Acute myeloid leukemia or myelodysplastic syndrome (AML/MDS) and overall mortality with chemotherapy (CT) and granulocyte colony-stimulating factor (G-CSF): A meta-analysis of randomized controlled trials (RCTs)

Abstract

9524 Background: To evaluate the risk of AML/MDS and overall mortality in patients receiving CT ± G-CSF, a meta-analysis of RCTs were conducted. Methods: Electronic databases searched through August 2008 identified 3,794 articles for initial screening. Eligibility included RCTs of solid tumor or lymphoma patients randomized to CT ± primary G-CSF support, ≥2 years follow-up and reporting AML/MDS or all second malignancies. Pre-specified study categories included: a)same dose/schedule, b)dose-dense or c)dose-escalated CT. Primary outcomes were AML/MDS and mortality. Dual blinded data extraction was performed. Relative risk (RR) and absolute risk difference (ARD) were estimated by Mantel-Haenszel. Results: Median follow-up was 54 months. 12,642 patients were randomized to CT ± primary G-CSF support. Second malignancies were reported in 3.3% and 3.2% with and without G-CSF, respectively (P=.942). RR for AML/MDS with CT+G-CSF compared to control was 1.92 [P=.006] with ARD increase of 0.4% [P=.008]. RR for AML/MDS in study categories to receive the same, dose-dense or dose-escalated CT+G-CSF were 1.95 [P=.346], 1.20 [P=.666] and 2.47 [P=.006], respectively. RR for mortality with CT+G-CSF was 0.898 [P<.0001] with ARD decrease of 3.3% [P<.0001]. RR for mortality in study categories to receive the same, dose-dense or dose-escalated CT+G-CSF were 0.95 [P=.140], 0.84 [P<.001] and 0.91 [P=.019], respectively. Delivered relative dose intensities (RDI) were 1.18, 1.46 and 1.23 in studies planned to receive the same, dose-dense or dose-escalated CT, respectively. A significant association was observed between delivered RDI and reduced mortality [P=.013]. No differences in estimates of AML/MDS or mortality were observed between industry and non-industry-funded studies. Conclusions: Risk of AML/MDS is increased with dose escalated CT+G-CSF. Nevertheless, CT+G-CSF is associated with greater reductions in overall mortality. Dose-dense regimens are associated with the greatest RR reduction in mortality and lowest risk of AML/MDS. Further research is needed to differentiate any impact of G-CSF on the risk of AML/MDS from that due to increased CT intensity. [Table: see text]