Cytokine Release Syndrome after Tisagenlecleucel Infusion in Pediatric Patients with Refractory/Relapsed B-Lineage Acute Lymphoblastic Leukemia: Is there a Role for Diclofenac?
Authors:   Department of Pediatric, Hematology-Oncology and Bone Marrow Transplantation Unit, Monza and Brianza Foundation for Children and their Mums, San Gerardo Hospital, Italy, S Napolitano , S Bonanomi ,   Department of Pediatric, Hematology-Oncology and Bone Marrow Transplantation Unit, Monza and Brianza Foundation for Children and their Mums, San Gerardo Hospital, Italy, A Rovelli ,   Department of Pediatric, Hematology-Oncology and Bone Marrow Transplantation Unit, Monza and Brianza Foundation for Children and their Mums, San Gerardo Hospital, Italy, A Biondi ,   Department of Pediatric, Hematology-Oncology and Bone Marrow Transplantation Unit, Monza and Brianza Foundation for Children and their Mums, San Gerardo Hospital, Italy, A Balduzzi ,   Department of Pediatric, Hematology-Oncology and Bone Marrow Transplantation Unit, Monza and Brianza Foundation for Children and their Mums, San Gerardo Hospital, Italy, G Ottaviano ,   Molecular and Cellular Immunology Unit, University College of London, Great Ormond Street Institute of Child Health, United Kingdom, L Bettini ,   Monza and Brianza Foundation for Children and their Mums, Tettamanti Laboratory, Italy, V Russotto ,   Department of Emergency and Intensive Care, University Hospital San Gerardo, Italy, R Ronad ,   Department of Emergency and Intensive Care, University Hospital San Gerardo, Italy
Published: June 2021

Background: Cytokine Release Syndrome (CRS) is a major complication after Chimeric-Antigen Receptor (CAR) T cell treatment, characterized by an uncontrolled sistemic inflammatory reaction. The potential role of diclofenac in the management of CRS has been investigated in five pediatric patients treated for relapsed/refractory B-lineage acute lymphoblastic leukemia. Procedure: 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. Vital signs, O2 requirement, SpO2/FiO2 ratio and dosage of diclofenac and vasopressors until CRS resolution were recorded. 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-value 0.02). A clinical benefit was achieved by hampering the progression of tachypnea and, mainly, tachycardia. Despite fever control, CRS progressed in four of the five patients and hypotension requiring vasopressors, fluid retention, besides 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 a better fever control, which translates into symptom relief and improvement of tachycardia, but could not prevent the progression of CRS.