Donor-derived CD19-targeted CAR-NK cells induce complete remission in a child with relapsed B-ALL after failure of blinatumomab and autologous CD19-targeted CAR-T.
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Relapse remains the primary cause of treatment failure and death in pediatric B-cell acute lymphoblastic leukemia (B-ALL). Novel therapeutic approaches are imperative for those who are refractory to blinatumomab and chimeric antigen receptor T (CAR-T) cell therapy. CAR-natural killer (NK) cells have emerged as promising candidates for novel cancer immunotherapies, with enhanced antitumor activity and low rates of adverse events. However, data on the efficacy of CAR-NK cells for treating pediatric relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) are lacking.We report a challenging case of a boy with relapsed B-ALL after blinatumomab who failed to respond to autologous CD19-targeted CAR-T cell therapy and mitoxantrone-based reinduction chemotherapy. The patient achieved a complete remission after donor-derived CD19-targeted CAR-NK cell infusion, experiencing a grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS), which was completely controlled by timely treatment. Then, the patient received the same donor-derived hematopoietic stem cell transplantation (HSCT) and remains in complete remission for a year post-HSCT.Our case provides an example of the utility of CAR-NK cell therapy as a bridge to HSCT in treating pediatric R/R B-ALL, despite the occurrence of ICANS as a manageable toxicity.