Chimeric antigen receptor-modified T cells for acute lymphoid leukemia.
Level 4 - case-series / case-control
Case series of two patients without a control group.
PubMed 23527958 · doi:10.1056/NEJMoa1215134
What was done
Two pediatric patients with relapsed and refractory pre-B-cell acute lymphoblastic leukemia received infusions of CTL019 chimeric antigen receptor T cells directed against CD19, at doses of 1.4x10^6 to 1.2x10^7 cells per kilogram of body weight.
What was found
CTL019 T cells expanded more than 1000-fold compared to initial engraftment levels in both patients, trafficking to the bone marrow and persisting in cerebrospinal fluid for at least 6 months. Both patients achieved complete remission. One patient remained in remission at 11 months, while the other relapsed approximately 2 months after treatment with CD19-negative blasts. Eight grade 3 or 4 adverse events occurred. Both patients developed cytokine-release syndrome and B-cell aplasia. Severe cytokine-release syndrome in one patient was successfully managed with etanercept and tocilizumab without halting CAR T-cell expansion or efficacy.
Why it matters
This report provides early proof-of-concept that CD19-directed CAR T cells can clear aggressive, treatment-refractory acute lymphoblastic leukemia in vivo, while identifying target-antigen loss and cytokine-release syndrome as key management considerations.
Limits
The report includes only two patients and lacks a control arm. Follow-up is limited, and precise response rates, toxicities, and long-term durability cannot be generalized from this sample.
Cited by
- supports In 2012, Emily Whitehead became the first pediatric patient treated with CAR-T cell therapy for refractory leukemia at the University of Pennsylvania.
- supports Following CAR-T cell therapy in 2012, pediatric leukemia patient Emily Whitehead remained cancer-free and matriculated as a pre-med student at the University of Pennsylvania.