International Journal of Hematology

DOI: 10.1007/s12185-019-02714-x Pages: 627-634

Bortezomib-containing therapy in Japanese children with relapsed acute lymphoblastic leukemia

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

2. National Cancer Center Hospital, Department of Pediatric Oncology

3. National Hospital Organization Nagoya Medical Center, Department of Pediatrics

4. Osaka City General Hospital, Department of Pediatric Hematology and Oncology

5. Fukushima Medical University Hospital, Department of Pediatric Oncology

6. National Hospital Organization Nagoya Medical Center, Clinical Research Center

7. Tokyo Women’s Medical University Hospital, Department of Pharmacy

Correspondence to:
Daisuke Hasegawa
Tel: +81-3-3547-3330
Email: hase-dai@umin.net

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Abstract

Outcomes of children treated for relapsed acute lymphoblastic leukemia (ALL) remain poor. Bortezomib (BZM), a proteasome inhibitor, has shown promising activity against lymphoid malignancies. We conducted a phase I study to evaluate the safety and tolerability of multidrug chemotherapy including BZM in Japanese children with relapsed ALL. Three of five children with relapsed ALL enrolled in the study between November 2014 and April 2016 were evaluated. BZM (1.3 mg/m2) was administered on days 8, 11, 15, and 18 of multidrug induction chemotherapy. Pharmacokinetic studies were performed. Age at study entry was 5, 7, and 7 years old, respectively. Two patients had hyperdiploid B-precursor ALL, and one had T cell ALL. Although all patients experienced grade 3–4 hematologic toxicity and grade 3 elevation of aminotransferases, no dose-limiting toxicities were observed. The maximum tolerated dose was defined as 1.3 mg/m2. Peripheral neuropathy and respiratory complications were not observed. Complete remission was achieved in all three patients. The mean maximum plasma concentration and area under the concentration–time curve was 74.0 ng/mL and 73.9 ng h/mL, respectively. Thus, adding BZM to 5-drug induction chemotherapy appears safe and well-tolerated in Japanese children with relapsed ALL.

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