The effect of G-CSF on the in vitro cytotoxicity of cytarabine and fludarabine in the FLAG combination in pediatric acute myeloid leukemia.

Isabelle Hubeek, Elena Litvinova, Godefridus J. Peters, Richard Broekhuizen, Eric G. Haarman, Dieuwke R. Huismans, Jacqueline Cloos, Christian M. Zwaan, Gudrun Fleischhack, Ursula Creutzig, Gertjan J.L. Kaspers

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The combination of fludarabine, cytarabine (ara-C) and G-CSF (FLAG) is routinely used in the treatment of acute myeloid leukemia (AML). In this study we characterized the interactions between fludarabine, ara-C and G-CSF in vitro using AML blasts. Exposure to G-CSF alone resulted in a higher leukemic cell survival (LCS), which might be indicative of increased proliferation. The LCS decreased significantly from 69.7 to 54.0% when blasts were exposed to G-CSF 21 h prior to incubation with ara-C (p=0.01). In contrast, LCS increased significantly (from 55.6 to 69.0%; p=0.04) after sequential exposure to G-CSF and fludarabine. Exposure to 4 combinations of fludarabine (4 h; 0.14 microM and 0.55 microM) and ara-C (96 h; 0.21 and 0.82 microM) (FLA) resulted in additive cytotoxicity. The triple combination (FLAG), 21 h 5 microM G-CSF followed by 4 h fludarabine (0.14 and 0.55 microM) and finally ara-C (0.21 and 0.82 microM) for 96 h also resulted in an additive cell kill. In conclusion, these data support the clinical use of G-CSF in combination with ara-C, and the combination of ara-C and FLA. Pre-exposure to G-CSF before FLA (FLAG) did not result in increased cytotoxicity in our experiments, indicative of similar anti-leukemic activity.

Original languageEnglish
Pages (from-to)1823-1829
Number of pages7
JournalInternational journal of oncology
Issue number6
Publication statusPublished - 1 Dec 2004

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