Results of the Dana-Farber Cancer Institute ALL Consortium Protocol 95-01 for children with acute lymphoblastic leukemia

• Published in: Blood 2007-02, Vol.109 (3), p.896-904
• Main Authors: Moghrabi, Albert, Levy, Donna E., Asselin, Barbara, Barr, Ronald, Clavell, Luis, Hurwitz, Craig, Samson, Yvan, Schorin, Marshall, Dalton, Virginia K., Lipshultz, Steven E., Neuberg, Donna S., Gelber, Richard D., Cohen, Harvey J., Sallan, Stephen E., Silverman, Lewis B.
• Format: Article
• Language: English
• Subjects: Adolescent; Asparaginase - therapeutic use; Cardiotonic Agents - therapeutic use; Child; Child, Preschool; Clinical Trials and Observations; Combined Modality Therapy; Cranial Irradiation; Disease-Free Survival; Doxorubicin - therapeutic use; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Infant; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality; Precursor Cell Lymphoblastic Leukemia-Lymphoma - radiotherapy; Razoxane - therapeutic use; Treatment Outcome
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2006-06-027714

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.