Maintenance sorafenib is superior to prophylactic donor lymphocyte infusion at improving the prognosis of acute myeloid leukemia with FMS-like tyrosine kinase 3 internal tandem duplication after allogeneic hematopoietic stem cell transplantation
Maintenance sorafenib is superior to prophylactic donor lymphocyte infusion at improving the prognosis of acute myeloid leukemia with FMS-like tyrosine kinase 3 internal tandem duplication after allogeneic hematopoietic stem cell transplantation
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维持索拉非尼在改善同种异体造血干细胞移植后 FMS 样酪氨酸激酶 3 内部串联重复的急性髓系白血病的预后方面优于预防性供体淋巴细胞输注
DOI：
10.1038/s41409-020-01015-w
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发表时间：
2020-08
影响因子：
4.8
通讯作者：
He Huang
中科院分区：
文献类型：
--
作者：
Jimin Shi;Liqin Cao;Yi Luo;Yanmin Zhao;Yamin Tan;Jian Yu;Xiaoyu Lai;Yuanyuan Zhu;Yongxian Hu;Jingsong He;Jie Sun;Weiyan Zheng;Guoqing Wei;He Huang
Fms 样酪氨酸激酶 3 内部串联重复 (FLT3-ITD) 发生在约 25% 的成人急性髓系白血病 (AML) 病例中，即使在异基因造血细胞移植 (allo-HSCT) 后，也是复发风险增加和生存率低下的独立危险因素 [1]。 allo-HSCT 后预防性供体淋巴细胞输注 (pDLI) 是预防某些高危 AML 患者复发的经典治疗方法。近年来，索拉非尼被证明在移植后维持治疗中可有效改善FLT3-ITD阳性AML患者的预后[2]。然而，比较索拉非尼维持治疗与 pDLI 在预防 FLT3-ITD 阳性 AML 患者 alloHSCT 后复发方面的数据有限。我们对2014年1月至2018年12月期间在我中心接受allo-HSCT的68例FLT3-ITD阳性AML患者进行了回顾性研究。其供体为HLA全合相关供体（n = 21）、无关供体（n = 7）和HLA单倍体相关供体（n = 40）。为了防止allo-HSCT后AML复发，24例患者接受索拉非尼维持治疗（A组），12例患者接受pDLI（B组），其余32例移植后未接受pDLI或维持索拉非尼治疗的患者作为对照组（C组）。所有接受 pDLI 或索拉非尼维持治疗的患者均具有完全供体嵌合状态，且微小残留病 (MRD) 和 FLT3ITD 突变均为阴性。使用基于标准聚合酶链式反应 (PCR) 的 FLT3 分子技术进行化疗或 alloHSCT 后的 MRD 监测。移植后第-3天至+90天环孢菌素A（CsA）的维持浓度为150-250ng/ml，然后每月逐渐减少33%，在+150至+180天停药，除非发生GVHD。当患者接受 pDLI 时，继续使用免疫抑制剂，除非出现 DLI 相关的 GVHD，否则不会给患者施用额外的免疫抑制剂。组间比较采用分类变量的卡方统计量和连续变量的独立样本T检验。急性移植物抗宿主病 (aGVHD) 和慢性 GVHD (cGVHD) 根据先前描述的方法进行分级 [3, 4]。美国国家癌症研究所通用毒性标准（4.0 版）[5] 用于评估不良事件的严重程度。使用 Kaplan-Meier 方法绘制总生存期 (OS) 和无白血病生存期 (LFS)，并使用对数秩检验进行比较。非复发死亡率 (NRM) 和 GVHD 的累积发生率以及复发的累积发生率 这些作者的贡献相同：Jimin Shi、Liqin Cao
Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) occurs in ~25% of adult acute myeloid leukemia (AML) cases and is an independent risk factor for increased risk of relapse and inferior survival, even after allogeneic hematopoietic cell transplantation (allo-HSCT) [1]. Prophylactic donor lymphocyte infusion (pDLI) after allo-HSCT is a classical treatment for preventing relapse in some high-risk AML patients. In recent years, sorafenib was proven effective at improving the prognosis of FLT3-ITDpositive AML patients in the setting of post transplantation maintenance therapy [2]. However, there are limited data comparing maintenance sorafenib with pDLI at preventing relapse in FLT3-ITD-positive AML patients after alloHSCT. We performed a retrospective study with 68 FLT3-ITDpositive AML patients who received allo-HSCT in our center from January 2014 to December 2018. Their donors were HLA-identical related donors (n= 21), unrelated donors (n= 7), and HLA haplo-identical related donors (n= 