Allogeneic stem cell transplant (ASCT) with HLA matched donors is increasingly used for older patients with AML/MDS. It remains unclear if haploidentical transplantation (haploSCT) is a suitable option for older patients with this disease. We analyzed 43 patients with AML/MDS (median age 61 years) who underwent a haploSCT at our institution. Read More
Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan; Division of Hematology, Department of Medicine, Jichi Medical University, Shimotsuke, Japan. Electronic address:
The optimal conditioning regimen for elderly patients in allogeneic hematopoietic stem cell transplantation (allo-HCT) remains unclear. We retrospectively analyzed 1607 patients aged 50 years or older with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or myelodysplastic syndrome (MDS) who underwent allo-HCT using fludarabine/busulfan (FB) or fludarabine/melphalan (FM) between 2007 and 2014. We compared the clinical outcomes among FB2 (busulfan at 6. Read More
Department of Learning Health Sciences, University of Michigan School of Medicine, Ann Arbor, MI.
One of the significant modifications to the Common Rule is the requirement that prospective participants are given information sufficient for a "reasonable person". However, there is limited research on what types of information patients, caregivers, and providers consider "key information". Although certain aspects of informed consent (IC) may be considered standard, considering individualized needs and preferences of patients is necessary for patient-centered consent. Read More
Mixed donor chimerism following hematopoietic cell transplantation for sickle cell disease (SCD) can result in resolution of disease symptoms but symptoms recur when donor chimerism is critically low. The relationship between chimerism, hemoglobin S (HbS) level and symptomatic disease was correlated retrospectively in 95 patients who had chimerism reports available at day 100, 1 and 2 years after transplantation. Recurrent disease was defined as recurrence of vaso-occlusive crises, acute chest syndrome, or stroke, and/or HbS level >50%. Read More
Conditioning regimens excluding total body irradiation (TBI) following by hematopoietic stem cell transplantation (HSCT) have been shown to be feasible in treating acute lymphoblastic leukemia (ALL). However, it is commonly believed that for extramedullary involvements of ALL in sanctuary sites such as central nervous system (CNS), TBI shall not be abandoned. In this study, the outcomes of pediatric ALL patients with (CNS(+)) and without CNS involvement (CNS(-)) treated with a TBI-free allogeneic HSCT were retrospectively compared. Read More
Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA; Department of Medicine, Weill Cornell Medical College, New York, NY, 10065, USA.
The late adverse events in long-term survivors after myeloablative conditioned allogeneic hematopoietic cell transplantation with ex-vivo CD34+ selection are not well characterized. Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, we assessed all grade ≥ 3 toxicities from the start conditioning to date of death, relapse, or last contact in 131 patients that survived > 1-year post-transplantation, identifying 285 individual toxicities among 17 organ-based toxicity groups. Read More
Some patients with veno-occlusive disease (VOD) have multi-organ dysfunction (MOD) and multiple teams are involved in their daily care in the pediatric intensive care units (PICU). Cardio-respiratory dysfunction is critical in these patients as it needs immediate action. Whether to use non-invasive or invasive ventilation strategy may be a difficult decision in the setting of mucositis or other comorbidities in patients with VOD. Read More
Center for Cellular Therapies and Research, AABB, Bethesda, MD.
Hematopoietic cell transplantation (HCT) using an HLA-identical sibling donor offers a very high likelihood of cure with good outcomes for patients with sickle cell disease (SCD), and alternative donor HCT for SCD is an area of active clinical research. HCT is thus potentially an option for a growing number of patients with SCD, but this expanded use of HCT has raised several ethical questions. Specifically, who is eligible for HCT, both in terms of disease severity and psychosocial factors? Should affected children with matched sibling donors be transplanted only when they have declared themselves as having significant symptomatology? In regards to donors, special ethical challenges include the use of pre-implantation genetic diagnosis to conceive an HLA-identical sibling. Read More
Abnormal pulmonary function is prevalent in survivors of allogeneic hematopoietic cell transplantation. Post-transplant recovery of pulmonary function, and its effect on survival in children is not known. This is a retrospective cohort study of 308 children followed for 10 years after transplantation at a single institution. Read More
Biol Blood Marrow Transplant 2017 Aug 30. Epub 2017 Aug 30.
