HLA class I supertypes and HLA class I alleles influence the outcome after allogeneic hematopoietic stem cell transplant from unrelated matched donor

Zorana Grubic; Marija Burek Kamenaric; Marija Maskalan; Lana Desnica; Mirta Mikulic; Katarina Stingl Jankovic; Nadira Durakovic; Radovan Vrhovac; Ranka Serventi Seiwerth; Renata Zunec

doi:10.1016/j.trim.2024.102167

HLA class I supertypes and HLA class I alleles influence the outcome after allogeneic hematopoietic stem cell transplant from unrelated matched donor

Transpl Immunol. 2024 Dec 21:102167. doi: 10.1016/j.trim.2024.102167. Online ahead of print.

Affiliations

¹ Tissue Typing Centre, Clinical Department for Transfusion Medicine and Transplantation Biology, University Hospital Centre Zagreb, Croatia. Electronic address: zgrubic@kbc-zagreb.hr.
² Tissue Typing Centre, Clinical Department for Transfusion Medicine and Transplantation Biology, University Hospital Centre Zagreb, Croatia.
³ Department of Hematology, Internal Clinic, University Hospital Centre Zagreb, Zagreb, Croatia.

PMID: 39716646
DOI: 10.1016/j.trim.2024.102167

Abstract

This retrospective study analyses the impact HLA heterozygosity, supertypes, and alleles have on incidence of graft versus host disease (GvHD), relapse, overall survival (OS), disease-free survival (DFS) and transplant-related mortality (TRM) after HSCT. The study included patients who underwent HSCT, typed at allele resolution level for HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 loci. The analysis performed on the entire patient cohort (N = 232) showed that HLA-B07 supertype positive patients demonstrated decreased incidence of relapse, better OS and DFS in comparison to those negative for HLA-B07 supertype. Further, a higher incidence of TRM was observed among patients positive for HLA-B27 supertype. Significant association of the HLA-A*02:01 allele presence with decreased incidence of GvHD was found. The occurrence of HLA-A*11:01 allele was associated with a worse OS, DFS and a higher rate of TRM. The analysis of the subgroup of patients with AML or MDS (N = 148) showed an association of HLA-A24 supertype with a worse OS. The HLA-B07 supertype positive patients demonstrated a lower incidence of relapse and a better DFS. A decline in OS and a higher TRM rate were observed among patients positive for HLA-B27 supertype. The presence of HLA-A*11:01 allele was indicative of a worse OS, DFS and a higher rate of TRM. The associations of HLA and HSCT clinical outcome parameters found in this study justify further investigation of this matter.

Keywords: Alleles; HLA; HSCT; Haplotypes; Supertypes.