40). To prevent AML relapse after allo-HSCT, 24 patients received maintenance sorafenib (group A), 12 patients received pDLI (group B), and the remaining 32 patients who did not receive pDLI or maintenance sorafenib post transplantation were included as the control group (group C). All patients who received pDLI or maintenance sorafenib had full donor chimerism and were negative for minimal residual disease (MRD) and the FLT3ITD mutation. MRD monitoring after chemotherapy or alloHSCT was performed using standard polymerase chain reaction (PCR)-based molecular techniques for FLT3. The maintenance concentration of cyclosporin A (CsA) was 150–250 ng/ml from day −3 to day +90 after transplantation and then tapered at 33% per month for discontinuation on day +150 to +180 unless GVHD developed. When patients received a pDLI, immunosuppressive agents were continued, and additional immunosuppressive agents were not administered to patients unless DLI-related GVHD developed. Comparisons among the groups were performed by using the chi-square statistic for categorical variables and the independent samples T test for continuous variables. Acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD) were graded according to previously described methods [3, 4]. The National Cancer Institute Common Toxicity Criteria (version 4.0) [5] was used to evaluate the severity of adverse events. Overall survival (OS) and leukemia-free survival (LFS) were plotted using the Kaplan–Meier method and compared using the log-rank test. The cumulative incidences of nonrelapse mortality (NRM) and GVHD and the cumulative incidence of relapse These authors contributed equally: Jimin Shi, Liqin Cao
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影响因子：
4.8
作者：
S. Kothari;A. Artz;S. M. Lee;N. Fulton;Jae-Hyun Park;W. Stock;R. Larson;O. Odenike;J. Kline;J. LaBelle;S. Kosuri;P. Riedell;Yusuke Nakamura;M. Bishop;Hongtao Liu
通讯作者：
S. Kothari;A. Artz;S. M. Lee;N. Fulton;Jae-Hyun Park;W. Stock;R. Larson;O. Odenike;J. Kline;J. LaBelle;S. Kosuri;P. Riedell;Yusuke Nakamura;M. Bishop;Hongtao Liu
使用 DLI 预防复发可提高晚期急性白血病患者 HLA 相同移植后的生存率：一项多中心研究
影响因子：
2.1
作者：
Wang, Yu;Liu, Dai-Hong;Huang, Xiao-Jun
通讯作者：
Huang, Xiao-Jun
DOI：
10.1016/j.bbmt.2014.12.001
发表时间：
2015-03
期刊：
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
影响因子：
--
作者：
Jagasia MH;Greinix HT;Arora M;Williams KM;Wolff D;Cowen EW;Palmer J;Weisdorf D;Treister NS;Cheng GS;Kerr H;Stratton P;Duarte RF;McDonald GB;Inamoto Y;Vigorito A;Arai S;Datiles MB;Jacobsohn D;Heller T;Kitko CL;Mitchell SA;Martin PJ;Shulman H;Wu RS;Cutler CS;Vogelsang GB;Lee SJ;Pavletic SZ;Flowers ME
通讯作者：
Flowers ME
影响因子：
2.7
作者：
Antar, Ahmad;Kharfan-Dabaja, Mohamed A.;Bazarbachi, Ali
通讯作者：
Bazarbachi, Ali
DOI：
--
发表时间：
2011
期刊：
Journal of B.U.ON. : official journal of the Balkan Union of Oncology
影响因子：
--
作者：
N. Govedarović;G. Marjanovic
通讯作者：
N. Govedarović;G. Marjanovic