Histocompatibility testing guidelines for hematopoietic stem cell transplantation using volunteer donors: report from The World. Marrow Donor Association.
Bone Marrow Transplantation, (1999) 24, 119–121 1999 Stockton Press All rights reserved 0268–3369/99 $12.00 http://www.stockton-press.co.uk/bmt
Special report Histocompatibility testing guidelines for hematopoietic stem cell transplantation using volunteer donors: report from The World Marrow Donor Association CK Hurley1, JA Wade2, M Oudshoorn3, D Middleton4, D Kukuruga5, C Navarrete6, F Christiansen7, J Hegland8, E-C Ren9, I Andersen10, SA Cleaver11, C Brautbar12 and C Raffoux13 on behalf of the Quality Assurance and Donor Registries Working Groups of the World Marrow Donor Association 1
Department of Microbiology and Immunology, Georgetown University Medical School, Washington DC, USA; 2Regional Histocompatibility Laboratory, The Toronto Hospital, University of Toronto, Toronto, Ontario, Canada; 3Europdonor Foundation and Department of Immunohematology and Bloodbank, Leiden University Medical Centre, Leiden, The Netherlands; 4Northern Ireland Regional Histocompatibility and Immunogenetics Laboratory, City Hospital, Belfast, Ireland; 5Department of Pathology, Wayne State University, Detroit, MI, USA; 6Department of Histocompatibility and Immunogenetics, The London Cord Blood Bank, NBS-London and the South East, London, UK; 7Department of Clinical Immunology, Royal Perth Hospital, Perth, Australia; 8 National Marrow Donor Program, Minneapolis, MN, USA; 9Singapore Bone Marrow Donor Program, National University of Singapore, Singapore; 10Norwegian Bone Marrow Donor Registry, Institute of Transplantation Immunology, The National Hospital, Oslo, Norway; 11The Anthony Nolan Bone Marrow Trust, The Royal Free Hospital, London, UK; 12Tissue Typing Unit, Hadassah ˆ Medical Organization, Jerusalem, Israel; and 13France Greffe de Moelle, Hopital Saint-Louis, Paris, France
Summary: The World Marrow Donor Association has formulated guidelines for establishing the extent and quality of histocompatibility testing for unrelated donor registries, umbilical cord blood banks, and transplant centers involved in international exchange of hematopoietic stem cells for allogeneic transplantation. The ability to identify unrelated stem cell donors in one country for patients in another country requires cooperation and standardization in many areas. The adoption of guidelines for histocompatibility testing, such as those summarized in this report, will facilitate these opportunities and rapidly provide accurately typed donors for patients in need. Keywords: marrow transplantation; donor registries; histocompatibility testing
One goal of the World Marrow Donor Association (WMDA) is to provide recommendations for standardized practice in stem cell transplantation involving volunteer donors in one country who provide stem cells for unrelated patients in another country.1,2 The goal of this document is to outline general guidelines that might be used to establish the extent and quality of histocompatibility testing for unrelated donor registries, umbilical cord blood banks, and Correspondence: CK Hurley, E404 Research Building, Georgetown University Medical Center, 3970 Reservoir Road NW, Washington DC 20007, USA Received 24 December 1998; accepted 3 March 1999
transplant centers involved in international allogeneic stem cell transplants. Other reports include a more extensive discussion of these guidelines.3,4
Summary of WMDA Recommended Histocompatibility Testing Guidelines for Unrelated Hematopoietic Stem Cell Transplant I Adult Volunteer Donor Registry A HLA loci to test (1) HLA-A,-B,-DR should be tested for each donor prior to initial listing on the registry. B Method of testing (1) DNA-based testing is recommended for HLA-A,-B and required for HLA-DR. (2) If serology is used for HLA-A,-B, a DNA-based method must be used to define antigens in the population tested which are frequently missed and/or misassigned. C Level of resolution of testing (1) At the minimum, serologic split/low level DNA-based resolution is recommended to define HLA-A,-B,-DR types. D Quality control of testing procedures
