Gurion, R., Belnik-Plitman, Y., Gafter-Gvili, A., Paul, M., Vidal, L., Ben-Bassat, I., . . . Raanani, P. (2011). Colony-stimulating factors for prevention and treatment of infectious complications in patients with acute myelogenous leukemia. Cochrane Database of Systematic Reviews, 9, CD008238.

The purpose of the article is to assess the influence of colony-stimulating factors (CSFs) on the prevention and treatment of infectious complications in patients with acute myelogenous leukemia (AML).

The Cochrane Central Register of Controlled Trials, MEDLINE (January 1966 to July 2010), and LILACS (through December 2009) databases were searched, as were ongoing trials and conference proceedings from January 2002 to June 2010 from the European Group for Bone and Marrow Transplantation, the Annual Meeting of the European Hematology Association, the Annual Meeting of the Society for Hematology and Stem Cells, and the Center for International Blood and Marrow Transplant Research (CIBMTR).

Articles included in this review were randomized, controlled trials that compared the addition of CSFs during and following chemotherapy to chemotherapy alone in patients with AML and included age, type of AML (morphology criteria according to the FAB classification), leukemia type (de novo AML, secondary AML, refractory AML, relapsed AML), white blood cell count, platelet count, and treatment stage (induction, consolidation, relapse).

Articles were excluded if they were reporting on 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).

1,421 total references were retrieved.

Following a review of each study by two reviewers, statistical analyses were conducted including relative risk with a 95% confidence interval (CI) for dichotomous data and hazard ratios for time-to-event outcome. Cochrane handbook criteria were used to assess study quality.

• 19 studies were included in the final review.
• The total sample size of the combined studies was 5,256.
• The sample size across studies ranged from 53–803.
• The patient population was diagnosed with AML (per World Health Organization 2008 classification), were at any stage of treatment following chemotherapy, and were of all ages.
• The ages varied per study with one pediatric study including patients younger than 16 years old (Nakajima) and another (Lehrnbecher) aged 0–18. Four studies contained patients aged 15–60, six contained patients older than age 55, and eight had patients older than age 15.
• Chemotherapy regimens also varied and included numerous agents used as induction, consolidation, or salvage therapy, or conditioning regimens for HCT.
• All patients in the intervention arms of the studies evaluated received CSF (G-CSF or GM-CSF), IV or subcutaneous, started with or following chemotherapy.
• Those receiving CSF as part of the HCT cell collection or conditioning were excluded.
   

Active treatment

No statistically significant differences were found between patients who received CSF with chemotherapy compared to those who did not. This included no differences in 30 day all-cause mortality (RR = 0.97; 95% CI [0.8, 1.18]) and end of follow-up (RR = 1.01; 95% CI [0.98, 1.05]), overall survival (HR = 1.00; 95% CI [0.93, 1.08]), complete remission (RR = 1.03; 95% CI [0.99, 1.07]), relapse (RR = 0.97; 95% CI [0.89, 1.05]), disease-free survival (HR = 1.00; 95% CI [0.9, 1.13]), decrease in bacteremias (RR = 0.96; 95% CI [0.82, 1.12]) or invasive fungal infections (RR = 1.4; 95% CI [0.9, 2.19]). There was a slight increase in adverse events requiring discontinuation of CSFs in intervention groups compared to controls (RR = 1.33; 95% CI [1.00, 1.56]). Among 17 studies in which duration of neutropenia was reported, in all but one study the duration of neutropenia was significantly shortened with CSFs. Several studies reported a significant shortening of duration of hospital stay with CSFs, while others showed no difference.

Administration of CSFs is associated with decreased episodes of febrile neutropenia and febrile days; however, it shows no statistically significant benefit of being administered with chemotherapy for improved survival and decreased infection rates. Since hematopoiesis is different in pediatric patients compared to adults (occurring in the bone marrow of long bones and at higher rates in pediatric populations, and in flat bones at slower rates in adults and older adults), benefits may be found in older age groups when using CSF with chemotherapy. Among the studies that had a mean age of patients at 58 years and older (n = 7), six of them showed more favorable outcomes in patients who received CSF.

The composite evaluation of all age groups together.

Implications for practice based on this study are unfavorable to use CSF for decreased infection rates among all age groups. Further evaluation in older age groups may be warranted.