Department of Medicine, Boston University School of Medicine and Boston Medical Center, USA; Amyloidosis Center and Section of Hematology and Oncology, Boston University School of Medicine and Boston Medical Center, USA. Electronic address:
The kidney is the most common organ affected by immunoglobulin light-chain (AL) amyloidosis and monoclonal immunoglobulin deposition disease (MIDD), often leading to end stage renal disease (ESRD). High-dose melphalan and stem cell transplantation (HDM/SCT) is effective for selected patients with AL amyloidosis, with high rates of complete hematologic responses and potential for improvement in organ dysfunction. Data on tolerability and response to HDM/SCT in patients with ESRD due to AL amyloidosis and MIDD are limited. Read More
Biol Blood Marrow Transplant 2017 Aug 30. Epub 2017 Aug 30.
Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China. Electronic address:
This study aimed at validating the predictive ability of the Center for International Blood and Marrow Transplant Research (CIBMTR) prognostic scoring system on the outcomes of patients with myelodysplastic syndromes (MDS) who had received human leukocyte antigen (HLA)-haploidentical related donor hematopoietic stem cell transplantation (haplo-HSCT). We also tried to propose and validate a more suitable prognostic scoring system. A total of 157 patients with MDS, who received haplo-HSCT, were enrolled. Read More
The composite endpoint GVHD free, relapse free survival (GRFS) has recently been developed as a tool to assess the success of allogeneic HCT and has been incorporated into recent randomized trials of GVHD prophylaxis by the Blood and Marrow Transplant Clinical Trials Network (BMTCTN). As developed, GRFS incorporates 'chronic GVHD requiring systemic immunosuppression' as a measure of clinically significant chronic GVHD (cGVHD). However, the decision to start patients on immunosuppression for chronic GVHD is subjective and physician dependent. Read More
Anti-thymocyte globulin (ATG) is used as prophylaxis against graft-versus-host-disease (GVHD). Current dosing regimens for ATG are empiric, weight-based, and do not account for patient-specific factors. Furthermore, the target of ATG, recipient T cells post-cytotoxic chemotherapy, is not a function of recipient weight. Read More
Since 2000, phase III randomized controlled trials (RCT) investigated the efficacy of rabbit anti-thymocyte globulins (ATG) in patients following allogeneic stem cell transplantation (allo-SCT). However, comparisons of different ATG formulations are lacking. Our aim was to synthesize all efficacy evidence, enabling a comparison of all available formulations of rabbit ATG in the allo-SCT setting. Read More
Adoptive cellular immunotherapy has been shown to be effective in the management of CMV reactivation and disease. It is unknown whether adjuvant dendritic cell vaccination will provide additional benefit in prophylaxis or treatment of CMV in HSCT patients. In this study, we administered prophylactic CMV-peptide specific T cell infusions, followed by 2 doses of intradermal CMV peptide-pulsed dendritic cell (DC) vaccine to 4 HSCT patients. Read More
Biol Blood Marrow Transplant 2017 Aug 28. Epub 2017 Aug 28.
Department of Internal Medicine, (Hematology, Oncology, Palliative Care and Infectious Diseases), Alb-Fils Kliniken, Göppingen, Germany. Electronic address:
We report the results of a single center analysis of a cohort of 39 patients treated between 1997 and 2016 for transplantion-associated thrombotic microangiopathy. We evaluated two subgroups of patients: 24 patients treated between 1997 and 2014 who received conventional therapy and 15 patients who were treated with the complement-inhibiting monoclonal antibody eculizumab between 2014 and 2016. The conventional therapy group was predominantly treated with defibrotide alone or in combination with plasmapheresis or rituximab. Read More
Late graft failure (LGF) without evidence of residual recipient cells is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-SCT) and often requires stem cell infusion from the same donor when the patient fails to respond to conventional therapies. We screened the peripheral blood (PB) of 14 patients who developed donor-type LGF at 2-132 months after allo-SCT for the presence of the markers for immune-mediated bone marrow (BM) failure. Increased glycosylphosphatidyl inositol-anchored protein-deficient (GPI-AP(-)) leukocytes, which accounted for 0. Read More
Bloodstream infections (BSI) are frequent and important infectious complications after hematopoietic cell transplantation (HCT). The aim of this study was to analyze the incidence, risk factors and outcome of pre-engraftment BSI after allogeneic HCT. A retrospective analysis of data from 553 consecutive patients transplanted in years 2010-2016 was performed. Read More
