Cancer Management and Research (Mar 2021)
Potential Effects of the FLT3-ITD Mutation on Chemotherapy Response and Prognosis of Acute Promyelocytic Leukemia
Abstract
Yu-hua Song,1 Peng Peng,1 Chun Qiao,2 Jian-yong Li,2 Qi-qiang Long,1 Hua Lu2 1Department of Haematology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 2Department of Haematology, First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Hua LuDepartment of Haematology, First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, No. 300 Guangzhou Road, Gulou District, Nanjing, 210029, Jiangsu Province, People’s Republic of ChinaTel +86 13951717512Fax +86 025-83626373Email [email protected]: To evaluate the influence of FLT3-ITD mutations on the treatment response and long-term survival of newly-diagnosed patients with acute promyelocytic leukemia (APL) treated with all-trans retinoic acid and arsenic trioxide.Methods: The long-term survival of 90 newly-diagnosed APL patients (age range 12– 75 years) was retrospectively analyzed.The FLT3-ITD mutation rate was assayed by polymerase chain reaction (PCR) amplification and sequencing analysis. Its impact on the treatment response, event-free survival(EFS), or overall survival(OS) was investigated in patients with and without the mutations.Results: The FLT3-ITD mutation rate in newly-diagnosed APL patients was 20% (18/90). The white blood cell (WBC) count at diagnosis in patients with mutations was significantly higher than that in patients without mutations while the FLT3-ITD mutation rate was higher in the high-risk group than in the low/intermediate-risk group. Patients with mutations had a significantly higher early death (ED) rate (16.67% vs 1.39%) for those lacking the mutation (P =0.024). However, the complete remission (CR) and differentiation syndrome (DS) rates in the two groups were similar. Kaplan Meier analysis for EFS and OS at five years showed a significant difference between the patients stratified by FLT3-ITD mutation status (log-rank P =0.010 and P =0.009, respectively).Conclusion: FLT3-ITD mutations can be related to high peripheral WBC counts in APL patients. APL patients with mutations displayed a higher ED rate compared to those without mutations. Patients carrying mutations had reduced five-year EFS and OS rates. Thus, reducing the overall death rate during induction treatment might be an effective way to improve the prognosis of patients with FLT3-ITD mutations.Keywords: acute promyelocytic leukemia, APL, FLT3-ITD, internal tandem duplication, ITD, prognosis, survival
