Alternative donor strategy in unrelated hematopoietic stem cell transplantation – outcome with mismatched donors

Abstract

Purpose

This study retrospectively investigated the association between the level of human leukocyte antigen (HLA) mismatches (MMs), direction of disparities and differences at particular HLA locus on clinical outcomes of hematopoietic stem cell transplantation (HSCT). Investigated outcomes were overall survival (OS) and disease-free survival (DFS), graft-versus-host disease (GvHD), relapse and non-relapse mortality (NRM).

Patients and methods

Study cohort included 108 adult patients transplanted between 2011 and 2021 and their 9/10 mismatched unrelated donors (MMUD). All individuals were typed for HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 loci using Polymerase Chain Reaction-Sequence Specific Primers, PCR-Sequence Based Typing and Next-Generation Sequencing. All statistical analyses were done in the MedCalc software, version 19.2.6.

Results

Patients with MMs at HLA-B locus demonstrated worse OS (P ​= ​0.0440, HR ​= ​2.00, n ​= ​20). Absence of HLA-DRB5 was associated with a higher incidence of GvHD (P ​= ​0.0112, HR ​= ​1.93, n ​= ​67). A lower incidence of GvHD was observed in patients with HLA class II MMs compared to patients with HLA class I MMs (P ​= ​0.0166, HR ​= ​1.94, n ​= ​29). Finally, analysis of PIRCHE score (PS) impact revealed that patients with HLA class II PS ​> ​10 in GvH direction showed higher incidence of GvHD compared to patients with HLA class II PS ​< ​10 (P ​= ​0.0073, HR ​= ​2.01, n ​= ​55).

Conclusion

Obtained results undisputedly indicate the necessity to further investigate this matter on a larger patient group, with focus on specific HLA alleles to define precisely priority criteria for selecting the best donor for all patients, thus improving the outcome of HSCT with an MMUD.