The degree of matching at HLA-DPB1 predicts for acute graft-versus-host disease and disease relapse following haematopoietic stem cell transplantation

Abstract

Summary:The importance of matching for HLA-DPB1 in unrelated donor haematopoietic stem cell (HSC) transplantation is little understood. Most transplant centres do not, currently, prospectively match for DPB1, but emerging data show that DPB1 matching does play a role in determining outcome. We studied the impact of HLA-DPB1 matching on outcome in 143 recipients of T-cell depletion transplants, who matched with their respective unrelated donors (allelic level) at HLA-A, -B, -C, -DRB1 and -DQB1. Of those matched at DPB1, 47.2% (17/36) developed acute graft-versus-host disease (aGvHD) as compared to 66.3% (55/83) of those who were mismatched. This led to a 19.1% (95% CI 0.1-38.3%) increase in the chance of developing aGvHD in mismatched patients (P ¼ 0.049). Relapse of the original disease occurred in 51 recipients; 23 of 37 (62%) matched at both DPB1 alleles, 28 of 82 (34%) were mismatched at one or two DPB1 alleles. Thus, there was a significantly higher relapse rate (P ¼ 0.0011) in transplant recipients who matched at both DPB1 alleles. In conclusion, a donor/recipient DPB1 match was associated with a significantly lower incidence of aGvHD and a significantly higher incidence of disease relapse. This study provides further evidence for an immunogenic role of HLA-DPB1 in HSC transplants.

Isolated HLA-C mismatches in unrelated donor transplantation for CML

“…29 Although HLA-DP incompatibilities are very frequent in unrelated donor/recipient combinations, our data do not exclude the possibility that DP-mismatches also contribute to GVHD and mortality. 30 What could be the reason that in spite of the high quality of HLA-typing, there is still no broad consensus on the relevance of single locus-mismatches? It could be that the groups analyzed differ according to the selection criteria of each transplantation center.…”

Impact of HLA-DPB1 Matching in Unrelated Allogeneic Stem Cell Transplantation: Results of Two Centers From Turkey

“…Later, Shaw et al studied the importance of HLA- International Journal of Hematology and Oncology DP matching in recipients of T-cell depleted unrelated ASCTs. 11 In this study, a significant decrease in aGVHD and higher relapse rate was observed in fully matched HLA-DPB1 ASCTs. But there was no significant difference in engraftment times and OS.…”

“…[10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] For instance, in the study by Loiseau et al reported increased frequency of severe aGVHD and poorer survival in two HLA-DP incompatibilities in a group of unrelated ASCT patients. 10 In this study they were not able show a significant relationship between HLA-DP mismatches and disease relapse.…”

Topical issues in unrelated donor haematopoietic stem cell transplants: a report from a workshop convened by the Anthony Nolan Trust in London – 2005

“…Bronwen Shaw began by providing a summary of her work at the ANRI and the ANT experience in this area. [2][3][4] She presented data on 423 UD-HSCT performed between 1996 and 2003 for whom four digit molecular tissue typing for 12 alleles and clinical follow-up data were available. The percentage of wellmatched (10/10) donor-recipient pairs (67%) in the ANT study was greater than that in any other study (44% in the Japanese Marrow Donor Programme study 5 and 47% in the Fred Hutchinson Cancer Research Center study 6 ), in part due to the time period over which the study was performed.…”