Autoimmune HLA alleles and neoantigens predict myelodysplastic syndrome outcomes after allogeneic HSCT: A CIBMTR analysis

TL;DR

This study shows that certain HLA alleles and neoantigen presentation can predict better outcomes for MDS patients after stem cell transplants.

Contribution

The study identifies specific HLA alleles and neoantigen presentation as independent predictors of survival in MDS patients post-transplant.

Findings

Class-I autoimmune HLA alleles correlate with longer relapse-free survival in MDS patients after allo-HSCT.

Improved donor MHC-II neoantigen presentation is linked to longer overall survival in MDS patients post-transplant.

Class-I autoimmune alleles enhance the graft-versus-leukemia effect of chronic GVHD in MDS patients.

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) offers curative potential for myelodysplastic syndrome (MDS), despite treatment-related mortality and relapse. We investigated how autoimmune human leukocyte antigen (HLA) alleles and mutanome-derived neoantigens influence post-transplantation outcomes. Donor and recipient HLA alleles, somatic mutations (508 genes; exome sequencing) and clinical covariates (N = 494 patients post-allo-HSCT [CIBMTR]) were evaluated. Class-I autoimmune alleles correlated with longer relapse-free survival (HR = 0.657, p = 0.011) (overall survival [OS]; HR = 0.787, p = 0.075). Improved calculated major histocompatibility complex-II (MHC-II) presentation of mutanome-derived neoantigens by donor HLA type correlated with longer OS (HR = 0.876, p = 0.034) (relapse-free survival; HR = 0.887, p = 0.083). Class-I auto-immune alleles plus chronic graft-versus-host disease (GVHD) enhanced the benefit of chronic GVHD alone for relapse-free survival (HR = 0.289, p < 0.001 vs. HR = 0.574, p = 0.031; comparison p = 0.021). Therefore, both autoimmune alleles and improved mutanome-derived neoantigen presentation correlated significantly and independently with relapse-free and OS, respectively, in a large multicenter group of MDS patients post-allo-HSCT. These factors warrant additional investigation for patient/donor selection.

•Class-I HLA autoimmune alleles correlate with longer RFS in MDS post-alloHSCT•Improved donor MHC-II neoantigen presentation predicts longer survival in MDS post-alloHSCT•Class-I autoimmune alleles enhance chronic GVHD’s graft-versus-leukemia effect in MDS

Class-I HLA autoimmune alleles correlate with longer RFS in MDS post-alloHSCT

Improved donor MHC-II neoantigen presentation predicts longer survival in MDS post-alloHSCT

Class-I autoimmune alleles enhance chronic GVHD’s graft-versus-leukemia effect in MDS

Interventions; Immunology; Immune response

Figures