Search

The development of hematopoietic stem cell transplantation (HSCT) programs can face significant challenges in most developing countries because such endeavors must compete with other government health care priorities, including the delivery of basic services. While this is may be a limiting factor, these countries should prioritize development of the needed expertise to offer state of the art treatments including transplantation, by providing financial, technological, legal, ethical and other needed support. This would prove beneficial in providing successful programs customized to the needs of their population, and potentially provide long-term cost-savings by circumventing the need for their citizens to seek care abroad. Costs of establishing HSCT program and the costs of the HSCT procedure itself can be substantial barriers in developing countries. Additionally, socioeconomic factors intrinsic to specific countries can influence access to HSCT, patient eligibility for HSCT and timely utilization of HSCT center capabilities. This report describes recommendations from the Worldwide Network for Blood and Marrow Transplantation (WBMT) for establishing HSCT programs with a specific focus on developing countries, and identifies challenges and opportunities for providing this specialized procedure in the resource constrained setting., Competing Interests: Declaration of Competing Interest None of the authors declare any relevant conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The development of hematopoietic stem cell transplantation (HSCT) programs can face significant challenges in most developing countries because such endeavors must compete with other government health care priorities, including the delivery of basic services. Although this is may be a limiting factor, these countries should prioritize development of the needed expertise to offer state-of-the-art treatments, including transplantation, by providing financial, technological, legal, ethical, and other needed support. This would prove beneficial in providing successful programs customized to the needs of their population and potentially provide long-term cost savings by circumventing the need for their citizens to seek care abroad. The costs of establishing an HSCT program and the costs of the HSCT procedure itself can be substantial barriers in developing countries. In addition, socioeconomic factors intrinsic to specific countries can influence access to HSCT, patient eligibility for HSCT, and timely utilization of HSCT center capabilities. This report describes recommendations from the Worldwide Network for Blood and Marrow Transplantation for establishing HSCT programs, with a specific focus on developing countries, and identifies challenges and opportunities for providing this specialized procedure in resource-constrained settings., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

The clinical utility of monitoring immune reconstitution after allotransplant was evaluated using data from Blood and Marrow Transplant Clinical Trials Network BMT CTN 0201 (NCT00075816), a multicenter randomized study of unrelated donor bone marrow (BM) vs granulocyte colony-stimulating factor (G-CSF)-mobilized blood stem cell (G-PB) grafts. Among 410 patients with posttransplant flow cytometry measurements of immune cell subsets, recipients of G-PB grafts had faster T-cell reconstitution than BM recipients, including more naive CD4 + T cells and T-cell receptor excision circle-positive CD4 + and CD8 + T cells at 3 months, consistent with better thymic function. Faster reconstitution of CD4 + T cells and naive CD4 + T cells at 1 month and CD8 + T cells at 3 months predicted more chronic graft-versus-host disease (GVHD) but better survival in G-PB recipients, but consistent associations of T-cell amounts with GVHD or survival were not seen in BM recipients. In contrast, a higher number of classical dendritic cells (cDCs) in blood samples at 3 months predicted better survival in BM recipients. Functional T-cell immunity measured in vitro by cytokine secretion in response to stimulation with cytomegalovirus peptides was similar when comparing blood samples from BM and G-PB recipients, but the degree to which acute GVHD suppressed immune reconstitution varied according to graft source. BM, but not G-PB, recipients with a history of grades 2-4 acute GVHD had lower numbers of B cells, plasmacytoid dendritic cells, and cDCs at 3 months. Thus, early measurements of T-cell reconstitution are predictive cellular biomarkers for long-term survival and response to GVHD therapy in G-PB recipients, whereas more robust DC reconstitution predicted better survival in BM recipients., (© 2019 by The American Society of Hematology.)

Hematopoietic cell transplantation (HCT) activity is increasing at an unprecedented pace with > 50,000 allogeneic transplants occurring annually worldwide. Establishing a functional HCT donor registry can be very challenging with respect to ethnicities, financial, technical, and geopolitical issues. Extensive planning steps are essential to overcome the expected challenges while establishing the registry, and to maintain its functionality. A few strategies can help move past those challenges and push the development of such registries forward. Authorities involved in HCT donor registry establishment will have to balance the advantages and costs of such a project and accommodate the emerging alternatives such as cord blood or related haploidentical transplants. Miscalculations and incomplete understanding of the various aspects of the process can have tremendous impact on the optimization of a HCT donor registry especially in developing countries. Herein we present some challenges in establishing such a registry and present potential solutions.

Competing Interests: The authors have indicated they have no potential conflicts of interest to disclose.

Patients with blood-related diseases often cannot identify a matched related donor and must seek donors in unrelated donor registries. These registries face the challenge of ensuring that potential donors are available when contacted. Donor attrition is especially problematic when there is only a single perfectly matched potential donor. One way to improve donor availability might be to present perfectly matched donors (high-priority donors [HPDs]) with more precise information about their match status. This project evaluated the impact of providing such information to HPDs at the National Marrow Donor Program (NMDP)/Be The Match. Objectives were to determine the acceptability of the new messaging to both HPDs and the donor contact representatives (DCRs) who delivered the message, consistency of message delivery, and whether the new messaging was associated with improved donor availability. Mixed methods were used to collect telephone interview data from HPDs, matched samples of non-HPDs, and DCRs. Donor availability data came from NMDP records. Key findings were as follows: (1) the HPD message was acceptable to potential donors and did not seem to produce undue pressure, (2) the message was acceptable to DCRs who became more comfortable and consistent in delivering the message over time, but (3) the new messaging did not significantly increase availability. Despite the lack of evidence for increased availability, there may be ethical benefits and little harm to providing well-matched donors with more information about their degree of matching. Research should examine stronger match status messages and delivery of new messaging to additional highly-matched donor groups., (Published by Elsevier Inc.)

