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Thomas, X. et al.

Xavier Thomas, Emmanuel Raffoux, Aline Renneville, Cecile Pautas, Stephane de Botton, Christine Terre, Claude Gardin, Sandrine Hayette, Claude Preudhomme, Herve Dombret,

Which AML subsets benefit from leukemic cell priming during chemotherapy? Long-term analysis of the ALFA-9802 GM-CSF study.

BACKGROUND: : Priming with granulocytic hematopoietic growth factors may modulate cell cycle kinetics of leukemic cells and render them more susceptible to phase-specific chemotherapeutic agents. In a first report, we have shown that priming with granulocyte-macrophage colony-stimulating factor (GM-CSF) may enhance complete remission (CR) rate and event-free survival (EFS) in younger adults with acute myeloid leukemia (AML). METHODS: : In this randomized trial, 259 patients with AML were randomized at baseline to receive or not receive GM-CSF concurrently with all cycles of chemotherapy. The effects of GM-CSF on survival were reported herein with a long-term follow-up and studied according to distinct biological subgroups defined on cytogenetics and molecular markers. RESULTS: : The EFS rate was better in the GM-CSF group (43% vs 34%; P = .04). GM-CSF did not improve the outcome in patients from good risk subgroups, while patients from poor risk subgroups benefited from GM-CSF therapy. In this population, the difference in terms of EFS probability was mainly observed in patients with high initial white blood cell count and in those with FLT3-ITD or MLL rearrangement. When combining these 2 molecular abnormalities for comparison of the effect of GM-CSF priming, the difference in terms of EFS was highly significant (5-year EFS, 39% with GM-CSF vs 8% without GM-CSF; P = .007). CONCLUSIONS: : Sensitization of leukemic cells and their progenitors by GM-CSF appears as a plausible strategy for improving the outcome of patients with newly diagnosed AML. Patients with poor-prognosis FLT3-ITD or MLL rearrangement might be a good target population to further investigate priming strategies. Cancer 2010. (c) 2010 American Cancer Society.[1]

References

Which AML subsets benefit from leukemic cell priming during chemotherapy? Long-term analysis of the ALFA-9802 GM-CSF study. Thomas, X., Raffoux, E., Renneville, A., Pautas, C., de Botton, S., Terre, C., Gardin, C., Hayette, S., Preudhomme, C., Dombret, H. Cancer (2010) [Pubmed]

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