The impact of frequent HLA haplotypes in high linkage disequilibrium on donor search and clinical outcome after unrelated haematopoietic SCT.
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.
Europdonor Foundation, Leiden, The Netherlands. joris@europdonor.nl
M M
MM
Jöris
A C
AC
Lankester
P A
PA
von dem Borne
J
J
Kuball
M
M
Bierings
J J
JJ
Cornelissen
M E
ME
Groenendijk-Sijnke
B
B
van der Holt
G W
GW
Haasnoot
H G M
HG
van der Zanden
S M
SM
van Walraven
J J
JJ
van Rood
F H J
FH
Claas
M
M
Oudshoorn
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D046148:Donor Selection / Q000379:methods*; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality* / Q000473:pathology / Q000517:prevention & control; D006680:HLA Antigens; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D015810:Linkage Disequilibrium; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D014184:Transplantation, Homologous; D061349:Unrelated Donors
D006680:HLA Antigens