Importance: Bone marrow or peripheral blood from unrelated donors may be used for hematopoietic cell transplantation. Information about the relative success of transplantation with these 2 graft sources would help physicians and patients choose between them., Objective: To compare patient-reported outcomes between patients randomized to receive 1 of 2 graft types for unrelated donor transplantation., Design, Setting, and Participants: This follow-up of a randomized clinical trial included English- or Spanish-speaking patients 16 years or older participating in a multicenter randomized clinical trial of unrelated donor bone marrow (BM) vs peripheral blood (PB) (N = 551) in hematopoietic cell transplantation for hematologic neoplasms. Patient-reported outcomes were collected from patients at enrollment and 0.5, 1, 2, and 5 years after transplantation., Interventions: Unrelated donor BM or PB hematopoietic cell transplantation., Main Outcomes and Measures: Functional Assessment of Cancer Therapy-Bone Marrow Transplant, Mental Health Inventory, occupational functioning, Lee Chronic Graft-vs-Host Disease Symptom Scale., Results: At 5 years after transplantation, 102 BM and 93 PB participants were alive and eligible for assessment (age ≥40 years or older: 104 [53.5%] male: 101 [51.8%]). The mean (SE) Mental Health Inventory Psychological Well-Being scores (78.9 [1.7] vs 72.2 [1.9]; P = .01; higher better) and Lee chronic graft-vs-host disease symptom scores (13.1 [1.5] vs 19.3 [1.6]; P = .004; lower better) were significantly better for BM recipients, adjusting for baseline scores and missing data. Recipients of BM were also more likely to be working full or part-time than recipients of PB (odds ratio, 1.5; 95% CI, 1.2-2.0; P = .002), adjusting for work status before transplantation. With a median follow-up of 73 months (range, 30-121 months) for survivors, no differences in survival (40% vs 39%; P = .84), relapse (32% vs 29%; P = .47), or treatment-related mortality (29% vs 32%; P = .44) between BM and PB were observed., Conclusions and Relevance: Recipients of unrelated donor BM had better psychological well-being, less burdensome chronic GVHD symptoms, and were more likely to return to work than recipients of PB at 5 years after transplantation. Bone marrow should be the standard of care for these types of transplant procedures., Trial Registration: clinicaltrials.gov Identifier: NCT00075816.

Objective: To implement a mentored laboratory quality stepwise implementation (LQSI) programme to strengthen the quality and capacity of Cambodian hospital laboratories., Methods: We recruited four laboratory technicians to be mentors and trained them in mentoring skills, laboratory quality management practices and international standard organization (ISO) 15189 requirements for medical laboratories. Separately, we trained staff from 12 referral hospital laboratories in laboratory quality management systems followed by tri-weekly in-person mentoring on quality management systems implementation using the LQSI tool, which is aligned with the ISO 15189 standard. The tool was adapted from a web-based resource into a software-based spreadsheet checklist, which includes a detailed action plan and can be used to qualitatively monitor each laboratory's progress. The tool - translated into Khmer - included a set of quality improvement activities grouped into four phases for implementation with increasing complexity. Project staff reviewed the laboratories' progress and challenges in weekly conference calls and bi-monthly meetings with focal points of the health ministry, participating laboratories and local partners. We present the achievements in implementation from September 2014 to March 2016., Findings: As of March 2016, the 12 laboratories have completed 74-90% of the 104 activities in phase 1, 53-78% of the 178 activities in phase 2, and 18-26% of the 129 activities in phase 3., Conclusion: Regular on-site mentoring of laboratories using a detailed action plan in the local language allows staff to learn concepts of quality management system and learn on the job without disruption to laboratory service provision.

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

Estimation of the National Marrow Donor Program's Be The Match Registry 8/8 (HLA-A, -B, -C, and -DRB1) high-resolution (HR) unrelated donor (URD) match rate was determined in a prior study for each of the 4 most frequent patient race/ethnic groups in the United States: white (WH), Hispanic (HIS), Asian/Pacific Islander (API), and African American (AFA). For patients without an 8/8 HLA-matched URD, a 7/8 match, with a single allele or antigen mismatch, is often accepted by many transplant centers. A follow-up study was designed to determine the 7/8 or better match rate among the 4 major race/ethnic groups, using the same study cohort. Of previously HR tested URDs in the Be The Match Registry, 1344 were randomly selected and treated as pseudo-patients where HR testing was performed to identify a 7/8-matched URD; 98% of WH and over 80% of non-WH race/ethnic groups (HIS, API, and AFA) had at least a 7/8 match identified. In most cases after first testing to identify an 8/8-matched URD, a 7/8-matched URD was identified after typing just 1 URD. Extending criteria to identify a 9/10 match (included HLA-DQB1) showed the 9/10 absolute match rate decreased between 14% and 21% from the 7/8 match rate for the non-WH groups. This study provides a baseline 7/8 and 9/10 or better HLA match rate that can be further supplemented using the additional worldwide URD inventory. URD match rate information can equip centers in clinical planning and the education of patients seeking a life-saving therapy., (Copyright © 2016 American Society for Blood and Marrow Transplantation. All rights reserved.)

Prior studies of allogeneic hematopoietic cell transplantation (HCT) therapy for the treatment of malignant or nonmalignant blood disorders assume a 30% likelihood that a patient will find a match among siblings and, therefore, a 70% likelihood of needing an unrelated donor source. This study utilizes birth data and statistical modeling to assess the adequacy of these estimates to describe the probability among US population cohorts segmented by race/ethnicity and age, including ages of greatest HCT utilization. Considerable variation in the likelihood of an HLA-identical sibling was found, ranging from 13% to 51%, depending upon patient age and race/ethnicity. Low sibling match probability, compounded with increased genetic diversity and lower availability among unrelated donors, put the youngest minority patients at the greatest risk for not finding a suitable related or unrelated HCT donor. Furthermore, the present 40-year decline in birth rates is expected to lead to 1.5-fold decrease in access to a matched sibling for today's young adults (18 to 44 years of age) when they reach peak HCT utilization years (near age 61 years) versus their contemporary adult counterparts (44 to 64 years). Understanding the sibling match probability by race/ethnicity and age cohort leads to forecasting the demand for unrelated HCT sources., (Copyright © 2016 American Society for Blood and Marrow Transplantation. All rights reserved.)