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(1) HLA testing laboratories must be accredited for HLA typing using specific standards for each methodology utilized in the testing. (2) Laboratories must participate in external and internal proficiency testing. (3) The HLA typing laboratory must be directed by an individual who has appropriate training and experience in histocompatibility, immunogenetics, and population genetics including histocompatibility testing expertise, preferably with an advanced medical or science degree. (4) Registries must establish approaches to monitor the quality of registry typing. (5) The registry should seek the advice of histocompatibility experts in the selection of HLA typing methodologies and design of strategies for achieving the optimal size and racial/ethnic composition. E Recording of HLA types in the registry database (1) WHO nomenclature must be used to record HLA types; an ‘X’ should be used to record an unknown serologic type. (2) Apparent homozygous antigens or alleles should be recorded once only unless confirmed homozygous by family segregation studies. (3) Data storage of donor HLA types or their equivalents must allow for rapid and reliable searches and for evaluation of the registry composition of HLA types and haplotypes. F Facilitating search requests (1) Registries (and banks) must respond to search requests and to requests for additional information and/or an aliquot of donor sample (ie blood or DNA required for additional histocompatibility testing) in a timely and defined fashion. (2) Donors (or cord blood units) selected for a specific patient must be placed on a ‘not available’ status until the transplantation date is reached. A maximum time limit for this status should be set in writing. II Umbilical Cord Blood Banks A The same guidelines as recommended for adult donor registries should be followed. III Transplant center’s laboratory for patient, family and selected donor typing A HLA loci and individuals to test (1) HLA-A,-B,-DR must be tested. Typing for other HLA loci including HLA-C, HLA-DRB3, -DRB4, -DRB5 and -DQB1 is highly recommended. (2) Typing of siblings and parents of the patient should be used, whenever possible, to identify any sibling donors, to confirm the patient’s HLA types, and to define haplotypes. An extended family typing might be undertaken to identify a related donor.
B Method of testing (1) DNA-based testing is highly recommended for HLAA,-B and required for HLA-DR particularly when typing either unrelated donors or related donors where family is not available to confirm genotypes. (2) If serology is used for HLA-A,-B, a DNA-based method must be used to define frequently misassigned or missed antigens in unrelated donors and should be used in related individuals when unequivocal haplotype assignment is not possible. (3) Other assays with clinical relevance may be utilized. C Level of resolution of testing (1) Family typing should utilize serologic split/ low level resolution typing. For patients without available family to confirm genotypes, for those whose search is to be extended to an unrelated donor, and for unrelated donors themselves, serologic split/low level resolution for HLA-A,-B and allele level for DRB1 is required, at a minimum. D Quality control of testing procedures (1) HLA laboratories for clinical testing must follow the same guidelines established for registry typing. (2) Cells or DNA should be retained from all transplant pairs for use in monitoring the impact of HLA matching on outcome, in evaluating the quality of transplant center typing, and in retesting as new reagents become available. E Recording and confirming HLA types (1) WHO nomenclature must be used to report HLA types. (2) Prior to transplant, typing of patient and donor must be repeated on fresh samples using an optimal set of reagents and methodology. Both patient and donor should be typed with the same set of reagents, methodology, and interpretation criteria, preferably in the same laboratory. F Time limits on testing (1) For those patients for whom transplantation is an appropriate therapy, family typings and preliminary unrelated searches should be performed early to facilitate consideration of treatment options.
Acknowledgements The Quality Assurance and Donor Registries Working Groups would like to thank the Board of the World Marrow Donor Association and other members of the organization for their comments and advice in developing these guidelines.
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References 1 Goldman JM. A special report: bone marrow transplants using volunteer donors – recommendations and requirements for a standardized practice throughout the world – 1994 update. Blood 1994; 84: 2833–2839. 2 Cleaver SA, Warren P, Kern M et al. A special report: donor work-up and transport of bone marrow – recommendations
and requirements for a standardized practice throughout the world. Bone Marrow Transplant 1997; 20: 621–629. 3 Hurley CK, Wade JA, Oudshoorn M et al. A special report: histocompatibility testing guidelines for hematopoietic stem cell transplantation using volunteer donors. Tissue Antigens 1999; 53: 394–406. 4 Hurley CK, Wade JA, Oudshoorn M et al. A special report: histocompatibility testing guidelines for hematopoietic stem cell transplantation using volunteer donors. Hum Immunol (in press).
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