In a 12-allele analysis HLA-DPB1 matching is associated with improved OS in leukaemic and myelodysplastic patients receiving myeloablative T-cell-depleted PBSCT from unrelated donors

Abstract

The effect on survival of including HLA-DPB1 in a 12-allele matching strategy was retrospectively evaluated in 130 patients with acute leukaemia and myelodysplasia undergoing T-cell-depleted PBSC transplantation using unrelated donors. Patients received alemtuzumab in vivo T-cell depletion as part of a myeloablative (MA; n ¼ 61) or reduced-intensity conditioning regimen (n ¼ 69). No difference in OS was seen with single-locus mismatching (mm) when 10 conventional alleles (HLA-A, B, C, DRB1 and DQB1) were considered. However, the addition of HLA-DPB1 matching data proved highly discriminatory. Mismatches were identified in 87% of patients previously considered fully matched (1DPmm ¼ 49pts: 2DPmm ¼ 28pts), and in the 9/10 group 22 patients were reclassified as double and 16 as triple mismatches. In 10/10 transplants, there was a distinct trend to poorer OS with double DPB1 mm. If all 12 loci were considered, 98% of single mm were at HLA-DPB1. Furthermore, cumulative mm at two or more loci was associated with significantly poorer 3-year OS (34% vs 48%, P ¼ 0.013: hazard ratio 1.8 (95% confidence interval 1.14-3.06; P ¼ 0.017), although his detrimental effect was only apparent using MA conditioning, in which reduced OS was associated with increased chronic GVHD (61% vs 16%, P ¼ 0.018) and nonrelapse mortality (30% vs 9%, P ¼ 0.039).

Is there any impact of HLA-DPB1 disparity in 10/10 HLA-matched unrelated hematopoietic SCT? Results of a French multicentric retrospective study

“…However, an adverse impact of HLA-DPB1 allelic mismatches in both GVH and HVG directions (2 vs 0, RR 1.73, 95% CI 1.09-2.73, P = 0.019, Table 2 and Supplementary Figure 1A) was observed on severe aGVHD III-IV incidence, confirming previous studies. 4,9,15,19,20 This adverse impact of HLA-DPB1 disparities remains also significant (P = 0.01) considering 0+1 vs 2 allelic mismatches (data not shown). Although not significant, a single HLA-DPB1 allelic mismatch results in increased risk of severe aGVHD III-IV (data not shown) underlying a possible dose effect of HLA-DPB1 mismatches.…”

BSHI Guideline: HLA matching and donor selection for haematopoietic progenitor cell transplantation

“…A single‐centre UK study of 130 patients transplanted for malignancies demonstrated a trend towards a negative impact of double HLA‐DPB1 mismatching on overall survival in patients otherwise matched for 10/10 HLA loci (HLA‐A, ‐B, ‐C, ‐DRB1, ‐DQB1). This finding was more evident in patients receiving myeloablative conditioning compared with those receiving RIC (Burt et al ., ).…”

Clinical outcomes of HLA‐DPB1 mismatches in 10/10 HLA‐matched unrelated donor‐recipient pairs undergoing allogeneic stem cell transplant

“…Recent literature has suggested that matching at the HLA‐DPB1 locus, in addition to the standard loci, may impact outcomes in ASCT . The β‐chain of the HLA‐DP antigen is known to be highly polymorphic, with 716 alleles encoding 591 proteins and 19 null variants, while the α‐chain has 44 alleles encoding 22 proteins .…”

“…[2][3][4][5][6][7][8][9][10] Recent literature has suggested that matching at the HLA-DPB1 locus, in addition to the standard loci, may impact outcomes in ASCT. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] The β-chain of the HLA-DP antigen is known to be highly polymorphic, with 716 alleles encoding 591 proteins and 19 null variants, while the α-chain has 44 alleles encoding 22 proteins. 27 While many of the HLA genes are in tight linkage disequilibrium (LD), the degree of LD is much lower between HLA-DP and the remainder of the HLA cluster due to a recombination hot spot between the HLA-DQ and HLA-DP loci.…”

“…Although a number of studies have suggested a relationship between HLA-DPB1 mismatch (or non-permissive mismatch) and suboptimal transplant outcomes, there are discordant studies, and matching at this locus is not always included in donor selection algorithms. [12][13][14][15][16][17][18][19][20][21] Because of the large degree of population differences in the HLA system, as well as variability in conditioning regimens and GVHD prophylaxis across institutions, selecting a large cohort of similar patients for reliable comparisons of outcomes in patients is challenging and may explain some of the differences in findings. Therefore, to better understand the importance of HLA-DPB1 matching, we performed a retrospective study evaluating outcomes in patients genotyped for HLA-DPB1 at our institution.…”