Impact of Pegfilgrastim on Hematological Reconstitution and Incidence of Neutropenic Fever after Consolidation Therapy with High-Dose Cytarabine in Acute Myeloid Leukemia: Comparative Analysis between AMLSG 07-04 and the German AML Intergroup Trial.

Therapy using high-dose cytarabine (HiDAC) according to the CALGB scheme (3g/m² bid. days 1,3,5) is recognized as a standard consolidation treatment for younger adult patients with acute myeloid leukemia (AML). Pegfilgrastim has been shown to be effective in reducing the duration of neutropenia in the treatment of solid tumors and it seems to be even more effective than Filgrastim in reducing the incidence of neutropenic fever. The objective of the current study is to investigate the effect of pegfilgrastim given after HiDAC consolidation within our AMLSG 07-04 clinical trial. The AMLSG 07-04 trial was initiated in September 2004 (age 18–60 yrs). Consolidation therapy consists of 3 cycles of HiDAC (3g/m² bid. days 1,3,5) with pegfilgrastim 6mg given at day 10 after start of chemotherapy. As a control group, patients randomized from AMLSG into the German AML Intergroup protocol using the same scheme for consolidation therapy with permitted interventional application of G-CSF were used. Data from 127 patients and a total of 285 cycles are available, including 104 patients of the AMLSG 07-04 trial and 23 patients of the German AML Intergroup trial. Data from all three cycles were pooled for the comparison between AMLSG 07-04 (prophylactic pegfilgrastim) and German AML Intergroup (interventional G-CSF) trials. The duration of leukopenia and neutropenia was significantly shorter in patients receiving prophylactic pegfilgrastim (p=0.01 and p=0.008, respectively) compared to patients with interventional G-CSF, which was given in 16% of the pts. This was paralleled by a lower incidence of neutropenic fever with 53% in patients receiving prophylactic pegfilgrastim compared to 77% in patients with interventional G-CSF (p=0.0004). Data from 12 patients and 23 cycles were available for pharmocokinetics of pegfilgrastim. The median peak G-CSF serum level was 221 ng/ml (range 57–553 ng/ml) measured between 24 and 48 hours after the administration of pegfilgrastim and median terminal half-life was 5 days (range 3–7 days). G-CSF serum levels returned to normal in all patients after neutrophil reconstitution. Multivariable regression analysis for longitudinal data on G-CSF serum levels revealed total leukocyte count (p=0.02) and presence of neutropenic fever (p=0.03) as statistically significant variables. In conclusion, the administration of pegfilgrastim shortened the duration of leuko- as well as neutropenia and reduced the rate of neutropenic fever in pts. with AML receiving consolidation therapy with high-dose cytarabine.