Background: The optimum preparative regimen for unrelated donor marrow transplantation in patients with severe aplastic anaemia remains to be established. We investigated whether the combination of fludarabine, anti-thymocyte globulin, and total body irradiation (TBI) would enable reduction of the cyclophosphamide dose to less than 200 mg/kg while maintaining engraftment and having a survival similar to or better than that with standard regimens using a cyclophosphamide dose of 200 mg/kg (known to be associated with significant organ toxicity) for unrelated donor transplantation for severe aplastic anaemia. We have previously shown that cyclophosphamide at 150 mg/kg resulted in excess toxicity and its omission (0 mg/kg) resulted in unacceptable graft failure (three of three patients had secondary graft failure). Here we report results for the 50 mg/kg and 100 mg/kg cohorts., Methods: In a multicentre phase 1-2 study, patients (aged ≤65 years) with severe aplastic anaemia, adequate organ function, and an unrelated adult marrow donor HLA matched at the allele level for HLA A, B, C, and DRB1 or mismatched at a single HLA locus received bone marrow grafts from unrelated donors. All patients received anti-thymocyte globulin (rabbit derived 3 mg/kg per day, intravenously, on days -4 to -2, or equine derived 30 mg/kg per day, intravenously, on days -4 to -2), fludarabine (30 mg/m(2) per day, intravenously, on days -5 to -2), and TBI (2 Gy). Cyclophosphamide dosing started at 150 mg/kg and was de-escalated in steps of 50 mg/kg (to 100 mg/kg, 50 mg/kg, and 0 mg/kg). The primary endpoint was the selection of the optimum cyclophosphamide dose based on assessments of graft failure (primary or secondary), toxicity, and early death during 100 days of follow-up after the transplant; this is the planned final analysis for the primary endpoint. This trial is registered with ClinicalTrials.gov, number NCT00326417., Findings: 96 patients had bone marrow transplant. At day 100, 35 (92%) of 38 patients were engrafted and alive in the cyclophosphamide 50 mg/kg cohort and 35 (85%) of 41 in the 100 mg/kg cohort. Cyclophosphamide 50 mg/kg and 100 mg/kg resulted in posterior means for fatality without graft failure of 0·7% (credible interval 0-3·3) and 1·4% (0-4·9), respectively. Three patients (8%) had graft failure with cyclophosphamide 50 mg/kg and six (15%) with cyclophosphamide 100 mg/kg. Four (11%) patients had major regimen-related toxicity with cyclophosphamide 50 mg/kg and nine (22%) with cyclophosphamide 100 mg/kg. The most common organ toxicity was pulmonary (grade 3 or 4 dyspnoea or hypoxia including mechanical ventilation), and occurred in three (8%) and four (10%) patients given cyclophosphamide 50 mg/kg and 100 mg/kg, respectively., Interpretation: Cyclophosphamide at 50 mg/kg and 100 mg/kg with TBI 2 Gy, fludarabine, and anti-thymocyte globulin results in effective conditioning and few early deaths after unrelated donor transplantation for severe aplastic anaemia. These doses of cyclophosphamide provide a framework for further regimen optimisation strategies., Funding: US National Heart, Lung, and Blood Institute and National Cancer Institute., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: The transplantation of cells, tissues, and organs has been recognised by WHO as an important medical task for its member states; however, information about how to best organise transplantation is scarce. We aimed to document the activity worldwide from the beginning of transplantation and search for region adapted indications and associations between transplant rates and macroeconomics., Methods: Between Jan 1, 2006, and Dec 31, 2014, the Worldwide Network for Blood and Marrow Transplantation collected data for the evolution of haemopoietic stem-cell transplantation (HSCT) activity and volunteer donors in the 194 WHO member states., Findings: 953,651 HSCTs (553,350 [58%] autologous and 400,301 [42%] allogeneic) were reported by 1516 transplant centres from 75 countries. No transplants were done in countries with fewer than 300,000 inhabitants, a surface area less than 700 km(2), and a gross national income per person of US$1260 or lower. Use of HSCT increased from the first transplant in 1957 to almost 10,000 by 1985. We recorded a cumulative total of about 100,000 transplants by 1995, and an estimated 1 million by December, 2012. Unrelated donor registries contributed 22·3 million typed volunteer donors and 645,646 cord blood products by 2012. Numbers of allogeneic HSCTs increased in the past 35 years with no signs of saturation (R(2)=0·989). Transplant rates were higher in countries with more resources, more transplant teams, and an unrelated donor infrastructure., Interpretation: Our findings show achievements and high unmet needs and give guidance for decisions; to grant access for patients, to provide a donor infrastructure, and to limit overuse by defining risk and region adapted indications for HSCT as an efficient and cost-effective approach for life-threatening, potentially curable diseases., Funding: Funding for this study was indirectly provided by support of the WBMT., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The National Marrow Donor Program's Be The Match Registry(®) facilitates the worldwide utilization of unrelated donor (URD) grafts for patients in need of a hematopoietic cell transplantation. In this study, we estimate the URD match rate for patients of White (WH), Hispanic (HIS), Asian/Pacific Islander (API), and African American/Black (AFA) race and ethnic groups. We chose 1344 URD at random as "pseudo-patients" (PP) to estimate the likelihood of finding an 8/8 or 10/10 high-resolution HLA-A,-B,-C,-DRB1 (and -DQB1) matched URD. Searches were conducted in the Be The Match Registry database for each PP at 2 time points: 2009 and 2012. URD who were a potential match for a PP by low/intermediate resolution were HLA typed by sequence-based typing to resolve the matching status. The 8/8 match rate for WH PP improved from 68% in 2009 to 72% in 2012. Corresponding match rates were 41% to 44% for HIS, 44% to 46% for API, and 27% to 30% for AFA, for 2009 and 2012, respectively. The 2012 10/10 match rates were 67% for WH, 38% for HIS, 41% for API, and 23% for AFA. These results provide baseline 8/8 and 10/10 match rate estimates by race for patients seeking an URD., (Copyright © 2015 American Society for Blood and Marrow Transplantation. All rights reserved.)

