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Infectious Complications of CD19-targeted Chimeric Antigen Receptor T-cell Therapy: a Multicenter Cohort Study
Jonathan Huggins1, Julia A Messina1, Jennifer Saullo1
1Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
Insights
Infections affect nearly a third of patients after chimeric antigen receptor T-cell (CART) therapy, mostly mild. This study describes post-CART infection epidemiology and characteristics to aid management.
Area of Science:
- Oncology
- Immunology
- Infectious Diseases
Background:
- Current understanding of post-chimeric antigen receptor T-cell (CART) therapy infections relies on limited single-center data.
- Limited sample sizes hinder comprehensive analysis of infection epidemiology and risk factors.
Purpose of the Study:
- To describe the epidemiology of infectious complications within one year following CD19 CART.
- To identify risk factors associated with post-CART infections.
- To explore predictors of early versus late and bacterial versus viral infections.
Main Methods:
- Multicenter cohort study of adult patients receiving CD19 CART between January 2018 and August 2021.
- Descriptive epidemiology of infectious complications.
- Fine-Gray subdistribution hazard models and logistic regression to identify risk factors.
Main Results:
- 31.2% of patients (97/311) experienced 131 infections within one year post-CART.
- Cumulative incidence: 19.0% viral, 20.9% bacterial, 2.3% fungal.
- Most infections were mild/moderate (86%); common infections included Clostridioides difficile, Gram-negative bacilli bloodstream infections, and respiratory viral infections. No independent predictors were found.
Conclusions:
- Infectious complications are common but generally mild after CART.
- While independent predictors were not identified, understanding infection characteristics is crucial for optimizing patient management.
- Further research may refine risk stratification and preventive strategies.
Background:
Our understanding of the epidemiology of and risk factors for postchimeric antigen receptor T-cell therapy (CART) infections is largely based on data from single-center studies with small sample sizes.
Methods:
This is a multicenter, cohort study of adult patients treated with CD19 CART between 1 January 2018 and 31 August 2021. The epidemiology of infectious complications occurring within the first year after CART is described. A Fine-Gray subdistribution hazard model was built to identify risk factors for infection. Logistic regression was used to explore risk factors for early (≤90 days post-CART) versus late (>90 days post-CART) and bacterial versus viral infection.
Results:
One hundred and thirty-one infections occurred in 97 of 311 patients (31.2%) within 1 year of CART. By infection type, the cumulative incidence of infection was 19.0% (viral), 20.9% (bacterial), and 2.3% (fungal). The majority of infections were mild or moderate in severity (86%). Clostridiodes difficile and bloodstream infections due to Gram-negative bacilli were common bacterial infections. Respiratory viral infections were the most common viral complication and fungal infections were rare. No independent predictors of infection were identified.
Conclusions:
Infectious complications occur in close to a third of patients post-CART but are generally mild in severity. Though we were not able to identify independent predictors of post-CART infection, a description of their clinical characteristics and epidemiology will help to optimize management of these common complications.
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