonephros(AGM)region on E10,followed by fetal liver and yolk sac.Subsequently,the fetal liver by E12 becomes the main tissue for definitive hematopoiesis.At a later time,HSC population in the fetal liver migrates to the bone marrow,which becomes the maior site of he-matopoiesis throughout normal adult life[1].

  14. Combination therapy of imatinib and donor lymphocyte infusion for chronic myeloid leukemia relapse after allogeneic hematopoietic stem cell transplantation%伊马替尼联合供者淋巴细胞输注治疗造血干细胞移植后慢性粒细胞白血病复发

    Institute of Scientific and Technical Information of China (English)

    钱思轩; 李建勇; 吴汉新; 张晓艳; 张苏江; 洪鸣; 张闰; 孙雪梅

    2008-01-01

    Objective To evaluate the efficiency of combination therapy of imatinib and donor lymphocyte infusion (DLI) for chronic myeloid leukemia (CML) relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods Patient 1 received peripheral blood stem cell transplantation from her HLA-identical sister, patient 2 received bone marrow transplantation from her HLA-identical brother and patient 3 received the transplantation of bone marrow in combined with peripheral blood stem cells following a conditioning regimen. For the prophylaxis of graft-versus-host disease (GVHD), patient 1 was treated with cyclosporine A (CsA) and mycophenolate mofetil (MMF), patient 2 with CsA, short course methotrexate (MTX), anti-thymocyte globulin and anti-CD25 monoclonal antibody,and patient 3 with CsA, MTX and MMF. They were treated with imatinib and DLI in hematologic relapse after HSCT. Results Patient 1 was treated with DLI on day + 30,+ 50 and + 70 after allo-HSCT,with CD3+ T lymphocyte cells of 0. 5 × 107 /kg,1.0×107 /kg and 2. 0 × 107 /kg respectively. She obtained a full donor ehimerism on short tandem repeats polymerase chain reaction (STR-PCR). She was treated with imatinib 400 nag daily and DLI with CD3+ T lymphocyte cells of 2. 5×107 /kg on day + 120 days for progression of disease. The bone marrow on day + 180 showed a full donor chimerism on STR-PCR. She died of extramedullary relapse 17 months after alloHSCT. For patient 2,cytogenetic analysis of bone marrow showed a male karyotype of 46,XY without any cytogenetic abnormalities, 100% cells on interphase nuclei revealed the XY genotype in the sex chromosome fluorescence in site hybridization(FISH) analysis and BCR-ABL fusion gene was negative on day + 35 after alIo-HSCT. Patient 2 relapsed on day + 100 after allo-HSCT,CsA was withdrawn and DLI with CD3+ T lymphocyte cells of 3. 9 × 107 /kg in combination with imatinib 500 mg was given daily. After treatment with DLI and imatinib for 30 days

  15. Allo-hematopoietic stem cell transplantation is a potential treatment for a patient with a combined disorder of hereditary spherocytosis

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xiao-hui; WANG Yu; ZHAO Ting; LIU Kai-yan; HUANG Xiao-jun; FU Hai-xia; XU Lan-ping; LIU Dai-hong; CHEN Huan; HAN Wei; CHEN Yu-hong; WANG Feng-rong; WANG Jing-zhi

    2012-01-01

    Both human hereditary spherocytosis (HS) and chronic myelogenous leukemia (CML) are life threatening.Herein we have reported the case of a woman with a combined disorder of HS and CML who underwent the matched sibling allogeneic stem cell transplantation.The complete donor erythroid cells were obtained.The red blood cell counts significantly improved throughout life comparing with pre-hematopoietic stem cell transplantation (HSCT).Reticulocyte counts normalized,and BCR-ABL was cleared away.The total bilirubin level was also corrected in this recipient.Our case is a rare example with a combined disorder of HS and CML following allogeneic stem cell transplantation.HS was not a contraindication for patient in the matched sibling transplant setting.

  16. Mixed T Lymphocyte Chimerism after Allogeneic Hematopoietic Transplantation Is Predictive for Relapse of Acute Myeloid Leukemia and Myelodysplastic Syndromes.

    Science.gov (United States)

    Lee, Hans C; Saliba, Rima M; Rondon, Gabriela; Chen, Julianne; Charafeddine, Yasmeen; Medeiros, L Jeffrey; Alatrash, Gheath; Andersson, Borje S; Popat, Uday; Kebriaei, Partow; Ciurea, Stefan; Oran, Betul; Shpall, Elizabeth; Champlin, Richard

    2015-11-01

    Chimerism testing after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) represents a promising tool for predicting disease relapse, although its precise role in this setting remains unclear. We investigated the predictive value of T lymphocyte chimerism analysis at 90 to 120 days after allo-HSCT in 378 patients with AML/MDS who underwent busulfan/fludarabine-based myeloablative preparative regimens. Of 265 (70%) patients with available T lymphocyte chimerism data, 43% of patients in first or second complete remission (CR1/CR2) at the time of transplantation had complete (100%) donor T lymphocytes at day +90 to +120 compared with 60% of patients in the non-CR1/CR2 cohort (P = .005). In CR1/CR2 patients, donor T lymphocyte chimerism ≤ 85% at day +90 to +120 was associated with a higher frequency of 3-year disease progression (29%; 95% confidence interval [CI], 18% to 46% versus 15%; 95% CI, 9% to 23%; hazard ratio [HR], 2.1; P = .04). However, in the more advanced, non-CR1/CR2 cohort, mixed T lymphocyte chimerism was not associated with relapse (37%; 95% CI, 20% to 66% versus 34%; 95% CI, 25% to 47%; HR, 1.3; P = .60). These findings demonstrate that early T lymphocyte chimerism testing at day +90 to +120 is a useful approach for predicting AML/MDS disease recurrence in patients in CR1/CR2 at the time of transplantation.

  17. Recent advances in haploidentical hematopoietic stem cell transplantation using ex vivo T cell-depleted graft in children and adolescents.

    Science.gov (United States)

    Im, Ho Joon; Koh, Kyung-Nam; Seo, Jong Jin

    2016-03-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for children and adolescents with various malignant and non-malignant diseases. While human leukocyte antigen (HLA)-identical sibling donor is the preferred choice, matched unrelated volunteer donor is another realistic option for successful HSCT. Unfortunately, it is not always possible to find a HLA-matched donor for patients requiring HSCT, leading to a considerable number of deaths of patients without undergoing transplantation. Alternatively, allogeneic HSCT from haploidentical family members could provide donors for virtually all patients who need HSCT. Although the early attempts at allogeneic HSCT from haploidentical family donor (HFD) were disappointing, recent advances in the effective ex vivo depletion of T cells or unmanipulated in vivo regulation of T cells, better supportive care, and optimal conditioning regimens have significantly improved the outcomes of haploidentical HSCT. The ex vivo techniques used to remove T cells have evolved from the selection of CD34(+) hematopoietic stem cell progenitors to the depletion of CD3(+) cells, and more recently to the depletion of αβ(+) T cells. The recent emerging evidence for ex vivo T cell-depleted haploidentical HSCT has provided additional therapeutic options for pediatric patients with diseases curable by HSCT but has not found a suitable related or unrelated donor. This review discusses recent advances in haploidentical HSCT, focusing on transplant using ex vivo T cell-depleted grafts. In addition, our experiences with this novel approach for the treatment of pediatric patients with malignant and non-malignant diseases are described.

  18. Construction of an allogenic chimeric mouse model for the study of the behaviors of donor stem cells in vivo

    Institute of Scientific and Technical Information of China (English)

    WANG Mo-lin; YAN Jing-bin; XIAO Yan-ping; HUANG Shu-zhen

    2005-01-01

    Background It is essential to establish an animal model for the elucidation of the biological behaviors of stem cells in vivo. We constructed a chimeric animal model by in utero transplantation for investigation of stem cell transplantation.Methods This chimerism was achieved by injecting the stem cells derived from the bone marrow of green fluorescence protein (GFP)-transgenic mice into fetal mice at 13.5 days of gestation. Several methods such as polymerase chain reaction (PCR), real-time PCR, fluorescence-assisted cell sorting (FACS) and fluorescence in situ hybridization (FISH) were used for the observation of donor cells.Results Under a fluorescence microscope, we observed the GFP cells of donor-origin in a recipient. PCR, FACS analysis and FISH indicated chimerism at various intervals. Real-time PCR indicated that some donor cells existed in chimera for more than 6 months.Conclusions Allogenic stem cells may exist in recipients for a long time and this allogenic animal model provides a useful tool for studying the behavior of hematopoietic stem cells and also offers an effective model system for the study of stem cells.

  19. Gs signaling in osteoblasts and hematopoietic stem cells.

    Science.gov (United States)

    Kronenberg, Henry M

    2010-03-01

    The heterotrimeric G protein Gs is a major mediator of the actions of several G protein-coupled receptors that target cells of the osteoblast lineage. For this reason, we generated chimeric mice with normal host cells and cells derived from embryonic stem cells missing the gene encoding the alpha subunit of Gs. While the mutant cells contributed to cortical osteoblasts and to hematopoietic cells in the liver, the marrow space contained few if any osteoblasts or hematopoietic cells missing Gs. Subsequent studies using the Cre-lox approach to delete Gsalpha from early cells of the osteoblast lineage and from hematopoietic stem cells were performed. These studies demonstrated the crucial roles of Gsalpha in osteoblastic cells in regulating the differentiation of osteoblasts and in supporting B-cell development as well as the essential role for Gsalpha in hematopoietic stem cells in allowing the homing of these cells to the marrow.

  20. Evolving concepts on the microenvironmental niche for hematopoietic stem cells.

    NARCIS (Netherlands)

    Raaijmakers, M.G.P.; Scadden, D.T.

    2008-01-01

    PURPOSE OF REVIEW: The hematopoietic stem cell niche is critical for the maintenance and proliferation of hematopoietic stem cells and, as such, is not only essential for steady-state hematopoiesis but may also be relevant to hematologic disease. The present review discusses recent advances in the u

  1. ROLE OF HEMATOPOIETIC STEM CELL TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    Angelo Michele Carella

    2012-10-01

    Full Text Available Hodgkin lymphoma is one of the most curable human tumors. Despite this, about 30% of these patients relapsed or are primary refractory to the first line treatment. Autografting is generally considered the standard of care for these patients. Alternative salvage strategies have been evaluated such as high dose sequential and tandem autografting strategies. In younger patients,  refractory or early relapsed after autografting, allogeneic stem cell transplantation has been employed but this approach has been followed by significant concerns since the treatment related mortality often exceeded 40-50%, and relapses were not uncommon. It is clear that patient selection remains an issue in all allografting reports. At the end, new drugs and novel treatment strategies, that are based on our understanding of the disease biology and signaling pathways, are needed to improve treatment outcome for these patients. The two leading compounds Brentuximab Vedotin and Panobinostat, are currently under evaluation  in several clinical trials.

  2. Donor lymphocyte infusion after allogeneic stem cell transplantation.

    Science.gov (United States)

    Castagna, Luca; Sarina, Barbara; Bramanti, Stefania; Perseghin, Paolo; Mariotti, Jacopo; Morabito, Lucio

    2016-06-01

    Allogeneic stem cell transplantation (allo-SCT) is considered the cornerstone in the treatment of several malignant and not malignant hematological diseases. However, relapse of hematological disease after allo-SCT is considered the most challenging point in the field. The risk can be reduced through optimal patients, donor and disease selection before allo-SCT, but harnessing donor immune system is an appealing way to treat or avoid disease relapse. Donor lymphocyte infusion (DLI) is a simple and effective therapy after allo-SCT. In this paper, the efficacy of DLI will be analyzed in different hematological diseases, focusing also on their therapeutic or pre-emptive use.

  3. Mouse bone marrow-derived mesenchymal stem cells inhibit leukemia/lymphoma cell proliferation in vitro and in a mouse model of allogeneic bone marrow transplant.

    Science.gov (United States)

    Song, Ningxia; Gao, Lei; Qiu, Huiying; Huang, Chongmei; Cheng, Hui; Zhou, Hong; Lv, Shuqing; Chen, Li; Wang, Jianmin

    2015-07-01

    The allogeneic hematopoietic stem cell (HSC) transplantation of mesenchymal stem cells (MSCs) contributes to the reconstitution of hematopoiesis by ameliorating acute graft‑versus‑host disease (aGVHD). However, the role of MSCs in graft‑versus‑leukemia remains to be determined. In the present study, we co‑cultured C57BL/6 mouse bone marrow (BM)‑derived MSCs with A20 murine B lymphoma, FBL3 murine erythroleukemia and P388 murine acute lymphocytic leukemia cells. Cell proliferation, apoptosis, cell cycle progression and the amount of cytokine secretion were then measured using a Cell Counting kit‑8, Annexin V/propidium iodide staining, flow cytometry and ELISA, respectively. We also established a model of allogeneic bone marrow transplantation (BMT) using BALB/c mice. Following the administration of A20 cells and MSCs, we recorded the symptoms and the survival of the mice for 4 weeks, assessed the T cell subsets present in peripheral blood, and, after the mice were sacrifice, we determined the infiltration of MSCs into the organs by histological staining. Our results revealed that the MSCs inhibited the proliferation of the mouse lymphoma and leukemia cells in vitro, leading to cell cycle arrest and reducing the secretion of interleukin (IL)‑10. In our model of allogeneic BMT, the intravenous injection of MSCs into the mice injected wth A20 cells decreased the incidence of lymphoma, improved survival, increased the fraction of CD3+CD8+ T cells, decreased the fraction of CD3+CD4+ T cells and CD4+CD25+ T cells in peripheral blood, and ameliorated the manifestation of aGVHD. The results from the present study indicate that MSCs may be safe and effective when used in allogeneic BMT for the treatment of hemotological malignancies.

  4. Clinical observation of feasibility and efficacy of decitabine bridge therapy followed by allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic syndrome and acute myeloid leukemia%地西他滨桥接异基因造血干细胞移植治疗骨髓增生异常综合征和急性髓样白血病的临床可行性和疗效研究

    Institute of Scientific and Technical Information of China (English)

    吴倩; 何广胜; 吴德沛; 孙爱宁; 仇惠英; 金正明; 苗瞄; 唐晓文; 韩悦

    2013-01-01

    Objective: To investigate the feasibility and efficacy of DAC (decitabine) bridge therapy followed by allo-HSCT (allogeneic hematopoietic stem cell transplantation) in patients with MDS (myelodysplastic syndrome) and AML (acute myeloid leukemia). Methods: Seven patients with MDS and 12 patients with AML received DAC bridge therapy followed by allo-HSCT. Results: With DAC bridge therapy, 4 MDS patients achieved complete remission/marrow complete remission and 3 remained stable disease before allo-HSCT. After successful engraftment attained in all the seven MDS patients, six survived without disease, one received donor lymphocyte infusion and obtained complete remission after relapse and eventually died of pneumonia. Of 12 AML patients, 6 achieved complete remission after DAC bridge therapy; 5 survived without disease, one still survived but having disease, and 6 had died. The rates of acute and chronic CVHD were 31.6% and 21.1%, respectively. The two-year overall survival rate and the two-year cumulative recurrence rate were 57.9% and 36.2% after allo-HSCT, respectively. The two-year cumulative recurrence-free rate was 23.6% after allo-HSCT. Conclusion: DAC regimen can be safely and efficiently administrated to bridge time to allo-HSCT in patients with MDS/AML.%目的:探讨地西他滨(decitabine,DAC)作为骨髓增生异常综合征(myelodysplastic syndrome,MDS)和急性髓样白血病(acute myeloid leukemia,AML)患者行异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo-HSCT)之前的桥接治疗的可行性和疗效.方法:对7例MDS患者和12例AML患者以DAC作为allo-HSCT之前的桥接治疗.结果:DAC桥接治疗后,7例MDS患者中,4例获得完全缓解(complete remission,CR) /mCR (marrow CR),3例为疾病稳定(stable disease,SD),之后行allo-HSCT成功,目前6例为无病生存,1例在复发后接受供者淋巴细胞输注(donor lymphocyte infusion,DLI)后达CR,后死于肺部感染;12例AML患者中,6例在DAC

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

  6. Evaluation of Quality of Life and Care Needs of Turkish Patients Undergoing Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Neslisah Yasar

    2016-01-01

    Full Text Available This descriptive study explored the quality of life and care needs of Turkish patients who underwent hematopoietic stem cell transplantation. The study sample consisted of 100 hematopoietic stem cell transplant patients. Their quality of life was assessed using Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale. The mean patient age was 44.99 ± 13.92 years. Changes in sexual functions, loss of hair, loss of taste, loss of appetite, and sleep disturbances were the most common symptoms. The quality of life of transplant patients was moderately affected; the functional well-being and social/family well-being subscales were the most adversely and least negatively affected (12.13 ± 6.88 dimensions, respectively. Being female, being between 50 and 59 years of age, being single, having a chronic disease, and having a history of hospitalization were associated with lower quality of life scores. Interventions to improve functional status, physical well-being, and emotional status of patients during the transplantation process may help patients cope with treatment-related impairments more effectively. Frequent screening and management of patient symptoms in order to help patients adapt to life following allogeneic hematopoietic stem cell transplantation are crucial for meeting care needs and developing strategies to improve their quality of life.

