Prognostic Significance of Fms-Like Tyrosine Kinase 3 Internal Tandem Duplication Mutation in Non-Transplant Adult Patients with Acute Myeloblastic Leukemia: A Systematic Review and Meta-Analysis

Document Type: Systematic Review and Meta-analysis

Authors

1 Department of Internal Medicine Division of Hematology and Medical Oncology, Faculty of Medicine Universitas Indonesia-Dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia.

2 Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Indonesia.

3 Faculty of Medicine, Universitas Indonesia, Indonesia.

Abstract

Background: Fms-like tyrosine kinase-3, internal tandem duplication (FLT3-ITD) mutation, is a known predictor for worse outcome in patients with acute myeloblastic leukemia (AML). However, the prognostic significance of FLT3-ITD mutation in adult, non-transplant patients is still unclear therefore we conducted a systematic review and meta-analysis to explain this issue. The main outcome was overall survival (OS), while additional outcomes included event-free survival (EFS). Methods: Seven Databases (ScienceDirect, Scopus, PubMed, Cochrane, SpringerLink, ProQuest, and EBSCOhost) were searched up to August 2020.  Studies investigating the prognostic value of AML in adults with FLT3-ITD mutational status were selected. Studies which patients had received transplantation, diagnosed with acute promyelocytic leukemia (APL) or secondary AML were excluded. The selected studies were divided into subgroups based on their cytogenetic profile. Summary hazard ratios (HR) and 95% confidence intervals (CI) were calculated using fixed-effects models. Heterogeneity tests were conducted and presented in I2 value. Forest plot was presented to facilitate understanding of the results. Publication bias was analyzed by Funnel Plot test. Results: A total of ten studies describing research conducted from 1999 to 2020, met the inclusion criteria for this study. Nine studies reported OS and four studies reported EFS in HR. The highest HR for OS is 6.33 (95% CI, 2.61-15.33; p < 0.001), for EFS is 3.58 (95% CI, 1.59 – 8.05); p = 0.002)., while the lowest for OS is 1.33 (95% CI, 0.88-2.01; P = 0.174) and for EFS is 1.29 (95% CI, 0.75-2.23; p = 0.34). Nine studies were included in meta-analysis with HR for OS 1.91 (95% CI, 1.59–2.30, p < 0.00001), whereas 4 studies were included in meta-analysis for EFS with HR 1.64 (95% CI, 1.25–2.14; p = 0.0003). Conclusion: FLT3-ITD mutation is associated with worse prognosis in adult, non-transplant patients with AML, both for OS and EFS.

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