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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:A potential role of preexisting inflammation in the development of acute myelopathy following CAR T-cell therapy for diffuse large B-cell lymphoma.
A potential role of preexisting inflammation in the development of acute myelopathy following CAR T-cell therapy for diffuse large B-cell lymphoma.
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抗CD19嵌合抗原受体(CAR)-T治疗在弥漫性大B细胞淋巴瘤(DLBCL)患者中诱发严重神经毒性的事件已被认识;然而,症状模式和严重程度因患者而异,差异很大。
我们报告了一例难治性DLBCL患者在成功接受CAR-T 治疗后出现急性脊髓病的特殊表现,同时伴有3级细胞因子释放综合征(CRS)和神经毒性。患者开始接受大剂量甲泼尼龙(MPS)治疗,神经症状迅速改善。
然而,该脊髓病患者(MP)出现严重下肢运动功能障碍,随后的脊髓MRI显示脊髓病,感觉平面位于T2节段。由MPS、静脉注射免疫球蛋白和阿那白滞素治疗组成的多模式治疗使脊髓病病情完全逆转,患者保持无癌状态。对MP在基线和CAR-T 输注后血清细胞因子时间趋势的评估,并与其他4例CAR-T 输注后出现不同程度CRS的DLBCL完全缓解患者进行比较,提示MP存在预先存在的基线炎症状态,且细胞因子水平发生改变。这些发现若得到类似病例研究的证实,有可能为CAR-T 治疗后脊髓病的表现及此类并发症的成功临床管理提供新的见解。
The event of anti-CD19 chimeric antigen receptor (CAR)-T therapy inducing serious neurotoxicity in patients with diffuse large B-cell lymphoma (DLBCL) is recognized; however, the patterns of symptoms and severity vary greatly from patient to patient.
We report an exceptional presentation of acute myelopathy in a refractory DLBCL following successful CAR-T treatment along with grade 3 cytokine release syndrome (CRS) and neurotoxicity. The patient was initiated on high-dose methylprednisolone (MPS) resulting in rapid improvement of neurological symptoms. Yet the myelopathy patient (MP) experienced severe lower limb motor deficit, and a subsequent spinal cord MRI revealed myelopathy with a sensory level at segment T2.
Multimodal therapy consisting of MPS, intravenous immunoglobulin and anakinra therapy resulted in complete reversal of myelopathy condition and the patient remained cancer free. The assessment of time trends of serum cytokines at baseline and post CAR-T infusion in MP compared to other 4 DLBCL complete responder patients with varying degree of CRS following CAR-T infusion, suggested pre-existing baseline inflammatory conditions in MP with altered levels of cytokines.
These findings, if corroborated by similar case studies, have the potential to generate novel insights into the manifestation of myelopathy following CAR-T therapy and the successful clinical management of such complications.
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