Factors Associated with Cytomegalovirus Reactivation Following Allogeneic Hematopoietic Stem Cell Transplantation: Human Leukocyte Antigens Might Be Among the Risk Factors

Abstract

Objective: Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (AHSCT) recipients. Current practice includes prophylactic and preemptive treatment modalities, which have risks, side effects, and costs of their own. There is no established risk scoring system that applies to all patients. We aimed to investigate the risk factors for CMV reactivation in AHSCT recipients.Materials and Methods: We retrospectively analyzed the risk factors for CMV reactivation in 185 consequent AHSCT recipients transplanted between September 2003 and December 2009 at the Stem Cell Transplantation Unit of Gazi University. Besides the standard transplant-related parameters, HLA antigens were also included among the variables analyzed. Results: Despite the very high rate of donor (94.6%) and recipient (100%) seropositivity, which are the so-called major risk factors in previous reports, our reactivation rate was much lower, with a frequency of 24.9%. The underlying disease, sex, conditioning regimen, and presence of antithymocyte globulin or fludarabine in the conditioning regimen had no impact on reactivation rate. CMV reactivation was significantly more frequent in recipients with graft-versus-host disease (GVHD) compared to those without GVHD (p<0.0001). CMV reactivation was significantly more frequent (p<0.05) in patients with HLA-B14, HLA-DRB1*01, and HLA-DRB1*13 antigens and less frequent in recipients with HLA-A11 and HLA-DRB1*04 antigens (p<0.05). Conclusion: Universal risk factors/scores that apply to all transplant recipients are required for tailored prophylaxis and/or treatment strategies for CMV reactivation. Uncovering the role of genetic factors, including HLA antigens, as possible risk factors might lead the way to risk-adaptive strategies for adoptive cellular therapy and/or vaccination.

The clinical and economic impact of cytomegalovirus infection in recipients of hematopoietic stem cell transplantation

“…In addition to CMV D/R serostatus, previous studies have identified the following risk factors for CMV‐I: age, GVHD, HLA mismatch, T‐cell depletion, mycophenolic acid, lymphopenia, and corticosteroids . In both multivariable regression analysis and random forest analysis, we confirmed that CMV D/R serostatus was the most important risk factor for CMV‐I.…”

Lymphocyte expansion after unrelated cord blood allogeneic stem cell transplantation in adults

“…4,9,10 Only two patients had a persistent indolent clonal T-cell expansion up to 18 months after UCB allo-HSCT. At variance with previous reports, 11 GvHD was not more frequent in lymphocytosis patients, nor HLA mismatched patients. However, post UCB allo-HSCT lymphocytosis patients with chronic GvHD had significantly more frequently a CD8 + expansion.…”

Interplay of Environmental, Individual and Genetic Factors in Rheumatoid Arthritis Provocation

“…RA-associated HLA alleles ⇒ susceptibility to certain trivial infections ⇒ increased infection incidence and duration [ 155 , 156 , 157 , 158 , 159 , 160 , 161 ].…”