肿瘤细胞治疗研究
英文原题:Allogeneic hematopoietic stem cell transplantation achieves complete response in refractory primary mediastinal large B-cell lymphoma after the failure of chemotherapy, CAR-T therapy, and PD-1 blockade.
Allogeneic hematopoietic stem cell transplantation achieves complete response in refractory primary mediastinal large B-cell lymphoma after the failure of chemotherapy, CAR-T therapy, and PD-1 blockade.
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原发性纵隔大B细胞淋巴瘤(PMBCL)通常对化疗有反应,而CAR-T 细胞疗法和程序性细胞死亡蛋白1(PD-1)抑制剂pembrolizumab等免疫疗法在复发/难治性病例中已显示出前景。
然而,针对PMBCL序贯使用多种免疫疗法的情况仍缺乏充分表征。在此,我们报告一例19岁女性PMBCL患者,累及纵隔及多个结外部位。化疗获得部分缓解后,她出现中枢神经系统复发,对大剂量甲氨蝶呤有反应,放疗使再生的纵隔病灶数量减少。随后,出现了对CAR-T 疗法和pembrolizumab均难治的新肝脏病灶。在局部肝脏放疗后,进行了异基因造血干细胞移植(allo-HSCT),结果达到完全缓解。移植后早期,她发生了急性移植物抗宿主病的肝炎变异型,这可能反映了移植物抗淋巴瘤(GVL)效应。尽管维持了缓解,患者仍于一年后死于多重三唑类耐药烟曲霉引起的播散性感染。本病例既突出了allo-HSCT在对多种免疫疗法难治的PMBCL中的潜在治愈作用,也突出了其重大风险。移植前使用pembrolizumab和局部放疗可能影响移植结局,值得进一步研究。
Primary mediastinal large B-cell lymphoma (PMBCL) typically responds to chemotherapy, and immunotherapies such as chimeric antigen receptor T-cell (CAR-T) therapy and the programmed cell death protein 1 (PD-1) inhibitor pembrolizumab have shown promise in relapsed or refractory cases.
However, the sequential use of multiple immunotherapies for PMBCL remains poorly characterized.
Here, we report a case of a 19-year-old female with PMBCL involving the mediastinum and multiple extranodal sites. After a partial response to chemotherapy, she developed a central nervous system relapse that responded to high-dose methotrexate, and the number of regrowing mediastinal lesions was reduced by radiotherapy. Subsequently, new hepatic lesions that were refractory to both CAR-T therapy and pembrolizumab emerged. Following localized liver radiotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was performed, resulting in complete response.
Early post-transplant, she developed a hepatitis variant of acute graft-versus-host disease, which may have reflected a graft-versus-lymphoma (GVL) effect. Despite maintaining response, the patient died one year later form a disseminated infection with multitriazole-resistant Aspergillus fumigatus.
This case highlights both the potential curative role and the substantial risks of allo-HSCT in PMBCL refractory to multiple immunotherapies. The pre-transplant use of pembrolizumab and localized radiotherapy may influence transplant outcomes and warrants further investigation.
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