High incidence of FLT3 mutations in adults with Acute Promyelocytic Leukemia (APL): Correlation with diagnostic features and treatment outcome (CALGB 9710)

2008 
7002 Background: Studies have associated activating mutations of FLT3 (FLT3+) with adverse outcomes in patients (pts) with APL, but little is known about the impact of adding Arsenic Trioxide (As2O3) to frontline APL treatment on the clinical outcome of pts harboring these mutations. Methods: We examined the incidence of FLT3+ in a subset of 78 adults with newly diagnosed APL entered onto CALGB 9710, a North American Intergroup phase III randomized trial that demonstrated a significant survival benefit from adding two 25-day courses of As2O3 to post-remission consolidation therapy (Powell, et al. ASCO 2007). FLT3 internal tandem duplications (ITD) and activation loop point mutations (D835) were identified using standard methods (InVivoScribe, San Diego). FLT3+ was correlated with other diagnostic/prognostic features including PML-RARA isoform type, initial white blood cell (WBC) count, and pt age, and with treatment response. Results: FLT3+ was identified in 42 pts (54%); 28 (36%) had an ITD, 17 (22%) had...
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