Tumor Lysis Syndrome in Patients Treated with Chimeric Antigen Receptor T-cell Therapy: A Retrospective Study

Abstract

Background: Chimeric antigen receptor T-cell (CAR T-cell) therapy has revolutionised cancer treatment, particularly for relapsed or refractory haematological malignancies. However, treatment-related toxicities, including tumour lysis syndrome (TLS), remain a significant concern. This retrospective study aimed to evaluate the incidence, healthcare outcomes and systemic complications in patients who developed TLS secondary to CAR T-cell therapy. Methods: Using the National Inpatient Sample (NIS) database from 2017 to 2019, adult hospitalisations with an ICD-10 procedure code for CAR T-cell therapy were identified. Cases were stratified into two cohorts based on the presence or absence of a secondary diagnosis of TLS. The primary outcomes evaluated were in-hospital mortality, length of stay (LOS) and total hospital charges. Secondary outcomes included systemic complications such as sepsis, acute kidney injury (AKI) and organ failure. Multivariable logistic and linear regression analyses were performed to adjust for baseline demographics, hospital characteristics and the Charlson Comorbidity Index. Results: Among 685 CAR T-cell therapy inpatient encounters, 58 hospitalisations developed TLS, representing an incidence rate of 8.47% (58/685). Demographics and baseline comorbidities were comparable between the two cohorts. The development of TLS was associated with nearly fivefold higher odds of in-hospital mortality (12% vs. 2.7%; aOR: 4.72, 95% CI: 1.61 to 13.80, $p < 0.01$), a prolonged mean length of stay (26.6 vs. 19.1 days; adjusted coefficient: 6.66 days, 95% CI: 1.41 to 11.90, $p = 0.013$) and a substantial increase in mean total hospital charges ($1,421,658 vs. $826,336; adjusted coefficient: $498,757, 95% CI: $138,090 to $859,424, $p < 0.01$). Furthermore, patients who developed TLS experienced a significantly higher incidence of severe systemic complications, including acute kidney injury, the need for haemodialysis, sepsis, acute respiratory failure, pneumonia and encephalopathy. Conclusion: TLS secondary to CAR T-cell therapy is a highly morbid toxicity associated with a nearly fivefold increase in hospital mortality, prolonged hospitalisation and a substantial economic healthcare burden. It is associated with severe multi-organ dysfunction and infectious complications. Structured prophylactic protocols and vigilant early monitoring strategies are important to mitigate these risks and improve survival outcomes in CAR T-cell recipients.