Effects of glycosylated recombinant human granulocyte colony-stimulating factor after high-dose cytarabine-based induction chemotherapy for adult acute myeloid leukaemia

The Australian Leukaemia Study Group (ALSG) investigated whether G-CSF woul d accelerate haemopoietic recovery after induction treatment for acute myel oid leukaemia (AML) intensified with high-dose cytarabine, and therefore im prove response rates and survival. Patients were randomised to receive leno grastim (glycosylated recombinant human G-CSF) 5 mug per kg body weight sub cutaneously daily from day 8 after starting chemotherapy, or no cytokine, f ollowing chemotherapy with cytarabine 3 g/m(2) every 12 h on days 1, 3, 5, and 7, together with idaruibicin 9 or 12 mg/m(2) on days 1, 2, and 3, plus etoposide 75 mg/m(2) on days 1 to 7 inclusive. Patients had untreated AML, and were aged 16 to 60 years. Overall, 54 evaluable patients were randomise d to receive lenograstim and 58 to no cytokine. Patients in the lenograstim arm had a significantly shorter duration of neutropenia <0.5x10(9)/l compa red to patients in the no cytokine arm (median 18 vs 22 days; P=0.0005), an d also shorter duration of total leucopenia <1.0 x 10(9)/l (17 vs 19 days; P=0.0002), as well as a reduction in duration of treatment with therapeutic intravenous antibiotics (20 vs 24 days; P=0.015) and a trend to reduced nu mber of days with fever >38.0 degreesC (9 vs 12 days; P=0.18). There were n o differences between the two groups in platelet recovery, red cell or plat elet transfusions, or non-haematological toxicities. For patients achieving CR after their first induction course, a reduction in the time to the star t of the next course of therapy was observed in the lenograstim arm, from a median of 40.5 days to a median of 36 days (P=0.082). The overall complete response rates to chemotherapy were similar, 81% in the lenograstim arm vs 75% for the no cytokine arm (P=0.5), and there was no significant differen ce in the survival durations. We conclude that the granulopoietic stimulati ng effect of G-CSF is observed after induction therapy for AML intensified by high-dose cytarabine, resulting in an improvement in a number of clinica lly important parameters with no major adverse effects.