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Ponatinib in pediatric patients with Philadelphia chromosome-positive leukemia: a retrospective survey of the Japan Children’s Cancer Group

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Abstract

Ponatinib is effective in adults with Philadelphia chromosome-positive (Ph+) leukemia, resistant or intolerant to second-generation tyrosine kinase inhibitors, but there are limited data on its use in children. The clinical courses of nine pediatric patients with Ph+ acute lymphoblastic leukemia (Ph+ ALL) and four with chronic myeloid leukemia (CML) who received ponatinib therapy were retrospectively reviewed. The median age at the start of ponatinib therapy was 12 years (range 8–16 years). Nine patients were male and four were female. Six patients received ponatinib alone, three received ponatinib with prednisolone, one received ponatinib with rituximab intrathecal therapy, and one received ponatinib with conventional chemotherapy. Two patients received ponatinib both alone and in combination with chemotherapy. The median dose and duration of ponatinib were 16.9 mg/m2 (7–34.3) and 1.1 months (0.2–22.7), respectively. Six patients with Ph+ ALL and two with CML responded to ponatinib. One of the eight patients who received ponatinib alone had grade 4 increased lipase levels. Grade 3 non-hematologic toxicities included elevated alanine aminotransferase levels (25%), elevated aspartate aminotransferase levels (25%), elevated gamma-glutamyl transferase levels (12.5%), hypertension (12.5%), and polymorphic erythema (12.5%). Ponatinib may be safe and effective in pediatric patients with Ph+ leukemia.

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Acknowledgements

We would like to thank the physicians working at the institutions affiliated with the JCCG who cooperated with this study by submitting the questionnaires. Especially, Masaki Yamamoto (Sapporo Medical University School of Medicine), Hideki Sano (Fukushima Medical University Hospital), Ryoko Suzuki (University of Tsukuba Hospital), Masanaka Sugiyama (National Cancer Center Hospital), Rintaro Ono (St. Luke's International Hospital), Ritsuo Nishiuchi (Kochi Health Sciences Center), Shuichi Ozono (Kurume University School of Medicine) and Nobuyuki Hyakuna (University of the Ryukyus Hospital) contributed to register each case in this study.

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Authors and Affiliations

  1. Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan

    Yuichi Kodama

  2. Department of Hematology and Oncology, Miyagi Children’s Hospital, Sendai, Japan

    Atsushi Sato

  3. Division of Pediatric Hematology and Oncology, Ibaraki Children’s Hospital, Mito, Japan

    Keisuke Kato

  4. Children’s Cancer Center, National Center for Child Health and Development, Tokyo, Japan

    Hirotoshi Sakaguchi

  5. Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Motohiro Kato

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

    Hirohide Kawasaki

  7. Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Hidefumi Hiramatsu & Itaru Kato

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

    Takashi Taga

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

    Hiroyuki Shimada

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  1. Yuichi Kodama
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  2. Atsushi Sato
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  3. Keisuke Kato
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  5. Motohiro Kato
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  7. Hidefumi Hiramatsu
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  8. Itaru Kato
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  9. Takashi Taga
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  10. Hiroyuki Shimada
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Correspondence to Yuichi Kodama.

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Kodama, Y., Sato, A., Kato, K. et al. Ponatinib in pediatric patients with Philadelphia chromosome-positive leukemia: a retrospective survey of the Japan Children’s Cancer Group. Int J Hematol 116, 131–138 (2022). https://doi.org/10.1007/s12185-022-03329-5

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  • DOI: https://doi.org/10.1007/s12185-022-03329-5

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