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Boo M.,National Marrow Donor Program | Van Walraven S.M.,Europdonor Foundation | Chapman J.,University of Sydney | Lindberg B.,National Marrow Donor Program | And 5 more authors.
Blood | Year: 2011

Hematopoietic stem cell transplantation is a curative procedure for life-threatening hematologic diseases. Donation of hematopoietic stem cells (HSCs) from an unrelated donor, frequently residing in another country, may be the only option for 70% of those in need of unrelated hematopoietic stem cell transplantation. To maximize the opportunity to find the best available donor, individual donor registries collaborate internationally. To provide homogeneity of practice among registries, the World Marrow Donor Association (WMDA) sets standards against which registries are accredited and provides guidance and regulations about unrelated donor safety and care. A basic tenet of the donor registries is that unrelated HSC donation is an altruistic act; nonpayment of donors is entrenched in the WMDA standards and in international practice. In the United States, the prohibition against remuneration of donors has recently been challenged. Here, we describe the reasons that the WMDA continues to believe that HSC donors should not be paid because of ethical concerns raised by remuneration, potential to damage the public will to act altruistically, the potential for coercion and exploitation of donors, increased risk to patients, harm to local transplantation programs and international stem cell exchange, and the possibility of benefiting some patients while disadvantaging others. © 2011 by The American Society of Hematology. Source

Dehn J.,National Marrow Donor Program | Buck K.,National Marrow Donor Program | Maiers M.,National Marrow Donor Program | Confer D.,National Marrow Donor Program | And 5 more authors.
Biology of Blood and Marrow Transplantation | Year: 2015

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. © 2015 American Society for Blood and Marrow Transplantation. Source

Schofl G.,DKMS Life Science Laboratory | Schmidt A.H.,German Bone Marrow Donor Center | Lange V.,DKMS Life Science Laboratory
Human Immunology | Year: 2016

While modern high-throughput sequence-based HLA genotyping methods generally provide highly accurate typing results, artefacts may nonetheless arise for numerous reasons, such as sample contamination, sequencing errors, read misalignments, or PCR amplification biases. To help detecting spurious typing results, we tested the performance of two probabilistic classifiers (binary logistic regression and random forest models) based on population-specific genotype frequencies. We trained the model using high-resolution typing results for HLA-DRB1, DQB1, and DPB1 from large samples of German, Polish and UK-based donors. The high predictive capacity of the best models replicated both in 10-fold cross-validation for each gene and in using independent evaluation data (AUC 0.820-0.893). While genotype frequencies alone provide enough predictive power to render the model generally useful for highlighting potentially spurious typing results, the inclusion of workflow-specific predictors substantially increases prediction specificity. Low initial DNA concentrations in combination with low-volume PCR reactions form a major source of stochastic error specific to the Fluidigm chip-based workflow at DKMS Life Science Lab. The addition of DNA concentrations as a predictor variable thus substantially increased AUC (0.947-0.959) over purely frequency-based models. © 2016 American Society for Histocompatibility and Immunogenetics. Source

Schmidt A.H.,German Bone Marrow Donor Center | Solloch U.V.,German Bone Marrow Donor Center | Pingel J.,German Bone Marrow Donor Center | Baier D.,German Bone Marrow Donor Center | And 7 more authors.
Human Immunology | Year: 2011

We present high-resolution allele and haplotype frequency (HF) estimations of the Polish population based on more than 20,000 registered stem cell donors. Sequencing-based donor human leukocyte antigen (HLA) typing led to unambiguous typing results in most cases (between 94.3% for HLA-DRB1 and 96.9% for HLA-B). HF estimations were carried out with a new, validated implementation of the expectation-maximization algorithm that allowed processing of data with ambiguities. Our results confirm several earlier results, for example, the relative commonness of the haplotype A*25:01g, B*18:01g, C*12:03, DRB1*04:01 in the Polish population. Because of the large sample size, we were able to obtain results of unprecedented accuracy. The estimated population-specific HFs were then used to analyze questions of strategic donor registry planning. Simulated matching probabilities by donor file size suggest that there is a need for intense donor recruitment efforts in Poland despite the large German donor registry and the genetic relatedness of both populations. Based on the current German registry size of approximately 4 million donors, the recruitment of 100,000 Polish donors would produce a stronger increase in matching probabilities for Polish patients than the recruitment of 3.3 million additional German donors. © 2011 American Society for Histocompatibility and Immunogenetics. Source

Hernandez-Frederick C.J.,German Bone Marrow Donor Center | Giani A.S.,German Bone Marrow Donor Center | Cereb N.,Histogenetics LLC | Sauter J.,German Bone Marrow Donor Center | And 5 more authors.
Tissue Antigens | Year: 2014

We describe 2127 new human leukocyte antigen (HLA) class I alleles found in registered stem cell donors. These alleles represent 28.9% of the currently known class I alleles. Comparing new allele sequences to homologous sequences, we found 68.1% nonsynonymous nucleotide substitutions, 28.9% silent mutations and 3.0% nonsense mutations. Many substitutions occurred at positions that have not been known to be polymorphic before. A large number of HLA alleles and nucleotide variations underline the extreme diversity of the HLA system. Strikingly, 156 new alleles were found not only multiple times, but also in carriers of various parentage, suggesting that some new alleles are not necessarily rare. Moreover, new alleles were found especially often in minority donors. This emphasizes the benefits of specifically recruiting such groups of individuals. © 2014 The Authors. Source

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