Risk factors and outcome of Chimeric Antigen Receptor T-Cell patients admitted to Pediatric Intensive Care Unit: CART-PICU study


Por: Marina Caballero Bellón, Alonso-Saladrigues A, Bobillo-Perez S, Faura A, Arqués L, Rivera C, Català-Temprano A, Dapena JL, Rives-Solà S and Jordán-García I

Publicada: 2 ago 2023 Ahead of Print: 2 ago 2023
Resumen:
IntroductionChimeric antigen receptor (CAR)T-cell CD19 therapy is an effective treatment for relapsed/refractory B-cell acute lymphoblastic leukemia. It can be associated with life-threatening toxicities which often require PICU admission. Purpose: to describe clinical characteristics, treatment and outcome of these patients. MethodsProspective observational cohort study conducted in a tertiary pediatric hospital from 2016-2021. Children who received CAR-T admitted to PICU were included. We collected epidemiological, clinical characteristics, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), treatment, length of stay and mortality. ResultsCAR T-cells (4-1BB constructs) were infused in 59 patients. Twenty-four (40.7%) required PICU admission, length of stay was 4 days (IQR 3-6). Median age was 8.3 years (range 4-24). Patients admitted to PICU presented higher disease burden before infusion: 24% blasts in bone marrow (IQR 5-72) vs. 0 (0-6.9), p<0.001. No patients with <5% blasts were admitted to PICU. Main reasons for admissions were CRS (n=20, 83.3%) and ICANS (n=3, 12.5%). Fourteen patients (58.3%) required inotropic support, 14(58.3%) respiratory. Sixteen patients (66.6%) received tocilizumab, 10(41.6%) steroids, 6(25.0%) anakinra, and 5(20.8%) siltuximab. Ten patients (41.6%) presented neurotoxicity, six of them severe (ICANS 3-4). Two patients died at PICU (8.3%) because of refractory CRS-hemophagocytic lymphohistyocitosis (carHLH) syndrome. There were no significant differences in relapse rate after CAR-T in patients requiring PICU, it was more frequently CD19 negative (p=0.344). DiscussionPICU admission after CAR-T therapy was mainly due to CRS. Supportive treatment allowed effective management and high survival. Some patients presenting with carHLH, can suffer a fulminant course.

Filiaciones:
Marina Caballero Bellón:
 Department of Hematology/Oncology, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu University of Barcelona, Barcelona, Spain

Alonso-Saladrigues A:
 Department of Hematology/Oncology, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu University of Barcelona, Barcelona, Spain

Bobillo-Perez S:
 Paediatric Intensive Care Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain

 Immunological and Respiratory Disorders in the Paediatric Critical Patient Research Group, Institut de Recerca Sant Joan de Déu, University of Barcelona, Barcelona, Spain

Faura A:
 Department of Hematology/Oncology, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu University of Barcelona, Barcelona, Spain

Arqués L:
 Department of Hematology/Oncology, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu University of Barcelona, Barcelona, Spain

Rivera C:
 Department of Hematology/Oncology, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu University of Barcelona, Barcelona, Spain

Català-Temprano A:
 Department of Hematology/Oncology, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu University of Barcelona, Barcelona, Spain

 Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain

Dapena JL:
 Department of Hematology/Oncology, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu University of Barcelona, Barcelona, Spain

Rives-Solà S:
 Department of Hematology/Oncology, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu University of Barcelona, Barcelona, Spain

 Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain

Jordán-García I:
 Paediatric Intensive Care Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain

 Paediatric Infectious Diseases Research Group, Institut de Recerca Sant Joan de Déu, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
ISSN: 16643224





Frontiers in Immunology
Editorial
FRONTIERS MEDIA SA, AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE CH-1015, SWITZERLAND, Suiza
Tipo de documento: Article
Volumen: 14 Número:
Páginas: 1219289-1219289
WOS Id: 001049665400001
ID de PubMed: 37600775
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