Journal
HEMATOLOGICAL ONCOLOGY
Volume 40, Issue 5, Pages 1041-1055Publisher
WILEY
DOI: 10.1002/hon.3046
Keywords
acute lymphoblastic leukemia; Philadelphia chromosome; VP16; CY; TBI
Categories
Funding
- Cell Science Research Foundation
- Ono Medical Research Foundation
- SGH Foundation
- MSD Life Science Foundation
- GlaxoSmithKline Research Grant
- American Society of Hematology
- Program for the Development of Next-generation Leading Scientists with Global Insight (L-INSIGHT) - Ministry of Education, Culture, Sports, Science and Technology (MEXT)
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The VP16/CY/TBI regimen showed better progression-free survival and reduced relapse rate in adult Ph+ ALL patients undergoing myeloablative allo-HSCT compared to the CY/TBI regimen. However, it did not significantly improve outcomes in Ph- ALL patients.
The medium-dose etoposide (VP16) added on cyclophosphamide (CY)/total body irradiation (TBI) is one of the intensified myeloablative conditioning regimens used in allogenic hematopoietic stem cell transplantation (allo-HSCT) for acute lymphoblastic leukemia (ALL). However, the patient subgroups who can actually benefit from VP16/CY/TBI compared to CY/TBI have not been precisely defined. Therefore, we conducted a multi-center retrospective study using the Japanese nationwide registry database to elucidate the efficacy of VP16/CY/TBI on post-transplant prognosis. Biological and clinical distinct subtypes (i.e., Philadelphia chromosome-positive (Ph+) and -negative (Ph-) ALL) were evaluated separately, which included 820 Ph+ and 1463 patients with Ph- ALL, respectively. Compared with the CY/TBI group, the VP16/CY/TBI group showed superior progression-free survival (PFS) in patients with Ph+ ALL (65% vs. 57% at 3 years after HSCT; adjusted hazard ratio (HR), 0.73; 95% confidence interval (CI), 0.55-0.98; p = 0.03), along with significantly reduced incidence of relapse (adjusted HR, 0.58; 95% CI, 0.37-0.90; p = 0.02) without the increase of non-relapse mortality (NRM). By contrast, in patients with Ph- ALL, VP16/CY/TBI did not improve PFS nor incidence of relapse; addition of VP16 reduced relapse (HR, 0.65; p = 0.06) in patients with Ph- ALL transplanted at CR1, while improved PFS was not observed (HR, 0.90; p = 0.52) due to increased NRM. This study demonstrated that VP16/CY/TBI is a more effective and well-tolerated regimen in comparison with CY/TBI in patients with myeloablative allo-HSCT for adult Ph+ ALL. Our findings can provide a novel algorithm for conditioning regimen selection in patients with adult ALL.
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