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

Authors :
Jöris MM
Lankester AC
von dem Borne PA
Kuball J
Bierings M
Cornelissen JJ
Groenendijk-Sijnke ME
van der Holt B
Haasnoot GW
van der Zanden HG
van Walraven SM
van Rood JJ
Claas FH
Oudshoorn M
Source :
Bone marrow transplantation [Bone Marrow Transplant] 2013 Apr; Vol. 48 (4), pp. 483-90. Date of Electronic Publication: 2012 Oct 15.
Publication Year :
2013

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.

Details

Language :
English
ISSN :
1476-5365
Volume :
48
Issue :
4
Database :
MEDLINE
Journal :
Bone marrow transplantation
Publication Type :
Academic Journal
Accession number :
23064039
Full Text :
https://doi.org/10.1038/bmt.2012.189