Relationship between certain HLA alleles and the risk of cytomegalovirus reactivation following allogeneic hematopoietic stem cell transplantation

• Published in: Transplant infectious disease 2022-08, Vol.24 (4), p.e13879-e13879
• Main Authors: Prem, Shruti, Remberger, Mats, Alotaibi, Ahmad, Lam, Wilson, Law, Arjun Datt, Kim, Dennis Dong Hwan, Michelis, Fotios V, Al-Shaibani, Zeyad, Lipton, Jeffrey Howard, Mattsson, Jonas, Viswabandya, Auro, Kumar, Rajat, Ellison, Cynthia
• Format: Article
• Language: English
• Subjects: Alleles; allogenic hematopoietic stem cell transplant; Antigens; Confidence intervals; Cytomegalovirus; cytomegalovirus reactivation; Donors; Gene frequency; Graft-versus-host reaction; Hematopoietic stem cells; Histocompatibility antigen HLA; HLA alleles; Leukocytes; Population genetics; Risk; Stem cell transplantation; Stem cells; Survival; Tissue typing; Transplantation; Transplants & implants; Viremia
• ISSN: 1398-2273; 1399-3062; 1399-3062
• DOI: 10.1111/tid.13879

Evidence is emerging to support an association between certain HLA alleles and the risk of cytomegalovirus (CMV) reactivation following allogeneic HSCT (allo-HSCT). The primary aim of this study was to identify HLA alleles associated with resistance or susceptibility to CMV reactivation. We studied 586 adults who underwent allo-HSCT for high-risk hematological malignancies. High resolution HLA typing data was available for recipient and donor. HLA Class I and II alleles observed at a frequency of > 5% in our population, were included in the analysis. A CMV viremia level of more than 200 IU/ml on weekly monitoring was considered to be indicative of CMV reactivation. The median follow-up time in surviving patients was 21 months (range 4-74 months). The cumulative incidence of CMV reactivation at 6 months in the entire cohort was 55% (95% CI 50.8%-59.2%). Mismatched donor, increasing recipient age, occurrence of AGVHD and recipient CMV seropositivity were associated with increased risk of CMV reactivation. HLA B*07:02 (HR 0.59, 95% CI 0.40-0.83) was associated with decreased risk of CMV reactivation. Patients who developed CMV reactivation had a lower incidence of relapse, higher transplant related mortality (TRM) and lower overall survival (OS) compared to those without CMV reactivation. There was an adverse correlation of OS and TRM with increasing numbers of CMV reactivations. We observed that HLA B*07:02 was associated with decreased risk of CMV reactivation. CMV reactivation was associated with lower relapse post-transplant, but this did not translate into a survival benefit due to higher transplant related mortality. This article is protected by copyright. All rights reserved.