Prognostic significance of FLT3-ITD length in AML patients treated with intensive regimens.

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2021-10-20

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Castaño-Bonilla, Tamara
Alonso-Dominguez, Juan M
Barragan, Eva
Rodriguez-Veiga, Rebeca
Sargas, Claudia
Gil, Cristina
Chillon, Carmen
Vidriales, Maria B
Garcia, Raimundo
Martinez-Lopez, Joaquin

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Nature Publishing Group
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Abstract

FLT3-ITD mutations are detected in approximately 25% of newly diagnosed adult acute myeloid leukemia (AML) patients and confer an adverse prognosis. The FLT3-ITD allelic ratio has clear prognostic value. Nevertheless, there are numerous manuscripts with contradictory results regarding the prognostic relevance of the length and insertion site (IS) of the FLT3-ITD fragment. We aimed to assess the prognostic impact of these variables on the complete remission (CR) rates, overall survival (OS) and relapse-free survival (RFS) of AML patients with FLT3-ITDmutations. We studied the FLT3-ITD length of 362 adult AML patients included in the PETHEMA AML registry. We tried to validate the thresholds of ITD length previously published (i.e., 39 bp and 70 bp) in intensively treated AML patients (n = 161). We also analyzed the mutational profile of 118 FLT3-ITD AML patients with an NGS panel of 39 genes and correlated mutational status with the length and IS of ITD. The AUC of the ROC curve of the ITD length for OS prediction was 0.504, and no differences were found when applying any of the thresholds for OS, RFS or CR rate. Only four out of 106 patients had ITD IS in the TKD1 domain. Our results, alongside previous publications, confirm that FLT3-ITD length lacks prognostic value and clinical applicability.

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MeSH Terms

Adolescent
Adult
Aged
Aged, 80 and over
Disease-Free Survival
Female
Humans
Leukemia, Myeloid, Acute
Male
Middle Aged
Mutation
Prognosis
Remission Induction
Retrospective Studies
Young Adult
fms-Like Tyrosine Kinase 3

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Sobrevida
Recurrencia
Curva ROC
Leucemia mieloide aguda
Mutación
Genes

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Keywords

Acute myeloid leukaemia, Molecular medicine, Oncogenesis, Prognostic markers

Citation

Castaño-Bonilla T, Alonso-Dominguez JM, Barragán E, Rodríguez-Veiga R, Sargas C, Gil C, et al. Prognostic significance of FLT3-ITD length in AML patients treated with intensive regimens. Sci Rep. 2021 Oct 20;11(1):20745.