Use of Granulocyte Colony-Stimulating Factor (G-CSF) Together with Induction and Intensification Chemotherapy (CT) in Adults with Primary Acute Myeloid Leukemia (AML).

We analyzed the complete remission (CR) rate and toxicity in patients (pts) with “de novo” AML enrolled in an intensive CT protocol including induction and intensification CT concurrently with G-CSF. Between December-2003 and April-2005 167 adults <70 years (96M/71F) with AML (M3 excluded) were enrolled in the LMA-2003, CETLAM protocol. Induction therapy consisted in 1 or 2 cycles of idarubicin, intermediate dose of ara-C and VP-16 (IDICE). Intensification CT included intermediate dose of ara-C and mitoxantrone. G-CSF was administered (150 mg/day sc) beginning the day before CT until the last day of treatment. G-CSF was postponed or interrupted in the event of leukocytosis (≥ 30x10⁹/L) until the white blood-cell count (WBC) was below this value. The median of age was 53 years (>60 years n=43). Cytogenetical analysis was available in 96% of pts. All pts with <30x109/L WBC (n=114) received G-CSF during induction CT and in 10 of them (9%) G-CSF was interrupted due to WBC >30x10⁹/L (n=3), bone pain (n=1) or infectious complications (n=6). In 21 of the 53 pts (39%) with WBC ≥ 30x10⁹/L at diagnosis G-CSF was administered after the counts were reduced (median period 4 days). After induction therapy CR was obtained in 69% of pts (n=115) (≤ 60 years: 69% and >60 years: 67%), 85% of them with a single CT course and 14% of pts (n=25) were considered as refractory. Treatment related mortality (TRM) was 16% (n=27) (≤ 60 years: 14% and >60 years: 21%) due to infection (n=17), hemorrhage (n=4) or multiorganic failure (n=6). The median duration of neutropenia (<0,5x10⁹/L) was 22 days (11–47) and thrombocytopenia <20x10⁹/L had a median duration of 18 days (6–40). One hundred and twelve pts in CR received intensification CT (≤ 60 years n=84 and >60 years n=28), 96% with concurrent G-CSF (in 8 cases was suppressed because of WBC >30x10⁹/L). Median neutropenia was 19 days (6–47) and thrombocytopenia had a median duration of 22 days (2–78). The intensification TRM was 7% (n=8): 5 pts >60 years (18%) vs 3 pts ≤ 60 years (3%) (p=0.02): being the infections (87% of cases, n=7) the main TRM cause. No significant differences were observed in the induction results between the present protocol and the previous one (LMA-99); post-intensification neutrophil and platelet recovery time were significantly longer for the current protocol: 21 and 22 days vs 17 and 16 days respectively (p<0.001). The use of G-CSF together with induction/intensification CT in “de novo” AML pts did not affect significantly neither CR rate nor TRM. The neutropenia period was longer after intensification if concurrent G-CSF was administered. Pts >60 years had a high TRM, mainly post-intensification CT. Longer follow-up is needed to evaluate the G-CSF effect on relapse and survival.