Cell-of-origin (COO) determination has emerged as an important prognostic factor for patients initially diagnosed with diffuse large B cell lymphoma (DLBCL). Specifically, the non-germinal center B cell like (non-GCB) subtype, comprising predominantly of the activated B cell-like (ABC) molecular subtype, has been shown to portend poor prognosis due to its more aggressive nature and resistance to standard CHOP-like chemotherapy compared to the GCB subtype. The recurrent MyD88 L265P mutation, present in 29% of ABC DLBCL, was reported as an independent poor prognostic factor for patients with newly diagnosed DLBCL. Read More
Graft failure (GF) is the most critical life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT) for aplastic anemia, for which a second transplantation would be the only effective treatment. However, optimal transplant procedures have not been established for the second transplantation in this setting. The outcome of 22 patients with aplastic anemia, aged ≥16 years, who underwent umbilical cord blood transplantation for GF after the first HSCT, was retrospectively analyzed using the registry database of the Japan Society for Hematopoietic Cell Transplantation. Read More
Fluid overload (FO) is commonly seen during hospitalization for allogeneic hematopoietic stem-cell transplantation (AHSCT). We hypothesized that FO is associated with transplant outcomes and evaluated this complication in two cohorts of patients and graded based on post-transplant weight gain, symptoms, and need for treatment, and was scored in real time by an independent team. The first cohort (study cohort) underwent haploidentical transplantation for hematologic malignancies (N=145) following a melphalan-based conditioning regimen. Read More
Recovery of myeloid-derived suppressor cells (MDSCs) and its relevance in clinical acute graft-versus-host disease (GVHD) and post-hematopoietic stem cell transplantation (HSCT) infections remain to be fully characterized. We examined the expansion of circulating monocytic (M-) MDSCs and granulocytic (G-) MDSCs at the time of engraftment in 130 patients undergoing allogeneic HSCT (allo-HSCT). The high M-MDSC group had a higher infection rate within 100 days, worse 1-year cumulative incidence of treatment-related mortality (TRM) and 2-year probability of event-free survival (EFS) than the G-MDSC group. Read More
Minor histocompatibility antigen (miHA) mismatches have been related to graft-versus-host disease (GVHD) after allogeneic stem cell transplantation, but this association remains controversial due to the lack of consistency in the results obtained by different groups. The CTLA-4 genotype of the donor has been reported to be relevant in the appearance of acute GVHD. We explored the effect of the donor's CTLA-4 genotype in the incidence of acute GVHD associated with HA-1, HA-8, or H-Y miHA mismatches in a large cohort of 1295 patients receiving an allogeneic transplant from an HLA-identical sibling donor. Read More
Even though hepatic veno-occlusive disease (VOD) is a potentially fatal complication of hematopoietic cell transplantation (HCT), there is paucity of research on the management of associated multiorgan dysfunction. To help provided standardized care for the management of these patients, the HCT Subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators and the Supportive Care Committee of the Pediatric Blood and Marrow Transplant Consortium, collaborated to develop evidence-based consensus guidelines. After conducting an extensive literature search, in part 2 of this series we discuss the management of fluids and electrolytes, renal dysfunction; ascites, pleural effusion, and transfusion and coagulopathy issues in patients with VOD. Read More
The number of patients eligible for allogeneic stem cell transplantation (allo-HSCT) has increased because of improvements in transplantation procedures. Among long-term survivors of allo-HSCT, chronic kidney disease (CKD) is a major cause of morbidity. We retrospectively analyzed the clinical data of 106 consecutive patients with a median age of 43 years (range, 17 to 73) who had undergone allo-HSCT at our institution between January 2001 and September 2009. Read More
Biol Blood Marrow Transplant 2017 Aug 15. Epub 2017 Aug 15.
Division of Hematology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; The Ottawa Hospital Bone Marrow Transplant Programme, University of Ottawa, Ottawa, Ontario, Canada. Electronic address:
Graft-versus-host disease (GVHD) is a leading cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (alloHCT). Prophylactic in vivo T cell depletion with antithymocyte globulin (ATG) has been associated with decreased GVHD rates in many alloHCT settings. Despite decades of clinical study, optimal ATG dosing has not been established. Read More
Biol Blood Marrow Transplant 2017 Aug 14. Epub 2017 Aug 14.
