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

• DOI: 10.1007/s12185-017-2395-x
• Publication Date: 2018-01-12T04:06:13Z
• Authors: Akira Shimada; Yuka Iijima-Yamas...; 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 Horibe; Yusuke Hara; Kentaro Oki; Yasuhide Hayashi; Shiro Tanaka; Souichi Adachi
• Keywords: Male; Adolescent; Clinical Studies as Topic; Hematopoietic Stem Cell Transplantation; Intracellular Signaling Peptides and Proteins; Infant; Nuclear Proteins; Histone-Lysine N-Methyltransferase; 3. Good health; Nuclear Pore Complex Proteins; Genetic Heterogeneity; Leukemia, Myeloid, Acute; 03 medical and health sciences; 0302 clinical medicine; Japan; Child, Preschool; Mutation; Histone Methyltransferases; Humans; Multicenter Studies as Topic; Female; Child; Alleles

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.