PB1744 THE ROLE OF FLT3 MUTATIONS IN ACUTE MYELOID LEUKEMIA: THE EFFECT ON THE COURSE OF THE DISEASE AND THE RESULTS OF THERAPY
Authors: Radzhabova A. , Voloshin S. , Martynkevich I. , Kuzyaeva A. , Shuvaev V. , Motyko E. , Kuvshinov A. , Schmidt A. , Polushkina L. , Buckeye M. , Ruzenkova Y. , Kleina E. , Samorodova A. , Garifullin A. , Tiranova S. , Zenina M. , Potihonova N. , Balashova V. , Chubukina J. , Chechetkin A. , Uspenskaya O. , Karyagina E. 
Published: June 2019

Background:

Acute myeloid leukemia (AML) is a group of diseases with various chromosomal aberrations (CA) and genetic abnormalities that have different prognostic significance. Approximately 45% of patients are not diagnosed with CA, which have intermediate risk. The prognosis of patients with normal karyotype (NK) is heterogeneous and requires stratifications with use polymerase chain reaction (PCR). The most mutations among AML patients are FLT3 gene mutations. This mutations are potential predictors of adverse prognosis, affecting the overall survival (OS) and disease‐free survival (DFS). The individualize approach to therapy and use target drugs can lead to improve the treatment efficiency.

Aims:

To determine impact of FLT3 gene mutations on survival in patients with AML.

Methods:

A retrospective study of the frequency of occurrence of FLT3 gene mutations and the assessment of their influence on the indicators of complete blood count (CBC) parameters, bone marrow, as well as disease outcomes in 199 patients with AML were conducted. To evaluate the status of FLT3, the polymerase chain reaction (PCR) method was used with further restriction and determination of 2 main types of mutations: FLT3‐ITD and FLT3‐TKD. The effect of the presence and type of FLT3 gene mutation on OS and DFS was analyzed. The statistical analysis included the Kruskall‐Wallis ANOVA tests and the analysis of OS and DFS using the Kaplan‐Meier estimator. Descriptive statistics technique included the arithmetic mean, median, 95% confidence interval, using Mann‐Whitney test.

Results:

In the studied group of patients with AML the frequency of occurrence of FLT3 gene mutations is 28.1% (FLT3‐ITD ‐ 22.6% (45/199), FLT3‐TKD ‐ 5.5% (11/199), the combination of FLT3‐ITD and FLT3‐TKD ‐ 1.0% (2/199)), the rest ‐ 70.9% (141/199) of patients without FLT3 gene mutations. Comparing CBC results, higher levels of leukocytosis (p = 0.0009) and blastosis of bone marrow (p = 0.01) were observed in group with FLT3+ mutation than without FLT3–. DFS results were significantly lower in FLT3+ group than in FLT3–group. The duration median of DFS in FLT3+ group was 8 months, in FLT3– group ‐ 20 months (p < 0.00001). Significant differences were obtained (p = 0.0002) in the duration of OS between the FLT3‐ITD+, FLT3‐TKD+ and FLT3– groups. The median OS was 16 months for the group with FLT3‐ITD+ mutation, 17 months for FLT3‐TKD+ and was not achieved for FLT3–group. Statistically significant differences in the duration of OS between groups with NK were obtained: the median of OS among FLT3+ patients was significantly less comparing with the FLT3– group: 13 months and not reached, respectively (p = 0.00015).

Summary/Conclusion:

AML is a heterogeneous group regarding prognosis and response to therapy in which the molecular genetic status is the decisive factor in the prognosis and the course of the disease. The introduction in clinical practice of kinase inhibitors in patients with AML FLT3+ would improve survival rates and quality of life of patients.