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Acute Leukemias

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

Leukemia volume 29, pages 290–296 (2015)Cite this article

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Abstract

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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Acknowledgements

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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Author notes

  1. K Koh and D Tomizawa: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology/Oncology, Saitama Children’s Medical Center, Saitama, Japan

    K Koh

  2. Department of Pediatrics, Tokyo Medical and Dental University, Tokyo, Japan

    D Tomizawa & S Mizutani

  3. Clinical Research Center, National Hospital Organization, Nagoya Medical Center, Aichi, Japan

    A Moriya Saito & K Horibe

  4. Department of Nutritional Science, Faculty of Psychological and Physical Science, Aichi Gakuin University, Aichi, Japan

    T Watanabe

  5. Department of Pediatrics, Osaka University, Osaka, Japan

    T Miyamura

  6. Department of Pediatrics, Mie University Graduate School of Medicine, Mie, Japan

    M Hirayama & T Deguchi

  7. Department of Pediatrics, Aomori Prefectural Central Hospital, Aomori, Japan

    Y Takahashi

  8. Department of Pediatrics, Niigata Cancer Center Hospital, Niigata, Japan

    A Ogawa

  9. Department of Hematology and Oncology, Children's Medical Center, Japanese Red Cross Nagoya First Hospital, Aichi, Japan

    K Kato

  10. Department of Pediatrics, University of Yamanashi, Yamanashi, Japan

    K Sugita

  11. Department of Control and Treatment of Infectious Disease, Chiba University Hospital, Chiba, Japan

    T Sato

  12. Department of Hematology/Oncology, Gunma Children’s Medical Center, Gunma, Japan

    Y Hayashi

  13. Department of Pediatrics, University of Tokyo, Tokyo, Japan

    J Takita

  14. Department of Pediatrics, Nara Medical University, Nara, Japan

    Y Takeshita

  15. Department of Pediatrics, Ama Municipal Hospital, Aichi, Japan

    M Tsurusawa

  16. Department of Pediatrics, Ehime University Graduate School of Medicine, Ehime, Japan

    E Ishii

Authors
  1. K Koh
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  2. D Tomizawa
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  11. T Sato
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  14. J Takita
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  16. M Tsurusawa
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  17. K Horibe
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  18. S Mizutani
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Corresponding author

Correspondence to D Tomizawa.

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Koh, K., Tomizawa, D., Moriya Saito, A. et al. Early use of allogeneic hematopoietic stem cell transplantation for infants with MLL gene-rearrangement-positive acute lymphoblastic leukemia. Leukemia 29, 290–296 (2015). https://doi.org/10.1038/leu.2014.172

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  • DOI: https://doi.org/10.1038/leu.2014.172

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