Oncotarget

Clinical Research Papers:

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, Seok Lee, Hee-Je Kim, Young-Woo Jeon, Sung-Eun Lee, Byung-Sik Cho, Dong-Gun Lee, Ki-Seong Eom, Yoo-Jin Kim, Chang-Ki Min, Seok-Goo Cho, Woo-Sung Min and Jong Wook Lee _

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Oncotarget. 2016; 7:17230-17241. https://doi.org/10.18632/oncotarget.7347

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Abstract

Jae-Ho Yoon1, Seok Lee1, Hee-Je Kim1, Young-Woo Jeon1, Sung-Eun Lee1, Byung-Sik Cho1, Dong-Gun Lee2, Ki-Seong Eom1, Yoo-Jin Kim1, Chang-Ki Min1, Seok-Goo Cho1, Woo-Sung Min1, Jong Wook Lee1

1Department of Hematology, Catholic Blood and Marrow Transplantation Center, Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea

2Division 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.


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