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Post-Transplant Events

Prediction of duration and success rate of unrelated hematopoietic stem cell donor searches based on the patient's HLA-DRB1 allele and DRB1-DQB1 haplotype frequencies

Bone Marrow Transplantation volume 44, pages 433–440 (2009)Cite this article

Abstract

Rapid identification of a matched unrelated donor is essential for patients in need of hematopoietic SCT. We carried out a retrospective evaluation of 549 unrelated donor searches (UDSs), which were completed in 2005 for 23 German transplant centers. On the basis of the patient's HLA-DRB1 allele and DRB1–DQB1 haplotype frequencies, UDSs were divided into four groups with different search success probability predictions. For 90.5% of the patients, an acceptable HLA-matched, and for 61.6% an HLA-A-B-Cw-DRB1-DQB1-identical (10/10 matched) unrelated donor was found. The median search duration was 22 days. In the groups with high (n=318), medium (n=157), low (n=56) and very low (n=18) UDS success probability, an acceptable donor was found for 99.1, 86.6, 75.0 and 22.2% of the patients, and a 10/10-matched donor was found for 78.3, 49.7, 17.9 and 4.5% of the patients, respectively. The median search duration was 20, 27, 45 and 477 days in the groups with high, medium, low and very low probability, respectively. The search success rate and duration can be predicted on the basis of the patient's HLA-DRB1 allele and HLA-DRB1-DQB1 haplotype frequencies. An unrelated donor can be found for most of the patients, even if the indication for transplantation is urgent.

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References

  1. Copelan EA . Hematopoietic stem-cell transplantation. N Engl J Med 2006; 354: 1813–1826.

    Article  CAS  PubMed  Google Scholar 

  2. Gratwohl A, Baldomero H, Frauendorfer K, Rocha V, Apperley J, Niederwieser D . The EBMT activity survey 2006 on hematopoietic stem cell transplantation: focus on the use of cord blood products. Bone Marrow Transplant 2008; 41: 687–705.

    Article  CAS  PubMed  Google Scholar 

  3. Deutsches Register für Stammzelltransplantationen Jahresbericht 2006. http://www.drst.de/download/jb2006.pdf. Accessed June 23, 2008.

  4. Ottinger H, Müller C, Beelen DW, Ehninger G, Schmitz N, Zander A et al. Developments and quality assurance in stem cell transplantation—data from the German national registry. Dtsch Arztebl 2006; 103: A2381–A2386.

    Google Scholar 

  5. Lee SJ, Klein J, Haagenson M, Baxter-Lowe LA, Confer DL, Eapen M et al. High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood 2007; 110: 4576–4583.

    Article  CAS  PubMed  Google Scholar 

  6. Grewal SS, Barker JN, Davies SM, Wagner JE . Unrelated donor hematopoietic cell transplantation: marrow or umbilical cord blood? Blood 2003; 101: 4233–4244.

    Article  CAS  PubMed  Google Scholar 

  7. Bone Marrow Donors Worldwide. Number of donors and cord blood units in the BMDW database. http://www.bmdw.org. Accessed June 23, 2008.

  8. van Rood JJ, Oudshoorn M . Eleven million donors in Bone Marrow Donors Worldwide! Time for reassessment? Bone Marrow Transplant 2008; 41: 1–9.

    Article  CAS  PubMed  Google Scholar 

  9. Hurley CK, Fernandez Vina M, Setterholm M . Maximizing optimal hematopoietic stem cell donor selection from registries of unrelated adult volunteers. Tissue Antigens 2003; 61: 415–424.

    Article  CAS  PubMed  Google Scholar 

  10. Heemskerk MBA, van Walraven SM, Cornelissen JJ, Barge RMY, Bredius RGM, Egeler RM et al. How to improve the search for an unrelated haematopoietic stem cell donor. Faster is better than more!. Bone Marrow Transplant 2005; 35: 645–652.

    Article  CAS  PubMed  Google Scholar 

  11. Tiercy JM, Nicoloso G, Passweg J, Schanz U, Seger R, Chalandon Y et al. The probability of identifying a 10/10 HLA-matched unrelated donor is highly predictable. Bone Marrow Transplant 2007; 40: 515–522.

