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  • Title: The prognostic impact of FLT3-ITD, NPM1 and CEBPa in cytogenetically intermediate-risk AML after first relapse.
    Author: Kurosawa S, Yamaguchi H, Yamaguchi T, Fukunaga K, Yui S, Kanamori H, Usuki K, Uoshima N, Yanada M, Takeuchi J, Mizuno I, Kanda J, Okamura H, Yano S, Tashiro H, Shindo T, Chiba S, Tomiyama J, Inokuchi K, Fukuda T.
    Journal: Int J Hematol; 2020 Aug; 112(2):200-209. PubMed ID: 32495317.
    Abstract:
    We evaluated the impact of FLT3-ITD, NPM1 mutations, and double mutant CEBPa (dmCEBPa) on overall survival (OS) after relapse in patients with cytogenetically intermediate-risk acute myeloid leukemia (AML) who were treated with chemotherapy alone in the first remission (CR1). Patients aged 16-65 years diagnosed with cytogenetically intermediate-risk AML, and who achieved CR1 were included. We retrospectively analyzed FLT3-ITD, NPM1 mutations and CEBPa using samples obtained at diagnosis, which therefore did not affect the therapeutic decisions. Among 235 patients who had achieved CR1, 152 relapsed, and 52% of them achieved second CR. The rate of achieving second CR was significantly higher (85%) in those with dmCEBPa. Patients with FLT3-ITD had significantly worse OS after relapse than those without (19% vs 41%, p = 0.002), while OS was comparable between patients with and without NPM1 mutations (37% vs 34%, p = 0.309). Patients with dmCEBPa had improved OS than those without (61% vs 32%, p = 0.006). By multivariate analysis, FLT3-ITD was independently associated with worse OS after relapse [hazard ratio (HR) 1.99, 95% CI 1.27-3.12, p = 0.003], and dmCEBPa with improved OS (HR 0.40, 95% CI 0.17-0.93, p = 0.033). Our data show that screening for these mutations at diagnosis is useful for facilitating effective therapeutic decision-making even after relapse.
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