Role of procalcitonin, C reactive protein and ferritin in cytokine release syndrome after CAR T-cell therapy in children and young adults
Creators: name: M, Caballero-Bellón
name: S, Bobillo-Perez
name: A, Català
name: A, Alonso-Saladrigues
name: A, Valls
name: S, Rives
name: I, Jordan
Publisher: name: Taylor & Francis
Year: 2025
Subjects: subject: Medicine
subject: Microbiology
subject: FOS: Biological sciences
subject: Biotechnology
subject: Immunology
subject: FOS: Clinical medicine
subject: Biological Sciences not elsewhere classified
subject: Cancer
subject: Hematology
subject: Virology

description: Purpose Chimeric antigen receptor (CAR) T-cell CD19 therapy has changed the treatment paradigm for patients with relapsed/refractory B-cell acute lymphoblastic leukemia. It is frequently associated with potentially severe toxicities: cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and admission to PICU is often required. Some biomarkers seem to correlate with CRS severity. Our goal is to elucidate the role of procalcitonin (PCT), C-reactive protein (CRP) and ferritin in the context of CRS following CAR T-cell infusion to predict its severity and PICU admission. Methods Prospective observational study (2016-2022) in children and young adult who received CAR T-cell therapy (Tisagenlecleucel/ARI-0001). We collected epidemiologic data, specific CAR T-cell toxicities, PICU admission, biomarker results (procalcitonin, CRP and ferritin), length of stay and mortality. Biomarkers were analyzed considering two values: the highest value during ward admission, and the highest overall value including PICU admission. Results Seventy-seven patients were included. Median age at infusion was 9.1 years (IQR 6-13), 49.4% were females. Before CAR T-cell infusion, the median bone marrow blast was 9% (IQR 0-59). The most frequent toxicity was CRS in 62 patients (80.5%), it was severe in 18 cases (23.4%). Fourteen patients (18.1%) had ICANS. Thirty-one patients (40.3%) required admission to the PICU. PCT and ferritin were higher in patients admitted to PICU (PCT 0.8 ng/ml vs 0.15 ng/ml, p &lt; 0.001, ferritin 5490 vs. 2900 ug/l, p &lt; 0.019). The proposed cut-off for PCT to predict admission to PICU is 0.55 ng/mL, presenting a sensitivity of 67.7% and a specificity of 86.7%. The maximum value of the three biomarkers was higher in those who presented any primary outcome: development of a severe CRS, the need for admission to PICU, and in-hospital mortality. Biomarkers were higher in those who needed inotropic or respiratory support. Conclusions PCT levels increase after CAR-T cell therapy in the setting of systemic inflammation and could be a predictor of PICU admission and evolution to death. Further research studying its role in the context of CRS and the differential diagnosis between infection and CRS is needed to better understand the biology of this biomarker and to define its value in clinical practice. Several biomarkers seem to correlate with CRS severity, however some of them are not widely available in the daily practice. In this study, we found that procalcitonin, a widely used biomarker for bacterial infection, increases after CAR T-cell therapy in the setting of systemic inflammation and could be a predictor for PICU admission and death. Therefore, we shown that PCT levels correlate with PICU admission and mortality more accurately than other biomarkers such as ferritin and C-reactive protein and that their use can have an impact in the daily practice.