Acute myeloid leukemia or myelodysplastic syndrome in randomized controlled clinical trials of cancer chemotherapy with granulocyte colony-stimulating factor: a systematic review.

Abstract

PURPOSE:

To evaluate the risk of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) and overall mortality in patients receiving chemotherapy with or without granulocyte colony-stimulating factor (G-CSF), a systematic review of randomized controlled trials (RCTs) was conducted.

METHODS:

Electronic databases searched through October 2008 identified 3,794 articles for initial screening. Eligibility included solid tumor or lymphoma patients randomly assigned to chemotherapy with or without G-CSF support, > or = 2 years of follow-up, and reporting AML/MDS or all second malignancies. Dual blinded data extraction was performed. Relative risk (RR) and absolute risk (AR) estimates +/- 95% CIs were calculated by the Mantel-Haenszel method.

RESULTS:

In the 25 eligible RCTs, 6,058 and 6,746 patients were randomly assigned to receive chemotherapy with and without initial G-CSF support, respectively. At mean and median follow-up across studies of 60 and 53 months, respectively, AML/MDS was reported in 22 control patients and 43 G-CSF-treated patients, with an estimated RR of 1.92 (95% CI, 1.19 to 3.07; P = .007) and AR increase of 0.41% (95% CI, 0.10% to 0.72%; P = .009). Deaths were reported in 1,845 patients randomly assigned to G-CSF and in 2,099 controls, for estimates of RR and AR decrease of 0.897 (95% CI, 0.857 to 0.938; P < .001) and 3.40% (95% CI, 2.01% to 4.80%; P < .001), respectively. Greater RR reduction for mortality was seen for both larger studies (P = .05) and greater chemotherapy dose-intensity (P = .012).

CONCLUSION:

Delivered chemotherapy dose-intensity and risk of AML/MDS are increased but all-cause mortality is decreased in patients receiving chemotherapy with G-CSF support. Greater reductions in mortality were observed with greater chemotherapy dose-intensity.

• Authors: Gary H Lyman, David C Dale, Debra A Wolff, Eva Culakova, Marek S Poniewierski, Nicole M Kuderer, Jeffrey Crawford
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 28 Issue 17 Pg. 2914-24 (Jun 10 2010) ISSN: 1527-7755 [Electronic] United States
• PMID: 20385991 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review, Systematic Review)

Chemical References

• Granulocyte Colony-Stimulating Factor

Topics

• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Granulocyte Colony-Stimulating Factor (therapeutic use)
• Humans
• Leukemia, Myeloid, Acute (drug therapy)
• Meta-Analysis as Topic
• Myelodysplastic Syndromes (drug therapy)
• Randomized Controlled Trials as Topic
• Treatment Outcome