Intensive consolidation with G-CSF support: Tolerability, safety, reduced hospitalization, and efficacy in acute myeloid leukemia patients ≥60 years

Abstract

The aim of this study was to evaluate the efficacy and feasibility of intensified consolidation therapy employing fludarabine and ARA-C in cycle 1 and intermediate-dose ARA-C (IDAC) in cycles 2 through 4, in elderly acute myeloid leukemia (AML) patients and to analyze the effects of pegfilgrastim on the duration of neutropenia, overall toxicity, and hospitalization-time during consolidation in these patients. Thirty nine elderly patients with de novo AML (median age 69.9 years) who achieved complete remission (CR) after induction-chemotherapy were analyzed. To examine the effect of pegfilgrastim on neutropenia and hospitalization, we compared cycles 2 and 4 where pegfilgrastim was given routinely from day 6 (IDAC-P) with cycle 3 where pegfilgrastim was only administered in case of severe infections and/or prolonged neutropenia. All four planned cycles were administered in 23/39 patients (59.0%); 5/39 patients (12.8%) received 3 cycles, 3/39 (7.7%) 2 cycles, and 8/39 (20.5%) one consolidation-cycle. The median duration of severe neutropenia was 7 days in cycle 2 (IDAC-P), 11.5 days in cycle 3 (IDAC), and 7.5 days in cycle 4 (IDAC-P) (P < .05). Median overall survival was 1.1 years and differed significantly between patients aged <75 and ≥75 years (P < .05). The probability to be alive after 5 years was 32%. Together, intensified consolidation can be administered in AML patients ≥60, and those who are <75 may benefit from this therapy. Routine administration of pegfilgrastim during consolidation shortens the time of neutropenia and hospitalization in these patients.

Figure 1

Survival of patients. Overall survival as calculated according to the method of Kaplan and Meier. The survival of all patients is indicated by the black solid line. The dashed black line represents the survival of patients aged <75 years and the grey solid line the survival of patients aged ≥75 years with a median survival of 1.5 years and 0.5 years, respectively. The difference in OS, between patients aged <75 years and ≥75 years were found to be statistically significant (P <.05)

Figure 2

Comparison of the duration of neutropenia (A) and hospitalization (B) between the 2nd, 3rd, and 4th consolidation cycle. The box represents the 25–75% percentile in each group, the horizontal line within boxes defines the median, and the whiskers represent the range. The differences in the duration of neutropenia among Consolidation 2, 3, and 4 were found to be significant as assessed by Friedman test (P <.05)

Figure 3

G-CSF levels and WBC counts. G-CSF levels (solid line) and WBC (dashed line) are presented as median and range in 18 consolidation cycles (FLAG, n = 16; IDAC, n = 2). Each point represents the median of the measurements available for this time point. Day 1 is the first day of pegfilgrastim administration