Outcomes of pediatric acute myeloid leukemia patients with FLT3-ITD mutations in the pre-FLT3 inhibitor era

Abstract

Background: Acute myeloid leukemia (AML) with internal tandem duplication in FMS-like tyrosine kinase 3 (FLT3-ITD) is associated with poor outcomes. This study aimed to analyze the outcomes of pediatric AML patients with FLT3-ITD mutations in the pre-FLT3 inhibitor era. Methods: We retrospectively reviewed and identified 18 patients diagnosed with non-M3 AML with FLT3-ITD mutations at Seoul National University Children's Hospital between May 2008 and August 2019. Results: The median age was 13 years (range, 6-19 yr). The median follow-up time was 43 months (range, 6-157 mo). Fourteen patients received BH-AC-based (N4-Behenoy1-1-β-D-arabinofuranosy1cytosine) and 4 received cytarabine-based induction chemotherapy. Complete remission (CR) was achieved in 72.2% of the patients after the first induction chemotherapy and 80% of the patients achieved CR after salvage therapy. The overall CR rate was 94% (17/18 patients). These 17 patients underwent hematopoietic stem cell transplantation (9 matched unrelated donors, 5 matched related donors, and 3 haploidentical donors). Relapse occurred in 22% of the patients. Event free survival and overall survival rates were 53.8±12.1% and 53.6±12.1%, respectively, and they were not significantly different according to the type of induction chemotherapy (P=0.690) or the type of donor (P=0.102). Conclusion: This study outlines the outcomes of pediatric AML patients with FLT3-ITD-mutations in one institution over a decade. Outcomes were significantly improved in this study compared to our previous report in 2004, where RFS and EFS were 0%. This study can provide baseline data for pediatric patients in the pre-FLT3 inhibitor era.

The Potential Transcriptomic and Metabolomic Mechanisms of ATO and ATRA in Treatment of FLT3-ITD Acute Myeloid Leukemia

“…FLT3-ITD mutation causes autonomous phosphorylation and activation of FLT3 protein, which continuously activates downstream signaling pathways and leads to abnormal proliferation of leukemia cells, leading to the occurrence, refractory and recurrence of leukemia. 4 – 7 At present, small-molecule tyrosine kinase inhibitors (TKIs) are the main treatment for FLT3-ITD mutant AML. 4 , 8 In recent years, a lot of inhibitors have been developed mainly to reduce the phosphorylation of FLT3 rather than to reduce the level of FLT3 mutant protein.…”

“…Therefore, the emergence of drug resistance is still a challenge for clinical application. 4 , 6 , 9 …”

Diagnostic challenges in acute monoblastic/monocytic leukemia in children

“…Another clinically relevant genetic aberration in AMoLs, not detectable with cytogenetic studies, is the FMS-like tyrosine kinase 3 (FLT3) gene mutation, described in about 5.5–26.5% of AMoLs in different pediatric cohorts ( 71 , 74 , 81 – 83 ). FLT3 belongs to the class III tyrosine kinase receptor family expressed on hematopoietic progenitors and promotes cell survival, proliferation, and differentiation being activated by an extracellular ligand (FLT3 ligand) ( 71 ).…”