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Acute Leukemias

Outcome of risk-based therapy for infant acute lymphoblastic leukemia with or without an MLL gene rearrangement, with emphasis on late effects: a final report of two consecutive studies, MLL96 and MLL98, of the Japan Infant Leukemia Study Group

Leukemia volume 21, pages 2258–2263 (2007)Cite this article

Abstract

We evaluated the efficacy of a treatment strategy in which infants with acute lymphoblastic leukemia (ALL) were stratified by their MLL gene status and then assigned to different risk-based therapies. A total of 102 patients were registered on two consecutive multicenter trials, designated MLL96 and MLL98, between 1995 and 2001. Those with a rearranged MLL gene (MLL-R, n=80) were assigned to receive intensive chemotherapy followed by hematopoietic stem cell transplantation (HSCT), while those with germline MLL (MLL-G, n=22) were treated with chemotherapy alone. The 5-year event-free survival (EFS) rate for all 102 infants was 50.9% (95% confidence interval, 41.0–60.8%). The most prominent late effect was growth impairment, observed in 58.9% of all evaluable patients in the MLL-R group. This plan of risk-based therapy appears to have improved the overall prognosis for infants with ALL, compared with previously reported results. However, over half the events in patients with MLL rearrangement occurred before the instigation of HSCT, and that HSCT-related toxic events comprised 36.3% (8/22) of post-transplantation events, suggesting that further stratification within the MLL-R group and the development of more effective early-phase intensification chemotherapy will be needed before the full potential of this strategy is realized.

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Acknowledgements

We thank John Gilbert for critical comments and editorial assistance. This study was supported in part by the Japan Leukemia Research Fund, the Japan Children's Cancer Association and a Grant-in-Aid for Cancer Research from the Ministry of Health and Welfare of Japan.

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Authors and Affiliations

  1. Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan

    D Tomizawa & S Mizutani

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

    K Koh

  3. Department of Pediatrics, Hiroshima University, Hiroshima, Japan

    T Sato

  4. Department of Medical Information Science, Kyushu University, Fukuoka, Japan

    N Kinukawa

  5. Department of Pediatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan

    A Morimoto

  6. Department of Pediatrics, Showa University Fujigaoka Hospital, Yokohama, Japan

    K Isoyama

  7. Department of Hematology and Oncology, Hyogo Children's Hospital, Kobe, Japan

    Y Kosaka

  8. Department of Pediatrics, Hokkaido Children's Hospital and Medical Center, Sapporo, Japan

    T Oda

  9. Department of Pediatrics, Okayama University, Okayama, Japan

    M Oda

  10. Department of Hematology and Oncology, Gunma Children's Medical Center, Shibukawa, Japan

    Y Hayashi

  11. Department of Hematology, Dokkyo Medical University, Tochigi, Japan

    M Eguchi

  12. Clinical Research Center, National Nagoya Hospital, Nagoya, Japan

    K Horibe

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

    T Nakahata

  14. Department of Pediatrics, Ehime University School of Medicine, Ehime, Japan

    E Ishii

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  1. D Tomizawa
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  2. K Koh
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  3. T Sato
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  6. K Isoyama
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  7. Y Kosaka
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  10. Y Hayashi
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  11. M Eguchi
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  14. S Mizutani
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  15. E Ishii
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Correspondence to D Tomizawa.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Tomizawa, D., Koh, K., Sato, T. et al. Outcome of risk-based therapy for infant acute lymphoblastic leukemia with or without an MLL gene rearrangement, with emphasis on late effects: a final report of two consecutive studies, MLL96 and MLL98, of the Japan Infant Leukemia Study Group. Leukemia 21, 2258–2263 (2007). https://doi.org/10.1038/sj.leu.2404903

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