Risk-stratified therapy for children with FLT3-ITD-positive acute myeloid leukemia: results from the JPLSG AML-05 study

Akira Shimada, Yuka Iijima-Yamashita, Akio Tawa, Daisuke Tomizawa, Miho Yamada, Shiba Norio, Tomoyuki Watanabe, Takashi Taga, Shotaro Iwamoto, Kiminori Terui, Hiroshi Moritake, Akitoshi Kinoshita, Hiroyuki Takahashi, Hideki Nakayama, Katsuyoshi Koh, Hiroaki Goto, Yoshiyuki Kosaka, Akiko Moriya Saito, Nobutaka Kiyokawa, Keizo HoribeYusuke Hara, Kentaro Oki, Yasuhide Hayashi, Shiro Tanaka, Souichi Adachi

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)


Acute myeloid leukemia harboring internal tandem duplication of FMS-like tyrosine kinase 3 (AMLFLT3-ITD) is associated with poor prognosis. We evaluated the results of the AML-05 study, in which all AMLFLT3-ITD patients were assigned to receive hematopoietic stem cell transplantation (HSCT) in the first remission (1CR). We also investigated the effects of additional genetic alterations on FLT3-ITD. The 5-year overall survival (OS) and event-free survival (EFS) rates among the 47 AMLFLT3-ITD patients were 42.2 and 36.8%, respectively. The 5-year disease-free survival rate among 29 patients without induction failure was 58.4%. We defined the allelic ratio (AR) of FLT3-ITD to WT > 0.7 as high. Significant differences were found in OS (AR-high, 20% vs. AR-low, 66%, p < 0.001) and EFS (13 vs. 50%, p = 0.004). All five patients with concurrent NPM1 mutations survived, while seven of eight patients who expressed the NUP98-NSD1 chimera failed to achieve 1CR and died. Multivariate analysis revealed that AR > 0.7 and expression of the NUP98-NSD1 chimera strongly impacted OS and EFS. Although all the AMLFLT3-ITD patients received HSCT at 1CR, the treatment outcome of AMLFLT3-ITD patients did not improve compared with those in a previous study. Heterogeneity was observed among AMLFLT3-ITD patients.

Original languageEnglish
Pages (from-to)586-595
Number of pages10
JournalInternational journal of hematology
Issue number5
Publication statusPublished - May 1 2018


  • AML
  • Alleric ratio
  • Childhood
  • FLT3-ITD
  • NUP98-NSD1

ASJC Scopus subject areas

  • Hematology


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