PUBLISHED BY
Grubic, Zorana; Maskalan, Marija; Burek Kamenaric, Marija; Desnica, Lana; Mikulic, Mirta; Stingl Jankovic, Katarina; Durakovic, Nadira; Serventi Seiwerth, Ranka; Vrhovac, Radovan; Zunec, Renata
PUBLISHED IN
Advances in Medical Sciences
PATIENTS
108
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.
HIGHLIGHTS
- Retrospective analysis of the impact of human leukocyte antigen (HLA) mismatches, their direction, and differences at specific HLA loci on the outcomes of hematopoietic stem cell transplantation (HSCT).
- 108 adult patients who underwent 9/10 mismatched unrelated donor (MMUD) transplants between 2011 and 2021. Different HLA loci, including HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1, were analyzed using various typing methods.
- HLA-B mismatches were associated with worse overall survival (OS), while the absence of HLA-DRB5 was linked to a higher incidence of graft-versus-host disease (GvHD). Patients with HLA class II mismatches had a lower incidence of GvHD compared to those with HLA class I mismatches. Additionally, higher PIRCHE scores in the GvH direction were associated with an increased incidence of GvHD.
- The findings suggest the need for further research on a larger patient population, focusing on specific HLA alleles to establish precise donor selection criteria, ultimately improving HSCT outcomes for patients with MMUDs.
