Children's Cancer Group trials in childhood acute lymphoblastic leukemia: 1983-1995

Since 1968, the Children's Cancer Group (CCG) has treated more than 16 000 children with acute lymphoblastic leukemia (ALL). Herein, we report improve ments 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 cumulat ive rates of isolated CNS relapses were 5.9% and 4.4%. Therapy based on the Berlin-Frankfurt-Munster 76/79 study improved outcomes for intermediate an d higher risk patients in the first series. For intermediate risk patients, delayed intensification (DI) was most crucial for improved outcome and cra nial irradiation was safely replaced with maintenance intrathecal methotrex ate, providing patients received intensified systemic therapy. In the secon d series,-randomized trials showed better outcome with one vs no DI phase f or lower risk patients, with two vs one DI phase for intermediate risk pati ents, and with the CCG 'augmented regimen' for higher risk patients with a slow day 7 marrow response. Cranial irradiation was safely replaced with ad ditional 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 stan dard risk patients. All patients received dexamethasone in DI. These succes sful treatment strategies form the basis for our current ALL trials.