Impact of HLA-DPB1 Matching on Clinical Outcomes after Haploidentical-Related Hematopoietic Stem Cell Transplantation

Abstract

Background: The impact of HLA-DPB1 compatibility and its role as a transplantation antigen in haploidentical-related hematopoietic stem cell transplant (haplo-R-HSCT) have not been established, and a negative effect on survival has been suggested. Objective: The objective of the determine was to study the frequency and clinical effects of incompatibility at the HLA-DPB1 locus in the haplo-R-HSCT setting. Methods: Clinical records and electronic files of 91 patients with a hematological disease who underwent haplo-HSCT from January 2009 to October 2017 in a university medical center were scrutinized. Overall survival (OS) was estimated by the Kaplan-Meier method; the cumulative incidence of transplant-related mortality (TRM) and relapse rates was determined. Acute graft-versus-host disease was assessed by binary logistic regression. Cox regression model with a 95% confidence interval was used to examine the association between the different variables and their effect on OS. Results: Of the 91 donor-recipient pairs, 24 (26.37%) shared complete DPB1 identity, 60 (65.93%) had a mismatch at one allele, and 7 (7.70%) were mismatched at two alleles. Twenty-four different HLA-DPB1 alleles were found; the most frequent were DPB1*04:01 (34.1%) and DPB1*04:02 (27.5%). Two-year OS, the cumulative incidence of TRM and relapse was 51.3 ± 6.8%, 28 ± 6% and 60 ± 7.8% for all haplo-related transplants, respectively, with no statistical difference between HLA-DPB1 matched and partially matched patients. In Cox regression analysis, no risk factors associated with OS, TRM, or relapses were identified. Conclusion: HLA-DPB1 mismatching in the haplo-R-HSCT setting did not influence transplant outcomes and was clinically tolerable. A high degree of homozygosity was found.

Distributions of the HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 alleles and haplotype frequencies of 1763 stem cell donors in the Colombian Bone Marrow Registry typed by next-generation sequencing

“…The role of the HLA-DPB1 has gained greater relevance due to its association with various pathologies, including cancer ( 59 ), autoimmune diseases, such as rheumatoid arthritis ( 60 ), responses to viral infection ( 61 ), and vaccines ( 62 , 63 ). Regarding stem cell transplants, there is still controversy about the inclusion of the HLA-DPB1 locus in the search algorithms for 12/12 histocompatibility ( 64 ) due to the increasing number of reports indicating that a mismatch in this locus increases the risk of developing GVHD ( 65 ). Data for HLA-DPB1 and other HLA class II loci is reported for the first time in high-resolution in Colombia.…”

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

“…All haploidentical donors will be at least a 5/10 match to the patient. There are currently no data that suggest a different outcome for haploidentical donors who may have no sharing of DP type due to recombination, that is 5/12 v 6/12 (Jaime‐Pérez et al., 2020). Additional HLA matching on the mismatched haplotype may be observed; however, the EBMT consensus recommendation (Ciurea et al., 2020) concluded that there was no evidence to support a beneficial effect of selecting haploidentical donors based on the degree of additional HLA matching due to heterogeneity in data currently available.…”