Contributions
Abstract: PB1742
Type: Publication Only
Background
Acute myeloid leukemia (AML) is an aggressive disease with extremely poor prognosis. Radical treatment like conventional chemotherapy (CT) +/– allogenic hematopoietic stem cell transportation (allo-HSCT), is rarely considered in elderly patients due to age, comorbidities and poor somatic state. The presence of mutations of the FLT3 gene (ITD or TKD) in AML is recognized as an adverse prognosis affecting the course of the disease, the development of relapses with decrease in overall survival (OS) and disease-free survival (DFS) of patients. Despite the high incidence of mutations FLT3-ITD and FLT3-TKD, the role of the allelic load of the mutant gene FLT3 has not been completely identified. Up to date we have no clinical studies with treatment individualized to elderly AML patients. The introduction of target therapy in AML gives hope for diminishing treatment side effects ang prolongation of life for elderly frail patients with AML.
Aims
To assess the frequency of FLT3 gene mutations and their influence on clinical manifestations, relapse rate, OS and DFS of patients with AML.
Methods
A retrospective study of the incidence of FLT3 gene mutation in blood or bone marrow and clinical outcomes in 199 AML patients (83 males) was conducted. Median age at the time of diagnosis was 52 years (20-86 years). The polymerase chain reaction (PCR) method with further restriction and determination of 2 main mutation types – internal tandem duplication (FLT3-ITD) and point mutation in "A-loop" (FLT3-TKD) was used to evaluate the FLT3 status.
Results
The incidences of FLT3 gene mutations were as follows: FLT3-ITD – 22,6% (45/199), FLT3-TKD – 5,5% (11/199), FLT3-ITD and FLT3–TKD in combination – 1,0% (2/199); the rest – 70.8% (141/199) patients did not have any mutation in the FLT3 gene (FLT3–). Complete blood counts have statistical significant differences in the white blood cells (p=0.0009) and the blast percent (p=0.01) between FLT3(-) and FLT3(+) patients. Chromosomal abnormalities were revealed in 38% (17/45) patients of FLT3-ITD+ group, 64% (7/11) – FLT3-TKD+ and in51% (72/141) of FLT3– cases. Both FLT3-ITD/TKD+ patients had normal karyotype,. No significant (p=0.2990) differences have been yielded in the duration of OS between groups of patients with normal karyotype and chromosomal aberrations, regardless of the presence or absence FLT3 gene mutations. The presence of FLT3-ITD+ mutation was associated with higher risk of AML relapse (p=0.00006) than FLT3-TKD+ or FLT3(-) patients. All patients received various CT regimens depending on age, performance status and comorbidity (7+3, 5+2, HAM). We observed significant (p=0.00024) differences in the OS between FLT3-ITD+, FLT3-TKD+ and FLT3– patients. Median OS were: 5.1 months for FLT3-ITD+; 7.1 months for FLT3-TKD+ and 13.0 months for FLT3– patients. Univariate analysis showed the next adverse factors for OS: any FLT3 gene mutation (p=0.00007) and fail to achieve remission (p=0.000001). Factors influencing DFS were as following: karyotype at disease onset (favorable, intermediate and unfavorable) (p=0.013), the presence of FLT3 mutations (p=0.0000013) and type of mutation (p=0.0001).
Conclusion
FLT3 mutations in AML patients give adverse prognosis for OS and DFS. There is urgent need to have molecular genetic markers screening in the AML workup at initial diagnosis and risk-adapted therapy choice.
Session topic: 4. Acute myeloid leukemia - Clinical
Abstract: PB1742
Type: Publication Only
Background
Acute myeloid leukemia (AML) is an aggressive disease with extremely poor prognosis. Radical treatment like conventional chemotherapy (CT) +/– allogenic hematopoietic stem cell transportation (allo-HSCT), is rarely considered in elderly patients due to age, comorbidities and poor somatic state. The presence of mutations of the FLT3 gene (ITD or TKD) in AML is recognized as an adverse prognosis affecting the course of the disease, the development of relapses with decrease in overall survival (OS) and disease-free survival (DFS) of patients. Despite the high incidence of mutations FLT3-ITD and FLT3-TKD, the role of the allelic load of the mutant gene FLT3 has not been completely identified. Up to date we have no clinical studies with treatment individualized to elderly AML patients. The introduction of target therapy in AML gives hope for diminishing treatment side effects ang prolongation of life for elderly frail patients with AML.
Aims
To assess the frequency of FLT3 gene mutations and their influence on clinical manifestations, relapse rate, OS and DFS of patients with AML.
Methods
A retrospective study of the incidence of FLT3 gene mutation in blood or bone marrow and clinical outcomes in 199 AML patients (83 males) was conducted. Median age at the time of diagnosis was 52 years (20-86 years). The polymerase chain reaction (PCR) method with further restriction and determination of 2 main mutation types – internal tandem duplication (FLT3-ITD) and point mutation in "A-loop" (FLT3-TKD) was used to evaluate the FLT3 status.
Results
The incidences of FLT3 gene mutations were as follows: FLT3-ITD – 22,6% (45/199), FLT3-TKD – 5,5% (11/199), FLT3-ITD and FLT3–TKD in combination – 1,0% (2/199); the rest – 70.8% (141/199) patients did not have any mutation in the FLT3 gene (FLT3–). Complete blood counts have statistical significant differences in the white blood cells (p=0.0009) and the blast percent (p=0.01) between FLT3(-) and FLT3(+) patients. Chromosomal abnormalities were revealed in 38% (17/45) patients of FLT3-ITD+ group, 64% (7/11) – FLT3-TKD+ and in51% (72/141) of FLT3– cases. Both FLT3-ITD/TKD+ patients had normal karyotype,. No significant (p=0.2990) differences have been yielded in the duration of OS between groups of patients with normal karyotype and chromosomal aberrations, regardless of the presence or absence FLT3 gene mutations. The presence of FLT3-ITD+ mutation was associated with higher risk of AML relapse (p=0.00006) than FLT3-TKD+ or FLT3(-) patients. All patients received various CT regimens depending on age, performance status and comorbidity (7+3, 5+2, HAM). We observed significant (p=0.00024) differences in the OS between FLT3-ITD+, FLT3-TKD+ and FLT3– patients. Median OS were: 5.1 months for FLT3-ITD+; 7.1 months for FLT3-TKD+ and 13.0 months for FLT3– patients. Univariate analysis showed the next adverse factors for OS: any FLT3 gene mutation (p=0.00007) and fail to achieve remission (p=0.000001). Factors influencing DFS were as following: karyotype at disease onset (favorable, intermediate and unfavorable) (p=0.013), the presence of FLT3 mutations (p=0.0000013) and type of mutation (p=0.0001).
Conclusion
FLT3 mutations in AML patients give adverse prognosis for OS and DFS. There is urgent need to have molecular genetic markers screening in the AML workup at initial diagnosis and risk-adapted therapy choice.
Session topic: 4. Acute myeloid leukemia - Clinical