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

被引：24

作者：

Shimada, Akira ^{[1
,2
]}

Iijima-Yamashita, Yuka ^{[2
]}

Tawa, Akio ^{[3
]}

Tomizawa, Daisuke ^{[4
]}

Yamada, Miho ^{[2
]}

Norio, Shiba ^{[5
]}

Watanabe, Tomoyuki ^{[6
]}

Taga, Takashi ^{[7
]}

Iwamoto, Shotaro ^{[8
]}

Terui, Kiminori ^{[9
]}

Moritake, Hiroshi ^{[10
]}

Kinoshita, Akitoshi ^{[11
]}

Takahashi, Hiroyuki ^{[12
]}

Nakayama, Hideki ^{[13
]}

Koh, Katsuyoshi ^{[14
]}

Goto, Hiroaki ^{[15
]}

Kosaka, Yoshiyuki ^{[16
]}

Saito, Akiko Moriya ^{[2
]}

Kiyokawa, Nobutaka ^{[17
]}

Horibe, Keizo ^{[2
]}

Hara, Yusuke ^{[21
]}

Oki, Kentaro ^{[17
]}

Hayashi, Yasuhide ^{[18
]}

Tanaka, Shiro ^{[19
]}

Adachi, Souichi ^{[20
]}

机构：

[1] Okayama Univ Hosp, Dept Pediat Hematol Oncol, Kita Ku, 2-5-1 Shikatacho, Okayama 7008558, Japan

[2] Nagoya Med Ctr, Clin Res Ctr, Natl Hosp Org, Nagoya, Aichi, Japan

[3] Osaka Med Ctr, Natl Hosp Org, Dept Pediat, Osaka, Japan

[4] Natl Ctr Child Hlth & Dev, Childrens Canc Ctr, Div Leukemia & Lymphoma, Tokyo, Japan

[5] Yokohama City Univ, Dept Pediat, Yokohama, Kanagawa, Japan

[6] Aichi Gakuin Univ, Dept Nutr Sci, Nisshin, Aichi, Japan

[7] Shiga Med Univ, Dept Pediat, Otsu, Shiga, Japan

[8] Mie Univ, Dept Pediat, Tsu, Mie, Japan

[9] Hirosaki Univ, Dept Pediat, Hirosaki, Aomori, Japan

[10] Miyazaki Univ, Dept Pediat, Miyazaki, Japan

[11] St Marianna Univ, Sch Med, Dept Pediat, Kawasaki, Kanagawa, Japan

[12] Toho Univ, Omori Med Ctr, Dept Pediat, Tokyo, Japan

[13] Kyushu Canc Ctr, Dept Pediat, Fukuoka, Japan

[14] Saitama Childrens Med Ctr, Dept Hematol Oncol, Saitama, Japan

[15] Kanagawa Childrens Med Ctr, Dept Hematol Oncol, Yokohama, Kanagawa, Japan

[16] Kobe Childrens Med Ctr, Dept Hematol Oncol, Kobe, Hyogo, Japan

[17] Natl Ctr Child Hlth & Dev, Dept Pediat Hematol & Oncol Res, Tokyo, Japan

[18] Gunma Childrens Med Ctr, Dept Hematol Oncol, Shibukawa, Japan

[19] Kyoto Univ, Grad Sch Med, Dept Clin Biostat, Kyoto, Japan

[20] Kyoto Univ, Dept Human Hlth Sci, Kyoto, Japan

[21] Gunma Univ, Dept Pediat, Maebashi, Gunma, Japan

来源：

INTERNATIONAL JOURNAL OF HEMATOLOGY | 2018年 / 107卷 / 05期

关键词：

AML; FLT3-ITD; Childhood; Alleric ratio; NUP98-NSD1; INTERNAL TANDEM DUPLICATION; PROGNOSTIC-SIGNIFICANCE; CELL TRANSPLANTATION; FLT3; INHIBITORS; POOR-PROGNOSIS; EXPRESSION; MUTATIONS; RELAPSE; IMPACT; NUP98/NSD1;

D O I：

10.1007/s12185-017-2395-x

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Acute myeloid leukemia harboring internal tandem duplication of FMS-like tyrosine kinase 3 (AML (FLT3-ITD)) is associated with poor prognosis. We evaluated the results of the AML-05 study, in which all AML (FLT3-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 AML (FLT3-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 AML (FLT3-ITD) patients received HSCT at 1CR, the treatment outcome of AML (FLT3-ITD) patients did not improve compared with those in a previous study. Heterogeneity was observed among AML (FLT3-ITD) patients.

引用

页码：586 / 595

页数：10

共 26 条

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