  7. Evaluation of Quality of Life and Care Needs of Turkish Patients Undergoing Hematopoietic Stem Cell Transplantation

    Science.gov (United States)

    Yasar, Neslisah

    2016-01-01

    This descriptive study explored the quality of life and care needs of Turkish patients who underwent hematopoietic stem cell transplantation. The study sample consisted of 100 hematopoietic stem cell transplant patients. Their quality of life was assessed using Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale. The mean patient age was 44.99 ± 13.92 years. Changes in sexual functions, loss of hair, loss of taste, loss of appetite, and sleep disturbances were the most common symptoms. The quality of life of transplant patients was moderately affected; the functional well-being and social/family well-being subscales were the most adversely and least negatively affected (12.13 ± 6.88) dimensions, respectively. Being female, being between 50 and 59 years of age, being single, having a chronic disease, and having a history of hospitalization were associated with lower quality of life scores. Interventions to improve functional status, physical well-being, and emotional status of patients during the transplantation process may help patients cope with treatment-related impairments more effectively. Frequent screening and management of patient symptoms in order to help patients adapt to life following allogeneic hematopoietic stem cell transplantation are crucial for meeting care needs and developing strategies to improve their quality of life. PMID:28116155

  8. Interleukin-1 regulates hematopoietic progenitor and stem cells in the midgestation mouse fetal liver

    OpenAIRE

    Orelio, Claudia; Peeters, Marian; Haak, Esther; van der Horn, Karin; Dzierzak, Elaine

    2009-01-01

    Hematopoietic progenitors are generated in the yolk sac and aorta-gonad-mesonephros region during early mouse development. At embryonic day 10.5 the first hematopoietic stem cells emerge in the aorta-gonad-mesonephros. Subsequently, hematopoietic stem cells and progenitors are found in the fetal liver. The fetal liver is a potent hematopoietic site, playing an important role in the expansion and differentiation of hematopoietic progenitors and hematopoietic stem cells. However, little is know...

  9. Other hematopoietic disorders

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008475 The significance of dynamic detection of WT1 expression on patients of hematologic malignancy following allogeneic hematopoietic stem cell transplantation. JIN Song(金松), et al. Instit Hematol, People’s Hosp, Peking Univ, Beijing 100044, Chin J Intern Med 2008;47(7):578-581. Objective To evaluate preliminarily the significance of dynamic detection of Wilms’ tumor gene (WT1) expression level on monitoring minimal

  10. Other hematopoietic disorders

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    2010371 The incidence and risk factors of late-onset non-infectious pulmonary complications after allogeneic hematopoietic stem cell transplantation. WU Tao(吴涛),et al.Dept Hematol,Nanfang Hosp,Nanfang Med Univ,Guangzhou 510515.Chin J Hematol 2010;31(4):249-252. Objective To analyze the incidence and the risk factors of late-onset non-infectious

  11. Indications of hematopoietic stem cell transplantations and therapeutic strategies of accidental irradiations; Indications des greffes de cellules souches hematopoietiques et strategies therapeutiques des irradiations accidentelles

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2003-07-01

    Produced by a group of experts, this document first discusses the issue of accidental irradiations in terms of medical management. They notably outline the peculiar characteristics of these irradiations with respect to therapeutic irradiations. They agreed on general principles regarding casualty sorting criteria and process, and their medical treatment (systematic hematopoiesis stimulation, allogeneic transplantation of hematopoietic stem cells). They discuss some practical aspects of these issues: casualty sorting within a therapeutic perspective (actions to be performed within 48 hours), therapeutic strategies (support therapy, use of cytokines, and therapy by hematopoietic stem cell transplant). They state a set of recommendations regarding the taking into care and diagnosis, therapeutic strategies, research perspectives, and teaching

  12. Development of hematopoietic stem cell activity in the mouse embryo.

    NARCIS (Netherlands)

    A.M. Müller (Albrecht); A. Medvinsky; J. Strouboulis (John); F.G. Grosveld (Frank); E.A. Dzierzak (Elaine)

    1994-01-01

    textabstractThe precise time of appearance of the first hematopoietic stem cell activity in the developing mouse embryo is unknown. Recently the aorta-gonad-mesonephros region of the developing mouse embryo has been shown to possess hematopoietic colony-forming activity (CFU-S) in irradiated recipie

  13. Activated allogeneic NK cells preferentially kill poor prognosis B-cell chronic lymphocytic leukemia cells

    Directory of Open Access Journals (Sweden)

    Diego Sanchez-Martinez

    2016-10-01

    Full Text Available Mutational status of TP53 together with expression of wild type (wt IGHV represents the most widely accepted biomarkers, establishing a very poor prognosis in B-cell chronic lymphocytic leukemia (B-CLL patients. Adoptive cell therapy using allogeneic HLA mismatched Natural Killer (NK cells has emerged as an effective and safe alternative in the treatment of acute myeloid and lymphoid leukemias that do not respond to traditional therapies. We have described that allogeneic activated NK cells eliminate hematological cancer cell lines with multidrug resistance acquired by mutations in the apoptotic machinery. This effect depends on the activation protocol, being B-lymphoblastoid cell lines (LCLs the most effective stimulus to activate NK cells. Here we have further analyzed the molecular determinants involved in allogeneic NK cell recognition and elimination of B-CLL cells, including the expression of ligands of the main NK cell activating receptors (NKG2D and NCRs and HLA mismatch. We present preliminary data suggesting that B-CLL susceptibility significantly correlates with HLA mismatch between NK cell donor and B-CLL patient. Moreover, we show that the sensitivity of B-CLL cells to NK cells depends on the prognosis based on TP53 and IGHV mutational status. Cells from patients with worse prognosis (mutated TP53 and wt IGHV are the most susceptible to activated NK cells. Hence, B-CLL prognosis may predict the efficacy of allogenic activated NK cells and, thus, NK cell transfer represents a good alternative to treat poor prognosis B-CLL patients who present a very short life expectancy due to lack of effective treatments.□

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

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

  15. 同胞全相合异基因造血干细胞移植治疗95例骨髓增生异常综合征患者的临床分析%The clinical analysis of allogeneic hematopoietic stem cell transplantation from human leukocyte antigen-identical siblings in 95 patients with myelodysplastic syndrome

    Institute of Scientific and Technical Information of China (English)

    赵婷; 黄晓军; 刘代红; 王景枝; 张晓辉; 王昱; 韩伟; 陈欢; 陈育红

    2014-01-01

    目的 探讨同胞全相合异基因造血干细胞移植(allo-HSCT)治疗骨髓增生异常综合征(MDS)的疗效与时机.方法 回顾分析2003年1月-2012年12月采用同胞全相合allo-HSCT治疗MDS及MDS转急性髓性白血病(AML) 95例.采用改良马利兰+环磷酰胺或氟达拉滨的预处理方案,行骨髓和/或外周血干细胞移植.结果 95例患者中93例白细胞植活,Ⅱ~Ⅳ度急性移植物抗宿主病(aGVHD)累计发生率为12.9%±3.5%;慢性移植物抗宿主病(cGVHD)3年累计发生率为80.3%±4.9%.3年累计复发率(RR)为25.9%±4.7%,非复发死亡率(NRM)为16.1%±4.0%.3年预期总生存(0S)率及无病生存(DFS)率分别为69.9%±5.0%和58.0%±5.4%.多因素分析显示,发生Ⅱ~Ⅳ度aGVHD和不发生cGVHD是OS的独立危险因素;国际预后积分系统(IPSS)分组是DFS的独立预后因素.将难治性贫血伴原始细胞增多转化型(RAEB-t)及MDS转AML患者(31例)分为移植前未化疗、化疗未缓解、化疗缓解3组,3年OS率分别为33.9%、32.7%、100.0%,化疗缓解组OS率明显高于另外两组(P<0.05),DFS率、RR率差异无统计学意义.结论 同胞全相合allo-HSCT是治疗MDS的有效手段,IPSS可预测移植后疗效,对于移植前疾病进展的患者,争取缓解后行allo-HSCT可能提高疗效,但尚需进一步临床对照研究.%Objective To evaluate the efficacy and optimize the timing of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from human leukocyte antigen (HLA)-identical siblings for myelodysplastic syndrome (MDS).Methods From January 2003 to December 2012,95 patients with MDS or secondary acute myeloid leukemia (AML) were treated with HLA-identical allo-HSCT in our hospital.The median age was 43 (21-59) years.Conditioning regimens including modified busulfan (Bu)/cyclophosphamide (Cy) or Bu/fludarabine (Flu) were used.All patients received transfusion of donor stem cells mobilized by granulocyte colony

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  17. The Neuropsychiatry of Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Mitchell R. Levy

    2006-06-01

    Full Text Available BACKGROUND AND OBJECTIVES: Regimens incorporating hematopoietic stem cell transplantation (HSCT have become widely utilized in disease treatments, particularly for cancer. These complex treatment programs also expose patients to central nervous system (CNS toxicities from chemotherapy, irradiation, infection, metabolic effects and immunosuppression. METHODS: Relevant recent medical literature from Medline and bibliographies in pertinent publications are reviewed with a focus on those cases and studies pertaining to neuropsychiatric effects of HSCT. RESULTS: High rates of neuropsychiatric sequelae occur on a continuum from acute to chronic. Adverse outcomes include focal CNS deficits and severe global manifestations such as seizures, encephalopathy and delirium. More graduated effects on cognition, energy and mood are frequently seen, impacting patient function. CONCLUSIONS: Additional research on neuropsychiatric outcomes and treatment interventions is needed in the HSCT setting. Risks for neuropsychiatric deficits should be part of an ongoing informed consent discussion among treating physicians, patients and families.

  18. 减量伏立康唑一级预防异基因造血干细胞移植后侵袭性真菌病的临床研究%Clinical investigation of reduced-dose voriconazole on primary prevention in invasive fungal disease after allogeneic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    邱志祥; 任汉云; 岑溪南; 欧晋平; 许蔚林; 王茫桔; 王莉红; 董玉君; 李渊

    2014-01-01

    目的 探讨静脉应用伏立康唑对异基因造血干细胞移植(allo-HSCT)后侵袭性真菌病(IFD)一级预防的疗效及耐受性.方法 移植前无真菌感染的allo-HSCT患者从预处理开始应用伏立康唑注射液,直至患者的中性粒细胞恢复至0.5× 109/L以上,以口服氟康唑者为对照组,分析两组间IFD易感因素有无差异,比较两组IFD发生率及药物不良反应的差异.结果 227例患者在移植后3个月内有33例(14.54%)发生IFD,中位随访38(5~76)个月,发生IFD患者累计死亡13例(33.96%),20例存活,总生存率60.61%;194例未发生IFD患者,累计死亡40例(19.89%),154例(79.38%)存活,两组间总生存率差异有统计学意义(P=0.029).227例患者中,83例应用伏立康唑行一级预防,发生IFD者7例(8.43%),对照组144例患者发生IFD 26例(18.06%),两组IFD发生率差异有统计学意义(P=0.048).对两组间的性别、年龄、既往有无慢性病、移植时是否为进展期血液病、移植方式、预处理方案、粒细胞缺乏时间、有无急性移植物抗宿主病、有无CMV感染等因素逐一进行比较,结果显示两组上述因素差异无统计学意义(P>0.05).伏立康唑和氟康唑两组间转氨酶升高患者比例差异无统计学意义(P>0.05).应用伏立康唑出现幻听或视觉障碍等不良反应的比例不高.结论 应用静脉伏立康唑对allo-HSCT患者行IFD的一级预防的效果明显优于氟康唑,且患者对治疗的耐受性良好.%Objective To investigate the efficacy and tolerability of intravenous vonconazole on primary prevention in invasive fungal disease (IFD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods At the time of conditioning regimen,patients without IFD was intravenously administered with voriconazole at a dose of 100 mg two times per day until neutrophils greater than 0.5 × 109/L.Patients treated with oral fluconazole,200 mg per day,were control group

  19. The value of the current diagnostic criteria of pulmonary invasive fungal infection after allogeneic hematopoietic stem cell transplantation%异基因造血干细胞移植后肺部侵袭性真菌感染现行诊断标准的应用价值

    Institute of Scientific and Technical Information of China (English)

    沈建良; 宫立众; 刘代红; 黄晓军

    2013-01-01

    Objective To analyze the practicality of current diagnostic criteria of invasive fungal infection (IFI) in patients with hematologic diseases/malignant tumors,so as to enhance the recognition of characteristics of pulmonary IFI after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods The clinical features of 51 cases with IFI after allo-HSCT were analyzed retrospectively.Results Pulmonary IFI accounted for 42.1% (51/121) of the whole infectious pneumonia diagnosed among the patients admitted during the study.One (2.0%) case was proven diagnosis ; 24 (47.1%) were probable diagnosis and 26(51.0%) were possible diagnosis.The using of immuno-suppressors and corticosteroids,and the presence of graft-versus-host disease (GVHD) were the main host factors.The patients with two or more host factors simultaneously accounted for 66.7% (34/51) of all pulmonary IFI patients.Totally 94.1% (48/51) of the patients with pulmonary IFI presented nodules and/or patches as the main features in high resolution computed tomography (HRCT) scanning.The positive rates of fungal antigen detection were 58.6% for G test and 33.3% for GM test,which were relatively high.Twenty patients (39.2%) showed decrease of arterial partial pressure of oxygen and hypoxia in blood-gas analysis.Conclusions For the diagnosis of pulmonary IFI post allo-HSCT,the administration of immuno-suppressors and corticosteroids,and the presence of GVHD were the main host factors.Nodules and/or patches were the main features in HRCT image.Fungus antigen detection is the main tool to support clinical diagnosis.%目的 分析我国现行血液病/恶性肿瘤患者侵袭性真菌感染诊断标准的可操作性,提高对异基因造血干细胞移植(allo-HSCT)后肺部侵袭性真菌感染特点的认识.方法 回顾性分析连续收治的51例allo-HSCT后肺部侵袭性真菌感染病例的临床特点.结果 肺部侵袭性真菌感染共占同期收

