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难治性弥漫大 B 细胞淋巴瘤患者 CAR-T 细胞治疗后治疗相关骨髓增生异常综合征快速进展为急性髓系白血病:一例病例报告

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.

PubMed 2026/07/14(内容时间) Front Oncol Q2 · IF 3.4(JCR 2025)

研究概要

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。

研究思路结论见上方概要

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。

展开英文摘要原文

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.

论文信息

作者
Chen L、Liu W
单位
Department of Laboratory Medicine, Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine (Baoshan Hospital, Shanghai University of Traditional Chinese Medicine), Shanghai, China.China
文献类型
病例报告
期刊
Frontiers in oncology2026
原文标识
PubMed 42523532 · DOI 10.3389/fonc.2026.1888595