title: Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group.
abstract: Children's Cancer Group-1991 selected 2 components from the Children's Cancer Group studies shown to be effective in high-risk acute lymphoblastic leukemia and examined them in children with National Cancer Institute standard-risk acute B-precursor lymphoblastic leukemia. These were (1) vincristine and escalating IV methotrexate (MTX) without leucovorin rescue during the interim maintenance (IM) phases and (2) addition of a second delayed intensification (DI) phase. Eligible patients (n = 2078) were randomly assigned to regimens containing either oral (PO) MTX, PO mercaptopurine, dexamethasone, and vincristine or IV MTX during IM phases, and regimens with either single DI or double DI. Five-year event-free survival (EFS) and overall survival for patients on the PO MTX arms were 88.7% ± 1.4% and 96% ± 0.9% versus 92.6% ± 1.2% and 96.5% ± 0.8% for those on the IV MTX arms (P = .009, P = .66). Five-year EFS and overall survival for patients who received single DI were 90.9% ± 1.3% and 97.1% ± 0.8% versus 90.5% ± 1.3% and 95.4% ± 3.8% for those who received double DI (P = .71, P = .12). No advantage was found for a second DI; however, replacement of PO MTX, PO mercaptopurine, vincristine, and dexamethasone during IM with vincristine and escalating IV MTX improved EFS.
authors.affiliation: Division of Hematology-Oncology, Rainbow Babies & Children's Hospital, Case Western Reserve University, Cleveland, OH 44106, USA. yousif.matloub@uhhospitals.org
authors.forename: Yousif
authors.initials: Y
authors.lastname: Matloub
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Bostrom
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Hunger
authors.forename: Linda C
authors.initials: LC
authors.lastname: Stork
authors.forename: Anne
authors.initials: A
authors.lastname: Angiolillo
authors.forename: Harland
authors.initials: H
authors.lastname: Sather
authors.forename: Mei
authors.initials: M
authors.lastname: La
authors.forename: Julie M
authors.initials: JM
authors.lastname: Gastier-Foster
authors.forename: Nyla A
authors.initials: NA
authors.lastname: Heerema
authors.forename: Scott
authors.initials: S
authors.lastname: Sailer
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Buckley
authors.forename: Blythe
authors.initials: B
authors.lastname: Thomson
authors.forename: Catherine
authors.initials: C
authors.lastname: Cole
authors.forename: James B
authors.initials: JB
authors.lastname: Nachman
authors.forename: Gregory
authors.initials: G
authors.lastname: Reaman
authors.forename: Naomi
authors.initials: N
authors.lastname: Winick
authors.forename: William L
authors.initials: WL
authors.lastname: Carroll
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Devidas
authors.forename: Paul S
authors.initials: PS
authors.lastname: Gaynon
mesh_terms: D000465:Algorithms; D000970:Antineoplastic Agents / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007223:Infant; D007275:Injections, Intravenous; D008297:Male; D008495:Medical Oncology / Q000379:methods / Q000458:organization & administration; D008727:Methotrexate / Q000008:administration & dosage*; D009367:Neoplasm Staging; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D012306:Risk; D012955:Societies, Medical
chemical_list: D000970:Antineoplastic Agents; D008727:Methotrexate