Alternating pulses of vincristine-prednisone with cytarabine-cyclophosphamide versus vincristine-prednisone in the maintenance therapy of acute lymphoblastic leukemia.

From January 1976 to December 1978, 347 children less than or equal to 15 years of age were entered in a collaborative controlled trial which included: induction (vincristine-daunorubicin-prednisone); intensification (cytarabine-cyclophosphamide); CNS prevention (intrathecal methotrexate-dexamethasone, three doses during induction and three weekly doses during the first month of maintenance, followed by one dose every 3 months for 48 months); and maintenance (6-mercaptopurine daily and methotrexate twice weekly with reinforcement pulse doses of either 1.5 mg/m2 X 1 of vincristine plus 40 mg/m2/day X 7 of prednisone [Arm A] or vincristine-prednisone alternating with 50 mg/m2 of cytarabine sc every 12 hours X 10 plus 600 mg/m2 X 1 of cyclophosphamide [Arm B]). Pulses were performed in both arms at 1, 2, 3, 4, and 6 months and every 3 months thereafter. Randomization was stratified according to age and initial wbc count. A total of 89% (310/347) of patients achieved complete remission. Duration of continuous complete remission was evaluated according to prognostic factor groups. At 5 years, 34.5% of patients with good prognosis, 24.8% with intermediate prognosis, and 12.8% with poor prognosis are in continuous complete remission. There is statistical difference between good versus poor prognosis (P less than 0.0005) and intermediate versus poor prognosis (P less than 0.025). Moreover, 5-year survival is 50.9%, 35.2%, and 18.2% in the good-, intermediate-, and poor-prognosis groups, respectively. Duration of continuous complete remission up to the first event (ie, bone marrow, CNS, or other extramedullary relapse, or death in complete remission), according to prognostic groups, did not differ in relation to reinforcement pulses (Arm A or B). We conclude that there was no benefit in alternating pulses of vincristine-prednisone with cyclophosphamide-cytarabine as used in this study.