Impact of CMV reactivation on relapse of acute myeloid leukemia after HCT is dependent on disease stage and ATG

Cytomegalovirus (CMV) reactivation is a frequent complication after allogeneic hematopoietic cell transplantation (HCT), whose impact on clinical outcome, in particular on leukemic relapse, is controversial. We retrospectively analyzed 687 HCT recipients with acute myeloid leukemia (AML) and ciclosporin-based immunosuppression to better understand the differential impact of CMV on transplant outcomes depending on AML disease stage and in vivo T cell depletion with antithymocyte globulin (ATG). Without ATG, CMV reactivation associated with significantly reduced relapse, yet its effect was more pronounced for advanced disease AML (P = .0002) than for patients in first complete remission (CR1, P = .0169). Depending on the disease stage, ATG exposure abrogated relapse protection following CMV reactivation in advanced stages (P = .796), while it inverted its effect into increased relapse for CR1 patients (P = .0428). CMV reactivation was associated with significantly increased nonrelapse mortality in CR1 patients without ATG (P = .0187) but not in those with advanced disease and ATG. Following CMV reactivation, only patients with advanced disease had significantly higher event-free survival rates as compared with patients without CMV. Overall, our data suggest that both ATG and disease stage modulate the impact of post-HCT CMV reactivation in opposite directions, revealing a level of complexity that warrants future studies regarding the interplay between antivirus and antitumor immunity.