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CHRONIC MYELOGENOUS LEUKEMIA

Growth retardation and adult height in pediatric patients with chronic-phase chronic myeloid leukemia treated with tyrosine kinase inhibitors

Leukemia volume 39, pages 508–511 (2025)Cite this article

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Although tyrosine kinase inhibitors (TKIs) have substantially improved chronic myeloid leukemia (CML) prognosis, long-term TKI exposure remains a major concern, especially among children. One critical challenge specific to the treatment of children with TKIs is growth retardation [1,2,3,4]. Recently, both first-generation TKI imatinib and second-generation TKI dasatinib were reported to impact growth in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia [5]. We have previously reported growth retardation in children with CML treated with imatinib, particularly those treated before reaching puberty [3]. Although patients often experience catch-up growth during puberty, the extent of this catch-up and the long-term impact of TKI exposure on adult height remain poorly understood.

We prospectively collected data from children diagnosed with chronic phase CML enrolled in the Japan Pediatric Leukemia and Lymphoma Study Group (JPLSG) CML-08 study. Height data were collected annually, starting two years before diagnosis. Adult height was defined as the maximum height measured when the height increase velocity was <1 cm/year. Height-standard deviation scores (SDS) were adjusted using age- and sex-adjusted Japanese norms [6], with data from 17 years and six months of age used for adult height-SDS. Puberty was defined as a testicular size ≥3 mL for males and breast Tanner 2 for females. Peak height velocity was defined as the increase in height velocity during the growth spurt, and age at peak height velocity was calculated from the growth curves [7]. The duration of TKI exposure before the growth spurt was defined as the duration of TKI exposure until peak height velocity. Parental height data were collected to predict adult height and range. Target height (TH), representing a child’s predicted adult height from parental heights, and target range (TR), a 95% confidence interval of target height, were calculated as follows (cm): males, TH = (mother’s height + father’s height + 13)/2, TR = TH ± 9; females, (mother’s height + father’s height − 13)/2, TR = TH ± 8 [8].

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Fig. 1: Changes in height-SDS, growth velocity, and adult height.

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Acknowledgements

This study was supported by Grants-in-Aid for Scientific Research from the Ministry of Health, Labour and Welfare.

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Authors and Affiliations

  1. Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan

    Haruko Shima & Hiroyuki Shimada

  2. Department of Nursing Science, Hirosaki University Graduate School of Health Sciences, Aomori, Japan

    Chikako Tono

  3. Sugita Genpaku Memorial Obama Municipal Hospital, Fukui, Japan

    Akihiko Tanizawa

  4. Department of Pediatrics, Soma General Hospital, Fukushima, Japan

    Masaki Ito

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

    Akihiro Watanabe

  6. Department of Hematology/Oncology, Tokyo Metropolitan Children’s Medical Center, Tokyo, Japan

    Yuki Yuza

  7. Department of Pediatrics, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Hiroshima, Japan

    Kazuko Hamamoto

  8. Department of Pediatrics, Nagoya University Graduate School of Medicine, Aichi, Japan

    Hideki Muramatsu

  9. Department of Pediatrics, Nagasaki University School of Medicine, Nagasaki, Japan

    Masahiko Okada

  10. Department of Pediatrics, Shinshu University School of Medicine, Nagano, Japan

    Shoji Saito

  11. Division of Hematology/Oncology, Kanagawa Children’s Medical Center, Kanagawa, Japan

    Hiroaki Goto

  12. Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

    Masaru Imamura

  13. Clinical Research Center, NHO Nagoya Medical Center, Aichi, Japan

    Akiko M. Saito

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

    Souichi Adachi

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

    Eiichi Ishii

Authors
  1. Haruko Shima
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  16. Hiroyuki Shimada
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Contributions

HShima was responsible for designing and executing the study protocol and conducting the research, analyzing the data, interpreting the results, and drafting and revising the manuscript and supplementary data. CT, AT, MI, AW, YY, KH, HM, and MO were responsible for designing and executing the study protocol and conducting the research. SS, HG and MI were responsible for conducting the research. AMS was responsible for designing the protocol and extracting and analyzing the data. SA and EI were responsible for executing the study protocol and conducting the research. HShimada was responsible for designing and executing the study protocol, conducting the research, and drafting and revising the manuscript. All authors contributed to the article and approved the submitted version.

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Correspondence to Haruko Shima.

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HG received lecture fees from Novartis. All other authors declare no competing interests.

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Shima, H., Tono, C., Tanizawa, A. et al. Growth retardation and adult height in pediatric patients with chronic-phase chronic myeloid leukemia treated with tyrosine kinase inhibitors. Leukemia 39, 508–511 (2025). https://doi.org/10.1038/s41375-024-02488-0

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