Outcomes of Critically Ill Children With Acute Lymphoblastic Leukemia and Cytokine Release Syndrome Due to Chimeric Antigen Receptor T Cell Therapy: US, Multicenter PICU, Cohort Database Study

Abstract

Objectives: Cytokine release syndrome (CRS) is a potentially lethal toxicity associated with chimeric antigen receptor T cell therapy for pediatric acute lymphoblastic leukemia (ALL). Outcomes after critical illness due to severe CRS are poorly described. Our aim was to characterize critical illness outcomes across a multicenter cohort of PICU patients with ALL and CRS.

Design: Multicenter retrospective cohort study.

Setting: Twenty-one PICUs contributing data to Virtual Pediatric Systems, LLC (January 2020-December 2021).

Patients: PICU patients with ALL or unclassified leukemia and CRS.

Interventions: None.

Measurements and main results: We identified 55 patients; 34 (62%) were 12 years or older, 48 (87%) were admitted from a hospital inpatient ward, and 23 (42%) received advanced organ failure support or monitoring. Fifty-one survived to PICU discharge (93%) including 19 of 23 (83%) who received advanced organ failure support or monitoring defined as receipt of noninvasive or invasive ventilation, cardiopulmonary resuscitation, extracorporeal membrane oxygenation, continuous renal replacement therapy, or placement of a tracheostomy, arterial catheter, hemodialysis catheter, or intracranial catheter. Twelve patients (22%) received invasive ventilation, nine of whom survived to PICU discharge. Two of four patients who received continuous renal replacement therapy and one of three patients who required cardiopulmonary resuscitation survived to PICU discharge. Lengths of PICU stay were median 3.0 days (interquartile range, 1.4-7.8 d) among PICU survivors, 7.8 (5.4-11.1) among those receiving advanced organ failure support or monitoring, and 7.2 days (interquartile range, 2.9-14.7 d) among nonsurvivors. Of the 51 patients who survived to PICU discharge, 48 (94%) survived the hospitalization.

Conclusions: PICU patients with CRS frequently received a high level of support, and the majority survived their PICU stay and hospitalization. Additional multicenter investigations of severe CRS are necessary to inform evidence-based practice.