Journal of Blood Disorders & Transfusion

Chimeric antigen receptorâ??modified T cells for acute lymphoid leukemia

4^th International Conference on Blood Malignancies & Treatment

April 18-19, 2016 Dubai, UAE

Stephan A Grupp

Childrens Hospital of Philadelphia, USA

Posters & Accepted Abstracts: J Blood Disord Transfus

Abstract:

Chimeric antigen receptor�??modified T cells with specificity for CD19 have shown promise in the treatment of chronic lymphocytic leukemia (CLL). It remains to be established whether chimeric antigen receptor T cells have clinical activity in acute lymphoblastic leukemia (ALL). Two children with relapsed and refractory pre�??B-cell ALL received infusions of T cells transduced with anti-CD19 antibody and a T-cell signaling molecule (CTL019 chimeric antigen receptor T cells), at a dose of 1.4�?106to 1.2�?107 CTL019 cells per kilogram of body weight. In both patients, CTL019T cells expanded to a level that was more than 1000 times as high as the initial engraftment level, and the cells were identified in bone marrow. In addition, the chimeric antigen receptor T cells were observed in the cerebrospinal fluid (CSF), where they persisted at high levels for at least 6 months. Eight grade 3 or 4 adverse events were noted. The cytokine-release syndrome and B-cell aplasia developed in both patients. In one child, the cytokine-release syndrome was severe; cytokine blockade with etanercept and to cilizumab was effective in reversing the syndrome and did not prevent expansion of chimeric antigen receptor T cells or reduce anti leukemic efficacy. Complete remission was observed in both patients and is on-going in one patient at 11 months after treatment. The other patient had a relapse, with blast cells that no longer expressed CD19, approximately 2 months after treatment. Chimeric antigen receptor�??modified T cells are capable of killing even aggressive, treatment-refractory acute leukemia cells in vivo. The emergence of tumor cells that no longer express the target indicates a need to target other molecules in addition to CD19 in some patients with ALL.

Biography :

Email: grupp@email.chop.edu