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 - Issue 4 p. 483- 490
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.
|acute GVHD, HLA haplotypes, linkage disequilibrium, non-HLA genes, unrelated donor search, unrelated HSCT|
|Bone Marrow Transplantation|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Jöris, M.M, Lankester, A.C, von dem Borne, P.A.K, Kuball, J, Bierings, M, Cornelissen, J.J, … Oudshoorn, M. (2013). The impact of frequent HLA haplotypes in high linkage disequilibrium on donor search and clinical outcome after unrelated haematopoietic SCT. Bone Marrow Transplantation, 48(4), 483–490. doi:10.1038/bmt.2012.189