The prognostic impact of FLT3-ITD, NPM1 and CEBPa in cytogenetically intermediate-risk AML after first relapse

Saiko Kurosawa, Hiroki Yamaguchi, Takuhiro Yamaguchi, Keiko Fukunaga, Shunsuke Yui, Heiwa Kanamori, Kensuke Usuki, Nobuhiko Uoshima, Masamitsu Yanada, Jin Takeuchi, Ishikazu Mizuno, Junya Kanda, Hiroshi Okamura, Shingo Yano, Haruko Tashiro, Takero Shindo, Shigeru Chiba, Junji Tomiyama, Koiti Inokuchi, Takahiro Fukuda

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)200-209
Number of pages10
JournalInternational journal of hematology
Volume112
Issue number2
DOIs
Publication statusPublished - 2020 Aug 1

Keywords

  • Acute myeloid leukemia
  • CEBPa
  • FLT3-ITD
  • First relapse
  • NPM1

ASJC Scopus subject areas

  • Hematology

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