Background: Hematopoietic stem-cell transplantation (HSCT) is a potentially lifesaving therapy for several blood cancers and other diseases. For patients without a suitable related HLA-matched donor, unrelated-donor registries of adult volunteers and banked umbilical cord-blood units, such as the Be the Match Registry operated by the National Marrow Donor Program (NMDP), provide potential sources of donors. Our goal in the present study was to measure the likelihood of finding a suitable donor in the U.S. registry., Methods: Using human HLA data from the NMDP donor and cord-blood-unit registry, we built population-based genetic models for 21 U.S. racial and ethnic groups to predict the likelihood of identifying a suitable donor (either an adult donor or a cord-blood unit) for patients in each group. The models incorporated the degree of HLA matching, adult-donor availability (i.e., ability to donate), and cord-blood-unit cell dose., Results: Our models indicated that most candidates for HSCT will have a suitable (HLA-matched or minimally mismatched) adult donor. However, many patients will not have an optimal adult donor--that is, a donor who is matched at high resolution at HLA-A, HLA-B, HLA-C, and HLA-DRB1. The likelihood of finding an optimal donor varies among racial and ethnic groups, with the highest probability among whites of European descent, at 75%, and the lowest probability among blacks of South or Central American descent, at 16%. Likelihoods for other groups are intermediate. Few patients will have an optimal cord-blood unit--that is, one matched at the antigen level at HLA-A and HLA-B and matched at high resolution at HLA-DRB1. However, cord-blood units mismatched at one or two HLA loci are available for almost all patients younger than 20 years of age and for more than 80% of patients 20 years of age or older, regardless of racial and ethnic background., Conclusions: Most patients likely to benefit from HSCT will have a donor. Public investment in donor recruitment and cord-blood banks has expanded access to HSCT. (Funded by the Office of Naval Research, Department of the Navy, and the Health Resources and Services Administration, Department of Health and Human Services.).

Hematopoietic stem cells can be procured from unrelated donors via either the bone marrow (BM) aspiration or peripheral blood stem cell (PBSC) collection methods. There is no evidence from prospective randomized trials in the unrelated donor setting about the relative health-related quality-of-life (HRQoL) benefits/costs to donors. The goals of this prospective longitudinal investigation were to describe and compare the donation-related HRQoL experiences of 332 BM and PBSC donors. Donors were interviewed before donation, 48 hours after donation, weekly until fully recovered, and at 6 and 12 months after donation. Before donation, BM donors had lower confusion, fewer concerns, and were more prepared for donation. Shortly after donation, BM donors reported more physical side effects. BM donors also reported more donation-related impact on their social activities. However, BM donors reported somewhat better psychological status and were more likely to indicate that the donation made their lives more meaningful. There were virtually no longer term differences in the experiences of the 2 donor groups, including no recovery time difference beginning 3 weeks after donation. Although BM donors may experience the process as more physically stressful and more psychologically beneficial in the short term, the longer term HRQoL consequences of BM and PBSC donors are similar., (Published by Elsevier Inc.)

Allogeneic hematopoietic cell transplantation (alloHCT) is a curative therapy for hematologic disorders including acute lymphoblastic and myeloid leukemia, chronic lymphocytic and myeloid leukemia, Hodgkin's and non-Hodgkin lymphoma, multiple myeloma, and myelodysplastic syndrome. To determine the utilization of alloHCT from unrelated donors (URDs) in the United States, we calculated the number of patients diagnosed with hematologic disorders age 20 to 74 years based on 2004 to 2008 Surveillance, Epidemiology and End Results and 2007 US Census data, estimated the percentage of patients who would be eligible for URD alloHCT after discounting the mortality rate during induction therapy and the rate of severe comorbidities, and compared these with the actual 2007 alloHCTs facilitated by the National Marrow Donor Program. We found that the number of URD alloHCT as a percentage of the estimated potential transplantations ranged from 11% for multiple myeloma to 54% for chronic myeloid leukemia, with an average percentage of 26% for all the disorders considered. In an analysis stratified by age groups (20 to 44, 45 to 64, and 65 to 74 years), the utilization of URD alloHCT was higher in younger patients than in older patients for all disorders. Of acute lymphoblastic and myeloid leukemia patients, approximately 66% underwent URD alloHCT later in the course of their disease (in second or greater complete remission). URD alloHCT is likely underused for potentially curable hematologic disorders, particularly in older patients. Understanding the reasons for low use of alloHCT may lead to strategies to expand the use of this curative therapy for more patients with hematologic disorders., (Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

The number of allogeneic hematopoietic SCTs performed globally each year continues to increase, paralleled by an increased demand for donors of therapeutic cells. Donor characteristics and collection procedures have undergone major changes during recent decades, and further changes are foreseen. Information on short- and long-term donor outcomes is of crucial importance to ensure maximal donor safety and availability. Current data, predominantly from unrelated donors, give reliable information on the frequent early events associated with donation-most of them of mild-to-moderate intensity. Information on the type and relative risk of serious adverse reactions is more limited. Moreover, only few data exist on long-term donor outcome. On the basis of this need, recommendations for a minimum data set for prospective donor follow-up were developed in a workshop with the participation of an international group of investigators actively involved in allogeneic stem cell donation under the auspices of and approved by the Worldwide Network for Blood and Marrow Transplantation. Establishment of a standardized global follow-up for both, related and unrelated, donors will enable monitoring of the short- and long-term safety profiles of hematopoietic cell donation and form a solid basis for future donor selection and counseling.

