决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Chimeric antigen receptor (CAR) T-cell therapy-related gastrointestinal toxicity: Histologic features and morphologic mimics.
本研究前瞻性识别了来自 3 例出现 CAR-T 细胞治疗相关 GI 毒性的患者的 5 组 GI 活检标本。
嵌合抗原受体(CAR)T细胞疗法是当前治疗血液系统恶性肿瘤的方法,未来也可能用于实体瘤。CAR-T细胞疗法的临床副作用已有充分记录,但胃肠道(GI)毒性的组织学相关表现仍少有报道。本研究前瞻性收集了3例出现CAR-T相关GI毒性患者的5组GI活检标本。患者在治疗后1.5至8个月出现腹痛、便血、非血性腹泻、体重下降及发热/寒战等症状。组织学检查显示,结肠活检呈移植物抗宿主病(GVHD)样损伤模式,特征包括上皮细胞凋亡、隐窝脱落和神经内分泌细胞巢。一例十二指肠活检显示上皮内淋巴细胞增多和绒毛变钝,类似乳糜泻。结肠和小肠活检中均明显缺乏CD20阳性B细胞及CD38阳性浆细胞。两例患者需要使用生物制剂治疗;另一例患者经糖皮质激素治疗后有所改善,但最终死于上呼吸道感染。这些发现强调,为准确诊断CAR-T相关GI毒性,必须结合症状起始时间与治疗时间进行分析。
Chimeric antigen receptor (CAR) T-cell therapy is a contemporary treatment modality for hematologic malignancies, with potential future applications in solid tumors. While the clinical side effects of CAR T-cell therapy are well-documented, histologic correlations of gastrointestinal (GI) toxicity remain underreported. This study prospectively identified 5 sets of GI biopsies from 3 patients presenting with CAR T-cell therapy-associated GI toxicity. Patients exhibited symptoms such as abdominal pain, hematochezia, non-bloody diarrhea, weight loss, and fever/chills, occurring 1.5-8 months post-therapy. Histologic examination revealed a graft versus host disease (GVHD)-like pattern of injury in colon biopsies, characterized by epithelial apoptosis, crypt dropout, and neuroendocrine cell nests. One duodenal biopsy showed intraepithelial lymphocytosis and villous blunting, mimicking celiac disease. A notable paucity of CD20-positive B-cells and CD38-positive plasma cells was observed in both colonic and small intestinal biopsies. Two patients required biologic agents for treatment, while one patient improved with corticosteroids but succumbed to an upper respiratory infection. The findings underscore the necessity of correlating symptom onset with therapy timing to achieve accurate diagnosis of CAR T-cell therapy-associated GI toxicity.
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