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Unrelated Donor Transplants

High resolution HLA class I and II typing and CTLp frequency in unrelated donor transplantation: a single-institution retrospective study of 69 BMTs

Bone Marrow Transplantation volume 27, pages 35–43 (2001)Cite this article

Abstract

The results of unrelated donor transplantation (URD-BMT) are difficult to analyze since the continuous advances in HLA typing technology allow the detection of new mismatches unknown at the time of transplantation. We sought to confirm that matched recipient–donor pairs are in fact often mismatched when advanced HLA typing techniques are used. We retrospectively studied the impact of the results of high resolution HLA typing for HLA class I (-A, -B, -C) and HLA class II (-DR, -DQ, -DP) loci, and cytotoxic T lymphocyte precursor (CTLp) frequency, on the outcome of 69 URD-BMT procedures. At the time of transplant, six (6/69) and two (2/69) donor–recipient pairs were mismatched for HLA classI (-A and -B by serology) and HLA class II, respectively, while one pair was mismatched for both HLA class I and II. Using high resolution DNA typing, HLA class I mismatches were found in 31 (45%) pairs and HLA class II mismatches in nine (13%) pairs. Twenty-three of the 69 pairs were HLA-C mismatched. Low CTLp frequencies were found among the 19 HLA class I matched pairs tested, and also in 5/14 mismatched pairs (of whom three had severe aGVHD). The overall survival of the cohort was 28 ± 6%. Among the 33 patients who were fully matched with their donors, the survival rate was 66% in the 18 patients with a standard hematological risk and 9% in the 15 high risk patients. Only two of the 33 patients developed severe aGVHD, and only one had graft rejection. Among the 36 mismatched pairs, the survival rate was 31% in the 13 patients with a standard hematological risk and 8% in the 23 high risk patients. Sixteen of these 36 patients died from severe aGVHD and four had graft failure or rejection. Three of the 10 patients with only an HLA-C mismatch died from severe aGVHD, and two had graft rejection. In conclusion: (1) donor–recipient matching based on high resolution HLA class I and II DNA typing is associated with significantly better outcome after URD-BMT; (2) the results of URD-BMT with classical GVHD prevention are comparable to those of geno-identical BMT when donor and recipient are fully matched for HLA-A, -B, -C, -DRB1 and -DQB1 on the basis of high resolution typing; (3) CTLp frequencies do not correlate constantly with HLA class I matching, and our results fail to show that CTLp assay can distinguish between permissable and non-permissable class I mismatches; (4) clinical trials involving donor–recipient pairs with known HLA class I mismatches are needed to improve aGVHD prevention without increasing graft failure rate. Bone Marrow Transplantation (2001) 27, 35–43.

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References

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

    CAS  PubMed  Google Scholar 

  2. 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 prognosis impact of HLA class I identity between donor and recipient Blood 1995 86: 3590–3597

    CAS  PubMed  Google Scholar 

  3. Anasetti C, Beatty PG, Storb R et al. Effect of HLA incompatibility on graft-versus-host disease, relapse, and survival after marrow transplantation for patients with leukemia or lymphoma Hum Immunol 1989 29: 79–97

    Article  Google Scholar 

  4. Ash RC, Casper JT, Chitamber CR et al. Successful allogeneic transplantation of T-cell-depleted bone marrow from closely HLA-matched unrelated donors New Engl J Med 1990 322: 485–494

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  6. DeVergie A, Apperley JF, Labopin M et al. European results of matched unrelated donor bone marrow transplantation for chronic myeloid leukemia. Impact of HLA class II matching. Chronic Leukemia Group for Blood and Marrow Transplantation Bone Marrow Transplant 1997 20: 11–19

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  8. Speiser DE, Tiercy JM; 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 

  9. 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 New Engl J Med 1998 339: 1177–1185

