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:Therapy-related myelodysplastic syndrome rapidly evolving to acute myeloid leukemia following CAR-T cell therapy in a patient with refractory diffuse large B-cell lymphoma: a case report.
本病例强调,持续性 CAR-T 后血细胞减少可作为潜在 t-MN 的早期表现,而非一过性血液毒性。对于既往广泛暴露于细胞毒性方案的患者,及时且全面的骨髓评估——包括形态学、流式细胞术、细胞遗传学和分子分析——至关重要,以避免灾难性的诊断延误。
持续性血细胞减少是复发或难治性弥漫大B细胞淋巴瘤(DLBCL)患者接受CAR-T 细胞治疗后日益被认识的并发症。虽然大多数病例源于短暂的免疫介导机制或骨髓储备耗竭,但对于表现为持续性、输血难治性血细胞减少的患者,必须高度怀疑继发性治疗相关髓系肿瘤(t-MN)。病例介绍:我们报告一例76岁女性,诊断为难治性DLBCL(非生发中心B细胞亚型,IIIA期,国际预后指数评分4分)。在接受多线化学免疫治疗(R-CDOP、R-CDOPE、R-ICE、局部放疗及一周期Pola-R-ICE)及随后的自体CAR-T细胞输注后,患者出现持续性全血细胞减少,以严重的输血难治性血小板减少为特征。2026年2月进行的全面骨髓评估显示多系发育异常、13%原始细胞、TP53缺失/突变及复杂核型,确诊为治疗相关骨髓增生异常综合征伴低原始细胞(t-MDS-LB)。两个月内,疾病迅速进展为急性髓系白血病(t-AML),异常髓系原始细胞达35%。启动阿扎胞苷联合维奈克拉治疗,但因严重骨髓抑制和严重感染而中止。
BACKGROUND: Persistent cytopenia following chimeric antigen receptor T-cell (CAR-T) therapy is an increasingly recognized complication in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). While most cases stem from transient, immune-mediated mechanisms or depleted bone marrow reserves, secondary therapy-related myeloid neoplasms (t-MN) must be strongly suspected in patients presenting with prolonged, transfusion-refractory cytopenias. CASE PRESENTATION: We report the case of a 76-year-old woman diagnosed with refractory DLBCL (non-germinal center B-cell subtype, stage IIIA, International Prognostic Index score of 4). Following multiple lines of chemo-immunotherapy (R-CDOP, R-CDOPE, R-ICE, local radiotherapy, and one cycle of Pola-R-ICE) and subsequent autologous CAR-T cell infusion, the patient developed persistent pancytopenia, characterized by severe, transfusion-refractory thrombocytopenia. A comprehensive bone marrow evaluation performed in February 2026 revealed multilineage dysplasia, 13% blasts, TP53 deletion/mutation, and a complex karyotype, establishing a diagnosis of therapy-related myelodysplastic syndrome with low blasts (t-MDS-LB). Within two months, the disease rapidly progressed to acute myeloid leukemia (t-AML) with 35% abnormal myeloid blasts. Combination therapy with azacitidine and venetoclax was initiated but discontinued due to profound myelosuppression and severe infection. CONCLUSION: This case underscores that persistent post-CAR-T cytopenia can serve as an early manifestation of an underlying t-MN rather than transient hematotoxicity. Prompt and comprehensive bone marrow assessments-incorporating morphology, flow cytometry, cytogenetics, and molecular profiling-are paramount for patients with extensive prior exposure to cytotoxic regimens to avoid catastrophic diagnostic delays.
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