Infectious complications in pediatric patients undergoing CD19+CD22+ chimeric antigen receptor T-cell therapy for relapsed/refractory B-lymphoblastic leukemia

Abstract

Abstract Chimeric antigen receptor T cell (CAR-T) therapy is effective in the treatment of relapsed/refractory acute B-lymphoblastic leukemia (R/R B-ALL); however, patients who receive CAR-T therapy are predisposed to infections, with considerable detrimental effects on long-term survival rates and the quality of life of patients. This study retrospectively analyzed infectious complications in 79 pediatric patients with R/R B-ALL treated with CAR-T cells at our institution. Overall, 53 patients developed 97 infections. Ten patients experienced 11 infections during lymphodepletion chemotherapy, 34 experienced 46 infections during the early phase (days 0 to + 30 after infusion), and 29 experienced 40 infections during the late phase (day + 31 to + 90 after infusion). Pathogens were identified in 31 infections, including 23 bacteria, seven viruses, and one fungus. Four patients were admitted to the intensive care unit for infection and one died. The following factors were associated with infection: pre-infusion tumor load, intensity of lymphodepleting chemotherapy, lymphocyte count before infusion, duration of neutrophil deficiency and lymphocyte reduction after infusion, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome grades, use of interleukin-6 receptor antagonists and glucocorticoids, intensive care unit admission, and peak value of regulatory T cell proportion within one week after infusion (all P < 0.05). CRS ≥ grade 3 was identified as a risk factor for infection (hazard ratio = 2.41, 95% confidence interval: 1.08–5.36, P = 0.031). Therefore, actively reducing the CRS grade may decrease the risk of infection and improve the long-term quality of life of these patients.