CYTOKINE RELEASE SYNDROME AFTER TISAGENLECLEUCEL INFUSION IN PEDIATRIC
PATIENTS WITH REFRACTORY/RELAPSED B-LINEAGE ACUTE LYMPHOBLASTIC
LEUKEMIA: IS THERE A ROLE FOR DICLOFENAC?
Abstract
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.