    Article  CAS  PubMed  Google Scholar 

  12. Hurley CK, Baxter Lowe LA, Logan B, Karanes C, Anasetti C, Weisdorf D et al. National Marrow Donor Program HLA-matching guidelines for unrelated marrow transplants. Biol Blood Marrow Transplant 2003; 9: 610–615.

    Article  PubMed  Google Scholar 

  13. Barker JN, Krepski TP, DeFor TE, Davies SM, Wagner JE, Weisdorf DJ . Searching for unrelated donor hematopoietic stem cells: availability and speed of umbilical cord blood versus bone marrow. Biol Blood Marrow Transplant 2002; 8: 257–260.

    Article  PubMed  Google Scholar 

  14. Müller CR, Ehninger G, Goldmann SF . Gene and haplotype frequencies for the loci HLA-A, HLA-B, and HLA-DR based on over 13 000 German blood donors. Hum Immunol 2003; 64: 137–151.

    Article  PubMed  Google Scholar 

  15. Hurley CK, Wagner JE, Setterholm MI, Confer DL . Advances in HLA: practical implications for selecting adult donors and cord blood units. Biol Blood Marrow Transplant 2006; 12: 28–33.

    Article  PubMed  Google Scholar 

  16. Hurley CK, Fernandez-Vina M, Hildebrand WH, Noreen HJ, Trachtenberg E, Williams TM et al. A high degree of HLA disparity arises from limited allelic diversity: analysis of 1775 unrelated bone marrow transplant donor-recipient pairs. Hum Immunol 2007; 68: 30–40.

    Article  CAS  PubMed  Google Scholar 

  17. German National Bone Marrow Donor Registry. German standards for unrelated blood stem cell donations. http://www.zkrd.de/fileadmin/download/German_StandardsV4.pdf. Accessed June 23, 2008.

  18. World Marrow Donor Association. World Marrow Donor Association international standards for unrelated hematopoietic stem cell donor registries. http://www.worldmarrow.org/fileadmin/WorkingGroups_Subcommittees/Accreditation/Documents/standards_history/WMDA_Standards_December_2007.pdf. Accessed March 11, 2009.

  19. Wiegand T, Raffoux C, Hurley CK, Kern M, Oudshoorn M, Raymond J et al. A special report: suggested procedures for international unrelated donor search from the donor registries and quality assurance working groups of the World Marrow Donor Association (WMDA). Bone Marrow Transplant 2004; 34: 97–101.

    Article  CAS  PubMed  Google Scholar 

  20. Ottinger HD, Müller CR, Goldmann SF, Albert E, Arnold R, Beelen DW et al. Second German consensus on immunogenetic donor search for allotransplantation of hematopoietic stem cells. Ann Hematol 2001; 80: 706–714.

    Article  CAS  PubMed  Google Scholar 

  21. Ottinger HD, Müller C, Riebschläger S, Arnold R, Beelen DW, Blasczyk R et al. Dritter Deutscher Konsensus zur immungenetischen Spenderauswahl für die allogene Stammzelltransplantation. http://www.dgiev.de/data/Konsensus_Version_AugustFinal_2005.pdf. Accessed June 23, 2008.

  22. Schreuder GMT, Hurley CK, Marsh SGE, Lau M, Maiers M, Kollman C et al. The HLA Dictionary 2001: a summary of HLA-A, -B, -C, DRB1/3/4/5 and -DQB1 alleles and their association with serologically defined HLA-A, -B, -C, -DR and -DQ antigens. Eur J Immunogenet 2001; 28: 565–596.

    Article  CAS  PubMed  Google Scholar 

  23. Klitz W, Maiers M, Spellman S, Baxter-Lowe LA, Schmeckpeper B, Williams TM et al. New HLA haplotype frequency reference standards: high resolution and large sample typing of HLA DR-DQ haplotypes in a sample of European Americans. Tissue Antigens 2003; 62: 296–307.

    Article  CAS  PubMed  Google Scholar 

  24. Knipper AJ, Hakenberg P, Enczmann J, Kuhröber A, Kiesel U, Kögler G et al. HLA-DRB1, 3, 4, 5 and -DQB1 allele frequencies and HLA-DR/DQ linkage disequilibrium of 231 German Caucasoid patients and their corresponding 821 potential unrelated stem cell transplants. Hum Immunol 2000; 61: 605–614.

