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The impact of frequent HLA haplotypes in high linkage disequilibrium on donor search and clinical outcome after unrelated haematopoietic SCT.
- 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.
- Subjects :
- Acute Disease
Adolescent
Adult
Child
Child, Preschool
Disease-Free Survival
Female
Graft vs Host Disease etiology
Graft vs Host Disease pathology
Graft vs Host Disease prevention & control
Histocompatibility Testing
Humans
Infant
Male
Retrospective Studies
Risk Factors
Survival Rate
Transplantation, Homologous
Donor Selection methods
Graft vs Host Disease mortality
HLA Antigens
Haplotypes
Hematopoietic Stem Cell Transplantation
Linkage Disequilibrium
Unrelated Donors
Subjects
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