Analysis of FLT3-Activating Mutations in Patients With Acute Myelogenous Leukemia in Jordan: Association With FAB Subtypes and Identification of Subgroups With Poor Prognosis

• Published in: Clinical lymphoma, myeloma and leukemia myeloma and leukemia, 2021-07, Vol.21 (7), p.e588-e597
• Main Authors: Halahleh, Khalid, Taqash, Ayat, Abdelkhaleq, Hadeel, Manasrah, Mohamad, Marie, Lina, Al-Rabi, Kamal
• Format: Article
• Language: English
• Subjects: Acute leukemia; Adolescent; Adult; Aged; AML; Bone Marrow - pathology; Child; Child, Preschool; Combined Modality Therapy - methods; Disease-Free Survival; DNA Mutational Analysis - statistics & numerical data; Female; FLT-3; fms-Like Tyrosine Kinase 3 - antagonists & inhibitors; fms-Like Tyrosine Kinase 3 - genetics; Gain of Function Mutation; HCT; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Infant; Jordan - epidemiology; KHCC; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - mortality; Leukemia, Myeloid, Acute - pathology; Leukemia, Myeloid, Acute - therapy; Male; Middle Aged; Molecular Epidemiology; Neoplasm Recurrence, Local - epidemiology; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - pathology; Prognosis; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Remission Induction; Transplantation, Homologous; Young Adult
• ISSN: 2152-2650; 2152-2669
• DOI: 10.1016/j.clml.2021.02.006

FLT3 mutations are common in acute myeloid leukemia (AML), particularly in French–American–British M2 subtype AML and in cytogenetically normal (CN) AML; however, its incidence in Jordan is poorly studied. An FLT3 mutation implies poor prognosis in AML patients. We aimed to assess the incidence and prognostic value of FLT3 mutations in AML in Jordan. One hundred thirty-two newly diagnosed unselected AML patients were included. Patient data were collected, including demographics as well as morphologic, cytogenetic, and molecular testing results. FLT3 mutations were detected by real-time reverse transcriptase PCR, next-generation sequencing, or both. Survival analysis and comparisons of incidence, remission rate, relapse, and survival outcomes between FLT3-mutated and wild-type groups were done and prognostic factors identified. FLT3 mutation was detected in 40% of AML patients. The highest incidence was associated with M2 subtype AML (47%) and CN-AML (50%). There was a significant negative association between FLT3 mutations and overall survival (OS), as well as a trend toward improved relapse-free survival, with 3-year OS being 19.17% vs 34.16% (P < .0001) and 33.6% vs 71.0% (P = .085), respectively. Patients with FLT3 mutation had a significantly better complete remission rate after induction (67.9% vs 63.3%, P = .001). Also, OS improved in patients with complete remission (P = .0015) and who then continued to allogeneic hematopoietic cell transplantation compared to FLT3 wild-type patients (P < .001). FLT3 mutation is common in Jordanian AML patients, with the highest incidence occurring in patients with M2 or CN disease. It implies a poor prognosis, with poor OS and relapse-free survival, which may be abrogated by early allogeneic transplantation and/or peritransplantation provision of FLT3 inhibitors. The FLT3 mutation is common in Jordanian acute myeloid leukemia patients, with the highest incidence in patients with French–American–British M2 disease or cytogenetically normal disease. This mutation implies poor prognosis.