GRANULOCYTE-COLONY-STIMULATING FACTOR AS AN ADJUNCT TO INDUCTION CHEMOTHERAPY FOR ADULT ACUTE LYMPHOBLASTIC-LEUKEMIA - A RANDOMIZED PHASE-III STUDY

Because of the recommendation to avoid the concomitant administration of growth factors and chemotherapy, there is only limited information on colony-stimulating factor (CSF) therapy in acute lymphoblastic leuk emia (ALL) induction protocols, in which cytotoxic drugs are administe red in divided doses over a prolonged period of time, thus requiring a simultaneous administration of growth factors and chemotherapy. We co nducted a prospective, randomized, controlled study to determine the s afety and efficacy of granulocyte colony-stimulating factor (G-CSF; fi lgrastim) as an adjunct to phase I of induction chemotherapy for adult ALL, Patients (n = 53) were randomized to receive no growth factor or G-CSF (5 mu g/kg/d subcutaneously) starting on day 2 of chemotherapy consisting of daunorubicin (45 mg/m(2)) and vincristine (1.5 mg/m(2)) on days 1, 8, 15, and 22; L-asparaginase (2500 U/m(2)) on days 1 throu gh 14; and prednisone (60 mg/m(2)) on days 1 through 28. A total of 25 patients in the G-CSF group and 26 patients in the control arm fulfil led the inclusion criteria of the study. G-CSF markedly ameliorated ne utropenia because the median proportion of days with neutropenia less than 1,000/mu L was 29% in the G-CSF group as compared with 84% in the control arm (P <.00005). The median time to reach absolute neutrophil counts (ANC) greater than or equal to 1,000/mu L was 16 days in G-CSF patients and 26 days in controls (P <.001). More importantly, G-CSF s ignificantly reduced the incidence of febrile neutropenia (12% v 42% i n controls, P <.05) and documented infections (40% v 77%, P <.05). No significant differences were found with regard to requirements for red blood cell transfusions and platelet concentrates. A total of 24 of 2 5 (96%) patients in the G-CSF group and 20 of 25 (80%) evaluable contr ol patients had complete remission after phase I of induction therapy. We conclude that G-CSF can be safely administered as an adjunct to in duction therapy of ALL and is clinically beneficial by ameliorating ne utropenia and reducing infectious complications, (C) 1997 by The Ameri can Society of Hematology.