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.

Figures

Figure 1

EFS for total group and subgroups of patients. (A) EFS of all 491 patients. With a median follow-up of 5.7 years, the 5-year EFS ± SE for all 491 patients treated on Protocol 95-01 was 82% ± 2%. (B) EFS for SR and HR patients. The 5-year EFS ± SE for SR patients (n = 272) was 86% ± 2% compared with 76% ± 3% for HR patients (n = 219; P = .01).

Figure 2

EFS results based on asparaginase, dexrazoxane, and CNS randomization. (A) EFS results of asparaginase randomization. The 5-year EFS for patients randomized to Erwinia asparaginase was 78% ± 4% compared with 89% ± 3% for those randomized to E coli asparaginase (P = .01). (B) EFS results of dexrazoxane randomization (HR patients only). The 5-year EFS for patients randomized to doxorubicin with dexrazoxane was 76% ± 4% compared with 77% ± 4% for those randomized to doxorubicin alone (P = .99). (C) EFS results of CNS randomization (SR patients only). The 5-year EFS for patients randomized to intrathecal therapy only (no radiation) was 83% ± 4% compared with 86% ± 4% for those randomized to 18-Gy cranial radiation (P = .26).