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Bortezomib combined with standard induction chemotherapy in Japanese children with refractory acute lymphoblastic leukemia

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Abstract

Bortezomib has been shown to be effective and well-tolerated in patients with refractory acute lymphoblastic leukemia (ALL) in the Therapeutic Advances in Childhood Leukemia trial. However, the safety and efficacy of bortezomib have not been evaluated in Japanese pediatric patients. Here, we report the results of a clinical trial designed to evaluate the safety of bortezomib combined with induction chemotherapy in Japanese children with refractory ALL. A total of six patients with B-precursor ALL were enrolled in this study. Four-dose bortezomib (1.3 mg/m2/dose) combined with two standard induction chemotherapies was used. Prolonged pancytopenia (grade 4) was observed in all patients. Four of the six patients developed severe infectious complications. Peripheral neuropathy (grade 2) occurred in five patients. The individual plasma bortezomib concentration–time profiles were not related to toxicity and efficacy. Five patients were evaluable for response, and four patients achieved complete response (CR) or CR without platelet recovery (80%). In conclusion, four-dose bortezomib (1.3 mg/m2/dose) combined with standard re-induction chemotherapy was associated with a high risk of infectious complications induced by prolonged neutropenia, although high efficacy has been achieved for Japanese pediatric patients with refractory ALL. Attention must be given to severe infectious complications when performing re-induction chemotherapy including bortezomib.

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Acknowledgements

We thank Ph.D. Osamu Sugita, Mrs. Nao Horie, Miss. Michi Yoshitani, Miss Nanako Ono, Mrs. Miyuki Yanagida, and Mrs. Minako Honmura for their excellent assistance in the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Pediatrics, Hokkaido University Hospital, N14W5 Kita-ku, Sapporo, 060-8638, Japan

    Akihiro Iguchi, Yuko Cho, Minako Sugiyama, Yukayo Terashita & Tadashi Ariga

  2. Department of Pediatrics, St. Luke’s International Hospital, Tokyo, Japan

    Yosuke Hosoya, Shinsuke Hirabayashi & Atsushi Manabe

  3. Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan

    Keisuke Hara & Tetsuya Aiba

  4. Department of Instrumental Analysis Advanced Science Research Center, Okayama University, Okayama, Japan

    Tsugumi Shiokawa & Hiroko Tada

  5. Department of Clinical Research & Medical Innovation Center, Hokkaido University Hospital, Sapporo, Japan

    Norihiro Sato

Authors
  1. Akihiro Iguchi
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  2. Yuko Cho
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  3. Minako Sugiyama
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  4. Yukayo Terashita
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  5. Tadashi Ariga
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  6. Yosuke Hosoya
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  7. Shinsuke Hirabayashi
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  8. Atsushi Manabe
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  9. Keisuke Hara
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  10. Tetsuya Aiba
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  11. Tsugumi Shiokawa
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  12. Hiroko Tada
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  13. Norihiro Sato
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Correspondence to Akihiro Iguchi.

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Iguchi, A., Cho, Y., Sugiyama, M. et al. Bortezomib combined with standard induction chemotherapy in Japanese children with refractory acute lymphoblastic leukemia. Int J Hematol 106, 291–298 (2017). https://doi.org/10.1007/s12185-017-2235-z

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  • DOI: https://doi.org/10.1007/s12185-017-2235-z

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