VALUE OF DIFFERENT MODALITIES OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR APPLIED DURING OR AFTER INDUCTION THERAPY OF ACUTE MYELOID-LEUKEMIA

Purpose: The hematopoietic growth factors (HGFs) introduced into induc tion chemotherapy (CT) of acute myeloid leukemia (AML) might be of ben efit to treatment outcome by at least two mechanisms. HGFs given on da ys simultaneously with CT might sensitize the leukemic cells and enhan ce their susceptibility to CT. HGFs applied after CT might hasten hema topoietic recovery and reduce morbidity or mortality. Materials and Me thods: We set out to evaluate the use of granulocyte-macrophage colony -stimulating factor (GM-CSF; 5 mu g/kg) in a prospective randomized st udy of factorial design (yes or no GM CSF during CT, and yes or no GM- CSF after CT) in patients aged 15 to 60 years (mean, 42) with newly di agnosed AML. GM-CSF was applied as follows: during CT only (+/-, n = 6 4 assessable patients), GM-CSF during and following CT (+/+, n = 66), no GM-CSF (-/-, n = 63), or GM-CSF after CT only (-/+, n = 60). Result s: The complete response (CR) rate wets 77%. At a median follow-up tim e of 42 months, probabilities of overall survival (OS) and disease-fre e survival (DFS) at 3 years were 38% and 37% in all patients. CR rates , OS, and DFS did not differ between the treatment groups (intention-t o-treat analysis). Neutrophil recovery (1.0 x 10(9)/L) and monocyte re covery were significantly faster in patients who received GM-CSF after CT (26 days v 30 days; neutrophils, P < .001; monocytes, P < .005). P latelet regeneration, transfusion requirements, use of antibiotics, fr equency of infections, and duration of hospitalization did not vary as a function of any of the therapeutic GM-CSF modalities. More frequent side effects leg, fever and fluid retention) were noted in GM CSF-tre ated patients predominantly related to the use of GM-CSF during CT. Co nclusion: Priming of AML cells to the cytotoxic effects of CT by the u se of GM-CSF during CT or accelerating myeloid recovery by the use of GM CSF after CT does not significantly improve treatment outcome of yo ung and middle-aged adults with newly diagnosed AML. (C) 1997 by Ameri can Society of Clinical Oncology.