title: Bortezomib combined with standard induction chemotherapy in Japanese children with refractory acute lymphoblastic leukemia.
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.
authors.affiliation: Department of Pediatrics, Hokkaido University Hospital, N14W5 Kita-ku, Sapporo, 060-8638, Japan. igurin66@med.hokudai.ac.jp.
authors.forename: Akihiro
authors.identifier: http://orcid.org/0000-0002-1367-3883
authors.initials: A
authors.lastname: Iguchi
authors.affiliation: Department of Pediatrics, Hokkaido University Hospital, N14W5 Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Cho
authors.affiliation: Department of Pediatrics, Hokkaido University Hospital, N14W5 Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Minako
authors.initials: M
authors.lastname: Sugiyama
authors.affiliation: Department of Pediatrics, Hokkaido University Hospital, N14W5 Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Yukayo
authors.initials: Y
authors.lastname: Terashita
authors.affiliation: Department of Pediatrics, Hokkaido University Hospital, N14W5 Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ariga
authors.affiliation: Department of Pediatrics, St. Luke's International Hospital, Tokyo, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Hosoya
authors.affiliation: Department of Pediatrics, St. Luke's International Hospital, Tokyo, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Hirabayashi
authors.affiliation: Department of Pediatrics, St. Luke's International Hospital, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Manabe
authors.affiliation: Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Hara
authors.affiliation: Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Aiba
authors.affiliation: Department of Instrumental Analysis Advanced Science Research Center, Okayama University, Okayama, Japan.
authors.forename: Tsugumi
authors.initials: T
authors.lastname: Shiokawa
authors.affiliation: Department of Instrumental Analysis Advanced Science Research Center, Okayama University, Okayama, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tada
authors.affiliation: Department of Clinical Research & Medical Innovation Center, Hokkaido University Hospital, Sapporo, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Sato
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D044466:Asian People; D000069286:Bortezomib / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D002648:Child; D002675:Child, Preschool; D003141:Communicable Diseases / Q000209:etiology; D006801:Humans; D060828:Induction Chemotherapy; D007223:Infant; D015448:Leukemia, B-Cell / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012306:Risk
chemical_list: D000069286:Bortezomib
keywords: Acute pediatric lymphoblastic leukemia; Bortezomib; Infectious complication; Japanese