  20. 地西他滨桥接异基因造血干细胞移植治疗骨髓增生异常综合征的疗效分析%Retrospective efficacy analysis of decitabine bridging allogeneic hematopoietic stem cell transplantation on the treatment of myelodysplastic syndrome

    Institute of Scientific and Technical Information of China (English)

    郑慧菲; 王婧; 周进; 王攀峰; 傅琤琤; 吴德沛; 孙爱宁; 仇惠英; 金正明

    2015-01-01

    目的 评价地西他滨桥接异基因造血干细胞移植(allo-HSCT)治疗骨髓增生异常综合征(MDS)的疗效及安全性.方法 回顾性分析2010年7月至2013年12月于苏州大学附属第一医院血液科接受allo-HSCT的MDS患者的临床特征及疗效,随机抽取25例接受地西他滨桥接allo-HSCT的MDS患者为桥接组,以同期33例未接受地西他滨行allo-HSCT的MDS患者为对照组,观察患者疗效、总生存(OS)及移植物抗宿主病(GVHD)发生情况.结果 桥接组患者移植前骨髓完全缓解率为64.0%(25例中16例),明显高于对照组的15.1%(33例中5例),差异有统计学意义(P<0.05);早期移植相关死亡率低于对照组(4.0%对18.2%),但差异无统计学意义(P=0.106).桥接组移植相关死亡率及2年OS率分别为12.0%及83.0%,与对照组的30.3%及59.0%比较差异均有统计学意义(P值均<0.05).桥接组14例患者发生急性GVHD(aGVHD),其中Ⅰ度7例、Ⅱ度3例、Ⅲ度4例;对照组16例患者发生aGVHD,其中Ⅰ度7例、Ⅱ度8例、Ⅲ度1例.结论 地西他滨桥接allo-HSCT治疗MDS安全且有效.%Objective To evaluate the efficacy of decitabine (DAC) bridging therapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myelodysplastic syndrome (MDS).Methods The clinical characteristics and curative effect of MDS patients who received allo-HSCT from 2010 July to 2013 December were retrospectively analyzed.Of them,25 MDS patients who received decitabine bridging allo-HSCT were randomly selected (referred to as the bridging group),while at the same time another 33 MDS patients who did not receive decitabine for allo-HSCT in MDS were also randomly selected as control group.The effect of decitabine bridging allo-HSCT on the patients' survival and occurrence of graft versus host disease (GVHD) was analyzed.Results With decitabine bridge therapy,64.0% patients (16/25) achieved marrow complete remission before allo

  1. Fetal liver stromal cells promote hematopoietic cell expansion

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Kun; Hu, Caihong [Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030 (China); Zhou, Zhigang [Shanghai 1st People Hospital, Shanghai Jiao Tong University, Shanghai 201620 (China); Huang, Lifang; Liu, Wenli [Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030 (China); Sun, Hanying, E-mail: shanhum@163.com [Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030 (China)

    2009-09-25

    Future application of hematopoietic stem and progenitor cells (HSPCs) in clinical therapies largely depends on their successful expansion in vitro. Fetal liver (FL) is a unique hematopoietic organ in which hematopoietic cells markedly expand in number, but the mechanisms involved remain unclear. Stromal cells (StroCs) have been suggested to provide a suitable cellular environment for in vitro expansion of HSPCs. In this study, murine StroCs derived from FL at E14.5, with a high level of Sonic hedgehog (Shh) and Wnt expression, were found to have an increased ability to support the proliferation of HSPCs. This effect was inhibited by blocking Shh signaling. Supplementation with soluble Shh-N promoted the proliferation of hematopoietic cells by activating Wnt signaling. Our findings suggest that FL-derived StroCs support proliferation of HSPCs via Shh inducing an autocrine Wnt signaling loop. The use of FL-derived StroCs and regulation of the Shh pathway might further enhance HPSC expansion.

  2. Chlamydia pneumoniae respiratory infection after allogeneic stem cell transplantation.

    Science.gov (United States)

    Geisler, William M; Corey, Lawrence

    2002-03-27

    Chlamydia pneumoniae is a common cause of upper and lower respiratory tract infections in immunocompetent patients; however, its role as a respiratory pathogen in immunocompromised hosts has been infrequently recognized. We describe C. pneumoniae lower respiratory tract infection in a 19-year-old male after allogeneic stem cell transplantation. The patient developed fever on day +14, and a subsequent computed tomography scan of the chest revealed a right lateral pleural-based opacity, which was then resected during thoracoscopy. Diagnosis was made by culture and staining of the resected tissue with C. pneumoniae-specific monoclonal antibodies, and azithromycin was administered. To the best of our knowledge, this is the first report of C. pneumoniae respiratory infection after stem cell or marrow transplantation. C. pneumoniae often coexists with other etiologic agents of pneumonia in immunocompromised patients. Considering the infrequency of infections from this organism in this clinical setting, one must still rule out other more likely respiratory pathogens.

  3. Parathyroid hormone mediates hematopoietic cell expansion through interleukin-6.

    Directory of Open Access Journals (Sweden)

    Flavia Q Pirih

    Full Text Available Parathyroid hormone (PTH stimulates hematopoietic cells through mechanisms of action that remain elusive. Interleukin-6 (IL-6 is upregulated by PTH and stimulates hematopoiesis. The purpose of this investigation was to identify actions of PTH and IL-6 in hematopoietic cell expansion. Bone marrow cultures from C57B6 mice were treated with fms-like tyrosine kinase-3 ligand (Flt-3L, PTH, Flt-3L plus PTH, or vehicle control. Flt-3L alone increased adherent and non-adherent cells. PTH did not directly impact hematopoietic or osteoclastic cells but acted in concert with Flt-3L to further increase cell numbers. Flt-3L alone stimulated proliferation, while PTH combined with Flt-3L decreased apoptosis. Flt-3L increased blasts early in culture, and later increased CD45(+ and CD11b(+ cells. In parallel experiments, IL-6 acted additively with Flt-3L to increase cell numbers and IL-6-deficient bone marrow cultures (compared to wildtype controls but failed to amplify in response to Flt-3L and PTH, suggesting that IL-6 mediated the PTH effect. In vivo, PTH increased Lin(- Sca-1(+c-Kit(+ (LSK hematopoietic progenitor cells after PTH treatment in wildtype mice, but failed to increase LSKs in IL-6-deficient mice. In conclusion, PTH acts with Flt-3L to maintain hematopoietic cells by limiting apoptosis. IL-6 is a critical mediator of bone marrow cell expansion and is responsible for PTH actions in hematopoietic cell expansion.

  4. American Society of Blood and Marrow Transplantation, European Society of Blood and Marrow Transplantation, Blood and Marrow Transplant Clinical Trials Network, and International Myeloma Working Group Consensus Conference on Salvage Hematopoietic Cell Transplantation in Patients with Relapsed Multiple Myeloma

    NARCIS (Netherlands)

    S. Giralt; L. Garderet (Laurent); B.G.M. Durie (Brian); G. Cook (Gordon); G. Gahrton (Gösta); B. Bruno (Benedetto); P. Hari (Paremesweran); H.M. Lokhorst (Henk); P.L. McCarthy (Philip); A. Krishnan (Amrita); P. Sonneveld (Pieter); H. Goldschmidt (Harmut); S. Jagannath (Sundar); B. Barlogie (Bart); M.V. Mateos; P. Gimsing (Peter); O. Sezer; J. Mikhael (Joseph); J. Lu (Jin); M.A. Dimopoulos (Meletios); R.N. Mazumder (Ramendra N.); A. Palumbo (Antonio); R. Abonour (Rafat); K. Anderson (Kenneth); M. Attal (Michel); J. Blade; J. Bird (Jenny); M. Cavo (Michele); R.L. Comenzo; J. de la Rubia (Javier); H. Einsele (Hermann); R. Garcia-Sanz (Ramon); J. Hillengass (Jens); S. Holstein (Sarah); H.E. Johnsen (Hans); D. Joshua; G. Koehne (Guenther); S. Kumar (Shaji); R. Kyle (Robert); X. Leleu; S. Lonial (Sagar); H. Ludwig (Heinz); H. Nahi (Hareth); A. Nooka (Anil); R.Z. Orlowski (Robert); S.V. Rajkumar (Vincent); A. Reiman (Anthony); P.G. Richardson (Paul Gerard); E. Riva (Eloisa); J. San Miguel (Jesús); I. Turreson (Ingemar); S. Usmani (Saad); D. Vesole (David); W. Bensinger; M. Qazilbash (Muzaffer); Y. Efebera (Yvonne); M. Mohty (Mohamad); C. Gasparreto (Christina); J. Gajewski (James); C.F. LeMaistre (Charles F.); C. Bredeson (Chris); P. Moreau; M. Pasquini (Marcelo); N. Kroeger (Nicolaus); E.A. Stadtmauer (Edward)

    2015-01-01

    textabstractIn contrast to the upfront setting in which the role of high-dose therapy with autologous hematopoietic cell transplantation (HCT) as consolidation of a first remission in patients with multiple myeloma (MM) is well established, the role of high-dose therapy with autologous or allogeneic

  5. A retrospective comparison of autologous and unrelated donor hematopoietic cell transplantation in myelodysplastic syndrome and secondary acute myeloid leukemia: a report on behalf of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT).

    NARCIS (Netherlands)

    Al-Ali, H.K.; Brand, R.; Biezen, A. van; Finke, J.; Boogaerts, M.; Fauser, A.A.; Egeler, M.; Cahn, J.Y.; Arnold, R.; Biersack, H.; Niederwieser, D.; Witte, T.J.M. de

    2007-01-01

    Hematopoietic cell transplantation (HCT) is an effective treatment for myelodysplasia (MDS) and secondary acute myeloid leukemia (sAML). In this study, outcome of 593 patients with MDS/sAML after autologous and allogeneic HCT from a matched unrelated donor (MUD) were compared. A total of 167 (28%) p

  6. Generation of mature hematopoietic cells from human pluripotent stem cells.

    Science.gov (United States)

    Togarrati, Padma Priya; Suknuntha, Kran

    2012-06-01

    A number of malignant and non-malignant hematological disorders are associated with the abnormal production of mature blood cells or primitive hematopoietic precursors. Their capacity for continuous self-renewal without loss of pluripotency and the ability to differentiate into adult cell types from all three primitive germ layers make human embryonic stem cells and induced pluripotent stem cells (hiPSCs) attractive complementary cell sources for large-scale production of transfusable mature blood cell components in cell replacement therapies. The generation of patient-specific hematopoietic stem/precursor cells from iPSCs by the regulated manipulation of various factors involved in reprograming to ensure complete pluripotency, and developing innovative differentiation strategies for generating unlimited supply of clinically safe, transplantable, HLA-matched cells from hiPSCs to outnumber the inadequate source of hematopoietic stem cells obtained from cord blood, bone marrow and peripheral blood, would have a major impact on the field of regenerative and personalized medicine leading to translation of these results from bench to bedside.

  7. Allogenic banking of dental pulp stem cells for innovative therapeutics.

    Science.gov (United States)

    Collart-Dutilleul, Pierre-Yves; Chaubron, Franck; De Vos, John; Cuisinier, Frédéric J

    2015-08-26

    Medical research in regenerative medicine and cell-based therapy has brought encouraging perspectives for the use of stem cells in clinical trials. Multiple types of stem cells, from progenitors to pluripotent stem cells, have been investigated. Among these, dental pulp stem cells (DPSCs) are mesenchymal multipotent cells coming from the dental pulp, which is the soft tissue within teeth. They represent an interesting adult stem cell source because they are recovered in large amount in dental pulps with non-invasive techniques compared to other adult stem cell sources. DPSCs can be obtained from discarded teeth, especially wisdom teeth extracted for orthodontic reasons. To shift from promising preclinical results to therapeutic applications to human, DPSCs must be prepared in clinical grade lots and transformed into advanced therapy medicinal products (ATMP). As the production of patient-specific stem cells is costly and time-consuming, allogenic biobanking of clinical grade human leukocyte antigen (HLA)-typed DPSC lines provides efficient innovative therapeutic products. DPSC biobanks represent industrial and therapeutic innovations by using discarded biological tissues (dental pulps) as a source of mesenchymal stem cells to produce and store, in good manufacturing practice (GMP) conditions, DPSC therapeutic batches. In this review, we discuss about the challenges to transfer biological samples from a donor to HLA-typed DPSC therapeutic lots, following regulations, GMP guidelines and ethical principles. We also present some clinical applications, for which there is no efficient therapeutics so far, but that DPSCs-based ATMP could potentially treat.

  8. Chimeric Antigen Receptor T Cells and Hematopoietic Cell Transplantation: How Not to Put the CART Before the Horse.

    Science.gov (United States)

    Kenderian, Saad S; Porter, David L; Gill, Saar

    2017-02-01

    Hematopoietic cell transplantation (HCT) remains an important and potentially curative option for most hematologic malignancies. As a form of immunotherapy, allogeneic HCT (allo-HCT) offers the potential for durable remissions but is limited by transplantation- related morbidity and mortality owing to organ toxicity, infection, and graft-versus-host disease. The recent positive outcomes of chimeric antigen receptor T (CART) cell therapy in B cell malignancies may herald a paradigm shift in the management of these disorders and perhaps other hematologic malignancies as well. Clinical trials are now needed to address the relative roles of CART cells and HCT in the context of transplantation-eligible patients. In this review, we summarize the state of the art of the development of CART cell therapy for leukemia, lymphoma, and myeloma and discuss our perspective of how CART cell therapy can be applied in the context of HCT.

  9. Quantitative assessment of T-cell repertoire recovery after hematopoietic stem cell transplantation

    Science.gov (United States)

    van Heijst, Jeroen W J; Ceberio, Izaskun; Lipuma, Lauren B; Samilo, Dane W; Wasilewski, Gloria D; Gonzales, Anne Marie R; Nieves, Jimmy L; van den Brink, Marcel R M; Perales, Miguel A; Pamer, Eric G

    2012-01-01

    Delayed T-cell recovery and restricted T-cell receptor (TCR) diversity after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are associated with increased risks of infection and cancer relapse. Technical challenges have limited faithful measurement of TCR diversity following allo-HSCT. Here we combined 5′-RACE PCR with deep sequencing, to quantify TCR diversity in 28 allo-HSCT recipients using a single oligonucleotide pair. Analysis of duplicate blood samples confirmed that the frequency of individual TCRs was accurately determined. After 6 months, cord blood graft recipients approximated the TCR diversity of healthy individuals, whereas recipients of T-cell-depleted peripheral blood stem cell grafts had a 28-fold and 14-fold lower CD4+ and CD8+ T-cell diversity, respectively. After 12 months, these deficiencies had improved for the CD4+, but not the CD8+ T-cell compartment. Overall, this method provides unprecedented views of T-cell repertoire recovery after allo-HSCT and may identify patients at high risk of infection or relapse. PMID:23435170

  10. Antitumor immunomodulatory activity of allogenic bone marrow cells on TiNi scaffold

    Science.gov (United States)

    Kokorev, O. V.; Hodorenko, V. N.; Cherdyntseva, N. V.; Gunther, V. E.

