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Excess treatment reduction including anthracyclines results in higher incidence of relapse in core binding factor acute myeloid leukemia in children

Leukemia volume 27, pages 2413–2416 (2013)Cite this article

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Patients with core binding factor acute myeloid leukemia (CBF-AML) with translocation (8;21)(q22;q22) [t(8;21)] and inversion of chromosome 16(p13.1q22), or its variant t(16;16) (p13.1;q22) [inv(16)], generally have favorable outcomes, as the probabilities of event-free survival (pEFS) and overall survival (pOS) were around 80% and 90%, respectively, in recent clinical trials of pediatric AML.1, 2, 3 It is well recognized that intensive post remission chemotherapy with high-dose cytarabine (HDCA) has contributed to the improved survival of CBF-AML.4, 5 Although there is evidence that high doses of anthracyclines—another key component of AML chemotherapy—improves the outcomes in children and adults with AML,6, 7 its effects in CBF-AML are not well established, unlike those of HDCA. Moreover, higher doses of anthracyclines are associated with increased risk of late cardiotoxicity, which could occur at a lower cumulative dose (for example, >300 mg/m2) in children than in adults.8 Therefore, it needs to be evaluated whether intensive use of HDCA could compensate for a reduction in the other treatment components, especially the cumulative anthracycline dose, by maintaining high pEFS and pOS and reducing the risk of late complications such as anthracycline-induced cardiotoxicity in particular.

The characteristics of patients at diagnosis in the AML-05 and AML99 studies are reported in Table 1. Sex, age and WBC count were comparable in both studies, but the distribution of French–American–British classification categories differed. This is because the patients were diagnosed according to the WHO classification (3rd edition) in AML-05, which included patients with low bone marrow blast percentages of 20–30% who are classified as having refractory anemia with excess blasts in transformation (RAEB-T). Additionally, while FLT3-ITD status was prospectively examined in all patients in AML-05, it was examined retrospectively in approximately 60% of patients in AML99, although the difference was not significant.

Table 1 Characteristics and treatment response of patients with CBF-AML in the AML-05 and AML99 studies
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Acknowledgements

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.

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Authors and Affiliations

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

    D Tomizawa

  2. Department of Pediatrics, National Hospital Organization, Osaka Medical Center, Osaka, Japan

    A Tawa

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

    T Watanabe

  4. Clinical Research Center, National Hospital Organization, Nagoya Medical Center, Nagoya, Japan

    A M Saito & K Horibe

  5. Division of Hematology and Oncology, Shizuoka Children’s Hospital, Shizuoka, Japan

    K Kudo

  6. Department of Pediatrics, Shiga University of Medical Science, Otsu, Japan

    T Taga

  7. Department of Pediatrics, Mie University School of Medicine, Tsu, Japan

    S Iwamoto

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

    A Shimada

  9. Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan

    K Terui

  10. Division of Pediatrics, Department of Reproductive and Developmental Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

    H Moritake

  11. Department of Pediatrics, St Marianna University School of Medicine, Kawasaki, Japan

    A Kinoshita

  12. Department of Pediatrics, Saiseikai Yokohama City Southern Hospital, Yokohama, Japan

    H Takahashi

  13. Department of Pediatrics, Fukuoka-Higashi Medical Center, National Hospital Organization, Koga, Japan

    H Nakayama

  14. Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan

    K Koh

  15. Department of Hematology/Oncology, Kanagawa Children’s Medical Center, Yokohama, Japan

    H Kigasawa

  16. Department of Hematology and Oncology, Hyogo Children’s Hospital, Kobe, Japan

    Y Kosaka

  17. Department of Laboratory Medicine, Tokai University School of Medicine, Isehara, Japan

    H Miyachi

  18. Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan

    T Nakahata

  19. Human Health Sciences, Kyoto University, Kyoto, Japan

    S Adachi

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Correspondence to D Tomizawa.

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Tomizawa, D., Tawa, A., Watanabe, T. et al. Excess treatment reduction including anthracyclines results in higher incidence of relapse in core binding factor acute myeloid leukemia in children. Leukemia 27, 2413–2416 (2013). https://doi.org/10.1038/leu.2013.153

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