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Nunes E.,AABB | Heslop H.,American Society for Blood and Marrow Transplantation ASBMT | Fernandez-Vina M.,American Society for Histocompatibility and Immunogenetics ASHI | Taves C.,American Society for Histocompatibility and Immunogenetics ASHI | And 8 more authors.
Human Immunology | Year: 2011

Histocompatibility testing for stem cell and solid organ transplantation has become increasingly complex as newly discovered human leukocyte antigen (HLA) alleles are described. HLA typing assignments reported by laboratories are used by physicians and donor registries for matching donors and recipients. To communicate effectively, a common language for histocompatibility terms should be established. In early 2010, representatives from clinical, registry, and histocompatibility organizations joined together as the Harmonization of Histocompatibility Typing Terms Working Group to define a consensual language for laboratories, physicians and registries to communicate histocompatibility typing information. The Working Group defined terms for HLA typing resolution, HLA matching and a format for reporting HLA assignments. In addition, definitions of verification typing and extended typing were addressed. The original draft of the Definitions of Histocompatibility Typing Terms was disseminated to colleagues from each organization to gain feedback and create a collaborative document. Commentary gathered during this 90-day review period were discussed and implemented for preparation of this report. Histocompatibility testing continues to evolve thus, the definitions agreed upon today, likely will require refinement and perhaps additional terminology in the future. © 2011 American Society for Histocompatibility and Immunogenetics.


Eberhard H..-P.,Zentrales Knochenmarkspender Register Deutschland ZKRD | Madbouly A.S.,National Marrow Donor Program NMDP | Gourraud P.A.,France Greffe de Moelle FGM | Balere M.L.,France Greffe de Moelle FGM | And 11 more authors.
Tissue Antigens | Year: 2013

Estimation of human leukocyte antigen (HLA) haplotype frequencies from unrelated stem cell donor registries presents a challenge because of large sample sizes and heterogeneity of HLA typing data. For the 14th International HLA and Immunogenetics Workshop, five bioinformatics groups initiated the 'Registry Diversity Component' aiming to cross-validate and improve current haplotype estimation tools. Five datasets were derived from different donor registries and then used as input for five different computer programs for haplotype frequency estimation. Because of issues related to heterogeneity and complexity of HLA typing data identified in the initial phase, the same five implementations, and two new ones, were used on simulated datasets in a controlled experiment where the correct results were known a priori. These datasets contained various fractions of missing HLA-DR modeled after European haplotype frequencies. We measured the contribution of sampling fluctuation and estimation error to the deviation of the frequencies from their true values, finding equivalent contributions of each for the chosen samples. Because of patient-directed activities, selective prospective typing strategies and the variety and evolution of typing technology, some donors have more complete and better HLA data. In this setting, we show that restricting estimation to fully typed individuals introduces biases that could be overcome by including all donors in frequency estimation. Our study underlines the importance of critical review and validation of tools in registry-related activity and provides a sustainable framework for validating the computational tools used. Accurate frequencies are essential for match prediction to improve registry operations and to help more patients identify suitably matched donors. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd 82 2 August 2013 10.1111/tan.12160 Original article Original articles © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


McDermott D.H.,National Institute of Allergy and Infectious Diseases | Conway S.E.,Brigham and Women's Hospital | Wang T.,Medical College of Wisconsin | Ricklefs S.M.,National Institute of Allergy and Infectious Diseases | And 6 more authors.
Blood | Year: 2010

Despite continual improvement, morbidity and mortality after hematopoietic stem cell transplantation (HSCT) remain high. The importance of chemokines in HSCT lies in their regulation of immune responses that determine transplantation outcomes. We investigated the role of recipient and donor chemokine system gene polymorphisms by using a candidate gene approach on the incidence of graft-versus-host disease and posttransplantation outcomes in 1370 extensively human leukocyte antigen-matched, unrelated donor-recipient pairs by using multivariate Cox regression models. Our analysis identified that recipients homozygous for a common CCR5 haplotype (H1/H1) had better disease-free survival (DFS; P = .005) and overall survival (P = .021). When the same genotype of both the donor and recipient were considered in the models, a highly significant association with DFS and overall survival was noted (P < .001 and P = .007, respectively) with absolute differences in survival of up to 20% seen between the groups at 3 years after transplantation (50% DFS for pairs with recipient CCR5 H1/H1 vs 30% for pairs with donor CCR5 H1/H1). This finding suggests that donor and/or recipient CCR5 genotypes may be associated with HSCT outcome and suggests new diagnostic and therapeutic strategies for optimizing therapy.


Bochtler W.,Zentrales Knochenmarkspender Register fur Deutschland ZKRD | Maiers M.,National Marrow Donor Program NMDP | Bakker J.N.A.,Europdonor Foundation | Baier D.M.,German Bone Marrow Donor Center | And 8 more authors.
Bone Marrow Transplantation | Year: 2013

For more than two decades, international cooperation and information technology have been playing key roles in the identification of suitable unrelated donors and cord blood units for hematopoietic SCT. To ensure consistent coding and interpretation of HLA data among the linked computer systems, the World Marrow Donor Association has standardized the extensions of the World Health Organization (WHO) Nomenclature for factors of the HLA system applied in practice. The first version of this report published in 2007 has become the reference for the technical validation of HLA information on donors and patients in the context of search and matching and is used by registries of volunteer unrelated hematopoietic stem cell donors and umbilical cord blood banks throughout the world. The present update became necessary after the major revision of the WHO HLA nomenclature in April 2010. It now covers issues arising when alleles are withdrawn or renamed because of the continuous updating of the WHO HLA nomenclature. In addition, formal validation and interpretation rules for the so-called 'multiple allele codes' have been added.

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