HLA-a*0101 Allele Is Associated with Increased Risk of Cutaneous Acute Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Introduction Acute graft-versus-host disease (aGVHD) remains a substantial cause of morbidity and mortality after unmodified and ex-vivo CD34+ selected/T-cell depleted (TCD) allogeneic hematopoietic stem cell transplantation (alloHSCT). We identified a cluster of patients who developed severe cutaneous aGVHD and expressed MHC class I HLA-A*0101. Objective To investigate if HLA-A*0101 expression correlates with an increased risk of severe cutaneous aGVHD after alloHSCT. Methods We evaluated 831 patients who received unmodified or TCD allograft at a single institution between 03/2010 and 02/2017. Patients who received cord blood transplants or Results HLA-A*0101 was expressed in 206 (25%) patients (98 TCD, 108 unmodified). These patients had similar demographics to those lacking HLA-A*0101 (Table). At day 180, patients expressing HLA-A*0101 had higher incidence of grade III-IV cutaneous aGVHD compared with patients lacking HLA-A*0101 expression in both the TCD (8% vs. 3%, p=0.027) and unmodified (11% vs. 4%, p=0.01) cohorts (Fig 1). In a multivariate cause-specific Cox model, the presence of HLA-A*0101 in the TCD alloHSCT cohort correlated with increased risk of grade III-IV cutaneous aGVHD [HR=2.79 (95% CI: 1.07-7.28), p=0.036] after adjusting for related status of donor. In the unmodified alloHSCT cohort, presence of HLA-A*0101 allele correlated with increased risk of grade III-IV cutaneous aGVHD [HR=2.68 (95% CI: 1.24-5.79), p = 0.012)] after adjusting for myeloablative v non-myeloablative conditioning and donor relationship status. There were no statistically significant differences in OS or TRM between HLA-A*0101 expressing vs non-expressing patients in the cohorts. Conclusions In this group, donor/recipient expression of HLA-A*0101 correlated with an increased incidence and severity of cutaneous aGVHD after TCD and unmodified alloHSCT. If confirmed in a larger cohort, these findings have potential practical implications in the development of prophylaxis or early therapeutic strategies targeting the skin in this high-risk population.