Colony-stimulating factors for prevention and treatment of infectious complications in patients with acute myelogenous leukemia

Background Acute myelogenous leukemia (AML) is a fatal bone marrow cancer. Colony-stimulating factors (CSFs) are frequently administered during and after chemotherapy to reduce complications. However, their safety with regard to disease-related outcomes and survival in AML is unclear. Therefore, we performed a systematic review and meta-analysis to evaluate the impact of CSFs on patient outcomes, including survival. Objectives To assess the safety/efficacy of CSFs with regard to disease-related outcomes and survival in patients with AML. Search strategy We conducted a comprehensive search strategy. We identified relevant randomized clinical trials by searching the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 7), MEDLINE (January 1966 to July 2010), LILACS (up to December 2009), databases of ongoing trials and relevant conference proceedings. Selection criteria Randomized controlled trials that compared the addition of CSFs during and following chemotherapy to chemotherapy alone in patients with AML. We excluded trials evaluating the role of CSFs administered for the purpose of stem cell collection and/or priming (e. g. before and/or only for the duration of chemotherapy). Data collection and analysis \ Two review authors appraised the quality of trials and extracted data. For each trial, we expressed results as relative risk (RR) with 95% confidence intervals (CI) for dichotomous data. We analyzed time-to-event outcomes as hazard ratios (HRs). Main results The search yielded 19 trials including 5256 patients. The addition of CSFs to chemotherapy yielded no difference in all-cause mortality at 30 days and at the end of follow up (RR 0.97; 95% CI 0.80 to 1.18 and RR 1.01; 95% CI 0.98 to 1.05, respectively) or in overall survival(HR 1.00; 95% 0.93 to 1.08). There was no difference in complete remission rates(RR 1.03; 95% CI 0.99 to 1.07), relapse rates(RR 0.97; 95% CI 0.89 to 1.05) and disease-free survival(HR 1.00; 95% CI 0.90 to 1.13). CSFs did not decrease the occurrence of bacteremias(RR 0.96; 95% CI 0.82 to 1.12), nor the occurrence of invasive fungal infections(RR 1.40; 95% CI 0.90 to 2.19). CSFs marginally increased adverse events requiring discontinuation of CSFs as compared to the control arm(RR 1.33; 95% CI 1.00 to 1.56). Authors' conclusions The addition of CSFs to chemotherapy does not adversely influence all-cause mortality, complete remission or relapse rates in patients with AML. Although the benefit of CSFs is limited to reduction of neutropenic and febrile days, they can be administered safely when necessary.