CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
异基因干细胞移植后复发的急性淋巴细胞白血病：挑战现有免疫治疗手段的治疗困境（病例报告）
英文原题：Relapsed acute lymphoblastic leukaemia after allogeneic stem cell transplantation: a therapeutic dilemma challenging the armamentarium of immunotherapies currently available (case reports).
查看英文原题
Relapsed acute lymphoblastic leukaemia after allogeneic stem cell transplantation: a therapeutic dilemma challenging the armamentarium of immunotherapies currently available (case reports).
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
中文摘要
如今，儿童急性淋巴细胞白血病（ALL）的生存率已超过 90%，但全身性 ALL 复发，尤其是造血干细胞移植（HSCT）后复发，仍预后不佳。目前尚无针对这种情形的标准治疗，因此常采用个体化治疗。本文通过两个临床案例，说明治疗医师面临的挑战：制定个体化策略，综合考虑传统化疗、免疫治疗和第二次异基因 HSCT 的作用。病例 1：一名 2 岁女孩患有婴儿型 KMT2A 重排 B 细胞前体 ALL，在异基因 HSCT 后出现早期孤立性骨髓复发。经桥接化疗和淋巴细胞清除化疗后，给予嵌合抗原受体（CAR）T 细胞 tisagenlecleucel 诱导缓解，随后接受来自 HLA 9/10 匹配母亲的第二次 HSCT。
病例 2：一名 16 岁女孩患有 B 细胞前体 ALL，在异基因 HSCT 后出现晚期孤立性骨髓复发，并发生包括 IV 期肾功能不全在内的严重治疗毒性。剂量减低的桥接化疗后，尽管存在 CD19 阴性克隆，仍给予 tisagenlecleucel 诱导缓解；由于既往毒性持续，未进行淋巴细胞清除。随后患者接受来自单倍体相合母亲的第二次异基因 HSCT。病例 2 在第二次 HSCT 后约第 180 天复发；病例 1 在第二次 HSCT 后超过 360 天仍处于完全缓解。两例均显示首次异基因 HSCT 后全身性 ALL 复发的治疗挑战，包括化疗耐药和既往治疗造成的持续性器官损伤。CAR-T 等免疫疗法可诱导缓解并使患者能够接受第二次异基因 HSCT。
然而，首次 HSCT 后全身性 ALL 复发的最佳治疗仍有待确定。
展开英文摘要原文
While survival rates in paediatric acute lymphoblastic leukaemia (ALL) nowadays exceed 90%, systemic ALL relapse, especially after haemopoietic stem cell transplantation (HSCT), is associated with a poor outcome. As there is currently no standardized treatment for this situation, individualized treatment is often pursued. Exemplified by two clinical scenarios, the aim of this article is to highlight the challenge for treating physicians to find a customized treatment strategy integrating the role of conventional chemotherapy, immunotherapeutic approaches and second allogeneic HSCT. Case 1 describes a 2-year-old girl with an early isolated bone marrow relapse of an infant KMT2A -rearranged B-cell precursor ALL after allogeneic HSCT. After bridging chemotherapy and lymphodepleting chemotherapy, chimeric antigen receptor (CAR) T-cells (tisagenlecleucel) were administered for remission induction, followed by a second HSCT from the 9/10 human leukocyte antigen (HLA)-matched mother.
Case 2 describes a 16-year-old girl with a late, isolated bone marrow relapse of B-cell precursor ALL after allogeneic HSCT who experienced severe treatment toxicities including stage IV renal insufficiency. After dose-reduced bridging chemotherapy, CAR T-cells (tisagenlecleucel) were administered for remission induction despite a CD19 - clone without prior lymphodepletion due to enhanced persisting toxicity. This was followed by a second allogeneic HSCT from the haploidentical mother.
While patient 2 relapsed around Day + 180 after the second HSCT, patient 1 is still in complete remission >360 days after the second HSCT. Both cases demonstrate the challenges associated with systemic ALL relapse after first allogeneic HSCT, including chemotherapy-resistant disease and persisting organ damage inflicted by previous therapy. Immunotherapeutic approaches, such as CAR T-cells, can induce remission and enable a second allogeneic HSCT.
However, optimal therapy for systemic ALL relapse after first HSCT remains to be defined.
论文信息
- 作者
- Poyer F、Füreder A、Holter W、Peters C、Boztug H、Dworzak M、Engstler G、Friesenbichler W
- 第一作者单位
- Department of Pediatric Haematology and Oncology, St. Anna Children's Hospital, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.Austria
- 通讯作者单位
- Department of Pediatric Haematology and Oncology, St. Anna Children's Hospital, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, 1090 Vienna, Austria.Austria
- 文献类型
- 病例报告
- 期刊
- Therapeutic advances in hematology2022
- 原文标识
- PubMed 35646299 · DOI 10.1177/20406207221099468
在 PubMed 查看 → 出版商原文（DOI） 全文 PDF（PMC）· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →