The Impact of <i>Flt3</i> Gene Mutations in Acute Promyelocytic Leukemia: A Meta-Analysis

• Main Authors: Gledson L. Picharski, Diancarlos P. Andrade, Ana Luiza M. R. Fabro, Luana Lenzi, Fernanda S. Tonin, Raul C. Ribeiro, Bonald C. Figueiredo
• Format: Article
• Language: English
• Published: MDPI AG 2019-09-01
• Series: Cancers
• Subjects: acute promyelocytic leukemia; APL; <i>FLT3</i>-ITD; <i>FLT3</i>-D835; WBC
• Online Access: https://www.mdpi.com/2072-6694/11/9/1311

The association of <i>FLT3</i> mutations with white blood cell (WBC) counts at diagnosis and early death was studied in patients with acute promyelocytic leukemia (APL). Publications indexed in databases of biomedical literature were analyzed. Potential publication bias was evaluated by analyzing the standard error in funnel plots using the estimated relative risk (RR). Mixed-effect models were used to obtain the consolidated RR. All analyses were conducted using the R statistical software package. We used 24 publications in the final meta-analysis. Of 1005 males and 1376 females included in these 24 publications, 645 had <i>FLT3</i>-ITD (internal tandem duplication) mutations. Information on <i>FLT3</i>-D835 mutations was available in 10 publications for 175 patients. Concurrent occurrence of the two mutations was rare. WBC count at diagnosis was &#8805;10 &#215; 10⁹/L in 351 patients. For patients with the <i>FLT3</i>-ITD mutation, RR was 0.59 for overall survival (OS) and 1.62 for death during induction. For those with <i>FLT3</i>-D835 mutations, the RR was 0.50 for OS and 1.77 for death during induction. RR for WBC count &#8805;10 &#215; 10⁹/L was 3.29 and 1.48 for patients with <i>FLT3</i>-ITD and <i>FLT3</i>-D835, respectively. APL patients with <i>FLT3</i>-ITD or <i>FLT3</i>-D835 are more likely to present with elevated WBC counts and poorer prognosis than those without these mutations.