title: No impact of high-dose cytarabine and asparaginase as early intensification with intermediate-risk paediatric acute lymphoblastic leukaemia: results of randomized trial TCCSG study L99-15.
abstract: The Tokyo Children's Cancer Study Group conducted a randomized controlled study to evaluate the effect of experimental early intensification using high-dose cytarabine and L-asparaginase in paediatric intermediate-risk (IR) acute lymphoblastic leukaemia (ALL). A total of 310 IR ALL patients were randomized to receive either experimental early intensification (n = 156) or standard early intensification including standard-dose cytarabine arm (n = 154) after induction therapy. The experimental arm consisted of high-dose cytarabine and L-asparaginase, while the standard arm consisted of standard-dose cytarabine, oral 6-mercaptopurine and cyclophosphamide. The probabilities of event-free survival at 8 years in the experimental and standard arms were 72·3 ± 3·7% and 77·5 ± 3·5%, respectively (P = 0·32). The 8-year overall survival rates for these two arms were 85·0 ± 3·0% and 86·9 ± 2·8%, respectively (P = 0·72). The frequency of infectious events was significantly higher in the experimental arm (66·4%) than in the standard arm (24·6%) (P < 0·001). In conclusion, experimental early intensification including high-dose cytarabine followed by L-asparaginase had no advantage over standard early intensification in paediatric IR ALL patients.
authors.affiliation: Department of Haematology/Oncology, Saitama Children's Medical Centre, Saitama, Japan; Department of Paediatrics, the University of Tokyo, Tokyo, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Kato
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Koh
authors.forename: Atsushi
authors.initials: A
authors.lastname: Manabe
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Saito
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hasegawa
authors.forename: Keiichi
authors.initials: K
authors.lastname: Isoyama
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Kinoshita
authors.forename: Miho
authors.initials: M
authors.lastname: Maeda
authors.forename: Yuri
authors.initials: Y
authors.lastname: Okimoto
authors.forename: Michiko
authors.initials: M
authors.lastname: Kajiwara
authors.forename: Takashi
authors.initials: T
authors.lastname: Kaneko
authors.forename: Kanji
authors.initials: K
authors.lastname: Sugita
authors.forename: Akira
authors.initials: A
authors.lastname: Kikuchi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsuchida
authors.forename: Akira
authors.initials: A
authors.lastname: Ohara
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012074:Remission Induction; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D003561:Cytarabine; D001215:Asparaginase
keywords: acute lymphoblastic leukaemia; child; early intensification; high-dose cytarabine; randomized trial