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

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 (<i>N</i> = 494 patients post-allo-HSCT [CIBMTR]) were evaluated. Class-I autoimmune alleles correlated with longer relapse-free survival (HR = 0.657, <i>p</i> = 0.011) (overall survival [OS]; HR = 0.787, <i>p</i> = 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, <i>p</i> = 0.034) (relapse-free survival; HR = 0.887, <i>p</i> = 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, <i>p</i> < 0.001 vs. HR = 0.574, <i>p</i> = 0.031; comparison <i>p</i> = 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.