文章：

CAR-T细胞疗法之旅：复发或难治性B-ALL的儿童与年轻患者经历

The journey to CAR T cell therapy: the pediatric and young adult experience with relapsed or refractory B-ALL

原文发布日期：2019-01-22

DOI: 10.1038/s41408-018-0164-6

类型: Review Article

开放获取: 是

英文摘要：

Outcomes of pediatric and young adult patients diagnosed with acute lymphoblastic leukemia (ALL) have improved significantly in the past few decades. Treatment advances have provided 5-year survival rates ranging from 78 to 91% depending on the age at diagnosis. However, approximately 2–3% of patients will present with refractory disease that is unresponsive to chemotherapy, and 10–15% of patients will relapse. Outcomes post-relapse show significantly reduced 5-year survival rates that continue to decrease with each subsequent relapse. Despite our increased understanding of risk factors and disease predictors, treatment strategies for patients with relapsed or refractory (r/r) disease, including variations of chemotherapy and stem cell transplant, remain ineffective for many patients. To improve outcomes of patients with r/r disease, immunotherapies targeting specific B cell antigens are being developed. Tisagenlecleucel is an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy recently approved by the US Food and Drug Administration for patients with refractory leukemia or those with second or later relapse. In this treatment strategy, a patient’s own T cells are transduced to express an anti-CD19 CAR that, when reintroduced into the patient, directs specific binding and killing of CD19+ B cells. In a phase 2, single-arm, multicenter, global study, tisagenlecleucel resulted in a remission rate of 81% in pediatric and adolescent patients with r/r B cell ALL. This review article summarizes four typical cases of pediatric and adolescent r/r B-cell ALL, focusing on the patient’s journey from initial diagnosis to treatment with CAR T cell therapy.

摘要翻译： 

在过去几十年中，被诊断为急性淋巴细胞白血病（ALL）的儿童和青年患者的预后已显著改善。治疗进展使得患者5年生存率根据诊断时年龄达到78%至91%不等。然而，约2-3%的患者会出现对化疗无反应的难治性疾病，另有10-15%的患者会经历复发。复发后的预后数据显示5年生存率显著降低，且随着每次后续复发持续下降。尽管我们对风险因素和疾病预测因子的理解不断深入，针对复发或难治性（r/r）疾病患者的治疗策略（包括化疗和干细胞移植的多种方案）对许多患者仍效果有限。为改善r/r疾病患者的预后，针对特定B细胞抗原的免疫疗法正在开发中。Tisagenlecleucel是一种自体抗CD19嵌合抗原受体（CAR）T细胞疗法，近期获美国食品药品监督管理局批准用于难治性白血病或二次及以上复发患者。该治疗策略通过转导患者自身的T细胞表达抗CD19 CAR，当回输至患者体内时可定向结合并清除CD19+ B细胞。在一项二期单臂多中心全球研究中，tisagenlecleucel使儿童及青少年r/r B细胞ALL患者的缓解率达到81%。本综述通过四个典型病例，重点阐述儿童及青少年r/r B细胞ALL患者从初诊到接受CAR-T细胞治疗的全过程。

原文链接：

The journey to CAR T cell therapy: the pediatric and young adult experience with relapsed or refractory B-ALL