Graft rejection after unrelated donor hematopoietic stem cell transplantation for thalassemia is associated with nonpermissive HLA-DPB1 disparity in host-versus-graft direction

Abstract

The success of allogeneic hematopoietic stem cell transplantation (HSCT) from matched unrelated donors (UDs) for ␤-thalassemia may be hampered by the occurrence of graft rejection. Here, we show that the rate of this complication can be reduced by selecting 5-loci HLAmatched donors without nonpermissive mismatches at HLA-DPB1, defined according to an algorithm previously described and based on principles of central T-cell tolerance. Seventy-two consecutive patients and their UDs, prospectively selected for matching at the allelic level for HLA-A, -B, -C, -DRB, and -DQB1 loci, were enrolled in the analysis. These pairs were either DPB1 matched/permissively mismatched (n ‫؍‬ 45, control group) or had at least one nonpermissive DPB1 mismatch in the host-versus-graft (HvG; n ‫؍‬ 17) or in the graft-versus-host (GvH; n ‫؍‬ 10) direction. In multivariate analysis, the risk of rejection was significantly increased in the group with HvG disparity (RR ‫؍‬ 7.42; 95% CI ‫؍‬ 1.29-42.68; P ‫؍‬ .02) as compared to the control group. A lower, statistically significant, probability of thalassemia-free survival was found in patients belonging to the HvG group as compared to controls (RR ‫؍‬ 5.15; 95% CI ‫؍‬ 1.58-16.82; P ‫؍‬ .01). These data suggest that in patients with thalassemia, the incidence of graft failure after HSCT may be reduced by appropriate selection of UDs, with such selection taking into account the functional rules of immunogenetics.

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

“…Fleischhauer et al reported an increased risk of graft failure with the presence of nonpermissive HLA-DPB1 mismatches, in a group of unrelated ASCT for betathalassemia patients. 15 Interestingly there was not increased risk of GVHD and decreased OS in non permissive HLA-DPB1 disparities in this study population. Later, Shaw et al once again analyzed the clinical importance of HLA-DPB1 in unrelated ASCT.…”

“…[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.…”

A novel conditioning regimen improves outcomes in β-thalassemia major patients using unrelated donor peripheral blood stem cell transplantation

“…Although Fleischhauer et al demonstrated that GR after UD-HSCT for thalassemia was associated with nonpermissive HLA-DPB1 disparities in the hostversus-graft direction, 23 the importance of HLA-DPB1 donorrecipient matching remains debatable. In the present study, GR 24 The use of PBSCT was not associated with a significantly increased risk of either acute or chronic GVHD.…”

Searching for alternative hematopoietic stem cell donors for pediatric patients

“…15 This algorithm, based on the identification of an immunogenic T-cell epitope shared by a defined subset of HLA-DBP1 alleles, which, if expressed by self-HLA-DP molecules protects from mounting a response against allogeneic HLA-DP antigens carrying the epitope, 15,16 proved also to predict the occurrence of graft failure in children with thalassemia major transplanted with BM cells from an unrelated volunteer. 17 Thus, at least in some groups of patients transplanted from an unrelated volunteer, the incidence of immune complications (namely GvHD and graft failure) can be reduced by appropriate selection of the donor, taking into account the functional rules of immune genetics. Besides HLA compatibility, several other patient-, donor-, disease-and transplant-related variables have been reported to influence the outcome of children given an allogeneic HSCT from an unrelated donor.…”