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Donor Selection

Highly diverged MHC class I mismatches are acceptable for haematopoietic stem cell transplantation

Bone Marrow Transplantation volume 40, pages 193–200 (2007)Cite this article

Abstract

A fully major histocompatilbility complex (MHC) matched donor is not available for the majority of patients in need of a haematopoietic stem cell transplantation (SCT), which illustrates the need for a tool to define acceptable MHC disparities. Previously, we noticed that a variety of single MHC class I mismatched allogeneic donor–recipient pairs did not elicit an allogeneic cytotoxic-lymphocyte (CTL) response in vitro if the MHC amino-acid sequences had five or more differences in the α-helices plus five or more differences in the β-sheet (⩾5α5β) (7). To address the clinical relevance of this observation, we analysed CTL precursor (CTLp) assay outcome and SCT outcome in 53 Dutch recipients of a single MHC class I mismatched graft from an unrelated donor. Overall patient survival was 44% after 4 years. In multivariate analysis, recipients of a ⩾5α5β mismatched graft with negative CTLp frequencies in vitro before transplantation demonstrated superior survival: survival at 4 years was 80% as compared to 47% in recipients of other mismatched grafts with negative CTLp frequencies (hazard ratio=0.131; 95% CI=(0.03–0.61); P=0.009). This option of acceptable mismatches may enlarge the pool of potentially acceptable stem cell donors.

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Acknowledgements

We thank the technologists of the HLA typing laboratory and the laboratory for cellular histocompatibility testing of the Leiden University Medical Center.

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Authors and Affiliations

  1. Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands

    M B A Heemskerk, D L Roelen, J J van Rood, F H J Claas, I I N Doxiadis & M Oudshoorn

  2. Europdonor Foundation, Leiden, The Netherlands

    M B A Heemskerk, J J van Rood & M Oudshoorn

  3. Department of Haematology, Erasmus MC/Daniel den Hoed, Rotterdam, The Netherlands

    J J Cornelissen

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  1. M B A Heemskerk
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Correspondence to M B A Heemskerk.

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Heemskerk, M., Cornelissen, J., Roelen, D. et al. Highly diverged MHC class I mismatches are acceptable for haematopoietic stem cell transplantation. Bone Marrow Transplant 40, 193–200 (2007). https://doi.org/10.1038/sj.bmt.1705721

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