Lin Zhang1, Yingxi Zuo1, Aidong Lu1, Jun Wu1, Yueping Jia1, Yu Wang2, Leping Zhang3. 1. Department of Pediatrics, Peking University People's Hospital, Beijing, China. 2. Research Department, Immunotech Applied Science Ltd, Beijing, China. 3. Department of Pediatrics, Peking University People's Hospital, Beijing, China. Electronic address: zhangleping@pkuph.edu.cn.
Abstract
BACKGROUND: chimeric antigen receptor-modified T cell (CAR-T) therapy is an effective and promising treatment for refractory and multiply relapsed B-cell acute lymphoblastic leukemia (B-ALL). Because of its side effects and poor responses such as neurotoxicity and cytokine release syndrome, patients with central nervous system leukemia were excluded in most previous clinical trials of CAR-T treatment. PATIENTS AND METHODS: We enrolled 3 B-ALL patients with central nervous system leukemia relapse. They were infused with CD19-specific CAR-Ts, and their clinical responses were evaluated by bone marrow smear, flow cytometry, and cytogenetic alterations detected by quantitative PCR, interleukin-6, and the expansion and persistence of circulating CAR-Ts in peripheral blood and cerebrospinal fluid. RESULTS: After CAR-T infusion, 2 of the 3 patients experienced bone marrow minimal residual disease-negative complete remission, and all patients tested negative for residual leukemia cells in cerebrospinal fluid tested by flow cytometry. These 3 patients experienced grade 2 or 3 cytokine release syndrome, which resolved completely after symptomatic treatment. None experienced neurotoxicity or needed further intensive care. CONCLUSION: CAR-T infusion is a potentially effective treatment for relapsed/refractory B-ALL patients with central nervous system involvement.
BACKGROUND: chimeric antigen receptor-modified T cell (CAR-T) therapy is an effective and promising treatment for refractory and multiply relapsed B-cell acute lymphoblastic leukemia (B-ALL). Because of its side effects and poor responses such as neurotoxicity and cytokine release syndrome, patients with central nervous system leukemia were excluded in most previous clinical trials of CAR-T treatment. PATIENTS AND METHODS: We enrolled 3 B-ALL patients with central nervous system leukemia relapse. They were infused with CD19-specific CAR-Ts, and their clinical responses were evaluated by bone marrow smear, flow cytometry, and cytogenetic alterations detected by quantitative PCR, interleukin-6, and the expansion and persistence of circulating CAR-Ts in peripheral blood and cerebrospinal fluid. RESULTS: After CAR-T infusion, 2 of the 3 patients experienced bone marrow minimal residual disease-negative complete remission, and all patients tested negative for residual leukemia cells in cerebrospinal fluid tested by flow cytometry. These 3 patients experienced grade 2 or 3 cytokine release syndrome, which resolved completely after symptomatic treatment. None experienced neurotoxicity or needed further intensive care. CONCLUSION: CAR-T infusion is a potentially effective treatment for relapsed/refractory B-ALL patients with central nervous system involvement.