This article summarizes major points from a newly released guide published online by the Office of the Assistant Secretary for Preparedness and Response (ASPR). The article reviews basic principles about radiation and its measurement, short-term and long-term effects of radiation, and medical countermeasures as well as essential information about how to prepare for and respond to a nuclear detonation. A link is provided to the manual itself, which in turn is heavily referenced for readers who wish to have more detail.

In light of continued uncertainty regarding postkidney donation medical, psychosocial and socioeconomic outcomes for traditional living donors and especially for donors meeting more relaxed acceptance criteria, a meeting was held in September 2010 to (1) review limitations of existing data on outcomes of living kidney donors; (2) assess and define the need for long-term follow-up of living kidney donors; (3) identify the potential system requirements, infrastructure and costs of long-term follow-up for living kidney donor outcomes in the United States and (4) explore practical options for future development and funding of United States living kidney donor data collection, metrics and endpoints. Conference participants included prior kidney donors, physicians, surgeons, medical ethicists, social scientists, donor coordinators, social workers, independent donor advocates and representatives of payer organizations and the federal government. The findings and recommendations generated at this meeting are presented., (©Copyright 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.)

As peripheral blood has surpassed bone marrow as a predominant source of stem cells for transplantation, use of the cytokine granulocyte colony-stimulating factor (G-CSF) to mobilize peripheral blood stem cells (PBSCs) is increasing. Issues regarding potential genotoxic effects of even short-term, low-dose G-CSF treatment for the healthy donors have been raised. To address the question of chromosomal instability, we used FISH to evaluate the peripheral blood lymphocytes of 22 PBSC donors and 22 matched controls at 5 time points over a 12-month period. The specimens obtained were a pre-G-CSF, followed by collections at the time of PBSC harvest (days 5-7) and at 2, 6, and 12 months after donation. Eight additional PBSC donors provided a single sample at 12 months. Nine loci (mapped to chromosomes 7, 8, 9, 17, 21, and 22) were evaluated for aneuploidy, including 3 mapped to chromosome 7 because of the specific relevance of monosomy 7. Replication timing was evaluated for chromosome 15 and 17 loci. No evidence was found of G-CSF-induced chromosomal instability. This work supports the epidemiologic data that have demonstrated no increased risk for hematologic malignancies in G-CSF-primed PBSC donors.

Purpose: To describe the history, composition, and activities of the Radiation Injury Treatment Network (RITN). The Radiation Injury Treatment Network® is a cooperative effort of the National Marrow Donor Program and the American Society for Blood and Marrow Transplantation. The goals of RITN are to educate hematologists, oncologists, and stem cell transplant practitioners about their potential involvement in the response to a radiation incident and provide treatment expertise. Injuries to the marrow system readily occur when a victim is exposed to ionising radiation. This focus therefore leverages the expertise of these specialists who are accustomed to providing the intensive supportive care required by patients with a suppressed marrow function. Following a radiological incident, RITN centres may be asked to: Accept patient transfers to their institutions; provide treatment expertise to practitioners caring for victims at other centres; travel to other centres to provide medical expertise; or provide data on victims treated at their centres. Moving forward, it is crucial that we develop a coordinated interdisciplinary approach in planning for and responding to radiological and nuclear incidents. The ongoing efforts of radiation biologists, radiation oncologists, and health physicists can and should complement the efforts of RITN and government agencies., Conclusion: RITN serves as a vital partner in preparedness and response efforts for potential radiological and nuclear incidents.

Shortage of manpower and center capacity is expected to be a major challenge to the anticipated future growth in the utilization of allogeneic hematopoietic cell transplantation (HCT) in the United States. Using data from the National Marrow Donor Program's Transplant Center Network Renewal Survey, we describe transplant center and transplant physician capacity in the United States from 2005 to 2009. Over this 5-year period, the number of allogeneic transplants increased by 30%, bed capacity increased by 17%, and physician full-time equivalents increased by 26%. The number of related donor HCT increased by 15% and unrelated donor HCT increased by 45%. In addition to large centers, small- and medium-sized centers also made a major contribution to overall national transplant volumes for both related and unrelated donor HCT. Increase in utilization of unrelated donor HCT occurred in centers irrespective of their size. The majority of transplant centers were performing more transplantations using existing physician and bed capacity. Our study provides important descriptions of allogeneic transplant activity and capacity of U.S. centers, and our data will assist policy makers plan for the projected growth in the use of transplantation., (2011 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Since its founding in 1986, the NMDP has grown into a large international organization, providing patients with access to more than 9.5 million adult donors on the Be The Match Registry and to more than 18.5 million adult donors worldwide. Patients searching through the NMDP also have access to nearly 165,000 CBUs from NMDP-affiliated cord blood banks and nearly 600,000 CBUs worldwide. Through aggressive recruitment to the Be The Match Registry, and by establishing connections to international registries, the NMDP gives patients in need of a transplant access to a large and diverse pool of unrelated donors and CBUs. This has resulted in a steady increase in the likelihood of finding a matching donor or CBU for searching patients of all races/ethnicities. The NMDP has also developed programs and initiatives that have successfully increased the efficiency of the search process, which has decreased the time to transplant. The NMDP has also developed strategies that have improved access to transplant, especially among minority racial/ethnic patient populations. These long-standing and ongoing efforts to grow the Be The Match Registry and to improve the search process resulted in a record number of NMDP-facilitated transplants in 2011--more than 5,500--and now have facilitated more than 50,000 transplants since 1986. However, the NMDP, using SEER data, has calculated that there are approximately 10,000 patients in the U.S. each year who could potentially benefit from unrelated donor HCT. The NMDP has therefore set a goal to facilitate 10,000 transplants annually. Although meeting this goal will require nearly doubling the annual rate of transplants, the NMDP is confident that it has the expertise, personnel, facilities, and commitment to achieve this goal.

