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Cytokine release syndrome after CAR infusion in pediatric patients with refractory/relapsed B-ALL: is there a role for diclofenac?

Napolitano, S; Ottaviano, G; Bettini, L; Russotto, V; Bonanomi, S; Rovelli, A; Biondi, A; ... Balduzzi, A; + view all (2021) Cytokine release syndrome after CAR infusion in pediatric patients with refractory/relapsed B-ALL: is there a role for diclofenac? Tumori Journal , 108 (6) pp. 556-562. 10.1177/03008916211053382. Green open access

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Abstract

BACKGROUND: Cytokine release syndrome (CRS) is a major complication after chimeric-antigen receptor T-cell treatment, characterized by an uncontrolled systemic inflammatory reaction. We investigated the potential role of diclofenac in the management of CRS in five pediatric patients treated for relapsed/refractory B-lineage acute lymphoblastic leukemia. METHODS: In case of persistent fever with fever-free intervals shorter than 3 hours, diclofenac continuous infusion was initiated, at the starting dose of 0.5 mg/Kg/day, the lowest effective pediatric dose in our experience, possibly escalated up to 1 mg/Kg/day, as per institutional guidelines. RESULTS: CRS occurred at a median of 20 hours (range 8–27) after tisagenlecleucel infusion. Diclofenac was started at a median of 20 hours (range 13–33) after fever onset. A mean of 3.07 febrile peaks without diclofenac and 0.95 with diclofenac were reported (p = 0.02). Clinical benefit was achieved by hampering the progression of tachypnea and tachycardia. Despite fever control, CRS progressed in four of the five patients, and hypotension requiring vasopressors and fluid retention, as well as hypoxia, occurred. Vasopressors were followed by 1–2 doses of tocilizumab (one in patient 2 and two in patients 3, 4, and 5), plus steroids in patients 4 and 5. CONCLUSION: Based on a limited number of patients, diclofenac leads to better fever control, which translates into symptom relief and improvement of tachycardia, but could not prevent the progression of CRS.

Type: Article
Title: Cytokine release syndrome after CAR infusion in pediatric patients with refractory/relapsed B-ALL: is there a role for diclofenac?
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1177/03008916211053382
Publisher version: https://doi.org/10.1177/03008916211053382
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Hematology-oncology, molecular oncology, pediatric oncology
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10142836
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