Acute Leukemias

Early use of allogeneic hematopoietic stem cell transplantation for infants with MLL gene-rearrangement-positive acute lymphoblastic leukemia

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Sixty-two infants with MLL gene-rearrangement-positive acute lymphoblastic leukemia (MLL-r ALL) were treated with the MLL03 protocol of the Japanese Pediatric Leukemia/Lymphoma Study Group: short-course intensive chemotherapy followed by early allogeneic hematopoietic stem cell transplantation (HSCT) within 4 months of the initial induction. The 4-year event-free survival and overall survival rates were 43.2% (95% confidence interval (CI)=30.7–55.1%) and 67.2% (53.8–77.4%), respectively. A univariate analysis showed younger age (<90 days at diagnosis), central nervous system disease and poor response to initial prednisolone therapy significantly associated with poor prognosis (P<0.05). In a multivariate analysis, younger age at diagnosis tended to be associated with poor outcome (hazard ratio=1.969; 95% CI=0.903–4.291; P=0.088). Although the strategy of early use of HSCT effectively prevented early relapse and was feasible for infants with MLL-r ALL, the fact that substantial number of patients still relapsed even though transplanted in their first remission indicates the limited efficacy of allogeneic HSCT for infants with MLL-r ALL. Considering the risk of severe late effects, indications for HSCT should be restricted to specific subgroups with poor risk factors. An alternative approach incorporating molecular-targeted drugs should be established.

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We thank all JPLSG investigators and the following investigators who contributed to the central diagnosis in this study: H Nakamura and S Yamagata (Chiba University, Chiba) for the BU pharmacokinetic study; Y Komada (Mie University Graduate School of Medicine, Mie) and H Ohta (Osaka University, Osaka) for immunophenotypic diagnostics; T Taki (Kyoto Prefectural University of Medicine, Kyoto) for the molecular biological analyses; and J Fujimoto (National Center for Child Health and Development, Tokyo) for the preservation of the diagnostic specimens. This work was supported by a Grant for Clinical Cancer Research and a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare of Japan.

Author Contributions

K Koh, DT, TM, MH, Y Takahashi, AO, K Kato, KS and EI (principal investigator) participated actively in the study conception and design; K Koh, DT and EI reviewed the data analysis and interpretation and were the main authors of the manuscript; AMS and TW conducted the statistical analysis; TS was responsible for the busulfan pharmacokinetic study; TD and MT were responsible for the immunophenotyping diagnostics; YH was responsible for coordinating the molecular biology analyses; K Koh, K Kato, JT and Y Takeshita recruited patients; MT, KH and SM contributed to the financial and administrative support of the study; and all authors contributed to the conduct of the trial and were involved in the review of the results and the final approval of the manuscript.

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Correspondence to D Tomizawa.

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The authors declare no conflict of interest.

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