Abstract
Background: Chimeric antigen receptor-T cell therapy with tisagenlecleucel has durable efficacy and manageable safety in pediatric relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, evidence of its efficacy and safety in patients with Down syndrome-associated B-ALL is currently limited.
Case Report: Here, we describe a male pediatric patient with Down syndrome-associated refractory B-ALL who was infused with tisagenlecleucel twice. He was minimal residual disease-negative and had central nervous system 1 status before and after each tisagenlecleucel infusion. Adverse events of special interest following the first infusion included grade 2 cytokine release syndrome, which resolved without the need for tocilizumab, and grade 1 immune effector cell-associated neurotoxicity syndrome. Though clinically well, B-cell recovery was detected <6 months after the first tisagenlecleucel infusion. The second tisagenlecleucel infusion, followed by pembrolizumab, was administered in an unsuccessful attempt to restore B-cell aplasia. Four years after the first tisagenlecleucel infusion, the patient is disease-free with no ongoing pembrolizumab toxicity.
Conclusions: Treatment with two doses of tisagenlecleucel was relatively safe and effective in this pediatric case with Down syndrome-associated relapsed/refractory B-ALL. The results also suggest that achieving long-term B-cell aplasia may not be required for long-term remission in some cases.