FLT3 mutations have no prognostic impact in elderly patients with acute myeloid leukemia and normal karyotype

Ferrara, Felicetto; Criscuolo, Clelia; Riccardi, Cira; Izzo, Tiziana; Pedata, Mariangela; Copia, Carolina; Vicari, Laura; Tarsitano, Marina; Palmieri, Salvatore; Pane, Fabrizio

doi:10.1002/ajh.21458

Cited by 17 publications

(13 citation statements)

References 39 publications

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“…The results of outcome analyses with respect to FLT3-ITD status among octogenarian patients with CN-AML are consistent with and extend previous reports showing that FLT3-ITD loses its prognostic effect in CN-AML patients who are older than 60 years, 39 and especially in those aged 70 years or older. 40 On the other hand, NPM1 © F e r r a t a S t o r t i F o u n d a t i o n mutations maintain their positive effect on clinical outcome in this age group.…”

Section: © F E R R a T A S T O R T I F O U N D A T I O Nsupporting

confidence: 79%

Intensive induction is effective in selected octogenarian acute myeloid leukemia patients: prognostic significance of karyotype and selected molecular markers used in the European LeukemiaNet classification

et al. 2013

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© F e r r a t a S t o r t i F o u n d a t i o nknown, 12-16 but few groups 6,7,17,18 have studied its effect in octogenarian AML patients and conclusions have been mixed. This may stem from the differences in classification systems among studies, treatments, inadequate numbers of patients or all of the above. We, therefore, evaluated whether the European LeukemiaNet (ELN) classification, 19 a modified ELN classification (i.e., a classification based only on karyotype, without molecular markers), and the ELN-associated molecular alterations FLT3-ITD and NPM1 mutations have prognostic significance in octogenarian AML patients receiving intensive induction treatment. Methods Patients, treatment, cytogenetic and molecular analysesWe analyzed octogenarian AML patients treated with intensive induction [cytarabine and anthracycline (7+3) or similar regimens] for whom pretreatment karyotyping information was available. The patients were drawn from the German-Austrian AML Study Group [AMLSG; 5 (0.5%) Pretreatment karyotype analyses were performed by the Cooperative Groups' institutional cytogenetic laboratories with the results confirmed by central karyotype review, or were performed centrally. The diagnosis of cytogenetically normal AML (CN-AML) was based on the analysis of ≥20 metaphase cells in bone marrow specimens subjected to short-term culture. 31 We used both a modified, karyotype only, ELN-based classification [including t(8;21) Statistical analysesEstimated probabilities of relapse-free survival and overall survival were calculated using the Kaplan-Meier method, and the logrank test evaluated differences between survival distributions. Associations for baseline demographic, clinical, and molecular features were compared using the Fisher exact and Wilcoxon rank sum tests for categorical and continuous variables, respectively. All analyses were two-sided, with a P-value <0.05 considered statistically significant.Response criteria are described in the Online Supplementary Material. ResultsThe 138 patients had a median age of 82 years (range, 80-89 years); 81 (59%) were male. One-hundred fifteen patients had de novo AML, 13 had secondary AML following an antecedent hematologic disorder (s-AML), nine had therapy-related AML (t-AML) and one had both s-AML and t-AML. Because there was no difference in complete response, relapse-free survival and overall survival rates between patients with de novo AML and s-AML/t-AML, all patients were considered together for outcome analyses. Thirteen (11%) patients had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 71 (58%) had a PS of 1, 31 (25%) had a PS of 2, six (5%) had a PS of 3 and one (1%) patient had a PS of 4; information on PS was not available for 16 of the patients. Normal karyotype was the most common cytogenetic finding (47.1%), followed by complex karyotype (14.5%) and sole +8 (9.4%). We first categorized patients according to the modified ELN classification into favorable (n=2), intermediate-I (n=65), intermediate-II (n=42) ...

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Section: © F E R R a T A S T O R T I F O U N D A T I O Nsupporting

confidence: 79%

Intensive induction is effective in selected octogenarian acute myeloid leukemia patients: prognostic significance of karyotype and selected molecular markers used in the European LeukemiaNet classification

et al. 2013

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“…Although NPM1 (Nucleophosmin 1) mutation has a favorable impact [8] in elderly NK-AML, there has been controversy surrounding the prognostic significance of FLT3-ITD (FMS-like tyrosine kinase receptor-3 internal tandem duplication) mutations in this subgroup. FLT3-ITD has been found to confer an adverse prognosis [9], whereas others did not confirm such association in elderly NK-AML [10][11][12]. In addition, we and others have previously identified immunophenotypic markers such as CD7, CD34, and CD56 with prognostic relevance in AML [13][14][15][16].…”

Section: Introductionmentioning

confidence: 76%

Prognostic value of immunophenotyping and gene mutations in elderly patients with acute myeloid leukemia with normal karyotype

et al. 2013

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“…3,[11][12][13]15,17 Both WBC 11,15,17,18 and LDH 12,17,18 at initial diagnosis have been described as influential factors for OS.…”

Section: Discussionmentioning

confidence: 99%

A novel prognostic model in elderly patients with acute myeloid leukemia: results of 909 patients entered into the prospective AML96 trial

Röllig

Thiede

Gramatzki

et al. 2010

Blood

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FLT3 mutations have no prognostic impact in elderly patients with acute myeloid leukemia and normal karyotype

Cited by 17 publications

References 39 publications

Intensive induction is effective in selected octogenarian acute myeloid leukemia patients: prognostic significance of karyotype and selected molecular markers used in the European LeukemiaNet classification

Intensive induction is effective in selected octogenarian acute myeloid leukemia patients: prognostic significance of karyotype and selected molecular markers used in the European LeukemiaNet classification

Prognostic value of immunophenotyping and gene mutations in elderly patients with acute myeloid leukemia with normal karyotype

A novel prognostic model in elderly patients with acute myeloid leukemia: results of 909 patients entered into the prospective AML96 trial

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