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HLA Matching

Isolated HLA-C mismatches in unrelated donor transplantation for CML

Bone Marrow Transplantation volume 34, pages 249–255 (2004)Cite this article

Summary:

HLA-incompatibility is a major factor associated with outcome of allogeneic stem cell transplantation, but little is known on the impact of isolated HLA-C mismatches. We analyzed the outcome of 114 CML patients transplanted with marrow from unrelated donors of whom 24 were mismatched for HLA-C only (9/10 match). Univariate estimates of 5-year survival (SRV) (median follow-up: 47 months) in the HLA-matched group were 68±12 vs 42±20% (P=0.03) for the patients mismatched for HLA-C only and 33±33% in the mismatched group (non-HLA-C single mismatches and multiple mismatches) (P=0.0004). Disease stage, GVHD-prophylaxis (T-cell depletion), CMV-status and HLA-incompatibility were the risk factors associated (all P⩽0.005) with poor outcome. In the multivariate analysis, patients mismatched for loci other than HLA-C were at high risk of an adverse outcome (death: RR, 2.9; CI, 1.6–5.4, P=0.008, transplant-related mortality (TRM): RR, 3; CI, 1.5–5.9, P=0.0015). For patients mismatched for HLA-C only, the increased risk was of borderline significance (death: RR, 1.9; CI, 1–3.9, P=0.06, TRM: RR, 2.1; CI, 1–4.5, P=0.07). In spite of their lower expression, HLA-C antigens still represent relevant transplantation barriers that should be considered when searching for an unrelated donor.

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References

  1. Santamaria P, Reinsmoen NL, Lindstrom AL et al. Frequent HLA class I and DP sequence mismatches in serologically (HLA-A, HLA-B, HLA-DR) and molecularly (HLA-DRB1, HLA-DQA1, HLA-DQB1) HLA-identical unrelated bone marrow transplant pairs. Blood 1994; 83: 280–287.

    CAS  PubMed  Google Scholar 

  2. Rufer N, Tiercy J-M, Breur-Vriesendorp B et al. Histoincompatibilities in ABDR-matched unrelated donor recipient combinations. Bone Marrow Transplant 1995; 16: 641–646.

    CAS  PubMed  Google Scholar 

  3. Scott I, O'Shea J, Bunce M et al. Molecular typing shows a high level of HLA class I incompatibility in serologically well matched donor/patient pairs: implications for unrelated bone marrow donor selection. Blood 1998; 92: 4864–4871.

    CAS  PubMed  Google Scholar 

  4. Prasad VK, Kernan NA, Heller G et al. DNA typing for HLA-A and HLA-B identifies disparities between patients and unrelated donors matched by HLA-A and HLA-B serology and HLA-DRB1. Blood 1999; 93: 399–409.

    CAS  PubMed  Google Scholar 

  5. Beatty PG, Anasetti C, Hansen JA et al. Marrow transplantation from unrelated donors for treatment of hematologic malignancies: effect of mismatching for one HLA locus. Blood 1993; 81: 249–253.

    CAS  PubMed  Google Scholar 

  6. Kernan NA, Bartsch G, Ash R et al. Analysis of 462 transplantations from unrelated donors facilitated by the national marrow donor program. N Engl J Med 1993; 328: 593–602.

    Article  CAS  PubMed  Google Scholar 

  7. Petersdorf EW, Longton GM, Anasetti C et al. The significance of HLA-DRB1 matching on clinical outcome after HLA-A, B, DR identical unrelated donor marrow transplantation. Blood 1995; 86: 1606–1613.

    CAS  PubMed  Google Scholar 

  8. Spencer A, Szydlo RM, Brookes PA et al. Bone marrow transplantation for chronic myeloid leukemia with volunteer unrelated donors using ex vivo or in vivo T-cell depletion: major prognostic impact of HLA class I identity between donor and recipient. Blood 1995; 86: 3590–3597.

    CAS  PubMed  Google Scholar 

  9. Speiser DE, Tiercy J-M, Rufer N et al. High resolution HLA matching associated with decreased mortality after unrelated bone marrow transplantation. Blood 1996; 87: 4455–4462.

