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

1Department 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; 8National 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: transplant centers involved in international allogeneic stem cell transplants. Other reports include a more extensive dis- The World Marrow Donor Association has formulated cussion of these guidelines.3,4 guidelines for establishing the extent and quality of his- tocompatibility testing for unrelated donor registries, umbilical cord blood banks, and transplant centers Summary of WMDA Recommended involved in international exchange of hematopoietic Histocompatibility Testing Guidelines for Unrelated stem cells for allogeneic transplantation. The ability to Hematopoietic Stem Cell Transplant identify unrelated stem cell donors in one country for patients in another country requires cooperation and I Adult Volunteer Donor Registry standardization in many areas. The adoption of guide- lines for histocompatibility testing, such as those sum- A HLA loci to test marized in this report, will facilitate these opportunities and rapidly provide accurately typed donors for (1) HLA-A,-B,-DR should be tested for each donor prior patients in need. to initial listing on the registry. Keywords: marrow transplantation; donor registries; his- tocompatibility testing B Method of testing

(1) DNA-based testing is recommended for HLA-A,-B and One goal of the World Marrow Donor Association required for HLA-DR. (WMDA) is to provide recommendations for standardized (2) If serology is used for HLA-A,-B, a DNA-based practice in stem cell transplantation involving volunteer method must be used to define antigens in the donors in one country who provide stem cells for unrelated population tested which are frequently missed and/or patients in another country.1,2 The goal of this document is misassigned. to outline general guidelines that might be used to establish the extent and quality of histocompatibility testing for unre- C Level of resolution of testing lated donor registries, umbilical cord blood banks, and (1) At the minimum, serologic split/low level DNA-based resolution is recommended to define HLA-A,-B,-DR Correspondence: CK Hurley, E404 Research Building, Georgetown Uni- types. versity Medical Center, 3970 Reservoir Road NW, Washington DC 20007, USA Received 24 December 1998; accepted 3 March 1999 D Quality control of testing procedures HLA testing guidelines for volunteer donors CK Hurley et al 120 (1) HLA testing laboratories must be accredited for HLA B Method of testing typing using specific standards for each methodology utilized in the testing. (1) DNA-based testing is highly recommended for HLA- (2) Laboratories must participate in external and internal A,-B and required for HLA-DR particularly when proficiency testing. typing either unrelated donors or related donors where (3) The HLA typing laboratory must be directed by an family is not available to confirm genotypes. individual who has appropriate training and experience (2) If serology is used for HLA-A,-B, a DNA-based in histocompatibility, immunogenetics, and population method must be used to define frequently misassigned genetics including histocompatibility testing expertise, or missed antigens in unrelated donors and should be preferably with an advanced medical or science degree. used in related individuals when unequivocal haplotype (4) Registries must establish approaches to monitor the assignment is not possible. quality of registry typing. (3) Other assays with clinical relevance may be utilized. (5) The registry should seek the advice of histocompat- ibility experts in the selection of HLA typing method- ologies and design of strategies for achieving the opti- C Level of resolution of testing mal size and racial/ethnic composition. (1) Family typing should utilize serologic split/ low level E Recording of HLA types in the registry database resolution typing. For patients without available family to confirm genotypes, for those whose search is to be (1) WHO nomenclature must be used to record HLA types; extended to an unrelated donor, and for unrelated an ‘X’ should be used to record an unknown sero- donors themselves, serologic split/low level resolution logic type. for HLA-A,-B and allele level for DRB1 is required, (2) Apparent homozygous antigens or alleles should be at a minimum. recorded once only unless confirmed homozygous by family segregation studies. D Quality control of testing procedures (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 (1) HLA laboratories for clinical testing must follow the and haplotypes. 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 match- F Facilitating search requests ing on outcome, in evaluating the quality of transplant center typing, and in retesting as new reagents (1) Registries (and banks) must respond to search requests become available. and to requests for additional information and/or an ali- quot of donor sample (ie blood or DNA required for additional histocompatibility testing) in a timely and E Recording and confirming HLA types defined fashion. (2) Donors (or cord blood units) selected for a specific (1) WHO nomenclature must be used to report HLA types. patient must be placed on a ‘not available’ status until (2) Prior to transplant, typing of patient and donor must be the transplantation date is reached. A maximum time repeated on fresh samples using an optimal set of limit for this status should be set in writing. reagents and methodology. Both patient and donor should be typed with the same set of reagents, method- ology, and interpretation criteria, preferably in the II Umbilical Cord Blood Banks same laboratory. A The same guidelines as recommended for adult donor registries should be followed. F Time limits on testing

III Transplant center’s laboratory for patient, family and (1) For those patients for whom transplantation is an selected donor typing appropriate therapy, family typings and preliminary unrelated searches should be performed early to facili- A HLA loci and individuals to test tate consideration of treatment options. (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. Acknowledgements (2) Typing of siblings and parents of the patient should be used, whenever possible, to identify any sibling donors, The Quality Assurance and Donor Registries Working Groups to confirm the patient’s HLA types, and to define would like to thank the Board of the World Marrow Donor haplotypes. An extended family typing might be under- Association and other members of the organization for their com- taken to identify a related donor. ments and advice in developing these guidelines. HLA testing guidelines for volunteer donors CK Hurley et al 121 References 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: 1 Goldman JM. A special report: bone marrow transplants using histocompatibility testing guidelines for hematopoietic stem volunteer donors – recommendations and requirements for a cell transplantation using volunteer donors. Tissue Antigens standardized practice throughout the world – 1994 update. 1999; 53: 394–406. Blood 1994; 84: 2833–2839. 4 Hurley CK, Wade JA, Oudshoorn M et al. A special report: 2 Cleaver SA, Warren P, Kern M et al. A special report: donor histocompatibility testing guidelines for hematopoietic stem work-up and transport of bone marrow – recommendations cell transplantation using volunteer donors. Hum Immunol (in press).