    Article  CAS  PubMed  Google Scholar 

  25. Pedron B, Yakouben K, Adjaoud D, Auvrignon A, Landman J, Guerin V et al. Listing of common HLA alleles and haplotypes based on the study of 356 families residing in the Paris, France, area: implications for unrelated hematopoietic stem cell donor selection. Hum Immunol 2005; 66: 721–731.

    Article  CAS  PubMed  Google Scholar 

  26. Tallman MS, Rowlings PA, Milone G, Zhang M, Perez WS, Weisdorf D et al. Effect of postremission chemotherapy before human leukocyte antigen-identical sibling transplantation for acute myelogenous leukaemia in first complete remission. Blood 2000; 96: 1254–1258.

    CAS  PubMed  Google Scholar 

  27. Platzbecker U, Thiede C, Füssel M, Geissler G, Illmer T, Mohr B et al. Reduced intensity conditioning allows for up-front allogeneic hematopoietic stem cell transplantation after cytoreductive induction therapy in newly-diagnosed high-risk acute myeloid leukemia. Leukemia 2006; 20: 707–714.

    Article  CAS  PubMed  Google Scholar 

  28. Rubinstein P, Carrier C, Scaradavou A, Kurtzberg J, Adamson J, Migliaccio AR et al. Outcomes among 562 recipients of placental-blood transplants from unrelated donors. N Engl J Med 1998; 339: 1565–1577.

    Article  CAS  PubMed  Google Scholar 

  29. Gluckman E, Rocha V . Cord blood transplant: strategy of alternative donor search. Springer Semin Immunopathol 2004; 26: 143–154.

    Article  PubMed  Google Scholar 

  30. Laughlin MJ, Eapen M, Rubinstein P, Wagner JE, Zhang M, Champlin RE et al. Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. N Engl J Med 2004; 351: 2265–2275.

    Article  CAS  PubMed  Google Scholar 

  31. Rocha V, Labopin M, Sanz G, Arcese W, Schwerdtfeger R, Bosi A et al. Transplants of umbilical-cord blood or bone marrow from unrelated donors in adults with acute leukaemia. N Engl J Med 2004; 351: 2276–2285.

    Article  CAS  PubMed  Google Scholar 

  32. Takahashi S, Ooi J, Tomonari A, Konuma T, Tsukada N, Oiwa-Monna M et al. Comparative single-institute analysis of cord blood transplantation from unrelated donors with bone marrow or peripheral blood stem-cell transplants from related donors in adult patients with hematologic malignancies after myeloablative conditioning regimen. Blood 2007; 109: 1322–1330.

    Article  CAS  PubMed  Google Scholar 

  33. McGlave PB, Ou Shu X, Wen W, Anasetti C, Nademanee A, Champlin R et al. Unrelated donor marrow transplantation for chronic myelogenous leukaemia: 9 years’ experience of the National Marrow Donor Program. Blood 2000; 95: 2219–2225.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank S Sander for her constructive comments on this paper, and SC Martindale for his editorial corrections of the English grammar. This analysis has been presented in part at the European Bone Marrow Transplantation Annual Meeting in Lyon, March 2007.

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Authors and Affiliations

  1. Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, University of Ulm & German Red Cross Blood Donation Service, Baden-Wuerttemberg, Hessen, Germany

    K Hirv, K Bloch, M Fischer, H Schrezenmeier & J Mytilineos

  2. Institute of Transfusion Medicine, University of Ulm & German Red Cross Blood Donation Service, Baden-Wuerttemberg, Hessen, Germany

    K Hirv, K Bloch, M Fischer, H Schrezenmeier & J Mytilineos

  3. Institute of Biometrics, University of Ulm, Ulm, Germany

    B Einsiedler

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  1. K Hirv
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Correspondence to K Hirv.

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Hirv, K., Bloch, K., Fischer, M. et al. Prediction of duration and success rate of unrelated hematopoietic stem cell donor searches based on the patient's HLA-DRB1 allele and DRB1-DQB1 haplotype frequencies. Bone Marrow Transplant 44, 433–440 (2009). https://doi.org/10.1038/bmt.2009.53

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