Impact of asparaginase discontinuation on outcomes of children with acute lymphoblastic leukaemia receiving the Japan Association of Childhood Leukaemia Study <scp>ALL</scp>‐02 protocol

  • Hisashi Ishida
    Department of Pediatrics Okayama University Hospital Okayama Japan
  • Toshihiko Imamura
    Department of Pediatrics Kyoto Prefectural University of Medicine, Graduate School of Medical Science Kyoto Japan
  • Yasuhisa Tatebe
    Department of Pharmacy Okayama University Hospital Okayama Japan
  • Takashi Ishihara
    Department of Pediatrics Nara Medical University Kashihara Japan
  • Kimiyoshi Sakaguchi
    Department of Pediatrics Hamamatsu University School of Medicine Hamamatsu Japan
  • Souichi Suenobu
    Division of General Pediatrics and Emergency Medicine Oita University Faculty of Medicine Yufu Japan
  • Atsushi Sato
    Department of Hematology/Oncology Miyagi Children's Hospital Sendai Japan
  • Yoshiko Hashii
    Department of Pediatrics Osaka University Graduate School of Medicine Suita Japan
  • Takao Deguchi
    Department of Pediatrics Mie University Tsu Japan
  • Yoshihiro Takahashi
    Department of Pediatrics Aomori Prefectural Central Hospital Aomori Japan
  • Daiichiro Hasegawa
    Department of Hematology/Oncology Hyogo Prefectural Kobe Children's Hospital Kobe Japan
  • Takako Miyamura
    Department of Pediatrics Osaka University Graduate School of Medicine Suita Japan
  • Akihiro Iguchi
    Department of Pediatrics Hokkaido University Hospital Sapporo Japan
  • Koji Kato
    Department of Hematology Oncology, Children's Medical Center Japanese Red Cross Nagoya First Hospital Nagoya Japan
  • Akiko Saito‐Moriya
    Clinical Research Center National Hospital Organization Nagoya Medical Center Nagoya Japan
  • Junichi Hara
    Department of Pediatric Hematology/Oncology Osaka City General Hospital Osaka Japan
  • Keizo Horibe
    Clinical Research Center National Hospital Organization Nagoya Medical Center Nagoya Japan

説明

<jats:title>Summary</jats:title><jats:p>Asparaginase is an essential drug for acute lymphoblastic leukaemia (ALL) treatment, but has several side effects, and its discontinuation often compromises patient outcomes. In the prospective Japan Association of Childhood Leukaemia Study ALL‐02 protocol, two major changes were made: (1) additional chemotherapies to compensate for the reduction of treatment intensity when asparaginase was discontinued and (2) more intensive concomitant corticosteroid administration, relative to our previous ALL‐97 protocol. In ALL‐02 study, 1192 patients were included and L‐asparaginase was discontinued for 88 (7.4%). Discontinuation due to allergy was markedly decreased relative to the ALL‐97 protocol (2.3% vs 15.4%). Event‐free survival (EFS) among patients with T‐ALL was compromised when L‐asparaginase was discontinued, as well as among patients with high‐risk B‐cell ALL, especially when discontinued before maintenance therapy. Moreover, multivariate analysis identified discontinuation of L‐asparaginase as an independent poor prognostic factor for EFS. In the current study, additional chemotherapies failed to fully compensate for L‐asparaginase discontinuation, illustrating the difficulty of replacing asparaginase with other classes of drugs, although this study was not designed to evaluate the effect of these modifications. Concomitant intensive corticosteroid treatment may help to reduce allergy to asparaginase. These results will assist in further optimization of asparaginase use.</jats:p>

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