Treatment of elderly patients with acute myeloid leukemia (AML) is characterized by a low complete remission (CR) rate of less than 50% and short remission duration with a median disease-free survival (DFS) of less than one year (Rowe et al., Blood 2004). Sensitization of leukemic cells with growth factors may enhance the efficacy of chemotherapy in AML patients. Aims of this randomized prospective, oligocenter study were 1) to assess whether induction chemotherapy given simultaneously with and followed by G-CSF (G-CSFpriming) was superior to G-CSF following induction (G-CSFpost) with regard to CR rate and DFS in pts aged older than 60 yrs with previously untreated de novo and secondary AML and 2) to examine the feasibility of an early consolidation therapy followed by autologous stem cell transplantation (ASCT) as late consolidation. Between 01/00 and 04/04, a total of 116 eligible patients (median age 67 yrs) were randomly assigned to receive G-CSFpriming (n=57) or G-CSFpost (n=59) during two remission-induction cycles consisting of idarubicin, cytarabine and etoposide (IdAV) with daily application of 5μg/kg G-CSF (Neupogen®, Amgen). Pts achieving a CR received early consolidation using fludarabine, cytarabine, idarubicin, G-CSF (mini-FlagIda) and PBSC harvest, followed by ASCT. Pts lacking PBSC due to mobilization failure were optionally treated with a second cycle of mini-FlagIda. After induction chemotherapy, 74 out of 116 pts (63.8%) achieved CR. Response was not significantly different in the G-CSFpost vs. G-CSFpriming group (67.8 vs. 59.6%), nor was recovery of neutrophils. Of 74 complete responders, 44 have relapsed and 3 died in CR. Median remission duration was 15.2 and 14.7 months in the G-CSFpost and G-CSFpriming group, resp. Median DFS was 16.5 months and the probability of DFS at 4 yrs 21.2%, with no significant difference between the treatment groups and a median follow-up of 22 months at the time of this interim analysis. Mini-FlagIda consolidation was administered to 51 out of 74 CR patients (68.9%). The number of circulating CD34+ cells was monitored in 43 patients. The probability of mobilizing at least 1x106/kg CD34+ cells was significantly lower in the G-CSFpriming compared to the G-CSFpost group with 29.4% (5/17 pts) and 59.2% (16/26 pts), resp (p<0.05). ASCT was performed in 10 pts resulting in a significantly better 4-yr DFS (55%) compared to 10 pts treated with a second course of mini-FlagIda (22%, p<0.05). The major reason for not being autografted in spite of efficient collecting of CD34+ cells was early relapse. Conclusion: In elderly pts with de novo or secondary AML, G-CSF priming did not enhance the antileukemic efficacy of induction chemotherapy and had no significant impact on overall treatment outcome compared with G-CSF administered after induction. As ASCT proved to be an effective consolidation modality for CR patients mobilizing sufficient amounts of CD34+ cells, the detrimental effect of G-CSF priming on the collection of PBSC is clinically relevant.>

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