Maude Shannon L, Shpall Elizabeth J, Grupp Stephan A
Division of Oncology and.
University of Texas M.D. Anderson Cancer Center, Houston, TX.
Hematology Am Soc Hematol Educ Program. 2014 Dec 5;2014(1):559-64. doi: 10.1182/asheducation-2014.1.559. Epub 2014 Nov 18.
Relapsed and refractory leukemias pose substantial challenges in both children and adults, with very little progress being made in more than a decade. Targeted immunotherapy using chimeric antigen receptor (CAR)-modified T cells has emerged as a potent therapy with an innovative mechanism. Dramatic clinical responses with complete remission rates as high as 90% have been reported using CAR-modified T cells directed against the B-cell-specific antigen CD19 in patients with relapsed/refractory acute lymphoblastic leukemia. Supraphysiologic T-cell proliferation, a hallmark of this therapy, contributes to both efficacy and the most notable toxicity, cytokine release syndrome, posing a unique challenge for toxicity management. Further studies are necessary to identify additional targets, standardize approaches to cytokine release syndrome management, and determine the durability of remissions.
复发和难治性白血病对儿童和成人都构成了重大挑战，十多年来进展甚微。使用嵌合抗原受体（CAR）修饰的T细胞进行靶向免疫治疗已成为一种具有创新机制的有效疗法。在复发/难治性急性淋巴细胞白血病患者中，使用针对B细胞特异性抗原CD19的CAR修饰T细胞已报告了高达90%的完全缓解率的显著临床反应。超生理T细胞增殖是这种疗法的一个标志，它既有助于疗效，也导致了最显著的毒性——细胞因子释放综合征，这对毒性管理提出了独特的挑战。需要进一步研究以确定其他靶点，规范细胞因子释放综合征的管理方法，并确定缓解的持久性。
