title: Oral 6-mercaptopurine versus oral 6-thioguanine and veno-occlusive disease in children with standard-risk acute lymphoblastic leukemia: report of the Children's Oncology Group CCG-1952 clinical trial.
abstract: The Children's Cancer Group 1952 (CCG-1952) clinical trial studied the substitution of oral 6-thioguanine (TG) for 6-mercaptopurine (MP) and triple intrathecal therapy (ITT) for intrathecal methotrexate (IT-MTX) in the treatment of standard-risk acute lymphoblastic leukemia. After remission induction, 2027 patients were randomized to receive MP (n = 1010) or TG (n = 1017) and IT-MTX (n = 1018) or ITT (n = 1009). The results of the thiopurine comparison are as follows. The estimated 7-year event-free survival (EFS) for subjects randomized to TG was 84.1% (+/- 1.8%) and to MP was 79.0% (+/- 2.1%; P = .004 log rank), although overall survival was 91.9% (+/- 1.4%) and 91.2% (+/- 1.5%), respectively (P = .6 log rank). The TG starting dose was reduced from 60 to 50 mg/m(2) per day after recognition of hepatic veno-occlusive disease (VOD). A total of 257 patients on TG (25%) developed VOD or disproportionate thrombocytopenia and switched to MP. Once portal hypertension occurred, all subjects on TG were changed to MP. The benefit of randomization to TG over MP, as measured by EFS, was evident primarily in boys who began TG at 60 mg/m(2) (relative hazard rate [RHR] 0.65, P = .002). The toxicities of TG preclude its protracted use as given in this study. This study is registered at http://clinicaltrials.gov as NCT00002744.
authors.affiliation: Division of Hematology-Oncology, Doernbecher Children's Hospital/Oregon Health & Science University, Portland, OR 97239, USA. storkl@ohsu.edu
authors.forename: Linda C
authors.initials: LC
authors.lastname: Stork
authors.forename: Yousif
authors.initials: Y
authors.lastname: Matloub
authors.forename: Emmett
authors.initials: E
authors.lastname: Broxson
authors.forename: Mei
authors.initials: M
authors.lastname: La
authors.forename: Rochelle
authors.initials: R
authors.lastname: Yanofsky
authors.forename: Harland
authors.initials: H
authors.lastname: Sather
authors.forename: Ray
authors.initials: R
authors.lastname: Hutchinson
authors.forename: Nyla A
authors.initials: NA
authors.lastname: Heerema
authors.forename: April D
authors.initials: AD
authors.lastname: Sorrell
authors.forename: Margaret
authors.initials: M
authors.lastname: Masterson
authors.forename: Archie
authors.initials: A
authors.lastname: Bleyer
authors.forename: Paul S
authors.initials: PS
authors.lastname: Gaynon
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced*; D006801:Humans; D006975:Hypertension, Portal / Q000139:chemically induced; D007223:Infant; D007278:Injections, Spinal; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage* / Q000009:adverse effects*; D008727:Methotrexate / Q000008:administration & dosage; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D013866:Thioguanine / Q000008:administration & dosage* / Q000009:adverse effects*
chemical_list: D015122:Mercaptopurine; D013866:Thioguanine; D008727:Methotrexate