    Article  CAS  Google Scholar 

  10. 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 

  11. 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 

  12. 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 

  13. Mason PM, Parham P . HLA class I region sequences Tissue Antigens 1998 51: 417–466

    Article  CAS  Google Scholar 

  14. Scott I, Bunce M, Brookes P et al. The role of cellular and molecular class I HLA typing in selection of unrelated bone marrow donors Exp Hematol 1995 23: 744–747

    Google Scholar 

  15. Bunce M, Barnardo MC, Procter J et al. High resolution HLA-C typing by PCR-SSP: identification of allelic frequencies and linkage disequilibria in 604 unrelated random UK caucasoids and a comparison with serology Tissue Antigens 1996 48: 680–691

    Article  CAS  Google Scholar 

  16. Grundschober C, Rufer N, Sanchez Mazas A et al. Molecular characterization of HLA-C incompatibilities in HLA-ABDR-matched unrelated bone marrow donor–recipient pairs Tissue Antigens 1997 49: 612–623

    Article  CAS  Google Scholar 

  17. Kaminski E, Sharroch C, Hows J et al. Frequency analysis of cytotoxic T lymphocyte precursors: possible relevance to HLA-matched unrelated donor bone marrow transplantation Bone Marrow Transplant 1988 3: 149–155

    CAS  PubMed  Google Scholar 

  18. Storb R, Deeg HJ, Appelbaum F et al. Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia New Engl J Med 1986 314: 729–735

    Article  CAS  Google Scholar 

  19. Glucksberg H, Storb R, Fefer A et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HLA-matched sibling donors Transplantation 1974 18: 295–304

    Article  CAS  Google Scholar 

  20. Mittal KK, Mickey MR, Singal DP, Terasaki PI . Serotyping for hemotransplantation. Refinement of microdroplet lymphocyte cytotoxicity test Transplantation 1968 3: 913–927

    Article  Google Scholar 

  21. Mercier B, Al Daccack R, Samaan A et al. HLA-DRB1 and -DQB1 typing by PCR amplification using sequence-specific primers (PCR-SSP): assessment after 1 year of routine use by three laboratories Eur J Immunogenet 1994 21: 105–123

    Article  CAS  Google Scholar 

  22. Mercier B, Ferec C, Dufosee F, Huart JJ . Improvement in the HLA-DQB1 typing by PCR-RFLP: introduction of constant restriction sites in one of the primers as digestion verifies Tissue Antigens 1992 40: 86–89

    Article  CAS  Google Scholar 

  23. Christiansen FT, Witt CS, Dawkins RL . Questions in marrow matching: the implications of ancestral haplotypes for routine practice Bone Marrow Transplant 1991 8: 83–86

    CAS  PubMed  Google Scholar 

  24. 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 

  25. Colonaa M, Spies T, Strominger JL et al. Alloantigen recognition by two human natural killer cell clones is associated with HLA-C or closely linked gene Proc Natl Acad Sci USA 1992 89: 7983–7985

    Article  Google Scholar 

  26. Lanier LL, Gumperz JE, Parham P et al. The NKB1 and HP3E4 NK cell receptors are structurally distinct glycoproteins and independently recognize polymorphic HLA-B and HLA-C molecules J Immunol 1995 154: 3320–3327

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. HLA Laboratory Blood Center, Créteil, France

    N El Kassar, CM Joseph, P Salesses & P Bierling

  2. Immunology Laboratory, Créteil, France

    S Legouvello & JP Farcet

  3. BMT Unit, Henri Mondor Hospital, Créteil, France

    C Rieux, C Cordonnier, JP Vernant & M Kuentz

Authors
  1. N El Kassar
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  2. S Legouvello
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  3. CM Joseph
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  4. P Salesses
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  5. C Rieux
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  6. C Cordonnier
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  7. JP Vernant
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  8. JP Farcet
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El Kassar, N., Legouvello, S., Joseph, C. et al. High resolution HLA class I and II typing and CTLp frequency in unrelated donor transplantation: a single-institution retrospective study of 69 BMTs. Bone Marrow Transplant 27, 35–43 (2001). https://doi.org/10.1038/sj.bmt.1702733

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