AML is a heterogeneous disease and the actual most reliable prognostic factor is the karyotype. Mutations of NPM1 and FLT3 constitute the most frequent molecular genetic alterations in patients with AML. Their prognostic impact is now well recognized, especially in young patients with intermediate prognosis karyotype. However few studies have focused on elderly patients. We retrospectively studied the prevalence of NPM1 mutation and FLT3 internal tandem duplications (ITD) and its association with complete remission (CR) and survival in 86 patients aged 61 years or older treated between 1996 and 2007 for acute non promyelocytic leukemia with intermediate karyotype in the Institut Paoli-Calmettes, Marseille, and the university hospital of Toulouse. All patients received intensive induction chemotherapy (“3+7” regimen). Median age was 70 years (range, 61–79). The median follow-up of surviving patients was 34 months. 44 patients (51%) had NPM1 mutation and 21 had FLT3-ITD (24%). In the NPM1 mutated group, there were significantly more: female patients, absence of antecedent hematologic disorder, de novo AML, and low CD34 expression. In the FLT3-ITD group, there were significantly more: female patients, increased white blood cell counts and peripheral blood blasts. Overall CR rate was 67%; median disease free survival (DFS) and overall survival (OS) were 11 and 10 months, respectively. CR rate was negatively associated with a poor performans status and a high score previously described including assessment of comorbidities (

Etienne et al., Cancer 2007; 109(7):1376–83
). CR rate was 57% versus 72% for patients with FLT3-ITD compared to patients with wild-type FLT3 (p 0.2), and 64% versus 71% for the NPM1 mutated group compared with the NPM1 non-mutated group (p 0.5). Median OS was 6 months versus 12 months for patients with FLT3-ITD mutation versus wild type patients (p = 0.04). Median OS was 9 months for patients with NPM1 mutation and did not differ from non-mutated patients. No significant difference in term of CR rate and OS was found between the 29 patients carrying NPM1 mutation without FLT3-ITD and the 57 other patients without NPM1 mutation or with FLT3-ITD. Median DFS was 21 months versus 9 months for these two groups, respectively (p 0.2). These results confirm the prognostic impact of FLT3-ITD in our series of old patients with AML. Unlike young patients, NPM1 mutated elderly patients have a similar outcome than NPM1 wild type patients. The absence of prognostic impact of NPM1 mutation without FLT3-ITD has to be validated on larger prospective cohort. FLT3 status should be taken into account for treatment choices in elderly patients.

Topics:
chemotherapy regimen, flt3 gene, leukemia, myelocytic, acute, ms-like tyrosine kinase 3, mutation, npm1 gene, older adult, genes, impedance threshold device, karyotype determination procedure

Disclosures: No relevant conflicts of interest to declare.

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2008, The American Society of Hematology
2008
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