¹Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

²Division of Hematology/Oncology, Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA, USA

³Department of Biostatistical Science, Dana-Farber Cancer Institute, Boston, MA, USA

⁴Department of Hematology/Oncology, University of Rochester Medical Center, Rochester, NY, USA

⁵Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada

⁶San Jorge Children's Hospital, Puerto Rico, USA

⁷Maine Children's Cancer Program, The Barbara Bush Children's Hospital at Maine Medical Center, Portland, ME, USA

⁸Hospital Ste Justine, Montreal, Quebec, Canada

⁹Le Centre Hospitalier de L'Université, Laval, Quebec, Canada

¹⁰Department of Pediatrics, Oschner Medical Institutions, New Orleans, LA, USA

¹¹Schneider Children's Hospital, New Hyde Park, NY, USA

¹²Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA

Correspondence to: L B Silverman, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA; Fax: 617 632 3977

The Dana-Farber Cancer Institute (DFCI) ALL consortium has been conducting clinical trials in childhood acute lymphoblastic leukemia (ALL) since 1981. The treatment backbone has included intensive, multi-agent remission induction, early intensification with weekly, high-dose asparaginase, cranial radiation for the majority of patients, frequent vincristine/ corticosteroid pulses during post-remission therapy, and for high-risk patients, doxorubicin during intensification. Between 1981 and 1995, 1255 children with newly diagnosed ALL were evaluated on four consecutive protocols: 81-01 (1981-1985), 85-01 (1985-1987), 87-01 (1987-1991) and 91-01 (1991-1995). The 5-year event-free survival (EFS) rates (± standard error) for all patients by protocol were as follows: 74 ± 3% (81-01), 78 ± 3% (85-01), 77 ± 2% (87-01) and 83 ± 2% (91-01). The 5-year EFS rates ranged from 78 to 85% for patients with B-progenitor phenotype retrospectively classified as NCI standard-risk, 63-82% for NCI high-risk B-progenitor patients, and 70-79% for patients with T cell phenotype. Results of randomized studies revealed that neither high-dose methotrexate during induction (protocol 87-01) nor high-dose 6-mercaptopurine during intensification (protocol 91-01) were associated with improvement in EFS compared with standard doses. Current studies continue to focus on improving efficacy while minimizing acute and late toxicities. Leukemia (2000) 14, 2247-2256.

acute lymphoblastic leukemia; childhood; asparaginase; doxorubicin