¹Department of Pediatric Hematology-Oncology, Children's Hospital, Los Angeles, CA, USA

²Department of Pediatrics, duPont Hospital for Children, Wilmington, DE, USA

³Department of Genetics, Hughes Institute, St Paul, MN, USA

⁴Children's Cancer Group, Arcadia, CA, USA

⁵Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

⁶Division of Pediatrics, MD Anderson Cancer Center, Houston, TX, USA

Correspondence to: P S Gaynon, The Children's Cancer Group, Attention Ms Lucia Noll, PO Box 60012, Arcadia, CA 91066-6012, USA; Fax: 626 445 4334

Since 1968, the Children's Cancer Group (CCG) has treated more than 16 000 children with acute lymphoblastic leukemia (ALL). Herein, we report improvements obtained in CCG trials during two successive series of studies (1983-1988 and 1989-1995). Overall, 10-year EFS was 62% ± 10% for the 1983-1988 series and 72% ± 1% for the 1988-1995 series (P < 0.0001). Five-year cumulative rates of isolated CNS relapses were 5.9% and 4.4%. Therapy based on the Berlin-Frankfurt-Münster 76/79 study improved outcomes for intermediate and higher risk patients in the first series. For intermediate risk patients, delayed intensification (DI) was most crucial for improved outcome and cranial irradiation was safely replaced with maintenance intrathecal methotrexate, providing patients received intensified systemic therapy. In the second series, randomized trials showed better outcome with one vs no DI phase for lower risk patients, with two vs one DI phase for intermediate risk patients, and with the CCG 'augmented regimen' for higher risk patients with a slow day 7 marrow response. Cranial irradiation was safely replaced with additional intrathecal methotrexate for higher risk patients with a rapid day 7 marrow response. In a subsequent study, substitution of dexamethasone in place of prednisone in induction and maintenance improved outcome for standard risk patients. All patients received dexamethasone in DI. These successful treatment strategies form the basis for our current ALL trials. Leukemia (2000) 14, 2223-2233.

children; acute lymphoblastic leukemia; treatment; outcome