Improved prognosis with additional medium‐dose VP16 to CY/TBI in allogeneic transplantation for high risk ALL in adults |
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| Authors: | Yasuyuki Arai Tadakazu Kondo Akio Shigematsu Junji Tanaka Kazuteru Ohashi Takahiro Fukuda Michihiro Hidaka Naoki Kobayashi Koji Iwato Toru Sakura Makoto Onizuka Yukiyasu Ozawa Tetsuya Eto Mineo Kurokawa Kaoru Kahata Naoyuki Uchida Yoshiko Atsuta Shuichi Mizuta Shinichi Kako |
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| Affiliation: | 1. Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan;2. Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland;3. Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan;4. Department of Hematology, Tokyo Women's Medical University, Tokyo, Japan;5. Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan;6. Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan;7. Department of Hematology, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan;8. Department of Hematology, Hiroshima Red Cross Hospital & Atomic‐bomb Survivors Hospital, Hiroshima, Japan;9. Leukemia Research Center, Saiseikai Maebashi Hospital, Maebashi, Japan;10. Department of Hematology/Oncology, Tokai University School of Medicine, Isehara, Japan;11. Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan;12. Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan;13. Department of Cell Therapy and Transplantation Medicine, The University of Tokyo Hospital, Tokyo, Japan;14. Department of Hematology, Hokkaido University Hospital, Hokkaido, Japan;15. Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations, Toranomon Hospital, Tokyo, Japan;16. Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan;17. Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan;18. Department of Hematology, National Hospital Organization Toyohashi Medical Center, Toyohashi, Japan;19. Division of Hematology, Jichi Medical University, Saitama, Japan |
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| Abstract: | Allogeneic hematopoietic stem cell transplantation (HSCT) with the conventional cyclophosphamide and total body irradiation (CY/TBI) regimen is an essential therapeutic strategy for acute lymphoblastic leukemia (ALL) in adults. Medium‐dose etoposide (VP16, 30‐40 mg/kg) can be added to intensify this CY/TBI regimen and reduce relapse; however, differences in prognosis between the VP16/CY/TBI and CY/TBI regimens have not yet been fully analyzed. We conducted a retrospective cohort study using a Japanese transplant registry database to compare the prognosis between the VP16/CY/TBI (VP16, total 30‐40 mg/kg) (N = 376) and CY/TBI (N = 1178) regimens in adult patients with ALL transplanted at complete remission (CR) between January 1, 2000 and December 31, 2014. Our analyses indicated that VP16/CY/TBI significantly reduced relapse compared with CY/TBI (risk ratio, 0.75; 95% confidence interval [CI], 0.56‐1.00; P = .05) with a corresponding improvement in leukemia‐free survival (hazard ratio [HR], 0.76; 95%CI, 0.62‐0.93; P = .01), particularly in patients transplanted at CR1 with advanced‐risk (positive minimal residual disease, presence of poor‐risk cytogenetics, or an initial elevated leukocyte count) (HR, 0.75; 95%CI, 0.56‐1.00; P = .05) or those transplanted beyond CR2 (HR, 0.58; 95%CI, 0.39‐0.88; P = .01). The addition of VP16 did not increase post‐transplant complications or nonrelapse mortality (HR, 0.88; 95%CI, 0.65‐1.18; P = .38). This study is the first to reveal the efficacy of the addition of medium‐dose VP16 to CY/TBI in high‐risk ALL. To establish new myeloablative conditioning regimens including VP16, a large‐scale prospective study is necessary. |
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