Singbartl Kai, Rosenthal Allison, Leis Jose, Patel Bhavesh, Sen Ayan
Department of Critical Care Medicine, Mayo Clinic, Phoenix, AZ.
Division of Hematology/Oncology, Department of Medicine, Mayo Clinic, Phoenix, AZ.
Crit Care Explor. 2021 Jun 29;3(7):e0472. doi: 10.1097/CCE.0000000000000472. eCollection 2021 Jul.
Chimeric antigen receptor T-cell therapies (CAR-T) are transforming the treatment of B-cell leukemias and lymphomas. Cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome represent common, potentially life-threatening toxicities from chimeric antigen receptor T-cell therapy treatment.
We present a 53-year-old patient with primary refractory high-grade B-cell lymphoma who developed severe, refractory neurotoxicity following chimeric antigen receptor T-cell therapy but exhibited complete recovery after extracorporeal blood purification with CytoSorb (CytoSorbents, Monmouth Junction, NJ).Six days after chimeric antigen receptor T-cell therapy infusion, the patient developed cytokine release syndrome grade 3, prompting administration of dexamethasone and tocilizumab, a monoclonal antibody against the interleukin-6 receptor. His C-reactive protein levels started to decrease with tocilizumab and dexamethasone treatments. However, his ferritin levels continued to rise, and his interleukin-6 levels were above the upper detection threshold. Thirty-six hours later, the patient showed improved cytokine release syndrome but developed severe immune effector cell-associated neurotoxicity syndrome with predominant encephalopathy (grade 3) despite treatment with dexamethasone/methylprednisolone, tocilizumab, and anakinra. We therefore sought a rescue strategy to remove inflammatory mediators. Following emergency use authorization, we initiated extracorporeal blood purification with CytoSorb (CytoSorbents).Four-day extracorporeal blood purification resulted in complete resolution of immune effector cell-associated neurotoxicity syndrome and greater than 95% reduction in interleukin-6 levels without side effects. The patient was discharged home 10 days later with no signs of neurotoxicity or other secondary end-organ dysfunction.
Our case represents the first reported, successful application of extracorporeal blood purification with CytoSorb (CytoSorbents) to treat severe, refractory neurotoxicity following chimeric antigen receptor T-cell therapy.
嵌合抗原受体T细胞疗法（CAR-T）正在改变B细胞白血病和淋巴瘤的治疗方式。细胞因子释放综合征和免疫效应细胞相关神经毒性综合征是嵌合抗原受体T细胞疗法常见的、可能危及生命的毒性反应。
我们报告了一名53岁原发性难治性高级别B细胞淋巴瘤患者，其在接受嵌合抗原受体T细胞疗法后出现严重难治性神经毒性，但在使用CytoSorb（CytoSorbents公司，新泽西州蒙茅斯章克申）进行体外血液净化后完全康复。在输注嵌合抗原受体T细胞疗法6天后，患者出现3级细胞因子释放综合征，遂给予地塞米松和抗白细胞介素-6受体单克隆抗体托珠单抗治疗。托珠单抗和地塞米松治疗后，患者C反应蛋白水平开始下降。然而，其铁蛋白水平持续升高，白细胞介素-6水平高于检测上限。36小时后，患者细胞因子释放综合征有所改善，但尽管接受了地塞米松/甲泼尼龙、托珠单抗和阿那白滞素治疗，仍出现以脑病为主的严重免疫效应细胞相关神经毒性综合征（3级）。因此，我们寻求一种去除炎症介质的挽救策略。在紧急使用授权后，我们启动了使用CytoSorb（CytoSorbents）的体外血液净化治疗。为期4天的体外血液净化使免疫效应细胞相关神经毒性综合征完全缓解，白细胞介素-6水平降低超过95%，且无副作用。10天后患者出院，无神经毒性或其他继发性终末器官功能障碍的迹象。
我们的病例是首次报道成功应用CytoSorb（CytoSorbents）进行体外血液净化治疗嵌合抗原受体T细胞疗法后严重难治性神经毒性。
