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Conditioning Regimens

The impact of frequent HLA haplotypes in high linkage disequilibrium on donor search and clinical outcome after unrelated haematopoietic SCT

Bone Marrow Transplantation volume 48, pages 483–490 (2013)Cite this article

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Abstract

The MHC region on chromosome 6 contains a large number of non-HLA genes next to the HLA genes. Matching for HLA in unrelated hematopoietic SCT (HSCT) does not necessarily mean that these non-HLA genes are also matched. We selected 348 Northwest European patients transplanted with an HLA-A-, -B-, -C-, -DRB1-, -DQB1-matched unrelated donor (MUD) between 1987 and 2008. Patients’ haplotypes were identified via descend. We were unable to determine the haplotypes of the donor; therefore we used frequent haplotypes (FH) in high linkage disequilibrium (LD) as a proxy for haplotype matching. Presence of a FH in a patient positively affected the probability and speed of identifying a matched unrelated donor. Competing risk survival analysis showed that patients with one or two FH have a statistically significantly decreased probability of developing ⩾grade II acute GVDH (aGVHD) without increased risk of relapse compared to patients without FH (HR (95% CI): 0.53 (0.31–0.91)). This association was strongest for those FH with the highest LD between both HLA-A and -C or –B, and HLA-C or –B and -DRB1 (HR (95% CI): 0.49 (0.26–0.92)). These results extend evidence that non-HLA allele coding regions have a significant impact on development of ⩾grade II aGVHD. We conclude that there is more to successful HSCT than matching for HLA genes.

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Acknowledgements

We would like to thank the search coordinators at the Europdonor Foundation who performed all UD searches and the employees of the section of Immunogenetics and Transplantation Immunology of the LUMC for HLA typing of all donors and patients.

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Authors and Affiliations

  1. Europdonor Foundation, Leiden, The Netherlands

    M M Jöris, H G M van der Zanden, S M van Walraven, J J van Rood & M Oudshoorn

  2. Department of Immunohematology and Blood transfusion, LUMC, Leiden, The Netherlands

    M M Jöris, G W Haasnoot, J J van Rood, F H J Claas & M Oudshoorn

  3. Department of Pediatrics, LUMC, Leiden, The Netherlands

    A C Lankester

  4. Department of Hematology, LUMC, Leiden, The Netherlands

    PA von dem Borne

  5. Department of Hematology and Immunology, UMCU, Utrecht, The Netherlands

    J Kuball

  6. Wilhelmina Children’s Hospital, UMCU, Utrecht, The Netherlands

    M Bierings

  7. Department of Hematology, Erasmus MC-Daniel den Hoed, Rotterdam, The Netherlands

    J J Cornelissen

  8. HOVON Data Center, Erasmus MC-Daniel den Hoed, Rotterdam, The Netherlands

    M E Groenendijk-Sijnke & B van der Holt

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  1. M M Jöris
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Correspondence to M M Jöris.

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Jöris, M., Lankester, A., Borne, P. et al. The impact of frequent HLA haplotypes in high linkage disequilibrium on donor search and clinical outcome after unrelated haematopoietic SCT. Bone Marrow Transplant 48, 483–490 (2013). https://doi.org/10.1038/bmt.2012.189

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