Hemofiltration Successfully Eliminates Severe Cytokine Release Syndrome Following CD19 CAR-T-Cell Therapy.
Hemofiltration Successfully Eliminates Severe Cytokine Release Syndrome Following CD19 CAR-T-Cell Therapy.
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血液滤过成功消除 CD19 CAR-T 细胞治疗后严重的细胞因子释放综合征
DOI：
10.1097/cji.0000000000000243
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Liu Y;Chen X;Wang D;Li H;Huang J;Zhang Z;Qiao Y;Zhang H;Zeng Y;Tang C;Yang S;Wan X;Chen YH;Zhang Y
细胞因子释放综合征（CRS）仍然是嵌合抗原受体T（CAR-T）细胞治疗B细胞急性淋巴细胞白血病（B-ALL）和淋巴瘤的主要不良反应。因此，寻找治疗严重CRS的新策略迫在眉睫。我们进行了一项临床试验，以评估靶向CD 19的CAR-T细胞治疗复发性和化疗难治性B-ALL和淋巴瘤的安全性和有效性。一名10岁的B-ALL男孩在5个疗程的化疗后从未达到微小残留病（MRD）阴性状态，入组我们的研究，并接受了总计3.19×106/kg的自体CD 19 CAR-T细胞。在CAR-T细胞输注之前，初始淋巴细胞占骨髓细胞的41.8%，在输注后第14天降至1%，MRD<10−4。然而，该患者在CAR-T细胞治疗后发生了4级CRS、多器官衰竭、噬血细胞综合征、神经毒性和重度肺部感染。托珠单抗和糖皮质激素治疗对控制不良反应无效，相比之下，血液滤过立即改善了重度CRS，并防止了CAR-T细胞治疗引起的多器官功能障碍、肺炎和水囊炎的加重。所有副作用均在血液滤过后数天内消失。血液滤过帮助快速清除细胞因子，加快患者恢复，成功解决严重CRS危象。这是第一份报告，报告了成功使用血液滤过来消除CAR-T细胞治疗的不良反应。
Cytokine release syndrome (CRS) remains to be a major adverse effect of chimeric antigen receptor T (CAR-T) cell therapy in B-cell acute lymphoblastic leukemia (B-ALL) and lymphoma. It was urgent to explore novel strategy for managing severe CRS. We conducted a clinical trial to assess the safety and efficacy of CD19-targeting CAR-T-cells in the treatment of relapsed and chemotherapy-refractory B-ALL and lymphoma. A 10-year-old boy with B-ALL who never achieved minimal residual disease (MRD) negative status after 5 courses of chemotherapy was enrolled into our study and received a total of 3.19×106/kg autologous CD19 CAR-T-cells. Before CAR-T-cell infusion, naive lymphocytes made up 41.8% of bone marrow cells, which were reduced to 1% at the 14th day after transfusion, with MRD<10−4. However, this patient developed grade 4 CRS, multiple organ failure, hemophagocytic syndrome, neurotoxicity, and severe pulmonary infection after CAR-T-cell therapy. Tocilizumab and glucocorticoids treatment were ineffective for controlling the adverse effects and in contrast, hemofiltration immediately ameliorated the severe CRS and prevented the exacerbation of multiple organ dysfunction, pneumonia, and hydrosarca caused by CAR-T-cell therapy. All side effects disappeared within days following hemofiltration. Hemofiltration helped quickly clear cytokines, speeded up patient recover, and successfully resolved the severe CRS crisis. This was the first report, reporting the successful use of hemofiltration to eliminate adverse reactions of CAR-T-cell therapy.