Background: Allogeneic hematopoietic stem cell transplants from unrelated donors are routinely used in the treatment of patients with hematologic malignancies. These cellular products are often collected off-site and require transport from the collection site to transplantation centers. However, the effects of transport conditions and media on stem cell graft composition during short-term storage have not been well described., Study Design and Methods: Five bone marrow (BM), four filgrastim-mobilized peripheral blood stem cell (PBSC), and four nonmobilized peripheral blood mononuclear cell (PBMNC) products were collected from healthy volunteer donors and stored at 4 or 20°C for up to 72 hours in 10% PlasmaLyte A plus anticoagulants such as 10% acid citrate dextran-A (ACD-A) and/or 10 IU/mL heparin. Products were evaluated at 0, 24, 48, and 72 hours for cellular content, viability, and metabolic activities., Results: BM products maintained equivalent cell viability when stored at either 4 or 20°C over 72 hours, but cell viability was better maintained for PBSC products stored at 4°C. The mean viable CD34+ cell recovery for PBSC and BM products stored over 72 hours at 4°C was higher than 75%. Significantly lower CD34+ cell and colony-forming unit recoveries were seen in PBSC products but not BM products stored at room temperature. Faster lactic acid accumulation was observed in PBMNC and PBSC products stored without ACD-A., Conclusions: Seventy-two-hour storage of BM, PBSC, and PBMNC products at refrigerated temperature maintains optimal cell viability and recovery. Anticoagulation with ACD-A is preferred over heparin to reduce lactic acid accumulation in the product media., (© 2010 American Association of Blood Banks.)

Since the beginning of hematopoietic stem cell harvesting from volunteer unrelated donors, ensuring donor safety has been a necessary goal of all parties involved in the process. As donation of BM or PBSCs is not in the interest of the donor's own physical health, donor registries and transplantation centers must take into account both medical and ethical aspects involved in the donation procedure. One of the principal goals leading to the formation of the World Marrow Donor Association (WMDA) was to establish internationally acceptable standards for all aspects of unrelated donor care.

To test the hypothesis that the outcome of hematopoietic stem cell (HSC) grafts is at least partially determined by the cellular composition of the graft, the National Marrow Donor Program (NMDP) analyzed the correlation of cellular phenotypes of unrelated grafts with graft outcome. Samples from 94 bone marrow (BM) and 181 peripheral blood progenitor cell (PBPC) grafts for transplantations at 40 U.S. transplant centers between 2003 and 2005 were analyzed at a single immunophenotyping reference laboratory. Samples were shipped from transplant centers upon receipt of graft. Graft cellular composition included analysis of leukocyte total cell numbers, and subsets of myeloid [CD34(+), CD34(+) CD38(-)], lymphoid [CD3(+), CD3(+) CD4(+), CD3(+) CD8(+)], and activated lymphoid cells [CD3(+) CD25(+), CD3(+) CD69(+), CD3(+) HLA-DR(+)] coexpressing CD3(+). There was substantial variability in the cellular composition of BM and PBPC grafts before and after graft processing by red blood cell (RBC) removal or plasma depletion in preparation for transplant. With BM grafts, cellular composition was not associated with hematopoietic recovery, graft-versus-host disease (GVHD), or survival. With PBPC grafts, survival rates were higher with CD34(+)>5 x 10(6)/kg, 59% compared to 34% with CD34(+)< or =5 x 10(6)/kg at 1 year. Platelet recovery was higher with PBPC containing CD3(+) CD8(+) >8 x 10(7)/kg. Neutrophil recovery or GVHD could not be predicted by any cellular subsets of PBPC grafts. Although survival was superior with PBPC grafts containing >5 x 10(6) CD34(+)/kg, an optimal graft mix of myeloid, lymphoid, and activated lymphoid subsets was not identified., (Copyright 2010 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

The impact of non-HLA patient factors on the match of the selected unrelated donor (URD) for hematopoietic cell transplantation (HCT) has not been fully evaluated. National Marrow Donor Program (NMDP) data for 7486 transplants using peripheral blood stem cells (PBSCs) or bone marrow from years 2000 to 2005 were evaluated using multivariate logistic regression to identify independent non-HLA patient factors associated with completing a more closely matched URD transplant. Advanced (intermediate- and late-stage) disease was significantly associated with an increased likelihood of transplant using a less-matched (partially matched or mismatched) donor. Additionally, Black patients were 2.83 times, Asian patients 2.05 times, and Hispanic patients 1.73 times more likely to have a less-matched HCT donor than Caucasian patients. Younger patients, HCT at lower volume centers, and in earlier years had significantly higher likelihood of having a less HLA matched URD transplant. Our analysis provides encouraging evidence of HLA matching improvement in recent years. Initiating a patient's URD search early in the disease process, especially for patients from non-Caucasian racial and ethnic groups, will provide the best likelihood for identifying the best available donor and making informed transplant decisions.

Background: The National Institutes of Health (NIH) Roadmap for Medical Research aims to increase the efficiency and speed of clinical research. We report results and lessons learned from a key component of the Roadmap, the Clinical Research Networks initiative., Methods: Twelve diverse, experienced, large, clinical research networks were funded for 3 years to develop strategies for integrating, expanding, and increasing the interoperability of clinical research networks in support of the Roadmap goals. Network leaders met periodically in person and by teleconference to describe common challenges encountered and solutions used for expansion and increased interoperability., Results: These networks developed innovative solutions to technical challenges, including strategies for interoperability of information systems and management of complex information system technologies (eg, "brokering" to address data system incompatibility, data transfer, and security requirements), and solutions to human factor challenges at the individual, group, intraorganizational, and interorganizational levels (eg, applying collaborative organizing and decision-making processes based on key principles)., Conclusions: These solutions can provide guidance to existing and future clinical research networks, particularly those forming as part of the NIH Clinical Translation Science Award program. Remaining technical and human factor challenges, however, as well as the largely unmet need for consistent funding for network infrastructure and maintenance, stand in the way of fulfilling the vision of a robust future role for clinical research networks.

