肿瘤细胞治疗研究
英文原题：Secondary peripheral T-cell lymphoma in a patient with DLBCL harboring BLM mutation following CD19/CD22 bispecific CAR-T cell therapy.
我们描述了一例继发性外周 T 细胞淋巴瘤（PTCL），其来源于一名携带致病性胚系 BLM p.L107Ffs*36 变异的复发或难治性 B 细胞淋巴瘤患者输注的 CD19/CD22-4-1BB-CD3-lenti 双特异性嵌合抗原受体（CAR）-T 细胞。
我们描述了一例继发性外周 T 细胞淋巴瘤（PTCL），其来源于一名携带致病性胚系 BLM p.L107Ffs*36 变异的复发或难治性 B 细胞淋巴瘤患者输注的 CD19/CD22-4-1BB-CD3-lenti 双特异性嵌合抗原受体（CAR）-T 细胞。整合基因组与分子分析证实，该 PTCL 克隆性来源于输注的 CAR-T 产品，并揭示了一个多步骤致癌过程，涉及预先存在的驱动突变（BLM）、体细胞 TET2 突变（p.R1261H 和 p.E1755*）以及基因组不稳定性。癌症相关基因（NF1、CBX5、RNF213 等）中的克隆性 CAR 载体整合事件被鉴定为克隆扩增的标志物，尽管尚无功能证据支持其直接的致癌作用。我们承认，该病例处于克隆性淋巴增殖性疾病与显性 PTCL 之间的谱系中，并且术语仍在不断演变。该病例提示，对 CAR-T 治疗后疑似复发者需要进行再活检，并凸显了传统产品评估在检测癌前克隆方面的局限性。
We describe a case of secondary peripheral T-cell lymphoma (PTCL) arising from infused CD19/CD22-4-1BB-CD3 -lenti bispecific chimeric antigen receptor (CAR)-T cells in a patient with relapsed or refractory B-cell lymphoma who carried a pathogenic germline BLM p.L107Ffs*36 variant. Integrated genomic and molecular analyses confirmed that the PTCL was clonally derived from the infused CAR-T product and revealed a multistep oncogenic process involving pre-existing driver mutations ( BLM ), somatic TET2 mutations (p.R1261H and p.E1755*), and genomic instability. Clonal CAR vector integration events in cancer-associated genes ( NF1, CBX5, RNF213, etc) were identified as markers of clonal expansion, although no functional evidence supports a direct oncogenic role. We acknowledge that this case lies on a spectrum between clonal lymphoproliferative disorder and overt PTCL, and terminology continues to evolve. This case suggests a need for re-biopsy of suspected relapses after CAR-T therapy and highlights the limitations of conventional product assessment in detecting premalignant clones.
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