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.
Highlights
Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults
Intensive chemotherapy regimens were administered to 161 patients (idarubicin + cytarabine; 3 + 7, n = 151 and 2 + 5, n = 8; IDA-FLAG, n = 1 and FLAG, n = 1)
This study shows that the size of FLT3-ITD mutations has no prognostic impact in terms of survival, relapse or complete remission (CR) rate among newly diagnosed AML patients treated with first-line intensive regimens
Summary
Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults. The clinical behavior and genetic characteristics of the disease are h eterogeneous[1]. FMS-like tyrosine kinase-3 internal tandem duplication (FLT3-ITD) is one of the most frequent mutations found in AML patients. Mutations of FLT3 are found in approximately 30% of newly diagnosed AML patients and appear either as ITDs (≈ 25%) or point mutations in the tyrosine kinase domain (TKD) (7–10%)[4]. FLT3-ITD is located within exon 14, corresponding to JMD, in 70% of AML patients, while 30% of ITDs span exon 15, corresponding to the TKD1 domain. There are numerous and contradictory manuscripts regarding the prognostic importance of the length and insertion site of the ITD fragment. We performed an analysis of the correlation of FLT3-ITD length and insertion sites with the mutational landscape of AML, which has not been carried out far
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