CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Donor Hematopoietic Stem Cell/Lymphocyte Maintenance Treatment After CAR T-Cell Therapy in Patients With B-Cell Acute Lymphoblastic Leukemia Relapse Following Stem Cell Transplant.
Donor Hematopoietic Stem Cell/Lymphocyte Maintenance Treatment After CAR T-Cell Therapy in Patients With B-Cell Acute Lymphoblastic Leukemia Relapse Following Stem Cell Transplant.
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对于异基因造血干细胞移植(allo-HSCT)后复发的B细胞急性淋巴细胞白血病(B-ALL)患者,如何维持抗CD19嵌合抗原受体(CAR)修饰T细胞疗效是一个紧迫问题。
本研究旨在比较供者造血干细胞输注(DSI)与供者淋巴细胞输注(DLI)作为维持治疗的疗效;研究对象为allo-HSCT后复发、经抗CD19 CAR-T 治疗达到完全缓解(CR)的复发/难治性B-ALL患者。共22例allo-HSCT后复发的B-ALL患者接受抗CD19 CAR-T 治疗。对CAR-T 应答者给予DSI或DLI作为维持治疗。
我们比较两组的临床应答、急性移植物抗宿主病(aGVHD)、CAR-T 细胞扩增和不良事件。本研究中,19例患者接受DSI/DLI维持治疗。治疗后第365天,DSI组无进展生存期和总生存期均高于DLI组。DSI组中4例患者(36.4%)发生I级或II级aGVHD;DLI组仅1例患者发生II级aGVHD。DSI组CAR-T 细胞峰值高于DLI组。DSI后11例患者中有9例IL-6和TNF水平再次升高,而DLI组未见这种情况。
我们的发现提示,对于allo-HSCT后复发、并通过CAR-T 治疗达到CR的B-ALL患者,DSI是一种可行的维持治疗。
Maintaining the efficacy of anti-CD19 chimeric antigen receptor modified (CAR) T-cell therapy in patients with B-cell acute lymphoblastic leukemia (B-ALL) relapse after allogeneic hematopoietic stem cell transplant (allo-HSCT) is an urgent problem.
In this study, we aimed to compare the efficacy of donor hematopoietic stem cell infusion (DSI) therapy and donor lymphocyte infusion (DLI) therapy as a maintenance therapy after R/R B-ALL patients achieved CR in anti-CD19-CAR T-cell therapy but relapsed after allo-HSCT. In total, 22 B-ALL patients who relapsed after allo-HSCT received anti-CD19-CAR T-cell therapy. Patients who responded to CAR T-cell therapy received DSI or DLI as maintenance therapy.
We compared the clinical responses, acute graft versus host disease (aGVHD), expansion of CAR-T-cells, and adverse events between the two groups. In our study, 19 patients received DSI/DLI as maintenance therapy. After DSI/DLI therapy, progression-free survival and overall survival were higher in the DSI group than in the DLI group at 365 days.
The grades I and II of aGVHD was observed in four patients (36. 4%) in the DSI group. Only one patient developed grade II aGVHD in the DLI group. The peaks of CAR T-cells in the DSI group were higher than those in the DLI group. IL-6 and TNF- levels increased again in nine of 11 patients after DSI but not in the DLI group.
Our findings indicate that for B-ALL patients who relapse after allo-HSCT, DSI is a feasible maintenance therapy if CR is obtained with CAR-T-cell therapy.
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