title: Results of the Dana-Farber Cancer Institute ALL Consortium Protocol 95-01 for children with acute lymphoblastic leukemia.
abstract: The Dana-Farber Cancer Institute (DFCI) Childhood ALL Consortium Protocol 95-01 was designed to minimize therapy-related morbidity for children with newly diagnosed ALL without compromising efficacy. Patients participated in randomized comparisons of (1) doxorubicin given with or without dexrazoxane, a cardioprotectant (high-risk patients), (2) intensive intrathecal chemotherapy and cranial radiation (standard-risk patients), and (3) Erwinia and Escherichia coli asparaginase (all patients). Between 1996 and 2000, 491 patients (aged 0-18 years) were enrolled (272 standard risk and 219 high risk). With a median of 5.7 years of follow-up, the estimated 5-year event-free survival (EFS) for all patients was 82%+/-2%. Dexrazoxane did not have a significant impact on the 5-year EFS of high-risk patients (P=.99), and there was no significant difference in outcome of standard-risk patients based on type of central nervous system (CNS) treatment (P=.26). Compared with E coli asparaginase, Erwinia asparaginase was associated with a lower incidence of toxicity (10% versus 24%), but also an inferior 5-year EFS (78%+/-4% versus 89%+/-3%, P=.01). We conclude that (1) dexrazoxane does not interfere with the antileukemic effect of doxorubicin, (2) intensive intrathecal chemotherapy is as effective as cranial radiation in preventing CNS relapse in standard-risk patients, and (3) once-weekly Erwinia is less toxic than E coli asparaginase, but also less efficacious.
authors.affiliation: Division of Hematology and Oncology, Sainte-Justine Hospital, University of Montreal, Quebec, Canada. albert.moghrabi@umontreal.ca
authors.forename: Albert
authors.initials: A
authors.lastname: Moghrabi
authors.forename: Donna E
authors.initials: DE
authors.lastname: Levy
authors.forename: Barbara
authors.initials: B
authors.lastname: Asselin
authors.forename: Ronald
authors.initials: R
authors.lastname: Barr
authors.forename: Luis
authors.initials: L
authors.lastname: Clavell
authors.forename: Craig
authors.initials: C
authors.lastname: Hurwitz
authors.forename: Yvan
authors.initials: Y
authors.lastname: Samson
authors.forename: Marshall
authors.initials: M
authors.lastname: Schorin
authors.forename: Virginia K
authors.initials: VK
authors.lastname: Dalton
authors.forename: Steven E
authors.initials: SE
authors.lastname: Lipshultz
authors.forename: Donna S
authors.initials: DS
authors.lastname: Neuberg
authors.forename: Richard D
authors.initials: RD
authors.lastname: Gelber
authors.forename: Harvey J
authors.initials: HJ
authors.lastname: Cohen
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Sallan
authors.forename: Lewis B
authors.initials: LB
authors.lastname: Silverman
mesh_terms: D000293:Adolescent; D001215:Asparaginase / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D011929:Razoxane / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D002316:Cardiotonic Agents; D011929:Razoxane; D004317:Doxorubicin; D001215:Asparaginase