Kinetics of immune reconstitution after anti‐CD19 chimeric antigen receptor T cell therapy in relapsed or refractory acute lymphoblastic leukemia patients
Ying Wang, Hujun Li, Xuguang Song, Kunming Qi, Hai Cheng, Jiang Cao, Ming Shi, Zhiling Yan, Guangjun Jing, Bin Pan, Wei Sang, Xiangmin Wang, Kai Zhao, Chong Chen, Wei Chen, Junnian Zheng, Zhenyu Li, Kailin Xu
Abstract
INTRODUCTION: Anti-CD19 chimeric antigen receptor (CAR) -T cells, which recognize and kill both B lymphoblasts and normal B cells, result in B cell aplasia and humoral immunodeficiency. However, there were only a few detailed reports on the profile of immune reconstitution after anti-CD19 CAR-T cell therapy. METHODS: Thirty nine patients with relapsed or refractory (R/R) B cell acute lymphoblastic leukemia (ALL) receiving anti-CD19 CAR-T cell therapy were enrolled. Subjects died, relapsed, received other treatment, or lost to follow-up within 60 days post-infusion were excluded. 21 patients were finally selected. Laboratory and clinical data were collected for analysis of immune reconstitution. RESULTS: CD8+ cells were the first to recover with a median time on day 21(7-87), followed by CD16/CD56+ cells on day 28(14-87), and finally CD4+ cells with only 5(23.81%) patients recovered within 60 days post-infusion. CD4/CD8 ratio was inverted, sustaining for at least 1 year. B cell aplasia occurred in all patients and CD19+ cells returned to normal on a median time of day 79(41-118). All patients developed hypogammaglobulinemia with a median onset time of 2 weeks post-infusion. IgG recovered in 6 patients with a median time on day 184(89-346). IgM recovered on days 212, 242, and 346 in 3 patients. IgA recovered most slowly and remained low >1 year postinfusion. A total of 9 infections occurred in 6(28.57%) patients. CONCLUSIONS: Our data showed prolonged reconstitution of immune function, especially humoral immunity, in R/R B cell ALL patients receiving anti-CD19 CAR-T cell therapy.