Long-term results of a prospective randomized trial evaluating G-CSF priming in intensive induction chemotherapy followed by autologous stem cell transplantation in elderly patients with acute myeloid leukemia

Abstract

Few studies have evaluated granulocyte colony-stimulating factor (G-CSF) priming in elderly patients with intensively treated acute myeloid leukemia (AML), and no data are available for genetically defined AML subgroups. We provide long-term results (median follow-up 7.6 years) of a randomized trial in which 183 patients (median age 67 years) received G-CSF prior to (G-CSF priming) or after two cycles of induction chemotherapy. CR rates with G-CSF priming and G-CSF post-chemotherapy were comparable (57 vs. 67 %, p = 0.153), with overall survival (OS) probabilities of 14 vs. 17 % at 10 years. Induction mortality was significantly higher with G-CSF priming (23 vs. 10 %, p = 0.015), primarily in normal karyotype (NK) AML. In this subgroup, a trend for better relapse-free survival (RFS) was observed with G-CSF priming (44 vs. 22 % at 10 years, p = 0.074) but did not translate into an OS benefit. G-CSF priming had no impact on AML with FLT3-ITD and NPM mutations and did not improve outcome in patients with adverse cytogenetics. In a landmark analysis, late consolidation with autologous stem cell transplantation or a second consolidation cycle significantly improved RFS compared with one consolidation cycle (21.0 vs. 12.8 months, p = 0.046). Future studies on G-CSF priming should be restricted to NK AML and used only in post-remission therapy.

Mathematical modeling of the impact of cytokine response of acute myeloid leukemia cells on patient prognosis

“…The survival after the first relapse is also significantly increased for group 1 (p = 0.03). These results are in line with reports from literature stating that autonomous leukemic cell growth has a negative impact on patient prognosis 4 , 5 and also with the finding that in some trials patient subgroups with unfavorable risk do not respond to cytokine priming before chemotherapy 11 , 12 .

Figure 5 Patient data compatible only with model of cytokine independent AML correlates with poor overall survival.

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Feasibility and efficacy of outpatient therapy with intermediate dose cytarabine, fludarabine and idarubicin for patients with acute myeloid leukaemia aged 70 or older

“…Based on reports of improvement in DFS and OS in adult patients with ‘standard risk’ AML , we used G‐CSF concurrent with chemotherapy. The use of G‐CSF in elderly patients with AML has been scarcely assessed, and several studies have shown a trend to better relapse‐free survival without improvement in OS .…”

An extensive pharmacokinetic, metabolic and toxicological review of elderly patients under intensive chemotherapy for acute myeloid leukemia

“…This was a long-term (median follow-up 7.6 years) randomized trial in which 183 patients (median age 67 years) received G-CSF prior to (G-CSF priming) or after two cycles of induction CT. They found little or no improvement and concluded that G-CSF priming should be restricted to normal karyotype AML and used only in post-remission therapy [102].…”

“…Several studies have been carried out to determine the optimum time and type of growth factor administration [99][100][101]. However, a recent study by Bug et al [102] evaluated granulocyte colony-stimulating factor (G-CSF) priming in elderly patients with intensively treated AML. This was a long-term (median follow-up 7.6 years) randomized trial in which 183 patients (median age 67 years) received G-CSF prior to (G-CSF priming) or after two cycles of induction CT.…”