    CAS  PubMed  Google Scholar 

  10. Sasazuki T, Juji T, Morishima Y et al. Effect of matching of class I HLA alleles on clinical outcome after transplantation of hematopoietic stem cells from an unrelated donor. Japan Marrow Donor Program. N Engl J Med 1998; 339: 1177–1185.

    Article  CAS  PubMed  Google Scholar 

  11. Petersdorf EW, Gooley TA, Anasetti C et al. Optimizing outcome after unrelated marrow transplantation by comprehensive matching of HLA class I and II alleles in the donor and recipient. Blood 1998; 92: 3515–3520.

    CAS  PubMed  Google Scholar 

  12. Hansen JA, Gooley TA, Martin PJ et al. Bone marrow transplants from unrelated donors for patients with chronic myeloid leukemia. N Engl J Med 1998; 338: 962–968.

    Article  CAS  PubMed  Google Scholar 

  13. Petersdorf EW, Hansen JA, Martin PJ et al. Major-histocompatibility-complex class I alleles and antigens in hematopoietic-cell transplantation. N Engl J Med 2001; 345: 1794–1800.

    Article  CAS  PubMed  Google Scholar 

  14. Petersdorf EW, Kollman C, Hurley CK et al. Effect of HLA class II gene disparity on clinical outcome in unrelated donor hematopoietic cell transplantation for chronic myeloid leukemia: the US National Marrow Donor Program Experience. Blood 2001; 98: 2922–2929.

    Article  CAS  PubMed  Google Scholar 

  15. Weisdorf DJ, Anasetti C, Antin JH et al. Allogeneic bone marrow transplantation for chronic myelogenous leukemia: comparative analysis of unrelated versus matched sibling donor transplantation. Blood 2002; 99: 1971–1977.

    Article  CAS  PubMed  Google Scholar 

  16. Morishima Y, Sasazuki T, Inoko H et al. The clinical significance of human leukocyte antigen (HLA) allele compatibility in patients receiving a marrow transplant from serologically HLA-A, HLA-B, and HLA-DR matched unrelated donors. Blood 2002; 99: 4200–4206.

    Article  CAS  PubMed  Google Scholar 

  17. Nagler A, Brautbar C, Slavin S, Bishara A . Bone marrow transplantation using unrelated and family related donors: the impact of HLA-C disparity. Bone Marrow Transplant 1996; 18: 891–897.

    CAS  PubMed  Google Scholar 

  18. Petersdorf EW, Longton GM, Anasetti C et al. Association of HLA-C disparity with graft failure after marrow transplantation from unrelated donors. Blood 1997; 89: 1818–1823.

    CAS  PubMed  Google Scholar 

  19. Roosnek E, Tiercy J-M . The search for an unrelated HLA compatible stem cell donor. Curr Opin Hematol 1999; 6: 365–370.

    Article  CAS  PubMed  Google Scholar 

  20. Tiercy JM, Villard J, Roosnek E . Selection of unrelated bone marrow donors by serology, molecular typing and cellular assays. Transpl Immunol 2002; 10: 215–221.

    Article  CAS  PubMed  Google Scholar 

  21. McCutcheon JA, Gumperz J, Smith KD et al. Low HLA-C expression at cell surfaces correlates with increased turnover of heavy chain mRNA. J Exp Med 1995; 181: 2085–2095.

    Article  CAS  PubMed  Google Scholar 

  22. Ruggeri L, Capanni M, Casucci M et al. Role of natural killer cell alloreactivity in HLA-mismatched hematopoietic stem cell transplantation. Blood 1999; 94: 333–339.

    CAS  PubMed  Google Scholar 

  23. Tiercy J-M, Bujan-Lose M, Chapuis B et al. Bone marrow transplantation with unrelated donors: what is the probability to identify an HLA-A/B/CwDRB1/B3/B5/DQB1-matched donor? Bone Marrow Transplant 2000; 26: 441.

