title: Intrathecal triple therapy decreases central nervous system relapse but fails to improve event-free survival when compared with intrathecal methotrexate: results of the Children's Cancer Group (CCG) 1952 study for standard-risk acute lymphoblastic leukemia, reported by the Children's Oncology Group.
abstract: The Children's Cancer Group (CCG) 1952 clinical trial for children with standard-risk acute lymphoblastic leukemia (SR-ALL) compared intrathecal (IT) methotrexate (MTX) with IT triples (ITT) (MTX, cytarabine, and hydrocortisone sodium succinate [HSS]) as presymptomatic central nervous system (CNS) treatment. Following remission induction, 1018 patients were randomized to receive IT MTX and 1009 ITT. Multivariate analysis identified male sex, hepatomegaly, CNS-2 status, and age younger than 2 or older than 6 years as significant predictors of isolated CNS (iCNS) relapse. The 6-year cumulative incidence estimates of iCNS relapse are 3.4% +/- 1.0% for ITT and 5.9% +/- 1.2% for IT MTX; P = .004. Significantly more relapses occurred in bone marrow (BM) and testicles with ITT than IT MTX, particularly among patients with T-cell phenotype or day 14 BM aspirate containing 5% to 25% blasts. Thus, the estimated 6-year event-free survivals (EFS) with ITT or IT MTX are equivalent at 80.7% +/- 1.9% and 82.5% +/- 1.8%, respectively (P = .3). Because the salvage rate after BM relapse is inferior to that after CNS relapse, the 6-year overall survival (OS) for ITT is 90.3% +/- 1.5% versus 94.4% +/- 1.1% for IT MTX (P = .01). It appears that ITT improves presymptomatic CNS treatment but does not improve overall outcome.
authors.affiliation: Department of Pediatrics, University of Wisconsin Children's Hospital, Madison, WI 53792-4108, USA. yhmatloub@wisc.edu
authors.forename: Yousif
authors.initials: Y
authors.lastname: Matloub
authors.forename: Susan
authors.initials: S
authors.lastname: Lindemulder
authors.forename: Paul S
authors.initials: PS
authors.lastname: Gaynon
authors.forename: Harland
authors.initials: H
authors.lastname: Sather
authors.forename: Mei
authors.initials: M
authors.lastname: La
authors.forename: Emmett
authors.initials: E
authors.lastname: Broxson
authors.forename: Rochelle
authors.initials: R
authors.lastname: Yanofsky
authors.forename: Raymond
authors.initials: R
authors.lastname: Hutchinson
authors.forename: Nyla A
authors.initials: NA
authors.lastname: Heerema
authors.forename: James
authors.initials: J
authors.lastname: Nachman
authors.forename: Marilyn
authors.initials: M
authors.lastname: Blake
authors.forename: Linda M
authors.initials: LM
authors.lastname: Wells
authors.forename: April D
authors.initials: AD
authors.lastname: Sorrell
authors.forename: Margaret
authors.initials: M
authors.lastname: Masterson
authors.forename: John F
authors.initials: JF
authors.lastname: Kelleher
authors.forename: Linda C
authors.initials: LC
authors.lastname: Stork
mesh_terms: D000367:Age Factors; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D019046:Bone Marrow Neoplasms / Q000556:secondary; D002490:Central Nervous System / Q000473:pathology; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000031:analogs & derivatives; D007278:Injections, Spinal; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D012008:Recurrence; D012074:Remission Induction; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors; D013601:T-Lymphocytes / Q000473:pathology; D013736:Testicular Neoplasms / Q000556:secondary; D013997:Time Factors
chemical_list: D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine; C007133:hydrocortisone hemisuccinate; D006854:Hydrocortisone; D008727:Methotrexate