Journal
AMERICAN JOURNAL OF HEMATOLOGY
Volume 93, Issue 1, Pages 47-57Publisher
WILEY
DOI: 10.1002/ajh.24933
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Funding
- Ministry of Education, Science, Sports, and Culture in Japan
- Japan Agency for Medical Research and Development, AMED
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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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