Dataset Information

Association between FLT3-ITD and additional chromosomal abnormalities in the prognosis of acute promyelocytic leukemia.

ABSTRACT:

Objectives

Internal tandem duplications of the Fms-like tyrosine kinase 3 gene (FLT3-ITD) and additional chromosomal abnormalities (ACA) are prognostic factors in patients with acute promyelocytic leukemia (APL). This study aimed to determine the effect of the association between FLT3-ITD and ACA in the prognosis of APL.

Methods

This was a retrospective cohort study including 60 patients with APL treated with all-trans retinoic acid (ATRA) and chemotherapy. Five-year overall survival (OS) and progression-free survival (PFS) were analyzed in patient groups according to the presence of FLT3-ITD and ACA.

Results

FLT3-ITD was an independent adverse factor for 5-year PFS, and ACA was an independent adverse factor for 5-year OS. There were significant differences in OS and PFS among the groups: FLT3-ITD-negative without ACA, FLT3-ITD-positive without ACA, FLT3-ITD-negative with ACA, and FLT3-ITD-positive with ACA. The OS times were 52.917, 45.813, 25.375, and 23.417 months, and the PFS times were 48.833, 38.563, 23.250, and 17.333 months, respectively.

Conclusion

FLT3-ITD and ACA are associated with the poorest OS and PFS outcomes in patients with APL treated with chemotherapy plus ATRA.

SUBMITTER: Vu MP

PROVIDER: S-EPMC9791292 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

Association between <i>FLT3-ITD</i> and additional chromosomal abnormalities in the prognosis of acute promyelocytic leukemia.

Vu Minh Phuong MP Nguyen Cuc Nhung CN Vu Hoang H Nguyen Tuyet Mai TM Nguyen Tuan Tung TT Pham Phuong Thao PT

The Journal of international medical research 20221201 12

<h4>Objectives</h4>Internal tandem duplications of the Fms-like tyrosine kinase 3 gene (<i>FLT3-ITD)</i> and additional chromosomal abnormalities (ACA) are prognostic factors in patients with acute promyelocytic leukemia (APL). This study aimed to determine the effect of the association between <i>FLT3-ITD</i> and ACA in the prognosis of APL.<h4>Methods</h4>This was a retrospective cohort study including 60 patients with APL treated with all-trans retinoic acid (ATRA) and chemotherapy. Five-year ...[more]

PMID: 36539954

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Project description:Acute myeloid leukemia (AML) is an aggressive hematologic malignancy which is cured in a minority of patients. A FLT3-internal tandem duplication (ITD) mutation, found in approximately a quarter of patients with de novo AML, imparts a particularly poor prognosis. Patients with FLT3-ITD AML often present with more aggressive disease and have a significantly higher propensity for relapse after remission. The therapeutic approach for these patients has traditionally included intensive induction chemotherapy, followed by consolidative chemotherapy or hematopoietic cell transplantation (HCT). In recent years, multiple small molecule inhibitors of the FLT3 tyrosine kinase have been studied preclinically and in clinical trials. The earlier generation of these agents, often non-specific and impacting a variety of tyrosine kinases, produced at best transient peripheral blood responses in early clinical trials. Additionally, the combination of FLT3 inhibitors with cytotoxic regimens has not, as of yet, demonstrated an improvement in overall survival. Nevertheless, multiple current trials, including those with sorafenib, lestaurtinib, and midostaurin, continue to study the combination of FLT3 inhibitors with standard chemotherapy. Factors such as sustained FLT3 inhibition, protein binding, pharmacokinetics, and the presence of elevated FLT3-ligand levels appear to significantly impact the potency of these agents in vivo. In recent years, the development of more specific and potent agents has generated hope that FLT3 inhibitors may play a more prominent role in the treatment of FLT3-ITD AML in the near future. Nevertheless, questions remain regarding the optimal timing and schedule for incorporation of FLT3 inhibitors. The suitability, type, and timing of allogeneic HCT in the therapeutic approach for these patients are also issues which require further study and definition. Recent retrospective data appears to support the efficacy of allogeneic HCT in first complete remission, possibly due to a graft versus leukemia effect. However, larger prospective studies are necessary to further elucidate the role of HCT and its potential combination with FLT3 inhibitor therapy. We are hopeful that current clinical investigation will lead to an optimization and improvement of outcomes for these patients.