    Article  Google Scholar 

  24. Schaffer M, Aldener-Cannava A, Remberger M et al. Roles of HLA-B, HLA-C and HLA-DPA1 incompatibilities in the outcome of unrelated stem-cell transplantation. Tissue Antigens 2003; 62: 243–250.

    Article  CAS  PubMed  Google Scholar 

  25. van der Meer A, Allebes WA, Paardekooper J et al. HLA-C mismatches induce strong cytotoxic T-cell reactivity in the presence of an additional DRB/DQB mismatch and affect NK cell-mediated alloreactivity. Transplantation 2001; 72: 923–929.

    Article  CAS  PubMed  Google Scholar 

  26. Dini G, Lamparelli T, Rondelli R et al. Unrelated donor marrow transplantation for chronic myelogenous leukaemia. Br J Haematol 1998; 102: 544–552.

    Article  CAS  PubMed  Google Scholar 

  27. Drobyski WR, Klein J, Flomenberg N et al. Superior survival associated with transplantation of matched unrelated versus one-antigen-mismatched unrelated or highly human leukocyte antigen-disparate haploidentical family donor marrow grafts for the treatment of hematologic malignancies: establishing a treatment algorithm for recipients of alternative donor grafts. Blood 2002; 99: 806–814.

    Article  CAS  PubMed  Google Scholar 

  28. Davies SM, Ruggieri L, DeFor T et al. Evaluation of KIR ligand incompatibility in mismatched unrelated donor hematopoietic transplants. Killer immunoglobulin-like receptor. Blood 2002; 100: 3825–3827.

    Article  CAS  PubMed  Google Scholar 

  29. Bishara A, De Santis D, Witt CC et al. The beneficial role of inhibitory KIR genes of HLA class I NK epitopes in haploidentically mismatched stem cell allografts may be masked by residual donor-alloreactive T cells causing GVHD. Tissue Antigens 2004; 63: 204–211.

    Article  CAS  PubMed  Google Scholar 

  30. Shaw BE, Potter MN, Mayor NP et al. The degree of matching at HLA-DPB1 predicts for acute graft-versus-host disease and disease relapse following haematopoietic stem cell transplantation. Bone Marrow Transplant 2003; 31: 1001–1008.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by a grant of the Swiss National Science Foundation (# 3100-057557.99 and # 3100-65'357.01) and by the ‘Dr Henri Dubois-Ferrière-Dinu Lipatti' Foundation. We are grateful to Professor Michel Jeannet for his encouragement and support during the initial phase of the study. We thank Barbara Kervaire and Patricia Roux for their excellent technical support.

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Authors and Affiliations

  1. Division of Immunology and Allergology, University Hospital, Geneva, Switzerland

    J-M Tiercy & E Roosnek

  2. Diagnostic and Therapeutic Hematology, Kantonsspital Basel, Switzerland

    J Passweg & A Gratwohl

  3. Leiden University Medical Centre, Leiden, The Netherlands

    A van Biezen

  4. Bone Marrow Transplantation, University Hospital Hamburg, Germany

    A Zander & N Kröger

  5. Division of Hematology, University Hospital, Geneva, Switzerland

    B Chapuis & C Helg

  6. Medical Department, Section of Hematology, Rikshospitalet University Hospital, Oslo, Norway

    L Brinch

  7. Department of Hematology, Erasmus MC-Daniel Den Hoed Cancer Center, Rotterdam, The Netherlands

    J Cornelissen

  8. Europdonor Foundation and Department of Immunohematology and Blood Transfusion, LUMC, Leiden, The Netherlands

    M Oudshoorn

  9. Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland

    T Ruutu & L Volin

  10. Division of Hematology and Oncology, University of Leipzig, Leipzig, Germany

    D Niederwieser

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  1. J-M Tiercy
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on behalf of the Chronic Leukemia Working Party of the European Blood and Marrow Transplant Group (EBMT)

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Correspondence to J-M Tiercy.

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Tiercy, JM., Passweg, J., van Biezen, A. et al. Isolated HLA-C mismatches in unrelated donor transplantation for CML. Bone Marrow Transplant 34, 249–255 (2004). https://doi.org/10.1038/sj.bmt.1704569

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