Cytokine Release Syndrome After Chimeric Antigen Receptor T Cell Therapy for Acute Lymphoblastic Leukemia

作者：Julie C. Fitzgerald, Scott L. Weiss, Shannon L. Maude, David M. Barrett, Simon F. Lacey, J. Joseph Melenhorst, Pamela A. Shaw, Robert A. Berg, Carl H. June, David L. Porter, Noelle V. Frey, Stephan A. Grupp, David T. Teachey · 发表于：Critical Care Medicine · 年份：2016 · DOI：10.1097/ccm.0000000000002053 · 被引用次数：461 · 研究领域：CAR-T cell therapy research、Acute Lymphoblastic Leukemia research、Chemotherapy-induced cardiotoxicity and mitigation

OBJECTIVE: Initial success with chimeric antigen receptor-modified T cell therapy for relapsed/refractory acute lymphoblastic leukemia is leading to expanded use through multicenter trials. Cytokine release syndrome, the most severe toxicity, presents a novel critical illness syndrome with limited data regarding diagnosis, prognosis, and therapy. We sought to characterize the timing, severity, and intensive care management of cytokine release syndrome after chimeric antigen receptor-modified T cell therapy. DESIGN: Retrospective cohort study. SETTING: Academic children's hospital. PATIENTS: Thirty-nine subjects with relapsed/refractory acute lymphoblastic leukemia treated with chimeric antigen receptor-modified T cell therapy on a phase I/IIa clinical trial (ClinicalTrials.gov number NCT01626495). INTERVENTIONS: All subjects received chimeric antigen receptor-modified T cell therapy. Thirteen subjects with cardiovascular dysfunction were treated with the interleukin-6 receptor antibody tocilizumab. MEASUREMENTS AND MAIN RESULTS: Eighteen subjects (46%) developed grade 3-4 cytokine release syndrome, with prolonged fever (median, 6.5 d), hyperferritinemia (median peak ferritin, 60,214 ng/mL), and organ dysfunction. Fourteen (36%) developed cardiovascular dysfunction treated with vasoactive infusions a median of 5 days after T cell therapy. Six (15%) developed acute respiratory failure treated with invasive mechanical ventilation a median of 6 days after T cell therapy; five met...