Prognostic impact of low allelic ratio FLT3-ITD and NPM1 mutation in acute myeloid leukemia

• Published in: Blood advances Vol. 2; no. 20; pp. 2744 - 2754
• Main Authors: Sakaguchi, Masahiro, Yamaguchi, Hiroki, Najima, Yuho, Usuki, Kensuke, Ueki, Toshimitsu, Oh, Iekuni, Mori, Sinichiro, Kawata, Eri, Uoshima, Nobuhiko, Kobayashi, Yutaka, Kako, Shinichi, Tajika, Kenji, Gomi, Seiji, Shono, Katsuhiro, Kayamori, Kensuke, Hagihara, Masao, Kanda, Junya, Uchiyama, Hitoji, Kuroda, Junya, Uchida, Naoyuki, Kubota, Yasushi, Kimura, Shinya, Kurosawa, Saiko, Nakajima, Nana, Marumo, Atsushi, Omori, Ikuko, Fujiwara, Yusuke, Yui, Shunsuke, Wakita, Satoshi, Arai, Kunihito, Kitano, Tomoaki, Kakihana, Kazuhiko, Kanda, Yoshinobu, Ohashi, Kazuteru, Fukuda, Takahiro, Inokuchi, Koiti
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23.10.2018; American Society of Hematology
• Subjects: Myeloid Neoplasia
• ISSN: 2473-9529; 2473-9537; 2473-9537
• DOI: 10.1182/bloodadvances.2018020305

In the opinion of the European LeukemiaNet (ELN), nucleophosmin member 1 gene mutation (NPM1 mut)–positive acute myeloid leukemia (AML) with an fms-like kinase 3-internal tandem duplication (FLT3-ITD) allele ratio (AR) <0.5 (low AR) has a favorable prognosis, and allogeneic hematopoietic stem cell transplant (allo-HSCT) in the first complete remission (CR1) period is not actively recommended. We studied 147 patients with FLT3-ITD gene mutation–positive AML, dividing them into those with low AR and those with AR of ≥0.5 (high AR), and examined the prognostic impact according to allo-HSCT in CR1. Although FLT3-ITD AR and NPM1 mut are used in the prognostic stratification, we found that NPM1 mut–positive AML with FLT3-ITD low AR was not associated with favorable outcome (overall survival [OS], 41.3%). Moreover, patients in this group who underwent allo-HSCT in CR1 had a significantly more favorable outcome than those who did not (relapse-free survival [RFS] P = .013; OS P = .003). Multivariate analysis identified allo-HSCT in CR1 as the sole favorable prognostic factor (RFS P < .001; OS P < .001). The present study found that prognosis was unfavorable in NPM1 mut–positive AML with FLT3-ITD low AR when allo-HSCT was not carried out in CR1. •The ELN guideline classifying FLT3-ITD low allele ratio with NPM1 mutation as having a favorable prognosis is questionable.•Performing allo-HSCT during CR1 irrespective of the FLT3-ITD allele ratio and NPM1 mut status significantly improves outcome. [Display omitted]