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]