The National Marrow Donor Program (NMDP) is headquartered in Minneapolis, Minnesota, USA. Established in 1986, the NMDP currently operates the world's largest registry of unrelated adult donors and umbilical cord blood (UCB) units. Since its inception, the NMDP has benefited from continuous financial support provided by the US government through a series of contracts and grant awards. This funding has supported a large network of donor centers and the recruitment of millions of potential adult hematopoietic cell (HC) donors. More recently, the federal government has also supported a national registry for UCB units and expansion of the available UCB inventories. Today, the NMDP registry lists more than 6.7 million adult donors and 68,000 UCB units. Seventy-seven percent (5.2 million) of the adult donors and virtually all of the UCB units are fully typed for HLA A, B and DR. An additional 5 million donors are available for search through international collaborations. The NMDP currently facilitates more than 3600 recipients each year totaling more than 29,000 transplants since 1987.

The best unrelated donors (URD) for hematopoietic cell transplantation (HCT) are alleles matched at HLA-A, -B, -C, and DRB1. Earlier studies mostly used incomplete or lower resolution HLA typing for analysis of transplant outcome. To understand the impact of incomplete HLA characterization, we analyzed 14,797 URD HCT (1995-2006) using multivariable regression modeling adjusting for factors affecting survival. Of 21 matching cohorts, we identified 3 groups with significantly different outcomes. Well-matched cases had either no identified HLA mismatch and informative data at 4 loci or allele matching at HLA-A, -B, and -DRB1 (n = 7477, 50% of the population). Partially matched pairs had a defined, single-locus mismatch and/or missing HLA data (n = 4962, 34%). Mismatched cases had > or =2 allele or antigen mismatches (n = 2358, 16%). Multivariate adjusted 5-year survival estimates were: well-matched: 54.1 (95% confidence interval), 52.9-55.4), partially matched: 43.7 (42.3-45.2), and mismatched: 33.4 (32.5-36.5), P < .001. A better matched donor yielded 10%-11% better 5-year survival. Importantly, intermediate resolution -A, -B, and -DRB1 alleles matched "6/6 antigen matched" HCT had survival outcomes within the partially matched cohort. We suggest that these proposed HLA subgroupings be used when complete HLA typing is not available. This improved categorization of HLA matching status allows adjustment for donor-recipient HLA compatibility, and can standardize interpretations of prior URD HCT experience.

Prospective clinical trials for blood transplantation and BMT are made more difficult by limited patient numbers, heterogeneity of clinical management strategies, and high-intensity therapy with frequent and toxic competing hazards. To address the challenges of prospective clinical study of BMT, the Blood and Marrow Transplant Clinical Trials Network (BMT CTN), sponsored by the National Heart, Lung, and Blood Institute/National Cancer Institute, was established. The network's charge is to design and execute multicenter clinical trials requiring participation from the network and from noncore centers for successful performance and to address rare diseases and unique populations that could not be well studied in individual centers. The BMT CTN organizational structure, current portfolio of studies, and scientific agenda are reviewed. Opportunities for investigators in any institution to propose trials and participate are outlined.

Emergencies come at the most inopportune times. Some are totally unexpected, others come with short warnings. Although rare, an emergency comes with the potential to wreak disaster and pose serious risk to the services provided to hematopoietic cell transplant (HCT) patients. Yet, the consequences of an emergency can be mitigated by thinking the unthinkable and having a plan for emergency preparedness in place. Each HCT center should develop a plan containing steps of mitigation, preparedness, response and recovery. This report provides the framework for a HCT-specific emergency preparedness plan that can be used by individual centers to develop customized guidelines on preparing for, responding to, and recovering from an emergency.

Matching for HLA class I alleles, including HLA-C, is an important criterion for outcome of unrelated donor transplantation. However, haplotype-mismatched transplantations for myeloid malignancies, mismatched for killer immunoglobulin-like receptor (KIR) ligands in the graft-versus-host (GVH) direction, is associated with lower rates of graft-versus-host disease (GVHD), relapse, and mortality. This study investigated the effect of KIR ligand mismatching on the outcome of unrelated donor transplantation. The outcomes after 1571 unrelated donor transplantations for myeloid malignancies where donor-recipient pairs were HLA-A, -B, -C, and -DRB1 matched (n = 1004), GVH KIR ligand-mismatched (n = 137), host-versus-graft (HVG) KIR ligand-mismatched (n = 170), and HLA-B and/or -C-mismatched but KIR ligand-matched (n = 260) were compared using Cox regression models. Treatment-related mortality (TRM), treatment failure, and overall mortality were lowest after matched transplantations. Patients who received grafts from donors mismatched at the KIR ligand in the GVH or HVG direction and mismatched at HLA-B and/or C but matched at the KIR ligand had similar rates of TRM, treatment failure, and overall mortality. There were no differences in leukemia recurrence between the 4 groups. These results do not support the choice of an unrelated donor on the basis of KIR ligand mismatch determined from HLA typing.

