TY - JOUR
T1 - Risk-stratified therapy for children with FLT3-ITD-positive acute myeloid leukemia
T2 - results from the JPLSG AML-05 study
AU - Shimada, Akira
AU - Iijima-Yamashita, Yuka
AU - Tawa, Akio
AU - Tomizawa, Daisuke
AU - Yamada, Miho
AU - Norio, Shiba
AU - Watanabe, Tomoyuki
AU - Taga, Takashi
AU - Iwamoto, Shotaro
AU - Terui, Kiminori
AU - Moritake, Hiroshi
AU - Kinoshita, Akitoshi
AU - Takahashi, Hiroyuki
AU - Nakayama, Hideki
AU - Koh, Katsuyoshi
AU - Goto, Hiroaki
AU - Kosaka, Yoshiyuki
AU - Saito, Akiko Moriya
AU - Kiyokawa, Nobutaka
AU - Horibe, Keizo
AU - Hara, Yusuke
AU - Oki, Kentaro
AU - Hayashi, Yasuhide
AU - Tanaka, Shiro
AU - Adachi, Souichi
N1 - Funding Information:
This research was (partially) supported by the Practical Research for Innovative Cancer Control grant from the Japan Agency for Medical Research and Development, AMED.
Funding Information:
Acknowledgements We thank all doctors involved for participating in the JPLSG AML-05 study. This work was supported by a Grant for Clinical Cancer Research and a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour, and Welfare of Japan, and Japan Agency for Medical Research and Development (AMED). We thank Ryan Chastain-Gross, Ph.D., from Edanz Group (www.edanzediting .com/ac) for editing a draft of this manuscript.
Publisher Copyright:
© 2018, The Japanese Society of Hematology.
PY - 2018/5/1
Y1 - 2018/5/1
N2 - 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.
AB - 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.
KW - AML
KW - Alleric ratio
KW - Childhood
KW - FLT3-ITD
KW - NUP98-NSD1
UR - http://www.scopus.com/inward/record.url?scp=85042796956&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042796956&partnerID=8YFLogxK
U2 - 10.1007/s12185-017-2395-x
DO - 10.1007/s12185-017-2395-x
M3 - Article
C2 - 29330746
AN - SCOPUS:85042796956
SN - 0925-5710
VL - 107
SP - 586
EP - 595
JO - International Journal of Hematology
JF - International Journal of Hematology
IS - 5
ER -