# 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.

## Key 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