    2016-08-01

    The present study was undertaken to evaluate the feasibility of modulation of anti-tumor response by allogenic bone marrow cell transplantation into porous TiNi-based scaffold. Transplantation of bone marrow cells into porous TiNi-based scaffold leads to antitumor (35%) and antimetastatic (55%) effects. The lifetime of tumor-bearing animals and implanted allogenic bone marrow cells in incubator of TiNi increases up to 60%. The possible mechanisms of the effect of allogenic cells on tumor process are the stimulation of endogenous effectors of antitumor immunity.

  11. Allogenic banking of dental pulp stem cells for innovative therapeutics

    Institute of Scientific and Technical Information of China (English)

    Pierre-Yves; Collart-Dutilleul; Franck; Chaubron; John; De; Vos; Frédéric; J; Cuisinier

    2015-01-01

    Medical research in regenerative medicine and cellbased therapy has brought encouraging perspectives for the use of stem cells in clinical trials. Multiple types of stem cells, from progenitors to pluripotent stem cells, have been investigated. Among these, dental pulp stem cells(DPSCs) are mesenchymal multipotent cells coming from the dental pulp, which is the soft tissue within teeth. They represent an interesting adult stem cell source because they are recovered in large amount in dental pulps with non-invasive techniques compared to other adult stem cell sources. DPSCs can be obtained from discarded teeth, especially wisdom teeth extracted for orthodontic reasons. To shift from promising preclinical results to therapeutic applications to human, DPSCs must be prepared in clinical grade lots and transformed into advanced therapy medicinal products(ATMP). As the production of patient-specific stem cells is costly and time-consuming, allogenic biobanking of clinical grade human leukocyte antigen(HLA)-typed DPSC lines provides efficient innovative therapeutic products. DPSC biobanks represent industrial and therapeutic innovations by using discarded biological tissues(dental pulps) as a source of mesenchymal stem cells to produce and store, in good manufacturing practice(GMP) conditions, DPSC therapeutic batches. In this review, we discuss about the challenges to transfer biological samples from a donor to HLA-typed DPSC therapeutic lots, following regulations, GMP guidelines and ethical principles. We also present some clinical applications, for which there is no efficient therapeutics so far, but that DPSCs-based ATMP could potentially treat.

  12. Polycomb-group proteins in hematopoietic stem cell regulation and hematopoietic neoplasms

    NARCIS (Netherlands)

    Radulovic, V.; de Haan, G.; Klauke, K.

    2013-01-01

    The equilibrium between self-renewal and differentiation of hematopoietic stem cells is regulated by epigenetic mechanisms. In particular, Polycomb-group (PcG) proteins have been shown to be involved in this process by repressing genes involved in cell-cycle regulation and differentiation. PcGs are

  13. Human Placenta Is a Potent Hematopoietic Niche Containing Hematopoietic Stem and Progenitor Cells throughout Development

    NARCIS (Netherlands)

    C. Robin (Catherine); K. Bollerot (Karine); S.C. Mendes (Sandra); E. Haak (Esther); M. Crisan (Mihaela); F. Cerisoli (Francesco); I. Lauw (Ivoune); P. Kaimakis (Polynikis); R.J.J. Jorna (Ruud); M. Vermeulen (Mark); M.H. Kayser (Manfred); R. van der Linden (Reinier); P. Imanirad (Parisa); M.M.A. Verstegen (Monique); H. Nawaz-Yousaf (Humaira); N. Papazian (Natalie); E.A.P. Steegers (Eric); T. Cupedo (Tom); E.A. Dzierzak (Elaine)

    2009-01-01

    textabstractHematopoietic stem cells (HSCs) are responsible for the life-long production of the blood system and are pivotal cells in hematologic transplantation therapies. During mouse and human development, the first HSCs are produced in the aorta-gonad-mesonephros region. Subsequent to this emerg

  14. Cell cycle regulation of hematopoietic stem or progenitor cells.

    Science.gov (United States)

    Hao, Sha; Chen, Chen; Cheng, Tao

    2016-05-01

    The highly regulated process of blood production is achieved through the hierarchical organization of hematopoietic stem cell (HSC) subsets and their progenies, which differ in self-renewal and differentiation potential. Genetic studies in mice have demonstrated that cell cycle is tightly controlled by the complex interplay between extrinsic cues and intrinsic regulatory pathways involved in HSC self-renewal and differentiation. Deregulation of these cellular programs may transform HSCs or hematopoietic progenitor cells (HPCs) into disease-initiating stem cells, and can result in hematopoietic malignancies such as leukemia. While previous studies have shown roles for some cell cycle regulators and related signaling pathways in HSCs and HPCs, a more complete picture regarding the molecular mechanisms underlying cell cycle regulation in HSCs or HPCs is lacking. Based on accumulated studies in this field, the present review introduces the basic components of the cell cycle machinery and discusses their major cellular networks that regulate the dormancy and cell cycle progression of HSCs. Knowledge on this topic would help researchers and clinicians to better understand the pathogenesis of relevant blood disorders and to develop new strategies for therapeutic manipulation of HSCs.

  15. Reverse seroconversion of hepatitis B virus after hematopoietic stem cell transplantation.

    Science.gov (United States)

    Goyama, S; Kanda, Y; Nannya, Y; Kawazu, M; Takeshita, M; Niino, M; Komeno, Y; Nakamoto, T; Kurokawa, M; Tsujino, S; Ogawa, S; Aoki, K; Chiba, S; Motokura, T; Shiratori, Y; Hirai, H

    2002-11-01

    Hepatitis B virus (HBV) reactivation in patients previously positive for hepatitis B surface antibody (HBsAb), so-called reverse seroconversion, has been considered to be a rare complication after hematopoietic stem cell transplantation (HSCT). We experienced two patients who developed reverse seroconversion among nine who were HBsAb positive and Hepatitis B core antibody (HBcAb) positive before HSCT; one after autologous bone marrow transplantation (BMT) and another after allogeneic peripheral blood stem cell transplantation (PBSCT). We reviewed the literature and considered that reverse seroconversion of HBV after HSCT is not uncommon among HBsAb positive recipients. The use of corticosteroids, the lack of HBsAb in donor, and a decrease in serum HBsAb and HBcAb levels may predict reverse seroconversion after HSCT.

  16. Thrombotic microangiopathic syndromes associated with drugs, HIV infection, hematopoietic stem cell transplantation and cancer.

    Science.gov (United States)

    George, James N; Terrell, Deirdra R; Vesely, Sara K; Kremer Hovinga, Johanna A; Lämmle, Bernhard

    2012-03-01

    Thrombotic microangiopathy (TMA) has multiple etiologies. In the four disorders described in this review, the primary organ involved is the kidney. Drug-associated TMA can be an acute, immune-mediated disorder or the result of gradual, dose-dependent toxicity. TMA may occur in patients with advanced HIV infection, possibly mediated by angio-invasive infections. TMA following allogeneic hematopoietic stem cell transplantation may also be caused by drug toxicity; the pathogenesis may involve inhibition of vascular endothelial cell growth factor in renal podocytes. Malignancies of many types with systemic microvascular involvement may cause TMA. Recognition that these syndromes may mimic TTP is important to provide appropriate management and to avoid the inappropriate use of plasma exchange treatment.

  17. Enrichment of human hematopoietic stem/progenitor cells facilitates transduction for stem cell gene therapy.

    Science.gov (United States)

    Baldwin, Kismet; Urbinati, Fabrizia; Romero, Zulema; Campo-Fernandez, Beatriz; Kaufman, Michael L; Cooper, Aaron R; Masiuk, Katelyn; Hollis, Roger P; Kohn, Donald B

    2015-05-01

    Autologous hematopoietic stem cell (HSC) gene therapy for sickle cell disease has the potential to treat this illness without the major immunological complications associated with allogeneic transplantation. However, transduction efficiency by β-globin lentiviral vectors using CD34-enriched cell populations is suboptimal and large vector production batches may be needed for clinical trials. Transducing a cell population more enriched for HSC could greatly reduce vector needs and, potentially, increase transduction efficiency. CD34(+) /CD38(-) cells, comprising ∼1%-3% of all CD34(+) cells, were isolated from healthy cord blood CD34(+) cells by fluorescence-activated cell sorting and transduced with a lentiviral vector expressing an antisickling form of beta-globin (CCL-β(AS3) -FB). Isolated CD34(+) /CD38(-) cells were able to generate progeny over an extended period of long-term culture (LTC) compared to the CD34(+) cells and required up to 40-fold less vector for transduction compared to bulk CD34(+) preparations containing an equivalent number of CD34(+) /CD38(-) cells. Transduction of isolated CD34(+) /CD38(-) cells was comparable to CD34(+) cells measured by quantitative PCR at day 14 with reduced vector needs, and average vector copy/cell remained higher over time for LTC initiated from CD34(+) /38(-) cells. Following in vitro erythroid differentiation, HBBAS3 mRNA expression was similar in cultures derived from CD34(+) /CD38(-) cells or unfractionated CD34(+) cells. In vivo studies showed equivalent engraftment of transduced CD34(+) /CD38(-) cells when transplanted in competition with 100-fold more CD34(+) /CD38(+) cells. This work provides initial evidence for the beneficial effects from isolating human CD34(+) /CD38(-) cells to use significantly less vector and potentially improve transduction for HSC gene therapy.

  18. Allogeneic Mesenchymal Stem Cell Transplantation in Dogs With Keratoconjunctivitis Sicca

    Science.gov (United States)

    Bittencourt, Maura K. W.; Barros, Michele A.; Martins, João Flávio P.; Vasconcellos, Jose Paulo C.; Morais, Bruna P.; Pompeia, Celine; Bittencourt, Matheus Domingues; Evangelho, Karine dos Santos; Kerkis, Irina; Wenceslau, Cristiane V.

    2016-01-01

    Keratoconjunctivitis sicca (KCS) is a dysfunction in tear production associated with clinical signs, which include conjunctival hyperemia, ocular discharge, discomfort, pain, and, eventually, corneal vascularization and pigmentation. Immunosuppressive drugs are routinely administrated for long periods to treat KCS but with side effects and limited results. Evaluation of the clinical benefits of intralacrimal transplantation of allogeneic mesenchymal stem cells (MSCs) in dogs with mild–moderate and severe KCS was done. A total of 24 eyes with KCS from 15 dogs of different breeds were enrolled in the present study. A single transplantation of MSCs (1 × 106) directly into lacrimal glands (dorsal and third eyelid) was performed. The Schirmer tear tests (STTs) and ocular surface improvements were used to assess short- and long-term effects of these cells. The STTs were carried out on day 0 (before MSCs transplantation) and on days 7, 14, 21, and 28, as well as 6 and 12 months after MSC transplantation. Our data demonstrate that allogeneic MSC transplantation in KCS dogs is safe since no adverse effects were observed immediately after transplantation and in short- and long-term follow-ups. A statistically significant increase in the STT and ocular surface improvements was found in all eyes studied. In all the eyes with mild–moderate KCS, STT values reverted to those of healthy eyes, while in eyes with severe KCS, although complete reversion was not found, there was improvement in tear production and in other clinical signs. Our study shows that a single dose of a low number of MSCs can be used to treat KCS in dogs. In contrast to immunosuppressive drug use, MSC transplantation has an effect over a long period (up to 12 months), even after a single administration, and does not require daily drug administration. PMID:28003932

  19. Hematopoietic stem cell characterization and isolation.

    Science.gov (United States)

    Rossi, Lara; Challen, Grant A; Sirin, Olga; Lin, Karen Kuan-Yin; Goodell, Margaret A

    2011-01-01

    Hematopoietic stem cells (HSCs) are defined by the capabilities of multi-lineage differentiation and long-term self-renewal. Both these characteristics contribute to maintain the homeostasis of the system and allow the restoration of hematopoiesis after insults, such as infections or therapeutic ablation. Reconstitution after lethal irradiation strictly depends on a third, fundamental property of HSCs: the capability to migrate under the influence of specific chemokines. Directed by a chemotactic compass, after transplant HSCs find their way to the bone marrow, where they eventually home and engraft. HSCs represent a rare population that primarily resides in the bone marrow with an estimated frequency of 0.01% of total nucleated cells. Separating HSCs from differentiated cells that reside in the bone marrow has been the focus of intense investigation for years. In this chapter, we will describe in detail the strategy routinely used by our laboratory to purify murine HSCs, by exploiting their antigenic phenotype (KSL), combined with the physiological capability to efficiently efflux the vital dye Hoechst 33342, generating the so-called Side Population, or SP.

  20. Life-Threatening Adenovirus Infections in the Setting of the Immunocompromised Allogeneic Stem Cell Transplant Patients

    Directory of Open Access Journals (Sweden)

    Cedar J. Fowler

    2010-01-01

    Full Text Available A single institution case series of adenovirus infections after allogeneic hematopoietic stem cell transplantation is presented to highlight the consideration for adenovirus infections as an etiology in patients with rapid hepatic or other sudden organ deterioration in the setting of apparent GVHD stabilization. The series also highlights that survival is limited with these infections often due in part to concomitant opportunistic infections. In addition, the pathophysiological events, such as GVHD and hepatic dysfunction, may complicate the clinical picture and delay therapy of an opportunistic infection. This is particularly true for adenoviral infections as they also have a distinct clinical picture in immunocompromised patients when compared to immune competent patients. Adenovirus infections also have the additional challenge that its treatment, cidofovir, has associated toxicities that can delay its administration. Recent developments has yielded an assay that can be used in the early detection and for serial determinations of adenovirus in patients with advanced GVHD, as well as a new therapeutic agent currently undergoing clinical trials.

  1. Critical early events in hematopoietic cell seeding and engraftment.

    OpenAIRE

    Jerry Stein; Isaac Yaniv; Nadir Askenasy

    2005-01-01

    Durable hematopoietic stem cell engraftment requires efficient homing to and seeding in the recipient bone marrow. Dissection of cellular and molecular mechanisms by retrospective analysis of functional engraftment studies imposes severe limitations on the understanding of the early stages of this process. We have established an experimental approach for in vivo functional imaging of labeled cells at the level of recipient bone marrow in real time. The adhesive interaction of hematopoietic ce...

  2. Non-hematopoietic stem cell transplantation treatment of juvenile myelomonocytic leukemia: a retrospective analysis and definition of response criteria

    DEFF Research Database (Denmark)

    Bergstraesser, Eva; Hasle, Henrik; Rogge, Tim

    2007-01-01

    BACKGROUND: Juvenile myelomonocytic leukemia (JMML) is a rare myeloproliferative disease of infancy. Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the only curative treatment modality, while the role of anti-leukemic therapy prior to HSCT is uncertain. A comparative...... responses in solid organs compared to peripheral blood (PB). PROCEDURE: We therefore defined separate response criteria for white blood count (WBC), platelet count, liver size, and spleen size. We then retrospectively evaluated the efficacy of 129 treatment courses other than HSCT administered to 63...

  3. Associations between gastrointestinal toxicity, micro RNA and cytokine production in patients undergoing myeloablative allogeneic stem cell transplantation

    DEFF Research Database (Denmark)

    Pontoppidan, Peter Erik Lotko; Jordan, Karina Kwi Im; Carlsen, Anting Liu

    2015-01-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is a procedure with a high risk of treatment related mortality. The primary aim of the present study was to examine associations between markers of gastrointestinal toxicity, markers of systemic inflammation, and plasma levels of microRNA...... (miRNA) -155 and -146a during the first month after HSCT. The secondary aim was to characterize the impact of the toxic-inflammatory response on the function of circulating leukocytes during immune recovery. Thirty HSCT patients were included. Gastrointestinal injury was monitored by toxicity scores......, lactulose-mannitol test and plasma citrulline, as a measure of the enterocyte population. Nadir of citrulline and maximum of oral toxicity scores, intestinal permeability, CRP and plasma levels of IL-6 and IL-10 was seen at day +7 post-HSCT. miRNA-155 and mi-RNA-146a showed an inverse relation...

