CHEMOTHERAPY IN 998 UNSELECTED CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIAPATIENTS - RESULTS AND CONCLUSIONS OF THE MULTICENTER TRIAL ALL-BFM-86

In trial ALL-BFM 86, the largest multicenter trial of the Berlin-Frank furt-Munster (BFM) study group for childhood acute lymphoblastic leuke mia (ALL), treatment response was used as an overriding stratification factor for the first time. In the previous trial ALL-BFM 83, the in v ivo response to initial prednisone treatment was evaluated prospective ly. A blast cell count of greater than or equal to 1.000/mu L peripher al blood after a 7-day exposure to prednisone and one intrathecal dose of methotrexate (MTX) identified 10% of the patients as having a sign ificantly worse prognosis. In trial ALL-BFM 86 patients with greater t han or equal to 1,000/mu L blood blasts on day 8 were included in an e xperimental branch EG. Patients with <1,000/mu L blood blasts on day 8 were stratified by their leukemic cell burden into two branches, Stan dard Risk Group (SRG) and Risk Group (RG). SRG patients received an ei ght-drug induction followed by consolidation protocol M (6-mercaptopur ine, high-dose [HD] MTX 4 x 5 g/m(2)) and maintenance. RG patients wer e treated with an additional eight-drug reinduction element. For EG pa tients protocol M was replaced by protocol E (prednisone, HD-MTX, HD-c ytarabine, ifosfamide, mitoxantrone). All patients received intratheca l MTX therapy; only those of branches RG and EG received cranial irrad iation. In branch RG, patients were randomized to receive or not to re ceive late intensification (prednisone, vindesine, teniposide, ifosfam ide, HD-cytarabine) in the 13th month. During the trial reinduction th erapy was introduced in branch SRG, because in the follow-up of trial ALL-BFM 83 the randomized low-risk patients receiving reinduction did significantly better. Nine hundred ninety-eight evaluable patients wer e enrolled, 28.6% in SRG, 61.1% in RG, 10.3% in EG. At a median follow -up of 5.0 (range 3.4 to 6.9) years, the estimated 6-year event-free s urvival was 72% +/- 2% for the study population, 58% +/- 5% in branch SRG for the first 110 patients without reinduction therapy, 87% +/- 3% for the next 175 patients with reinduction therapy, 75% +/- 2% in bra nch RG, and 48% +/- 5% in branch EG. Late intensification did not sign ificantly affect treatment outcome of RG patients; however, only 23% o f the eligible patients were randomized. Prednisone poor response rema ined a negative prognostic parameter despite intensified therapy. The results confirmed the benefit of intensive reinduction therapy even fo r low-risk patients. The strategy of induction, consolidation, and int ensive reinduction may offer roughly 75% of unselected childhood ALL p atients the chance for an event-free survival. (C) 1994 by The America n Society of Hematology.