Impact of cytomegalovirus reactivation on relapse and survival in patients with acute leukemia who received allogeneic hematopoietic stem cell transplantation in first remission

// Jae-Ho Yoon 1 , Seok Lee 1 , Hee-Je Kim 1 , Young-Woo Jeon 1 , Sung-Eun Lee 1 , Byung-Sik Cho 1 , Dong-Gun Lee 2 , Ki-Seong Eom 1 , Yoo-Jin Kim 1 , Chang-Ki Min 1 , Seok-Goo Cho 1 , Woo-Sung Min 1 , Jong Wook Lee 1 1 Department of Hematology, Catholic Blood and Marrow Transplantation Center, Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea 2 Division of Infectious Diseases, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea Correspondence to: Jong Wook Lee, e-mail: jwlee@catholic.ac.kr Keywords: acute myeloid leukemia, acute lymphoid leukemia, cytomegalovirus, graft-vs-leukemia Received: December 12, 2015 Accepted: January 29, 2016 Published: February 12, 2016 ABSTRACT Cytomegalovirus (CMV)-reactivation is associated with graft-vs-leukemia (GVL) effect by stimulating natural-killer or T-cells, which showed leukemia relapse prevention after hematopoietic stem cell transplantation (HSCT). We enrolled patients with acute myeloid leukemia ( n = 197) and acute lymphoid leukemia ( n = 192) who underwent allogeneic-HSCT in first remission. We measured RQ-PCR weekly to detect CMV-reactivation and preemptively used ganciclovir (GCV) when the titer increased twice consecutively, but GCV was sometimes delayed in patients without significant graft-vs-host disease (GVHD) by reducing immunosuppressive agents. In the entire group, CMV-reactivation showed poor overall survival (OS). To evaluate subsequent effects of CMV-reactivation, we excluded early relapse and deaths within 100 days, during which most of the CMV-reactivation occurred. Untreated CMV-reactivated group ( n = 173) showed superior OS (83.8% vs. 61.7% vs. 74.0%, p < 0.001) with lower relapse rate (10.1% vs 22.1% vs. 25.5%, p = 0.004) compared to GCV-treated CMV-reactivated group ( n = 122) and CMV-undetected group ( n = 42). After excluding chronic GVHD, untreated CMV-reactivated group still showed lower relapse rate (9.4% vs. 24.1% vs. 30.2%, p = 0.006). Multivariate analysis showed adverse-risk karyotype and patients in other than untreated CMV-reactivated group were independent factors for relapse prediction. Our data showed possible GVL effect of CMV-reactivation and minimizing antiviral therapy may benefit for relapse prevention in acute leukemia.