  4. A case report of myelodysplastic syndrome treated with allogeneic transplantation of HLA-identical sibling using culture-expanded mesenchymal stem cells and hematopoietic stem cells originated from HBV infected donor%乙肝病毒感染供者来源异基因间充质干细胞联合非清髓性造血干细胞移植治疗骨髓增生异常综合征-难治性贫血一例

    Institute of Scientific and Technical Information of China (English)

    沈文怡; 陆化; 李建勇; 张建富; 李军; 周东辉

    2010-01-01

    Objective To evaluate the safety, efficiency and feasibility of HLA-identical sibling using culture-expanded mesenchymal stem cells and hematopoietic stem cells in treatment for myelodysplastic syndrome (MDS). Also to investigate for valid preventive measures to avoid the infection of HBV originated from donor. Methods A 46-years-old male patient with myelodysplastic syndrome-refractory anemia (MDSRA) got a cotransplantation of culture-expanded mensenchymal stem cells (MSC) and hematopoietic stem cells (HSCs) from HLA-identical sibling donor (his sister) who was infected by hepatitis B virus (HBV). Some measures were applicated in order to avoid the recipient from getting a HBV infection. The antiviral therapy to the donor was began early at the time 1 month before transplant, and HBV vaccine inoculation was used 2 month before transplant. High titer of anti-hepatis B immunoglobulin was used 1 week before transplant and 1 month after transplant the use of prophylactic anti-hepatis B drug treatment was begun. A non-myeloablative preparative regimen included fludarabine monophosphate (Flu, 120 mg/m2), cyclophosphamide (Cy, 1200 mg/m2)and antithymocyte globulin (ATG, 15 mg/kg) was given to him before culture-expanded mesenchymal stem cell and allogeneic peripheral blood stem cell from his HLA-matched sister. Results The regimen was well tolerated, and hemopoiesis was reconstituted on day 10 after transplant, idiochromosome detected by fluorescent in situ hybridization on day 30 showed XY 47/300 and on day 90 it was 7/300. No evidence of HBV infection was detected on day 60 after transplant. Conclusion The clinical course of this patient indicate that HLA-identical sibling culture-expanded mesenchymal stem cell transplantation combined with non-myeloablative stem cell transplantation can be an effective and safe approach in treatment of MDS.%目的 进一步探讨骨髓增生异常综合征-难治性贫血(MDS-RA)患者采用异基因造血干细胞移植的安全性

  5. Eradication of tumour cells by successive injections of allogeneic immune and hyperimmune peritoneal cells in a murine lymphoma system

    NARCIS (Netherlands)

    Dullens, H.F.J.; Woutersen, R.A.; Weger, R.A. de; Otter, W. den

    2006-01-01

    Allogeneic C57BL immune and hyperimmune (vs SL2) peritoneal cells are used for eradication of DBA/2 derived SL2 lymphoma cells injected into the peritoneal cavity of DBA/2 mice. SL2 bearing DBA/2 mice are treated with 3, 5, or 8 successive i.p. injections of 2 × 106 allogeneic C57BL immune or hyper

  6. Phase IV open-label study of the efficacy and safety of deferasirox after allogeneic stem cell transplantation.

    Science.gov (United States)

    Vallejo, Carlos; Batlle, Montserrat; Vázquez, Lourdes; Solano, Carlos; Sampol, Antonia; Duarte, Rafael; Hernández, Dolores; López, Javier; Rovira, Montserrat; Jiménez, Santiago; Valcárcel, David; Belloch, Vicente; Jiménez, Mónica; Jarque, Isidro

    2014-10-01

    This is the first prospective study of deferasirox in adult allogeneic hematopoietic stem cell transplant recipients with transfusional iron overload in hematologic malignancies. Patients at least six months post transplant were treated with deferasirox at a starting dose of 10 mg/kg/day for 52 weeks or until serum ferritin was less than 400 ng/mL on two consecutive occasions. Thirty patients were enrolled and 22 completed the study. A significant reduction from baseline in median serum ferritin and in liver iron concentration at 52 weeks was observed in the overall population: from 1440 to 755.5 ng/mL (P=0.002) and from 14.5 to 4.6 mg Fe/g dw (P=0.0007), respectively. Reduction in serum ferritin in patients who did not discontinue deferasirox therapy was significantly greater than that found in those who prematurely discontinued the treatment (from 1541 to 581 ng/mL vs. from 1416 to 1486 ng/mL; P=0.008). Drug-related adverse events, reported in 17 patients (56.7%), were mostly mild to moderate in severity. There were no drug-related serious adverse events. Twelve patients (40.0%) showed an increase of over 33% in serum creatinine compared to baseline and greater than the upper limit of normal on two consecutive visits. Two patients (6.7%) with active graft-versus-host disease showed an increase in alanine aminotransferase exceeding 10 times upper limit of normal; both resolved. In this prospective study, deferasirox provided a significant reduction in serum ferritin and liver iron concentration over one year of treatment in allogeneic hematopoietic stem cell transplant recipients with iron overload. In addition, the majority of adverse events related to deferasirox were mild or moderate in severity. (clinicaltrials.gov identifier:01335035).

  7. Differential effect of conditioning regimens on cytokine responses during allogeneic stem cell transplantation

    DEFF Research Database (Denmark)

    Andersen, J; Heilmann, C; Jacobsen, N;

    2006-01-01

    The purpose of this study was to characterize cytokine responses during conditioning in patients undergoing allogeneic stem cell transplantation (SCT) with the aim to identify which markers that may reliably reflect inflammatory activity during conditioning. We investigated inflammatory and anti...

  8. HLA-mismatched hematopoietic stem cell tranplantation for pediatric solid tumors

    Directory of Open Access Journals (Sweden)

    Andrea Pession

    2011-06-01

    Full Text Available Even if the overall survival of children with cancer is significantly improved over these decades, the cure rate of high-risk pediatric solid tumors such as neuroblastoma, Ewing’s sarcoma family tumors or rhabdomiosarcoma remain challenging. Autologous hematopoietic stem cell transplantation (HSCT allows chemotherapy dose intensification beyond marrow tolerance and has become a fundamental tool in the multimodal therapeutical approach of these patients. Anyway this procedure does not allow to these children an eventfree survival approaching more than 50% at 5 years. New concepts of allogeneic HSCT and in particular HLA-mismatched HSCT for high risk solid tumors do not rely on escalation of chemo therapy intensity and tumor load reduction but rather on a graft-versus-tumor effect. We here report an experimental study design of HLA-mismatched HSCT for the treatment of pediatric solid tumors and the inherent preliminary results.

  9. Successful Hematopoietic Stem Cell Transplantation Following a Cyclophosphamide-Containing Preparative Regimen with Concomitant Phenobarbital Administration

    Directory of Open Access Journals (Sweden)

    Catherine Weber

    2012-01-01

    Full Text Available Cyclophosphamide is an immunosuppressive agent and an anticancer prodrug which requires bioactivation catalyzed primarily by cytochrome P450 enzymes in order to be transformed into its active alkylating compounds. Concomitant administration of drugs known to inhibit or induce this enzyme system is a clinical concern. Herein, we present the case of a chronically ill 21-year-old patient who received high-dose cyclophosphamide, equine antithymocyte globulin (eATG, and total body irradiation (TBI followed by an allogeneic hematopoietic stem cell transplant (HSCT for severe aplastic anemia. Throughout her hospitalization, she continued to receive quadruple anticonvulsant therapy including phenobarbital for her long-standing seizure history. The preparative regimen was tolerated well aside from a hypersensitivity reaction to eATG, and minimal cyclophosphamide-related toxicities. Safe and effective administration of high-dose cyclophosphamide was possible with multidisciplinary care consisting of physician, nursing, pharmacy, neurology consultation, as well as social work and case management.

  10. Erythropoietic Potential of CD34+ Hematopoietic Stem Cells from Human Cord Blood and G-CSF-Mobilized Peripheral Blood

    Directory of Open Access Journals (Sweden)

    Honglian Jin

    2014-01-01

    Full Text Available Red blood cell (RBC supply for transfusion has been severely constrained by the limited availability of donor blood and the emergence of infection and contamination issues. Alternatively, hematopoietic stem cells (HSCs from human organs have been increasingly considered as safe and effective blood source. Several methods have been studied to obtain mature RBCs from CD34+ hematopoietic stem cells via in vitro culture. Among them, human cord blood (CB and granulocyte colony-stimulating factor-mobilized adult peripheral blood (mPB are common adult stem cells used for allogeneic transplantation. Our present study focuses on comparing CB- and mPB-derived stem cells in differentiation from CD34+ cells into mature RBCs. By using CD34+ cells from cord blood and G-CSF mobilized peripheral blood, we showed in vitro RBC generation of artificial red blood cells. Our results demonstrate that CB- and mPB-derived CD34+ hematopoietic stem cells have similar characteristics when cultured under the same conditions, but differ considerably with respect to expression levels of various genes and hemoglobin development. This study is the first to compare the characteristics of CB- and mPB-derived erythrocytes. The results support the idea that CB and mPB, despite some similarities, possess different erythropoietic potentials in in vitro culture systems.

  11. Clostridium difficile infection in Chilean patients submitted to hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Javier Pilcante

    2015-12-01

    Full Text Available ABSTRACT Introduction: Patients submitted to hematopoietic stem cell transplantation have an increased risk of Clostridium difficile infection and multiple risk factors have been identi- fied. Published reports have indicated an incidence from 9% to 30% of transplant patients however to date there is no information about infection in these patients in Chile. Methods: A retrospective analysis was performed of patients who developed C. difficile infection after hematopoietic stem cell transplantations from 2000 to 2013. Statistical analysis used the Statistical Package for the Social Sciences software. Results: Two hundred and fifty patients were studied (mean age: 39 years; range: 17-69, with 147 (59% receiving allogeneic transplants and 103 (41% receiving autologous trans- plants. One hundred and ninety-two (77% patients had diarrhea, with 25 (10% cases of C. difficile infection being confirmed. Twenty infected patients had undergone allogeneic trans- plants, of which ten had acute lymphoblastic leukemia, three had acute myeloid leukemia and seven had other diseases (myelodysplastic syndrome, chronic myeloid leukemia, severe aplastic anemia. In the autologous transplant group, five patients had C. difficile infection; two had multiple myeloma, one had amyloidosis, one had acute myeloid leukemia and one had germinal carcinoma. The overall incidence of C. difficile infection was 4% within the first week, 6.4% in the first month and 10% in one year, with no difference in overall survival between infected and non-infected groups (72.0% vs. 67.6%, respectively; p-value = 0.56. Patients infected after allogeneic transplants had a slower time to neutrophil engraftment compared to non-infected patients (17.5 vs. 14.9 days, respectively; p-value = 0.008. In the autologous transplant group there was no significant difference in the neutrophil engraftment time between infected and non-infected patients (12.5 days vs. 11.8 days, respectively; p

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

    Directory of Open Access Journals (Sweden)

    Bart eVaes

    2012-11-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

  15. Individualization of drug exposure in pediatric hematopoietic stem cell transplantation

    NARCIS (Netherlands)

    Bartelink, I.H.

    2012-01-01

    Allogeneic haematopoeitic stem cell transplantation is a potentially curative treatment for a variety of diseases. Its use is limited by 1) the risk of graft failures and relapse of malignant diseases, 2) transplantation-associated complications, and 3) late effects. There is a large and largely unp

  16. SBR-Blood: systems biology repository for hematopoietic cells.

    Science.gov (United States)

    Lichtenberg, Jens; Heuston, Elisabeth F; Mishra, Tejaswini; Keller, Cheryl A; Hardison, Ross C; Bodine, David M

    2016-01-04

    Extensive research into hematopoiesis (the development of blood cells) over several decades has generated large sets of expression and epigenetic profiles in multiple human and mouse blood cell types. However, there is no single location to analyze how gene regulatory processes lead to different mature blood cells. We have developed a new database framework called hematopoietic Systems Biology Repository (SBR-Blood), available online at http://sbrblood.nhgri.nih.gov, which allows user-initiated analyses for cell type correlations or gene-specific behavior during differentiation using publicly available datasets for array- and sequencing-based platforms from mouse hematopoietic cells. SBR-Blood organizes information by both cell identity and by hematopoietic lineage. The validity and usability of SBR-Blood has been established through the reproduction of workflows relevant to expression data, DNA methylation, histone modifications and transcription factor occupancy profiles.

  17. Allogeneic cell transplant expands bone marrow distribution by colonizing previously abandoned areas: an FDG PET/CT analysis.

    Science.gov (United States)

    Fiz, Francesco; Marini, Cecilia; Campi, Cristina; Massone, Anna Maria; Podestà, Marina; Bottoni, Gianluca; Piva, Roberta; Bongioanni, Francesca; Bacigalupo, Andrea; Piana, Michele; Sambuceti, Gianmario; Frassoni, Francesco

    2015-06-25

    Mechanisms of hematopoietic reconstitution after bone marrow (BM) transplantation remain largely unknown. We applied a computational quantification software application to hybrid 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) images to assess activity and distribution of the hematopoietic system throughout the whole skeleton of recently transplanted patients. Thirty-four patients underwent PET/CT 30 days after either adult stem cell transplantation (allogeneic cell transplantation [ACT]; n = 18) or cord blood transplantation (CBT; n = 16). Our software automatically recognized compact bone volume and trabecular bone volume (IBV) in CT slices. Within IBV, coregistered PET data were extracted to identify the active BM (ABM) from the inactive tissue. Patients were compared with 34 matched controls chosen among a published normalcy database. Whole body ABM increased in ACT and CBT when compared with controls (12.4 ± 3 and 12.8 ± 6.8 vs 8.1 ± 2.6 mL/kg of ideal body weight [IBW], P bones, ABM increased three- and sixfold in CBT and ACT, respectively, compared with controls (0.9 ± 0.9 and 1.7 ± 2.5 vs 0.3 ± 0.3 mL/kg IBW, P transplanted BM into previously abandoned BM sites.

  18. Use of the quality management system "JACIE" and outcome after hematopoietic stem cell transplantation.

    Science.gov (United States)

    Gratwohl, Alois; Brand, Ronald; McGrath, Eoin; van Biezen, Anja; Sureda, Anna; Ljungman, Per; Baldomero, Helen; Chabannon, Christian; Apperley, Jane

    2014-05-01

    Competent authorities, healthcare payers and hospitals devote increasing resources to quality management systems but scientific analyses searching for an impact of these systems on clinical outcome remain scarce. Earlier data indicated a stepwise improvement in outcome after allogeneic hematopoietic stem cell transplantation with each phase of the accreditation process for the quality management system "JACIE". We therefore tested the hypothesis that working towards and achieving "JACIE" accreditation would accelerate improvement in outcome over calendar time. Overall mortality of the entire cohort of 107,904 patients who had a transplant (41,623 allogeneic, 39%; 66,281 autologous, 61%) between 1999 and 2006 decreased over the 14-year observation period by a factor of 0.63 per 10 years (hazard ratio: 0.63; 0.58-0.69). Considering "JACIE"-accredited centers as those with programs having achieved accreditation by November 2012, at the latest, this improvement was significantly faster in "JACIE"-accredited centers than in non-accredited centers (approximately 5.3% per year for 49,459 patients versus approximately 3.5% per year for 58,445 patients, respectively; hazard ratio: 0.83; 0.71-0.97). As a result, relapse-free survival (hazard ratio 0.85; 0.75-0.95) and overall survival (hazard ratio 0.86; 0.76-0.98) were significantly higher at 72 months for those patients transplanted in the 162 "JACIE"-accredited centers. No significant effects were observed after autologous transplants (hazard ratio 1.06; 0.99-1.13). Hence, working towards implementation of a quality management system triggers a dynamic process associated with a steeper reduction in mortality over the years and a significantly improved survival after allogeneic stem cell transplantation. Our data support the use of a quality management system for complex medical procedures.