Division of Hematology/Oncology, University of Illinois Hospital & Health Sciences System, Chicago, Illinois; University of Illinois Cancer Center, Chicago, Illinois; University of Illinois Center for Global Health, Chicago, Illinois. Electronic address:
A xenograft model of stem cell rejection was developed by co-transplantating human CD34(+) and allogeneic CD3(+) T cells into NOD-scid ɣ-chain(null) mice. T cells caused graft failure when transplanted at any CD34/CD3 ratio between 1:50 and 1:.1. Read More
Graft-versus-host disease (GVHD) remains one of the major complications after allogeneic hematopoietic stem cell transplantation that is mainly treated with glucocorticoids such as prednisolone. In this study the influence of monocyte subpopulations, prednisolone, and 1α,25-dihydroxyvitamin D3 (1α,25-(OH)2D3) on the induction of a proinflammatory subset of Th17 cells (MDR(+)Th17.1) characterized by CCR6(+)CXCR3(hi)CCR4(lo)CCR10(-)CD161(+) and stable expression of the multidrug resistance protein type 1 (MDR1) was investigated. Read More
Biol Blood Marrow Transplant 2017 Aug 12. Epub 2017 Aug 12.
Department of Pediatrics, Charles-Bruneau Cancer Center, CHU Sainte-Justine Research Center, Montreal, Quebec, Canada; Department of Pediatrics, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada.
Busulfan (Bu) is a key component of conditioning regimens used before hematopoietic stem cell transplantation (SCT) in children. Different predictive methods have been used to calculate the first dose of Bu. To evaluate the necessity of further improvements, we retrospectively analyzed the currently available weight- and age-based guidelines to calculate the first doses in 101 children who underwent allogenic SCT in CHU Sainte-Justine, Montreal, after an intravenous Bu-containing conditioning regimen according to genetic and clinical factors. Read More
High-risk, recurrent, or refractory solid tumors in pediatric, adolescent, and young adult (AYA) patients have an extremely poor prognosis despite current intensive treatment regimens. We piloted an allogeneic bone marrow transplant platform using reduced-intensity conditioning (RIC) and partially HLA-mismatched (haploidentical) related donors for this population of pediatric and AYA solid tumor patients. Sixteen patients received fludarabine, cyclophosphamide, melphalan, and low-dose total body irradiation RIC haploidentical BMT (haploBMT) followed by post-transplantation cyclophosphamide (PTCy), mycophenolate mofetil, and sirolimus. Read More
The European Group for Blood and Marrow Transplantation (EBMT) risk score has been implemented as an important tool to predict patient outcomes after allogeneic hematopoietic stem cell transplantation. However, to our knowledge, this score has never been applied in cases of single umbilical cord blood transplantation (sUCBT). We retrospectively analyzed 207 consecutive patients with acute leukemia who received sUCBT at our center between February 2011 and December 2015. Read More
Infection-related mortality (IRM) is a substantial component of nonrelapse mortality (NRM) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). No scores have been developed to predict IRM before transplantation. Pretransplantation clinical and biochemical data were collected from a study cohort of 607 adult patients undergoing allo-HSCT between January 2009 and February 2017. Read More
Granulocyte transfusions (GTs) are seldom used as a life-saving therapy for neutropenic patients with severe infections. Despite compelling evidence of GT efficacy in retrospective and prospective case series, no study has been successful in demonstrating a definite advantage for recipients in controlled clinical trials. This review critically revises some aspects emerging from past experience that might have weakened the evidence of GT benefits. Read More
Improvements in supportive care have enabled the performance of allogeneic hematopoietic cell transplantation (HCT) in an increasingly older patient population. HCT is associated with neurocognitive impairment, which may be exacerbated in older adults due to the normal neurocognitive decline associated with aging. The goal of this study was to evaluate whether increasing age of allogeneic HCT recipients is associated with worse neurocognitive outcomes over time relative to a matched sample of individuals without cancer. Read More
Autologous hematopoietic stem cell transplantation (auto-HSCT) improves survival in patients with multiple myeloma (MM) and non-Hodgkin lymphoma (NHL). Traditionally, filgrastim (Neupogen; recombinant G-CSF) has been used in as a single agent or in combination with plerixafor for stem cell mobilization for auto-HSCT. In Europe, a biosimilar recombinant G-CSF (Tevagrastim) has been approved for various indications similar to those of reference filgrastim, including stem cell mobilization for auto-HSCT; however, in the United States, tbo-filgrastim (Granix) is registered under the original biological application and is not approved for stem cell mobilization. Read More
Predicting the duration of systemic therapy in patients with chronic graft-versus-host disease (cGVHD) is of critical clinical importance when counseling patients and for treatment planning. cGVHD characteristics associated with this outcome have not been studied in severely affected patients. The National Institutes of Health (NIH) cGVHD scoring provides a standardized set of organ severity measures that could represent clinically useful and reproducible predictive characteristics. Read More
Biol Blood Marrow Transplant 2017 Aug 7. Epub 2017 Aug 7.
Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Ramat-Gan, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Israel; Dr. Pinchas Bornstein Talpiot Medical Leadership Program, Chaim Sheba Medical Center, Ramat-Gan, Israel. Electronic address:
Allogeneic hematopoietic stem cell transplantation is a potentially curative treatment for many hematologic disorders. Maximizing the benefit of transplantation for disease control while minimizing the risk for associated complications remains the field's leading challenge. This challenge has prompted the development of multiple prognostic scoring systems over the last 2 decades. Read More
Recognizing the significant biological and clinical heterogeneity of mature T cell and natural killer (NK)/T cell lymphomas, the American Society for Blood and Marrow Transplantation invited experts to develop clinical practice recommendations related to the role of autologous hematopoietic cell transplantation (auto-HCT) and allogeneic HCT (allo-HCT) for specific histological subtypes. We used the GRADE methodology to aid in moving from evidence to decision making and ultimately to generating final recommendations. Auto-HCT in front-line consolidation is recommended in peripheral T cell lymphoma not otherwise specified (PTCL-NOS), angioimmunoblastic T cell lymphoma (AITL), anaplastic large cell lymphoma-anaplastic lymphoma kinase (ALCL-ALK)-negative, NK/T cell (disseminated), enteropathy-associated T cell lymphoma (EATL), and hepatosplenic lymphomas. Read More
Cord blood transplantation (CBT) from HLA-identical siblings is an attractive option for patients with bone marrow failure (BMF) syndrome because of the low risk of graft-versus-host disease (GVHD) and the absence of risk to the donor. We analyzed outcomes of 117 patients with inherited or acquired BMF syndrome who received CBT from a related HLA-identical donor in European Group for Blood and Marrow Transplantation centers between 1988 and 2014. Ninety-seven patients had inherited and 20 patients acquired BMF syndrome. Read More
Biol Blood Marrow Transplant 2017 Aug 7. Epub 2017 Aug 7.
The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia; National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Australia; Victorian Infectious Diseases Service, Royal Melbourne Hospital at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
Opportunistic infections such as cytomegalovirus (CMV) reactivation and invasive fungal disease (IFD) cause significant morbidity and mortality to recipients of hematopoietic stem cell transplant (HSCT). We aimed to characterize the risk and relationship of CMV reactivation post-HSCT to IFD in the current era of CMV viral load monitoring using highly sensitive plasma DNA. A multicenter, retrospective, cohort study was conducted of consecutive patients undergoing allogeneic HSCT from January 2006 to December 2010 in Melbourne, Australia. Read More
This study aimed to ascertain unmet needs in autologous and allogeneic hematopoietic cell transplantation (HCT) recipients actively followed in an established long-term survivorship clinic at Roswell Park Cancer Institute from 2006 to 2012. The Survivor Unmet Needs Survey (SUNS) was mailed to 209 eligible patients and returned by 110 (53% participation rate). SUNS includes 89 items covering 5 domains: Emotional Health, Access and Continuity of Care, Relationships, Financial Concerns, and Information. Read More
Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin. Electronic address:
Idiopathic pneumonia syndrome (IPS) is a complication of allogeneic hematopoietic stem cell transplantation (HSCT) that typically occurs within the first 100 days after transplantation. Tumor necrosis factor α (TNF-α) has been shown to be a key mediator of IPS, and the TNF-α binding protein etanercept appeared to improve IPS outcomes in small retrospective and prospective studies. IPS also has been observed to occur later (>100 days) after HSCT; however, little is known about the disease course and whether a TNF-α-based therapeutic strategy is efficacious in these patients. Read More
Clinical manifestation of high-grade fever and skin rash before neutrophil engraftment, termed pre-engraftment syndrome (PES) or pre-engraftment immune reaction, has been frequently observed after cord blood transplantation (CBT). The pathophysiology of PES is poorly understood, but cytokine storm during the early phase of CBT is thought to be 1 of the main cause of PES. However, the cytokine profiles of PES after CBT are unclear. Read More
High-dose melphalan (HDM) and autologous blood stem cell transplantation (ABSCT) is an effective treatment for transplantation-eligible patients with systemic light chain (AL) amyloidosis. Whereas most centers use granulocyte colony-stimulating factor (G-CSF) alone for mobilization of peripheral blood stem cells (PBSC), the application of mobilization chemotherapy might offer specific advantages. We retrospectively analyzed 110 patients with AL amyloidosis who underwent PBSC collection. Read More