A RANDOMIZED PHASE-III STUDY OF THE EFFICACY OF GRANULOCYTE-COLONY-STIMULATING FACTOR IN CHILDREN WITH HIGH-RISK ACUTE LYMPHOBLASTIC-LEUKEMIA

Overall chemotherapeutic treatment results in pediatric acute lymphobl astic leukemia (ALL) are good, with event-free survival (EFS) rates ov er 70%. However, for a subset of patients characterized by high-risk ( HR) features the outcome is less favorable, with EFS rates below 50%. Intensification of chemotherapy may improve the outcome for those pati ents, but increased toxicity, particularly myelosuppression, limits th e escalation of dose intensity. Recombinant methionyl human granulocyt e colony-stimulating factor (r-metHuG-CSF) is known to reduce myelosup pression after cancer chemotherapy in adults. The objective of this st udy was to examine the effect of r-metHuG-CSF on myelosuppression in H R pediatric ALL patients and on the overall response rate to chemother apy. Patients with HR pediatric ALL were randomized to receive nine al ternating cycles of chemotherapy according to the German ALL-Berlin-Fr ankfurt-Munster 90 protocol either alone or followed by r-metHuG-CSF a dministered prophylactically at a dose of 5 mu g/kg/d subcutaneously. In both groups, the planned interval between chemotherapy courses was a minimum of 21 days. We report here interim results of 34 patients. T he incidence of febrile neutropenia (absolute neutrophil count <0.5 x 10(9)/L and oral temperature greater than or equal to 38.5 degrees C) was 17% in children receiving r-metHuG-CSF, as compared with 40% in th e control group (P=.007). In addition, the median total duration of fe brile neutropenia was reduced from 20.3 to 6.2 days per patient (P=.02 ). Culture-confirmed infections occurred less frequently in the r-metH uG-CSF group (8% v 15%; P=.04), and the total duration of intravenous antibiotic use was significantly reduced from 32.2 days to 18.2 days p er patient (P=.02). A tighter adherence to the planned treatment sched ule was also facilitated by r-metHuG-CSF (P=.007). With a median follo w-up of 3.3 years, the estimated EFS of 4 years is 41% +/- 12%. In con clusion, r-metHuG-CSF administered prophylactically in the interval be tween chemotherapy courses significantly reduced febrile neutropenia, culture-confirmed infections, and duration of intravenous antibiotic a dministration and allowed for tighter adherence to the treatment sched ule. (C) 1996 by The American Society of Hematology.