  19. Use of the quality management system “JACIE” and outcome after hematopoietic stem cell transplantation

    Science.gov (United States)

    Gratwohl, Alois; Brand, Ronald; McGrath, Eoin; van Biezen, Anja; Sureda, Anna; Ljungman, Per; Baldomero, Helen; Chabannon, Christian; Apperley, Jane

    2014-01-01

    Competent authorities, healthcare payers and hospitals devote increasing resources to quality management systems but scientific analyses searching for an impact of these systems on clinical outcome remain scarce. Earlier data indicated a stepwise improvement in outcome after allogeneic hematopoietic stem cell transplantation with each phase of the accreditation process for the quality management system “JACIE”. We therefore tested the hypothesis that working towards and achieving “JACIE” accreditation would accelerate improvement in outcome over calendar time. Overall mortality of the entire cohort of 107,904 patients who had a transplant (41,623 allogeneic, 39%; 66,281 autologous, 61%) between 1999 and 2006 decreased over the 14-year observation period by a factor of 0.63 per 10 years (hazard ratio: 0.63; 0.58–0.69). Considering “JACIE“-accredited centers as those with programs having achieved accreditation by November 2012, at the latest, this improvement was significantly faster in “JACIE”-accredited centers than in non-accredited centers (approximately 5.3% per year for 49,459 patients versus approximately 3.5% per year for 58,445 patients, respectively; hazard ratio: 0.83; 0.71–0.97). As a result, relapse-free survival (hazard ratio 0.85; 0.75–0.95) and overall survival (hazard ratio 0.86; 0.76–0.98) were significantly higher at 72 months for those patients transplanted in the 162 “JACIE“-accredited centers. No significant effects were observed after autologous transplants (hazard ratio 1.06; 0.99–1.13). Hence, working towards implementation of a quality management system triggers a dynamic process associated with a steeper reduction in mortality over the years and a significantly improved survival after allogeneic stem cell transplantation. Our data support the use of a quality management system for complex medical procedures. PMID:24488562

  20. Immunoevasive pericytes from human pluripotent stem cells preferentially modulate induction of allogeneic regulatory T cells.

    Science.gov (United States)

    Domev, Hagit; Milkov, Irina; Itskovitz-Eldor, Joseph; Dar, Ayelet

    2014-10-01

    Isolated microvessel-residing pericytes and pericytes from human pluripotent stem cells (hPSCs) exhibit mesenchymal stem cell-like characteristics and therapeutic properties. Despite growing interest in pericyte-based stem cell therapy, their immunogenicity and immunomodulatory effects on nonactivated T cells are still poorly defined, in particular those of vasculogenic hPSC pericytes. We found that tissue-embedded and unstimulated cultured hPSC- or tissue-derived pericytes constitutively expressed major histocompatibility complex (MHC) class I and the inhibitory programmed cell death-ligand 1/2 (PD-L1/2) molecules but not MHC class II or CD80/CD86 costimulatory molecules. Pretreatment with inflammatory mediators failed to induce an antigen-presenting cell-like phenotype in stimulated pericytes. CD146+ pericytes from hPSCs did not induce activation and proliferation of allogeneic resting T cells independent of interferon (IFN)-γ prestimulation, similarly to pericytes from human brain or placenta. Instead, pericytes mediated a significant increase in the frequency of allogeneic CD25highFoxP3+ regulatory T cells when cocultured with nonactivated peripheral blood T cells. Furthermore, when peripheral blood CD25high regulatory T cells (Tregs) were depleted from isolated CD3+ T cells, pericytes preferentially induced de novo formation of CD4+CD25highFoxP3+CD127-, suppressive regulatory T cells. Constitutive expression of PD-L1/2 and secretion of transforming growth factor-β by hPSC pericytes directly regulated generation of pericyte-induced Tregs. Pericytes cotransplanted into immunodeficient mice with allogeneic CD25- T cells maintained a nonimmunogenic phenotype and mediated the development of functional regulatory T cells. Together, these findings reveal a novel feature of pericyte-mediated immunomodulation distinguished from immunosuppression, shared by native tissue pericytes and hPSC pericytes, and support the notion that pericytes can be applied for allogeneic

  1. Validation of the Hematopoietic Cell Transplantation-Specific Comorbidity Index: a prospective, multicenter GITMO study.

    Science.gov (United States)

    Raimondi, Roberto; Tosetto, Alberto; Oneto, Rosi; Cavazzina, Riccardo; Rodeghiero, Francesco; Bacigalupo, Andrea; Fanin, Renato; Rambaldi, Alessandro; Bosi, Alberto

    2012-08-09

    The development of tools for the prediction of nonrelapse mortality (NRM) after allogeneic hematopoietic stem cell transplantation (HSCT) would offer a major guidance in the therapeutic decision. Recently, the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) has been associated with increased NRM risk in several retrospective studies, but its clinical utility has never been demonstrated prospectively in an adequately sized cohort. To this aim, we prospectively evaluated a consecutive cohort of 1937 patients receiving HSCT in Italy over 2 years. HCT-CI was strongly correlated with both 2-year NRM (14.7%, 21.3%, and 27.3% in patients having an HCT-CI score of 0, 1-2, and ≥ 3, respectively) and overall survival (56.4%, 54.5%, and 41.3%, respectively). There was an excellent calibration between the predicted and observed 2-year NRM in patients having an HCT-CI score of 0 and 1-2, whereas in the ≥ 3 group the predicted NRM overestimated the observed NRM (41% vs 27.3%). HCT-CI alone was the strongest predictor of NRM in patients with lymphoma, myelodysplastic syndrome, and acute myeloid leukemia in first remission (c-statistics 0.66, 064, and 0.59, respectively). We confirm the clinical utility of the HCT-CI score that could also identify patients at low NRM risk possibly benefiting from an HSCT-based treatment strategy.

  2. Regulation of hematopoietic stem cells during mouse development

    NARCIS (Netherlands)

    C. Orelio (Claudia)

    2003-01-01

    textabstractThe hematopoietic system is comprised of many different cell types that fulfill important physiological functions throughout embryonic and adult stages of mouse development. As the mature blood cells have a limited life-span, the pool of blood cells needs constant replenishing. At the ba

  3. Salvage Second Hematopoietic Cell Transplantation in Myeloma

    Science.gov (United States)

    Michaelis, Laura C.; Saad, Ayman; Zhong, Xiaobo; Le-Rademacher, Jennifer; Freytes, Cesar O.; Marks, David I.; Lazarus, Hillard M.; Bird, Jennifer M.; Holmberg, Leona; Kamble, Rammurti T.; Kumar, Shaji; Lill, Michael; Meehan, Kenneth R.; Saber, Wael; Schriber, Jeffrey; Tay, Jason; Vogl, Dan T.; Wirk, Baldeep; Savani, Bipin N.; Gale, Robert P.; Vesole, David H.; Schiller, Gary J.; Abidi, Muneer; Anderson, Kenneth C.; Nishihori, Taiga; Kalaycio, Matt E.; Vose, Julie M.; Moreb, Jan S.; Drobyski, William; Munker, Reinhold; Roy, Vivek; Ghobadi, Armin; Holland, H. Kent; Nath, Rajneesh; To, L. Bik; Maiolino, Angelo; Kassim, Adetola A.; Giralt, Sergio A.; Landau, Heather; Schouten, Harry C.; Maziarz, Richard T.; Mikhael, Joseph; Kindwall-Keller, Tamila; Stiff, Patrick J.; Gibson, John; Lonial, Sagar; Krishnan, Amrita; Dispenzieri, Angela; Hari, Parameswaran

    2013-01-01

    Autologous hematopoietic cell transplantation (AHCT) as initial therapy of patients with multiple myeloma (MM) improves survival. However, data to support this approach for relapsed/progressive disease after initial AHCT (AHCT1) are limited. Using Center for International Blood and Marrow Transplant Research data, we report the outcomes of 187 patients who underwent a second AHCT (AHCT2) for the treatment of relapsed/progressive MM. Planned tandem AHCT was excluded. Median age at AHCT2 was 59 years (range, 28 to 72), and median patient follow-up was 47 months (range, 3 to 97). Nonrelapse mortality after AHCT2 was 2% at 1 year and 4% at 3 years. Median interval from AHCT1 to relapse/progression was 18 months, and median interval between transplantations was 32 months. After AHCT2, the incidence of relapse/progression at 1 and 3 years was 51% and 82%, respectively. At 3 years after AHCT2, progression-free survival was 13%, and overall survival was 46%. In multivariate analyses, those relapsing ≥36 months after AHCT1 had superior progression-free (P = .045) and overall survival (P = .019). Patients who underwent AHCT2 after 2004 had superior survival (P = .026). AHCT2 is safe and feasible for disease progression after AHCT1. In this retrospective study, individuals relapsing ≥36 months from AHCT1 derived greater benefit from AHCT2 compared with those with a shorter disease-free interval. Storage of an adequate graft before AHCT1 will ensure that the option of a second autologous transplantation is retained for patients with relapsed/progressive MM. PMID:23298856

  4. Hypomethylating agents after allogeneic blood stem cell transplantation

    Science.gov (United States)

    Rautenberg, Christina; Haas, Rainer; Kobbe, Guido

    2016-01-01

    Allogeneic blood stem cell transplantation (allo-SCT) is a potentially curative treatment for patients with myeloid malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), but relapse remains the major cause of treatment failure. So far, therapeutic options for patients with AML or MDS who relapse after allo-SCT generally consisted of palliative care, low-dose or intensive chemotherapy as well as cellular therapies such as donor lymphocyte infusions (DLI) and second transplantation in selected cases. Nevertheless, the prognosis of patients with myeloid malignancies relapsing after allo-SCT remains dismal therefore asking for novel treatment strategies. Considering their well-balanced profile of good efficacy and moderate toxicity in the non-transplant setting, the hypomethylating agents (HMA) azacitidine (Aza) and decitabine (DAC) have also been tested either alone or in combination with DLI in the post-transplant period. This review summarizes the current knowledge about the use of these two HMA as pre-emptive, salvage or consolidation therapy mostly retrieved from retrospective studies but also from a few prospective trials. Within this review, we also comment on some practical issues such as optimal dose and schedule, the choice of HMA candidates and the role of additional cellular interventions. Finally, we also give an overview on the assumed mode of actions, ongoing research, clinical studies and potential combination partners aiming to improve this treatment approach. PMID:28066786

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Related Hematopoietic Stem Cell Transplantation (HSCT) for Genetic Diseases of Blood Cells

    Science.gov (United States)

    2016-05-11

    Stem Cell Transplantation; Bone Marrow Transplantation; Peripheral Blood Stem Cell Transplantation; Allogeneic Transplantation,; Genetic Diseases; Thalassemia; Pediatrics; Diamond-Blackfan Anemia; Combined Immune Deficiency; Wiskott-Aldrich Syndrome; Chronic Granulomatous Disease; X-linked Lymphoproliferative Disease; Metabolic Diseases

  8. Hematopoietic stem cell transplantation for infantile osteopetrosis

    NARCIS (Netherlands)

    Orchard, Paul J.; Fasth, Anders L.; Le Rademacher, Jennifer L.; He, Wensheng; Boelens, Jaap Jan; Horwitz, Edwin M.; Al-Seraihy, Amal; Ayas, Mouhab; Bonfim, Carmem M.; Boulad, Farid; Lund, Troy; Buchbinder, David K.; Kapoor, Neena; OBrien, Tracey A.; Perez, Miguel A Diaz; Veys, Paul A.; Eapen, Mary

    2015-01-01

    We report the international experience in outcomes after related and unrelated hematopoietic transplantation for infantile osteopetrosis in 193 patients. Thirty-four percent of transplants used grafts from HLA-matched siblings, 13% from HLA-mismatched relatives, 12% from HLA-matched, and 41% from HL

  9. 氟达拉滨替代环磷酰胺的清髓性预处理化疗联合异基因造血干细胞移植治疗急性白血病的对照研究%Control study of fludarabine instead of cyclophosphamide in modified busulfan-cyclophosphamide as a myeloablative conditioning regimen for allogeneic hematopoietic stem cell transplantation for treatment of acute leukemia

    Institute of Scientific and Technical Information of China (English)

    胡凯; 王继军; 田磊; 万伟; 赵伟; 李其辉; 克晓燕

    2014-01-01

    目的 探讨氟达拉滨替代改良BuCy方案中环磷酰胺的预处理方案在异基因造血干细胞移植中的安全性及有效性.方法 对45例急性白血病患者进行异基因造血干细胞移植,其中23例采用改良BuCy预处理化疗,22例采用BuFlu方案(氟达拉滨每天40 mg/m2,用5d,来替代改良BuCy方案中的环磷酰胺)进行预处理化疗.移植均采用外周血造血干细胞移植.移植后观察比较两组预处理方案相关不良反应、植入、移植物抗宿主病(GVHD)、感染发生和长期随访下的无病生存情况.结果 除改良BuCy组1例患者死于预处理后脑出血,其余患者均获得成功植入.两组患者预处理不良反应发生率差异无统计学意义(P>0.05);BuFlu组患者病毒感染较改良BuCy组高(P=0.009),而Ⅲ~Ⅳ度急性GVHD发生率较低[26.1%(6/23)比4.5%(1/22),P=0.046].中位随访41个月,改良BuCy组非复发死亡4例(17.4%),BuFlu组非复发死亡2例(9.1%)(P=0.665).两组复发率分别为30.3%(7/23)和40.9%(9/22)(P=0.474);5年总生存率分别为(55.1±l 1.9)%和(61.4±10.8)%(P=0.659),无事件生存率分别为(44.5±12.1)%和(22.1±12.3)%(P=0.747).结论 氟达拉滨替代改良BuCy方案中环磷酰胺的预处理化疗耐受性较好,严重GVHD发生率低,总生存率无明显差异.应用时应注意移植中感染及复发的风险.%Objective To evaluate the fludarabine instead of cyclophosphamide in modified busulfancyclophosphamide (mBuCy) regimen as a new myeloablative conditioning regimen for the treatment of acute leukemia patients receiving allogeneic hematopoietic stem cell transplantation (HSCT).Methods The clinic data of 45 acute leukemia patients undergoing allogeneic HSCT were analyzed.Among them,23 patients received mBuCy as conditioning regimen and 22 patients received BuFlu regimen (fludarabine 40 mg·m-2·d-1 for 5 days,instead of cyclophosphamide in mBuCy).Hematopietic engraftment,regimen-related toxicity (RRT

  10. CD34-positive cells and their subpopulations characterized by flow cytometry analyses on the bone marrow of healthy allogenic donors

    Directory of Open Access Journals (Sweden)

    Jerusa Martins Carvalho

    Full Text Available CONTEXT AND OBJECTIVE: Counting and separating hematopoietic stem cells from different sources has importance for research and clinical assays. Our aims here were to characterize and quantify hematopoietic cell populations in marrow donors and to evaluate CD34 expression and relate this to engraftment. DESIGN AND SETTING: Cross-sectional study on hematopoietic stem cell assays, using flow cytometry on donor bone marrow samples, for allogenic transplantation patients at two hospitals in São Paulo. METHODS: Immunophenotyping of marrow cells was performed in accordance with positive findings of CD34FITC, CD117PE, CD38PE, CD7FITC, CD33PE, CD10FITC, CD19PE, CD14FITC, CD13PE, CD11cPE, CD15FITIC, CD22PE, CD61FITC and CD56PE monoclonal antibodies in CD45PerCP+ cells, searching for differentiation and maturation regions. CD34+ sorting cells were analyzed for CD38 and CD117. Rh-123 retention was done before and after sorting. Antigen expression and CD34+ cells were correlated with engraftment. RESULTS: In region R1, 0.1% to 2.8% of cells were CD34+/CD45+ and 1.1%, CD34+/CD45-. The main coexpressions of CD45+ cells were CD38, CD22, CD19 and CD56 in R2 and CD33, CD11c, CD14, CD15 and CD61 in R3 and R4. After sorting, 2.2x10(6 CD34+ cells were equivalent to 4.9% of total cells. Coexpression of CD34+/CD38+ and CD34+/CD117+ occurred in 94.9% and 82% of events, respectively. There was a positive relationship between CD34+ cells and engraftment. More than 80% of marrow cells expressed high Rh-123. CD34+ cell sorting showed that cells in regions of more differentiated lineages retained Rh-123 more intensively than in primitive lineage regions. CONCLUSION: We advocate that true stem cells are CD34+/CD45-/CD38-/low-Rh-123 accumulations.

