International Journal of Hematology

DOI: 10.1007/s12185-017-2235-z Pages: 291-298

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

1. Hokkaido University Hospital, Department of Pediatrics

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

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

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

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

Correspondence to:
Akihiro Iguchi
Tel: 81-11-706-5954



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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