Allogeneic Mesenchymal Cell Therapy in Anthracycline-Induced Cardiomyopathy Heart Failure Patients: The CCTRN SENECA Trial.
Allogeneic Mesenchymal Cell Therapy in Anthracycline-Induced Cardiomyopathy Heart Failure Patients: The CCTRN SENECA Trial.
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DOI：
10.1016/j.jaccao.2020.09.001
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发表时间：
2020-11
期刊：
影响因子：
--
通讯作者：
Cardiovascular Cell Therapy Research Network (CCTRN)
中科院分区：
文献类型：
--
作者：
Bolli R;Perin EC;Willerson JT;Yang PC;Traverse JH;Henry TD;Pepine CJ;Mitrani RD;Hare JM;Murphy MP;March KL;Ikram S;Lee DP;O'Brien C;Durand JB;Miller K;Lima JA;Ostovaneh MR;Ambale-Venkatesh B;Gee AP;Richman S;Taylor DA;Sayre SL;Bettencourt J;Vojvodic RW;Cohen ML;Simpson LM;Lai D;Aguilar D;Loghin C;Moyé L;Ebert RF;Davis BR;Simari RD;Cardiovascular Cell Therapy Research Network (CCTRN)
蒽环类药物诱发的心肌病（AIC）可能是不可逆的，预后不良，不成比例地影响女性和年轻人。同种异体骨髓间充质干细胞（allo-MSCs）的管理是一种有前途的方法来治疗心力衰竭（HF）。SENECA（癌症幸存者干细胞注射）是AIC中allo-MSC的1期研究。患有慢性AIC的癌症幸存者（平均年龄56.6岁; 68%为女性; NT-proBNP 1，426 pg/ml; 6例入组开放标签导入期，31例受试者以1：1随机化）经心内膜接受1 × 108例allo-MSC或溶媒。主要目标是安全性和可行性。次要疗效指标包括通过心脏磁共振成像（CMR）测量的心脏功能和结构、功能能力、生活质量（明尼苏达心力衰竭生活问卷）和生物标志物。共有97%的受试者成功接受了研究产品注射;所有分配的allo-MSC受试者均接受了目标剂量的细胞。随访访视的参与率很高（92%），在1年访视时成功收集了94%的终点。尽管58%的受试者使用了非CMR兼容器械，但84%的受试者在1年时成功采集了CMR终点。未报告新发肿瘤。在临床结果方面，allo-MSC组和赋形剂组之间没有显著差异。次要指标包括6分钟步行试验（p = 0.056）和明尼苏达心力衰竭生活问卷评分（p = 0.048），这倾向于支持allo-MSC组。在AIC患者的细胞治疗的首次人体研究中，allo-MSCs的经内分泌给药似乎是安全可行的，并且在大多数使用器械的HF患者中成功进行了CMR。这项研究为旨在评估AIC患者细胞治疗疗效的2期试验奠定了基础。(Stem癌症存活者中的细胞注射[SENECA]; NCT 02509156）
Anthracycline-induced cardiomyopathy (AIC) may be irreversible with a poor prognosis, disproportionately affecting women and young adults. Administration of allogeneic bone marrow–derived mesenchymal stromal cells (allo-MSCs) is a promising approach to heart failure (HF) treatment. SENECA (Stem Cell Injection in Cancer Survivors) was a phase 1 study of allo-MSCs in AIC. Cancer survivors with chronic AIC (mean age 56.6 years; 68% women; NT-proBNP 1,426 pg/ml; 6 enrolled in an open-label, lead-in phase and 31 subjects randomized 1:1) received 1 × 108 allo-MSCs or vehicle transendocardially. Primary objectives were safety and feasibility. Secondary efficacy measures included cardiac function and structure measured by cardiac magnetic resonance imaging (CMR), functional capacity, quality of life (Minnesota Living with Heart Failure Questionnaire), and biomarkers. A total of 97% of subjects underwent successful study product injections; all allo-MSC–assigned subjects received the target dose of cells. Follow-up visits were well-attended (92%) with successful collection of endpoints in 94% at the 1-year visit. Although 58% of subjects had non-CMR compatible devices, CMR endpoints were successfully collected in 84% of subjects imaged at 1 year. No new tumors were reported. There were no significant differences between allo-MSC and vehicle groups with regard to clinical outcomes. Secondary measures included 6-min walk test (p = 0.056) and Minnesota Living with Heart Failure Questionnaire score (p = 0.048), which tended to favor the allo-MSC group. In this first-in-human study of cell therapy in patients with AIC, transendocardial administration of allo-MSCs appears safe and feasible, and CMR was successfully performed in the majority of the HF patients with devices. This study lays the groundwork for phase 2 trials aimed at assessing efficacy of cell therapy in patients with AIC. (Stem Cell Injection in Cancer Survivors [SENECA]; NCT02509156)
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影响因子：
4.8
作者：
Bolli, Roberto;Hare, Joshua M.;Simari, Robert D.
通讯作者：
Simari, Robert D.
影响因子：
10.8
作者：
Florea, Victoria;Rieger, Angela C.;Hare, Joshua M.
通讯作者：
Hare, Joshua M.
影响因子：
24
作者：
Hicks, Karen A.;Tcheng, James E.;Wang, Tracy Y.
通讯作者：
Wang, Tracy Y.
影响因子：
120.7
作者：
STEINHERZ, LJ;STEINHERZ, PG;MURPHY, ML
通讯作者：
MURPHY, ML
DOI：
10.1001/jama.2012.25321
发表时间：
2012-12-12
期刊：
JAMA
影响因子：
--
作者：
Hare JM;Fishman JE;Gerstenblith G;DiFede Velazquez DL;Zambrano JP;Suncion VY;Tracy M;Ghersin E;Johnston PV;Brinker JA;Breton E;Davis-Sproul J;Schulman IH;Byrnes J;Mendizabal AM;Lowery MH;Rouy D;Altman P;Wong Po Foo C;Ruiz P;Amador A;Da Silva J;McNiece IK;Heldman AW;George R;Lardo A
通讯作者：
Lardo A