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

    Directory of Open Access Journals (Sweden)

    Tereza Martinu

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

  12. The Genetic Landscape of Hematopoietic Stem Cell Frequency in Mice

    Directory of Open Access Journals (Sweden)

    Xiaoying Zhou

    2015-07-01

    Full Text Available Prior efforts to identify regulators of hematopoietic stem cell physiology have relied mainly on candidate gene approaches with genetically modified mice. Here we used a genome-wide association study (GWAS strategy with the hybrid mouse diversity panel to identify the genetic determinants of hematopoietic stem/progenitor cell (HSPC frequency. Among 108 strains, we observed ∼120- to 300-fold variation in three HSPC populations. A GWAS analysis identified several loci that were significantly associated with HSPC frequency, including a locus on chromosome 5 harboring the homeodomain-only protein gene (Hopx. Hopx previously had been implicated in cardiac development but was not known to influence HSPC biology. Analysis of the HSPC pool in Hopx−/− mice demonstrated significantly reduced cell frequencies and impaired engraftment in competitive repopulation assays, thus providing functional validation of this positional candidate gene. These results demonstrate the power of GWAS in mice to identify genetic determinants of the hematopoietic system.

  13. Successful treatment of congenital erythropoietic porphyria using matched unrelated hematopoietic stem cell transplantation.

    Science.gov (United States)

    Martinez Peinado, Carmen; Díaz de Heredia, Cristina; To-Figueras, Jordi; Arias-Santiago, Salvador; Nogueras, Paloma; Elorza, Izaskun; Olivé, Teresa; Bádenas, Célia; Moreno, M José; Tercedor, Jesús; Herrero, Carmen

    2013-01-01

    Congenital erythropoietic porphyria (CEP), or Günther's disease, is an inborn error of metabolism produced by a deficiency of uroporphyrinogen III synthase (UROS), the fourth enzyme of the heme biosynthesis pathway. This enzymatic defect induces the accumulation of isomer I porphyrins in erythrocytes, skin, and tissues, producing various clinical manifestations. Severe cases are characterized by extreme photosensitivity, causing scarring and mutilations, and by hemolytic anemia, reducing life expectancy. CEP is caused by mutations in the UROS gene, and one of the most severe forms of the disease is associated with a cysteine to arginine substitution at residue 73 of the protein (C73R). CEP has been successfully treated only by the transplantation of hematopoietic precursors. We report the case of a male infant with severe postdelivery symptoms diagnosed with CEP and found to be homozygous for the C73R mutation. He underwent successful allogeneic bone marrow transplantation from a matched unrelated donor at 7 months of age. The hemolytic anemia was corrected and the porphyrin overproduction was significantly reduced. The patient remained asymptomatic after 1 year. This new case confirms that patients with severe CEP can benefit from early postnatal hematopoietic stem cell transplantation.

  14. Tacrolimus versus Cyclosporine after Hematopoietic Cell Transplantation for Acquired Aplastic Anemia.

    Science.gov (United States)

    Inamoto, Yoshihiro; Flowers, Mary E D; Wang, Tao; Urbano-Ispizua, Alvaro; Hemmer, Michael T; Cutler, Corey S; Couriel, Daniel R; Alousi, Amin M; Antin, Joseph H; Gale, Robert Peter; Gupta, Vikas; Hamilton, Betty K; Kharfan-Dabaja, Mohamed A; Marks, David I; Ringdén, Olle T H; Socié, Gérard; Solh, Melhem M; Akpek, Görgün; Cairo, Mitchell S; Chao, Nelson J; Hayashi, Robert J; Nishihori, Taiga; Reshef, Ran; Saad, Ayman; Shah, Ami; Teshima, Takanori; Tallman, Martin S; Wirk, Baldeep; Spellman, Stephen R; Arora, Mukta; Martin, Paul J

    2015-10-01

    Combinations of cyclosporine (CSP) with methotrexate (MTX) have been widely used for immunosuppression after allogeneic transplantation for acquired aplastic anemia. We compared outcomes with tacrolimus (TAC)+MTX versus CSP+MTX after transplantation from HLA-identical siblings (SIB) or unrelated donors (URD) in a retrospective cohort of 949 patients with severe aplastic anemia. Study endpoints included hematopoietic recovery, graft failure, acute graft-versus-host disease (GVHD), chronic GVHD, and mortality. TAC+MTX was used more frequently in older patients and, in recent years, in both SIB and URD groups. In multivariate analysis, TAC+MTX was associated with a lower risk of mortality in URD recipients and with slightly earlier absolute neutrophil count recovery in SIB recipients. Other outcomes did not differ statistically between the 2 regimens. No firm conclusions were reached regarding the relative merits of TAC+MTX versus CSP+MTX after hematopoietic cell transplantation for acquired aplastic anemia. Prospective studies would be needed to determine whether the use of TAC+MTX is associated with lower risk of mortality in URD recipients with acquired aplastic anemia.

  15. Dynamic changes in mouse hematopoietic stem cell numbers during aging

    NARCIS (Netherlands)

    de Haan, G; Van Zant, G

    1999-01-01

    To address the fundamental question of whether or not stem cell populations age, we performed quantitative measurements of the cycling status and frequency of hematopoietic stem cells in long-lived C57BL/6 (B6) and short-lived DBA/2 (DBA) mice at different developmental and aging stages. The frequen

  16. Hematopoietic development from human induced pluripotent stem cells.

    Science.gov (United States)

    Lengerke, Claudia; Grauer, Matthias; Niebuhr, Nina I; Riedt, Tamara; Kanz, Lothar; Park, In-Hyun; Daley, George Q

    2009-09-01

    A decade of research on human embryonic stem cells (ESC) has paved the way for the discovery of alternative approaches to generating pluripotent stem cells. Combinatorial overexpression of a limited number of proteins linked to pluripotency in ESC was recently found to reprogram differentiated somatic cells back to a pluripotent state, enabling the derivation of isogenic (patient-specific) pluripotent stem cell lines. Current research is focusing on improving reprogramming protocols (e.g., circumventing the use of retroviral technology and oncoproteins), and on methods for differentiation into transplantable tissues of interest. In mouse ESC, we have previously shown that the embryonic morphogens BMP4 and Wnt3a direct blood formation via activation of Cdx and Hox genes. Ectopic expression of Cdx4 and HoxB4 enables the generation of mouse ESC-derived hematopoietic stem cells (HSC) capable of multilineage reconstitution of lethally irradiated adult mice. Here, we explore hematopoietic development from human induced pluripotent stem (iPS) cells generated in our laboratory. Our data show robust differentiation of iPS cells to mesoderm and to blood lineages, as shown by generation of CD34(+)CD45(+) cells, hematopoietic colony activity, and gene expression data, and suggest conservation of blood patterning pathways between mouse and human hematopoietic development.

  17. Primary Immunodeficiency Diseases and Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Ayse Ozkan

    2014-02-01

    Full Text Available Hematopoietic stem cell transplantation (HSCT is the only curative therapy for primary immunodeficiency diseases. Early diagnosis, including prenatally, and early transplantation improve HSCT outcomes. Survival rates improve with advances in the methods of preparing hosts and donor cells, and in supportive and conditioning regimes.

  18. T-cell receptor excision circle levels after allogeneic stem cell transplantation are predictive of relapse in patients with acute myeloid leukemia and myelodysplastic syndrome.

    Science.gov (United States)

    Uzunel, Mehmet; Sairafi, Darius; Remberger, Mats; Mattsson, Jonas; Uhlin, Michael

    2014-07-15

    In this retrospective study, 209 patients with malignant disease were analyzed for levels of T-cell receptor excision circles (TRECs) for the first 24 months after allogeneic stem cell transplantation. CD3(+) cells were separated by direct antibody-coupled magnetic beads, followed by DNA extraction according to a standard protocol. The δRec-ψJα signal joint TREC was measured with real-time quantitative PCR. Patients were grouped based on malignant disease: chronic myeloid leukemia, chronic lymphatic leukemia, acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), and myelodysplastic syndrome (MDS). Patients were further subdivided based on TREC levels below (low-TREC) or above (high-TREC) median at each time point. TREC levels were then correlated to relapse incidence and relapse-free survival (RFS). For patients with AML, low TREC levels 2 months post-transplantation were correlated to high relapse incidence at 5 years (Pleukemia, high TREC levels were correlated with improved RFS (Pafter allogeneic hematopoietic stem cell transplantation.

  19. Lack of autophagy in the hematopoietic system leads to loss of hematopoietic stem cell function and dysregulated myeloid proliferation.

    Science.gov (United States)

    Mortensen, Monika; Watson, Alexander Scarth; Simon, Anna Katharina

    2011-09-01

    The regulated lysosomal degradation pathway of autophagy prevents cellular damage and thus protects from malignant transformation. Autophagy is also required for the maturation of various hematopoietic lineages, namely the erythroid and lymphoid ones, yet its role in adult hematopoietic stem cells (HSCs) remained unexplored. While normal HSCs sustain life-long hematopoiesis, malignant transformation of HSCs or early progenitors leads to leukemia. Mechanisms protecting HSCs from cellular damage are therefore essential to prevent hematopoietic malignancies. By conditionally deleting the essential autophagy gene Atg7 in the hematopoietic system, we found that autophagy is required for the maintenance of true HSCs and therefore also of downstream hematopoietic progenitors. Loss of autophagy in HSCs leads to the expansion of a progenitor cell population in the bone marrow, giving rise to a severe, invasive myeloproliferation, which strongly resembles human acute myeloid leukemia (AML).

  20. Mesenchymal stromal cells and hematopoietic stem cell transplantation.

    Science.gov (United States)

    Bernardo, Maria Ester; Fibbe, Willem E

    2015-12-01

    Mesenchymal stromal cells (MSCs) comprise a heterogeneous population of multipotent cells that can be isolated from various human tissues and culture-expanded ex vivo for clinical use. Due to their immunoregulatory properties and their ability to secrete growth factors, MSCs play a key role in the regulation of hematopoiesis and in the modulation of immune responses against allo- and autoantigens. In light of these properties, MSCs have been employed in clinical trials in the context of hematopoietic stem cell transplantation (HSCT) to facilitate engraftment of hematopoietic stem cells (HSCs) and to prevent graft failure, as well as to treat steroid-resistant acute graft-versus-host disease (GvHD). The available clinical evidence derived from these studies indicates that MSC administration is safe. Moreover, promising preliminary results in terms of efficacy have been reported in some clinical trials, especially in the treatment of acute GvHD. In this review we critically discuss recent advances in MSC therapy by reporting on the most relevant studies in the field of HSCT.

  1. [Endothelial origin for hematopoietic stem cells: a visual proof].

    Science.gov (United States)

    Boisset, Jean-Charles; Robin, Catherine

    2011-10-01

    Hematopoietic stem cells (HSC) are the source of all blood cell types produced during the entire life of an organism. They appear during embryonic development, where they will transit through different successive hematopoietic organs, before to finally colonize the bone marrow. Nowadays, the precise origin of HSC remains a matter of controversy. Different HSC precursor candidates, located in different anatomical sites, have been proposed. Here, we summarize and discuss the different theories in light of the recent articles, especially those using in vivo confocal microscopy technology.

  2. Sibling cord blood donor program for hematopoietic cell transplantation: the 20-year experience in the Rome Cord Blood Bank.

    Science.gov (United States)

    Screnci, Maria; Murgi, Emilia; Valle, Veronica; Tamburini, Anna; Pellegrini, Maria Grazia; Strano, Sabrina; Corona, Francesca; Ambrogi, Eleonora Barbacci; Girelli, Gabriella

    2016-03-01

    Umbilical cord blood (UCB) represents a source of hematopoietic stem cells for patients lacking a suitably matched and readily available related or unrelated stem cell donor. As UCB transplantation from compatible sibling provides good results in children therefore directed sibling UCB collection and banking is indicated in family who already have a child with a disease potentially treatable with an allogeneic hematopoietic stem cell transplantation. Particularly, related UCB collection is recommended when the patients urgently need a transplantation. To provide access to all patients in need, we developed a "Sibling cord blood donor program for hematopoietic cell transplantation". Here we report results of this project started 20years ago. To date, in this study a total of 194 families were enrolled, a total of 204 UCB samples were successfully collected and 15 pediatric patients have been transplanted. Recently, some authors have suggested novel role for UCB other than in the transplantation setting. Therefore, future studies in the immunotherapy and regenerative medicine areas could expand indication for sibling directed UCB collection.

  3. Scripts for TRUMP data analyses. Part II (HLA-related data): statistical analyses specific for hematopoietic stem cell transplantation.

    Science.gov (United States)

    Kanda, Junya

    2016-01-01

    The Transplant Registry Unified Management Program (TRUMP) made it possible for members of the Japan Society for Hematopoietic Cell Transplantation (JSHCT) to analyze large sets of national registry data on autologous and allogeneic hematopoietic stem cell transplantation. However, as the processes used to collect transplantation information are complex and differed over time, the background of these processes should be understood when using TRUMP data. Previously, information on the HLA locus of patients and donors had been collected using a questionnaire-based free-description method, resulting in some input errors. To correct minor but significant errors and provide accurate HLA matching data, the use of a Stata or EZR/R script offered by the JSHCT is strongly recommended when analyzing HLA data in the TRUMP dataset. The HLA mismatch direction, mismatch counting method, and different impacts of HLA mismatches by stem cell source are other important factors in the analysis of HLA data. Additionally, researchers should understand the statistical analyses specific for hematopoietic stem cell transplantation, such as competing risk, landmark analysis, and time-dependent analysis, to correctly analyze transplant data. The data center of the JSHCT can be contacted if statistical assistance is required.

