INTRODUCTION
Infants younger than 6-months of age diagnosed with precursor B-cell acute lymphoblastic leukemia (ALL) have a rare and aggressive form of leukemia associated with inferior outcomes, especially if associated with KMT2A gene rearrangements (KMT2A-r).[1-4] Dismal outcomes are observed despite intensive therapies including allogeneic hematopoietic stem cell transplantation (HSCT).[1,5-9] While a therapeutic advantage exists for early HSCT in a subset of high-risk infants with KMT2A-r ALL transplanted in a first complete remission, early disease recurrence, refractory or progressive disease often limits this approach.[6,8-12] Those who do proceed to HSCT frequently relapse without curative treatment options.[6, 13]
Tisagenlecleucel, an autologous anti-CD19 chimeric antigen receptor T-cell (CAR-T) agent, offers promise to patients with relapsed or refractory (r/r) ALL, demonstrating remission rates as high as 81% in both children and adolescents.[14-16] However, there is limited experience utilizing CAR-T in infants resulting from the exclusion of children <1 year of age from initial clinical trials.[1] The approach has been limited due to an infant’s smaller size and blood volume; concerns include cellular collection safety, the timing of autologous T-cell harvest during a patient’s treatment course, the optimal infusion dose, and the management of post-infusion toxicities.[10,17-19] There are inherent difficulties in obtaining sufficient autologous T-cells in infants to generate a suitable CAR-T product.[17-21] Whether CAR-T therapy alone is satisfactory to achieve durable long-term remissions remains under investigation for all recipients with little information in the setting of aggressive infantile ALL. Failure following CAR-T therapy is frequently secondary to antigen escape.[14,22] Multiple reports demonstrate superior outcomes and sustained remissions in pediatric and adult patients with r/r ALL receiving CAR-T as a bridge to allogeneic HSCT;[10,14,15] however, there is a dearth of data supporting the use of CAR-T therapy in infants.[18]
Here we present our experience in a high-risk infant with r/r KMT2A-r ALL who successfully received the CD19 CAR-T cell therapy, tisagenlecleucel, in tandem with haploidentical donor HSCT. This is the youngest infant to survive and achieve prolonged remission following CAR-T therapy and subsequent HSCT.[18]