Evaluation and management of victims of exposure to myelosuppressive radiation in a military, terrorist, or accidental event is challenging. The hematopoietic syndrome with marrow suppression and pancytopenia follows intermediate intensity radiation exposure and as such produces a clinical syndrome similar to that after myelosuppressive chemotherapy or stem cell transplantation. Therefore, hematologists, oncologists, and transplantation physicians have the opportunity and challenge to plan for care of irradiation victims. Management of the hematopoietic syndrome, as a component of acute radiation sickness, requires understanding its manifestations and implementation of clinical biodosimetry to provide appropriate therapeutic support. Hematopoietic growth factors may be of value if administered early as a component of supportive care. Planning for urgent stem cell transplantation for those with intermediate- to high-dose radiation (4-10 Gy) may be required. Establishing contingency plans for triage, assessment, supportive care, and treatment resembles the development of phase II trials, with defined eligibilities, treatment plans, and incorporated data collection to assess results and plan further improvements in care. The hematology/oncology community is most suited to participate in such contingency planning, and the necessary elements for its success are reviewed.

Outcome of unrelated donor marrow transplantation is influenced by donor-recipient matching for HLA. Prior studies assessing the effects of mismatches at specific HLA loci have yielded conflicting results. The importance of high-resolution matching for all HLA loci has also not been established. We therefore examined the effects of HLA matching (low or high resolution or both) on engraftment, graft-versus-host disease (GVHD), and mortality in 1874 donor-recipient pairs retrospectively typed at high resolution for HLA-A, -B, -C, -DRB1, -DQ, and -DP. Mismatches at HLA-A, -B, -C, and -DRB1 each had similar adverse effects on mortality. Only HLA-A mismatches demonstrated significant adverse effects on GVHD. These adverse effects on outcome were more evident in transplants with low-resolution versus only high-resolution mismatches. Mismatches for HLA-DQ or -DP did not significantly affect outcome. When high-resolution mismatches at HLA-A, -B, -C, and -DRB1 were considered together, adverse effects on survival and GVHD were observed. We therefore conclude that matching for HLA-C should be incorporated into algorithms for unrelated donor selection. High-resolution mismatches at HLA-A, -B, -C, and -DRB1 adversely affect outcome, but less so than low-resolution mismatches. When clinical circumstances allow, high-resolution class I typing may help optimize donor selection and improve outcome.

Since its founding in 1986, the NMDP has facilitated more than 16,000 transplants for patients with blood disorders such as leukemia and aplastic anemia, as well as immune system disorders and genetic disorders. The donors who provided the blood stem cells for these transplants came from the NMDP Registry, the world's largest and most diverse registry of potential blood stem cell donors. Initiating a search of the NMDP Registry for an HLA-matched unrelated donor is as simple as submitting to the NMDP a patient's HLA typing results along with basic demographic and disease information. If a suitable donor is identified, the NMDP coordinates the steps needed to bring the donated stem cells--whether they be marrow, PBSC, or cord blood--to a patient. After reading this article, physicians should have a greater understanding of the complicated process needed to bring about an unrelated donor stem cell transplant. A better understanding of the role the NMDP plays in unrelated donor stem cell transplantation reduces the chances that physicians and patients will have unrealistic expectations about the process. To initiate a preliminary search of the NMDP Registry, contact the NMDP Office of Patient Advocacy toll-free at 1-888-999-6743. A preliminary search reqest form can also be submitted via the NMDP website:www.marrow.org

We analyzed engraftment of unrelated-donor (URD) bone marrow in 5246 patients who received transplants facilitated by the National Marrow Donor Program between August 1991 and June 1999. Among patients surviving at least 28 days, 4% had primary graft failure (failure to achieve an absolute neutrophil count > 5 x 10(8)/L before death or second stem-cell infusion). Multivariate logistic regression analysis showed that engraftment was associated with marrow matched at HLA-A, HLA-B, and DRB1; higher cell dose; younger recipient; male recipient; and recipient from a non-African American ethnic group. More rapid myeloid engraftment was associated with marrow serologically matched at HLA-A and HLA-B, DRB1 match, higher cell dose (in non-T-cell-depleted cases), younger recipient, recipient seronegativity for cytomegalovirus (CMV), male donor, no methotrexate for graft-versus-host disease prophylaxis, and transplantation done in more recent years. A platelet count higher than 50 x 10(9)/L was achieved by 47% of patients by day 100. Conditional on survival to day 100, survival at 3 years was 61% in those with platelet engraftment at day 30, 58% in those with engraftment between day 30 and day 100, and 33% in those without engraftment at day 100 (P <.0001). Factors favoring platelet engraftment were higher cell dose, DRB1 allele match, recipient seronegativity for CMV, HLA-A and HLA-B serologically matched donor, and male donor. Secondary graft failure occurred in 10% of patients achieving initial engraftment, and 18% of those patients are alive. These data demonstrate that quality of engraftment is an important predictor of survival after URD bone marrow transplantation.

Increasingly strong medical and political pressures are stimulating consideration of the transplantation of baboon organs and cells into humans. Critical to the success of these xenotransplants is management of the immune system such that graft rejection and, in the case of bone marrow transplantation, graft-versus-host disease do not result in transplant failure. The polymorphic products of the major histocompatibility complex (MHC) are the primary barrier to successful allotransplantation, and here we describe class I MHC molecules from baboon (Papio anubis) to gain an understanding of how similarities and differences between baboon and human MHC molecules might affect xenograft survival and function. Comparative analyses of our five novel baboon class I molecules with defined HLA class I molecules demonstrate that the baboon class I molecule are up to 90% identical. Disparity between baboon class I proteins and their human homologues lies predominately at positions in the antigen-binding groove, while C-terminal portions of the class I heavy chain are more conserved between the two species. Such concentration of cross-species differences within the alpha1 and alpha2 domains involves a majority of substitutions at positions demonstrating polymorphism in human alleles; the location of substitutions distinguishing baboon and human molecules thus resembles the positioning of human class I allopolymorphisms. Because this preliminary characterization indicates that both baboon and human T cells with be restricted by xenogeneic class I molecules, immune responses triggered during baboon-to-human transplantation should mimic those arising during MHC mismatched human allotransplantation.