  4. DNA Damage Response in Hematopoietic Stem Cell Ageing

    Institute of Scientific and Technical Information of China (English)

    Tangliang Li; Zhong-Wei Zhou; Zhenyu Ju; Zhao-Qi Wang

    2016-01-01

    Maintenance of tissue-specific stem cells is vital for organ homeostasis and organismal longevity. Hematopoietic stem cells (HSCs) are the most primitive cell type in the hematopoietic system. They divide asymmetrically and give rise to daughter cells with HSC identity (self-renewal) and progenitor progenies (differentiation), which further proliferate and differentiate into full hematopoietic lineages. Mammalian ageing process is accompanied with abnormalities in the HSC self-renewal and differentiation. Transcriptional changes and epigenetic modulations have been implicated as the key regulators in HSC ageing process. The DNA damage response (DDR) in the cells involves an orchestrated signaling pathway, consisting of cell cycle regulation, cell death and senescence, transcriptional regulation, as well as chromatin remodeling. Recent studies employ-ing DNA repair-deficient mouse models indicate that DDR could intrinsically and extrinsically reg-ulate HSC maintenance and play important roles in tissue homeostasis of the hematopoietic system. In this review, we summarize the current understanding of how the DDR determines the HSC fates and finally contributes to organismal ageing.

  5. Hematopoietic progenitor cell mobilization for autologous transplantation - a literature review

    Directory of Open Access Journals (Sweden)

    Marco Aurélio Salvino

    2016-02-01

    Full Text Available ABSTRACT The use of high-dose chemotherapy with autologous support of hematopoietic progenitor cells is an effective strategy to treat various hematologic neoplasms, such as non-Hodgkin lymphomas and multiple myeloma. Mobilized peripheral blood progenitor cells are the main source of support for autologous transplants, and collection of an adequate number of hematopoietic progenitor cells is a critical step in the autologous transplant procedure. Traditional strategies, based on the use of growth factors with or without chemotherapy, have limitations even when remobilizations are performed. Granulocyte colony-stimulating factor is the most widely used agent for progenitor cell mobilization. The association of plerixafor, a C-X-C Chemokine receptor type 4 (CXCR4 inhibitor, to granulocyte colony stimulating factor generates rapid mobilization of hematopoietic progenitor cells. A literature review was performed of randomized studies comparing different mobilization schemes in the treatment of multiple myeloma and lymphomas to analyze their limitations and effectiveness in hematopoietic progenitor cell mobilization for autologous transplant. This analysis showed that the addition of plerixafor to granulocyte colony stimulating factor is well tolerated and results in a greater proportion of patients with non-Hodgkin lymphomas or multiple myeloma reaching optimal CD34+ cell collections with a smaller number of apheresis compared the use of granulocyte colony stimulating factor alone.

  6. DNA Damage Response in Hematopoietic Stem Cell Ageing.

    Science.gov (United States)

    Li, Tangliang; Zhou, Zhong-Wei; Ju, Zhenyu; Wang, Zhao-Qi

    2016-06-01

    Maintenance of tissue-specific stem cells is vital for organ homeostasis and organismal longevity. Hematopoietic stem cells (HSCs) are the most primitive cell type in the hematopoietic system. They divide asymmetrically and give rise to daughter cells with HSC identity (self-renewal) and progenitor progenies (differentiation), which further proliferate and differentiate into full hematopoietic lineages. Mammalian ageing process is accompanied with abnormalities in the HSC self-renewal and differentiation. Transcriptional changes and epigenetic modulations have been implicated as the key regulators in HSC ageing process. The DNA damage response (DDR) in the cells involves an orchestrated signaling pathway, consisting of cell cycle regulation, cell death and senescence, transcriptional regulation, as well as chromatin remodeling. Recent studies employing DNA repair-deficient mouse models indicate that DDR could intrinsically and extrinsically regulate HSC maintenance and play important roles in tissue homeostasis of the hematopoietic system. In this review, we summarize the current understanding of how the DDR determines the HSC fates and finally contributes to organismal ageing.

  7. DNA Damage Response in Hematopoietic Stem Cell Ageing

    Directory of Open Access Journals (Sweden)

    Tangliang Li

    2016-06-01

    Full Text Available Maintenance of tissue-specific stem cells is vital for organ homeostasis and organismal longevity. Hematopoietic stem cells (HSCs are the most primitive cell type in the hematopoietic system. They divide asymmetrically and give rise to daughter cells with HSC identity (self-renewal and progenitor progenies (differentiation, which further proliferate and differentiate into full hematopoietic lineages. Mammalian ageing process is accompanied with abnormalities in the HSC self-renewal and differentiation. Transcriptional changes and epigenetic modulations have been implicated as the key regulators in HSC ageing process. The DNA damage response (DDR in the cells involves an orchestrated signaling pathway, consisting of cell cycle regulation, cell death and senescence, transcriptional regulation, as well as chromatin remodeling. Recent studies employing DNA repair-deficient mouse models indicate that DDR could intrinsically and extrinsically regulate HSC maintenance and play important roles in tissue homeostasis of the hematopoietic system. In this review, we summarize the current understanding of how the DDR determines the HSC fates and finally contributes to organismal ageing.

  8. Donor NK cell licensing in control of malignancy in hematopoietic stem cell transplant recipients.

    Science.gov (United States)

    Nowak, Jacek; Kościńska, Katarzyna; Mika-Witkowska, Renata; Rogatko-Koroś, Marta; Mizia, Sylwia; Jaskuła, Emilia; Polak, Małgorzata; Mordak-Domagała, Monika; Lange, Janusz; Gronkowska, Anna; Jędrzejczak, Wiesław Wiktor; Kyrcz-Krzemień, Sławomira; Markiewicz, Mirosław; Dzierżak-Mietła, Monika; Tomaszewska, Agnieszka; Nasiłowska-Adamska, Barbara; Szczepiński, Andrzej; Hałaburda, Kazimierz; Hellmann, Andrzej; Komarnicki, Mieczysław; Gil, Lidia; Czyż, Anna; Wachowiak, Jacek; Barańska, Małgorzata; Kowalczyk, Jerzy; Drabko, Katarzyna; Goździk, Jolanta; Wysoczańska, Barbara; Bogunia-Kubik, Katarzyna; Graczyk-Pol, Elżbieta; Witkowska, Agnieszka; Marosz-Rudnicka, Anna; Nestorowicz, Klaudia; Dziopa, Joanna; Szlendak, Urszula; Warzocha, Krzysztof; Lange, And Andrzej

    2014-10-01

    Among cancers treated with allogeneic hematopoietic stem-cell transplantation (HSCT), some are sensitive to natural killer (NK) cell reactivity, described as the "missing self" recognition effect. However, this model disregarded the NK cell licensing effect, which highly increases the NK cell reactivity against tumor and is dependent on the coexpression of inhibitory killer cell immunoglobulin-like receptor (iKIR) and its corresponding HLA Class I ligand. We assessed clinical data, HLA and donor iKIR genotyping in 283 patients with myelo- and lymphoproliferative malignancies who underwent HSCT from unrelated donors. We found dramatically reduced overall survival (OS), progression free survival (PFS), and time to progression (TTP) among patients with malignant diseases with the lack of HLA ligand cognate with this iKIR involved in NK cell licensing in corresponding donor (events 83.3% vs. 39.8%, P = 0.0010; 91.6% vs. 47.7%, P = 0.00010; and 30.0% vs. 17.3%, P = 0.013, for OS, PFS, and TTP, respectively). The extremely adverse PFS have withstand the correction when patient group was restricted to HLA mismatched donor-recipient pairs. The incidence of aGvHD was comparable in two groups of patients. In malignant patients after HSCT the missing HLA ligand for iKIR involved in NK cell licensing in corresponding donor ("missing licensing proof") induced extremely adverse survival of the patients due to the progression of malignancy and not to the aGvHD. Avoiding the selection of HSCT donors with the "missing licensing proof" in the malignant patient is strongly advisable.

  9. Allogeneic and autologous mode of stem cell transplantation in regenerative medicine: which way to go?

    Science.gov (United States)

    Mamidi, Murali Krishna; Dutta, Susmita; Bhonde, Ramesh; Das, Anjan Kumar; Pal, Rajarshi

    2014-12-01

    Stem cell transplantation is a generic term covering different techniques. However there is argument over the pros and cons of autologous and allogeneic transplants of mesenchymal stem cells (MSCs) for regenerative therapy. Given that the MSCs have already been proven to be safe in patients, we hypothesize that allogeneic transplantation could be more effective and cost-effective as compared to autologous transplantation specifically in older subjects who are the likely victims of degenerative diseases. This analysis is based on the scientific logic that allogeneic stem cells extracted in large numbers from young and healthy donors could be physiologically, metabolically and genetically more stable. Therefore stem cells from young donors may be expected to exhibit higher vigor in secreting trophic factors leading to activation of host tissue-specific stem cells and also be more efficient in remodeling the micro-environmental niche of damaged tissue.

  10. Haemopedia: An Expression Atlas of Murine Hematopoietic Cells

    Directory of Open Access Journals (Sweden)

    Carolyn A. de Graaf

    2016-09-01

    Full Text Available Hematopoiesis is a multistage process involving the differentiation of stem and progenitor cells into distinct mature cell lineages. Here we present Haemopedia, an atlas of murine gene-expression data containing 54 hematopoietic cell types, covering all the mature lineages in hematopoiesis. We include rare cell populations such as eosinophils, mast cells, basophils, and megakaryocytes, and a broad collection of progenitor and stem cells. We show that lineage branching and maturation during hematopoiesis can be reconstructed using the expression patterns of small sets of genes. We also have identified genes with enriched expression in each of the mature blood cell lineages, many of which show conserved lineage-enriched expression in human hematopoiesis. We have created an online web portal called Haemosphere to make analyses of Haemopedia and other blood cell transcriptional datasets easier. This resource provides simple tools to interrogate gene-expression-based relationships between hematopoietic cell types and genes of interest.

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    Full Text Available Pol.Bld.50.AllAg.Hematopoietic_Stem_Cells hg19 RNA polymerase Blood Hematopoietic S...tem Cells SRX005153,SRX038919,SRX038920 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Bld.50.AllAg.Hematopoietic_Stem_Cells.bed ...

  6. File list: DNS.Bld.05.AllAg.Hematopoietic_Stem_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  7. File list: Unc.Bld.50.AllAg.Hematopoietic_Stem_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  8. File list: Unc.Bld.20.AllAg.Hematopoietic_Stem_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  9. File list: Pol.Bld.05.AllAg.Hematopoietic_Stem_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  10. File list: Pol.Bld.50.AllAg.Hematopoietic_Stem_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.50.AllAg.Hematopoietic_Stem_Cells mm9 RNA polymerase Blood Hematopoietic St...em Cells SRX180164 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Bld.50.AllAg.Hematopoietic_Stem_Cells.bed ...

  11. Current status and development of hematopoietic stem cell transplantation in China: a report from Chinese Hematopoietic Stem Cell Transplantation Register Group

    Institute of Scientific and Technical Information of China (English)

    XU Lan-ping; HUANG Xiao-jun

    2011-01-01

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has three decades history in China. During these periods,the number of HSCT has been increasing, donor and stem cell sources were expanded, indication of diseases and patients for HSCT extended. Forty-two HSCT units offered their data 1-6 times from July 2007 to June 2010. The annual increase rates were 8.8% to 10.8%. Matched sibling donor is 41%, mismatched related/haploidentical donor is 24%,unrelated volunteer donor is 16%, and umbilical cord blood is 2%. The indications of major disease entities are acute myeloid leukemia (AML, 35%), acute lymphobastic leukemia (ALL, 25%), chronic myeloid leukemia (CML, 21%), and myelodysplastic syndrome (MDS, 8%). The different opinions on the indication of HSCT were supported by some trials,matched/haploidentical HSCT fit for middle or high risk ALL and AML in first complete remission (CR1), the international prognosis score system (IPSS) - middle-Ⅱ/high risk MDS, CML in advanced stage and so on, when patients have no matched sibling donor. In the Peking University Institute of Hematology, Peking University People's Hospital,haploidentical HSCT has received a comparable result to matched simbling donor HSCT and unrelated matched donor HSCT; we suggest haploidentical donor might be a routine alternative donor for high-risk patents who need an urgent HSCT without matched related donor in special center.

  12. Low-dose decitabine combined with fractional allogeneic hematopoietic stem cell transfusion for treatment of elderly patients with acute myeloid leukemia transformed from myelodysplastic syndrome:a report of 2 cases%小剂量地西他滨联合异基因造血干细胞分次输注治疗老年骨髓增生异常综合征转急性髓性白血病2例报告

    Institute of Scientific and Technical Information of China (English)

    李云双; 陈永升; 聂伟业; 黄琴; 孔祥敬; 尹晓林

    2015-01-01

    Objective To explore the efficay of low-dose decitabine combined with fractional allogeneic hematopoietic stem cell transfusion( micro transplantation) for treatment of elderly patients with acute myeloid leukemia transformed from myelodysplastic syndrome ( MDS-AML) .Methods Two patients diagnosed as MDS-AML were treated with chemotherapy regimen of low-dose decitabine or decitabine combined with CAG(cytosine arabinoside+aclacinomycin) and micro transplantation.The donors were children of patients with human leukocyte antigen semi-matched.Peripheral blood stem cells from the donors were mobilized with granulocyte colony-stimulating factor and then collected. Patients transfused PBSC about 36 hours after the chemotherapy finished.The disease status,platelet levels,survival timeand side effects were observed.Re sults Two cases did not achieve complete response.The survival times of Case 1 and Case 2 were 2 months and 4 months respectively. The platelet level in Case 1 increased remarkably after treatment,and reached to the maximal level of 59 ×109/L.No platelet transfusion was observed in Case 1.In Case 2,the interval of platelet transfusion was prolonged,and the patient was gradually independent on platelet transfusions. No graft-versus-host disease occurred in the two patients.Conclusion For elderly patients with MDS-AML,low-dose decitabine combined with micro transplantation can not cure the disease,but can prolong the survival time,increase the level of platelet and improve the quality of life.%目的 观察小剂量地西他滨联合异基因造血干细胞分次输注(微移植)治疗老年骨髓增生异常综合征转急性髓性白血病( MDS-AML)的疗效. 方法 对2例确诊为MDS-AML患者分别予小剂量地西他滨或地西他滨联合CAG方案(阿糖胞苷+阿克拉霉素)化疗加微移植治疗,供者为人类白细胞抗原半相合的患者子女,采集重组人粒细胞集落刺激因子动员后的供者外周血

  13. Deficiency of GRP94 in the hematopoietic system alters proliferation regulators in hematopoietic stem cells.

    Science.gov (United States)

    Luo, Biquan; Tseng, Chun-Chih; Adams, Gregor B; Lee, Amy S

    2013-12-01

    We have previously reported that acute inducible knockout of the endoplasmic reticulum chaperone GRP94 led to an expansion of the hematopoietic stem and progenitor cell pool. Here, we investigated the effectors and mechanisms for this phenomenon. We observed an increase in AKT activation in freshly isolated GRP94-null HSC-enriched Lin(-) Sca-1(+) c-Kit(+) (LSK) cells, corresponding with higher production of PI(3,4,5)P3, indicative of PI3K activation. Treatment of GRP94-null LSK cells with the AKT inhibitor MK2206 compromised cell expansion, suggesting a causal relationship between elevated AKT activation and increased proliferation in GRP94-null HSCs. Microarray analysis demonstrated a 97% reduction in the expression of the hematopoietic cell cycle regulator Ms4a3 in the GRP94-null LSK cells, and real-time quantitative PCR confirmed this down-regulation in the LSK cells but not in the total bone marrow (BM). A further examination comparing freshly isolated BM LSK cells with spleen LSK cells, as well as BM LSK cells cultured in vitro, revealed specific