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High rates of ovarian function preservation after hematopoietic cell transplantation with melphalan-based reduced intensity conditioning for pediatric acute leukemia: an analysis from the Japan Association of Childhood Leukemia Study (JACLS)

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Abstract

Women are at high risk of hypergonadotropic hypogonadism after hematopoietic cell transplantation (HCT). Hypogonadism is universal after irradiation or busulfan. We hypothesized that reduced intensity conditioning (RIC) might protect ovarian function after HCT. We retrospectively reviewed data from patients with acute leukemia treated according to the Japan Association of Childhood Leukemia Study and nationwide multicenter study protocol. We selected 11 female patients with acute leukemia who received first HCT with RIC, had survived for three or more years after HCT, and were aged ≥ 12 years at the last follow-up visit. Median age at diagnosis, HCT, and last visit were 8, 10, and 17 years. Six patients received HLA-matched bone marrow (BM), two HLA-mismatched BM, and three cord blood. Melphalan was used as conditioning regimen in all patients. At the last visit, six of seven post-pubertal patients at transplantation recovered menstruation, and four of four patients who underwent transplantation at the pre-pubertal began menstruation. Height z scores showed no significant reduction between pre-transplant and post-transplant. No patients received growth hormone treatment. Only one recipient displayed subclinical hypothyroidism. Melphalan-based RIC may be an encouraging option for patients with acute leukemia to avoid ovarian and endocrine dysfunction after HCT.

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Authors and Affiliations

  1. Department of Pediatrics, Osaka Red Cross Hospital, Osaka, Japan

    Hisanori Fujino

  2. Japan Association of Childhood Leukemia Study Group (JACLS), Suita, Japan

    Hisanori Fujino, Hiroyuki Ishida, Akihiro Iguchi, Masaei Onuma, Koji Kato, Mariko Shimizu, Masahiro Yasui, Hiroyuki Fujisaki, Kazuko Hamamoto, Kana Washio, Hirotoshi Sakaguchi, Emiko Miyashita, Yuko Osugi, Etsuko Nakagami-Yamaguchi, Akira Hayakawa, Atsushi Sato, Yoshiyuki Takahashi & Keizo Horibe

  3. Department of Pediatrics, Kyoto City Hospital, Kyoto, Japan

    Hiroyuki Ishida

  4. Department of Pediatrics, Hokkaido University, Sapporo, Japan

    Akihiro Iguchi

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

    Masaei Onuma & Atsushi Sato

  6. Department of Hematology and Oncology, Children’s Medical Center, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    Koji Kato & Hirotoshi Sakaguchi

  7. Department of Hematology/Oncology, Osaka Women’s and Children’s Hospital, Izumi, Japan

    Mariko Shimizu & Masahiro Yasui

  8. Department of Pediatric Hematology/Oncology, Osaka City General Hospital, Osaka, Japan

    Hiroyuki Fujisaki

  9. Department of Pediatrics, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, Hiroshima, Japan

    Kazuko Hamamoto

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

    Kana Washio

  11. Department of Pediatrics, Osaka University, Suita, Japan

    Emiko Miyashita

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

    Yuko Osugi

  13. Department of Medical Quality and Safety Science, Osaka City University, Osaka, Japan

    Etsuko Nakagami-Yamaguchi

  14. Department of Pediatrics, Kobe University, Kobe, Japan

    Akira Hayakawa

  15. Department of Pediatrics, Nagoya University, Nagoya, Japan

    Yoshiyuki Takahashi

  16. Department of Pediatrics, National Hospital Organization Nagoya Medical Center, Nagoya, Japan

    Keizo Horibe

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  1. Hisanori Fujino
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Correspondence to Hisanori Fujino.

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Fujino, H., Ishida, H., Iguchi, A. et al. High rates of ovarian function preservation after hematopoietic cell transplantation with melphalan-based reduced intensity conditioning for pediatric acute leukemia: an analysis from the Japan Association of Childhood Leukemia Study (JACLS). Int J Hematol 109, 578–583 (2019). https://doi.org/10.1007/s12185-019-02627-9

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