e14549 Background: Chimeric antigen receptor T cells directed at CD19 (CART19) have shown promising results in the treatment of refractory/relapsed acute lymphoblastic leukemia and chronic lymphocytic leukemia. Evidence of efficacy on mass lesions such as extramedullary ALL and non-Hodgkin’s lymphoma is still emerging. Methods: Patient-derived T cells were transfected ex vivo with lentiviral vector encoding anti-CD19 scFv, human 4-1BB, and CD3ζ signaling domains. 2 patients with relapsed extramedullary ALL and 2 patients with relapsed DLBCL were enrolled (median age 25.5, range 17~35). Lymphodepletion regimens were fludarabine 50mg/m2 infused over 3 days, and cyclophosphamide 750mg/m2 infused over 3 days in DLBCL patients or over 2 days in ALL patients. CART19 were infused one time or fractionated over 3 days with dose from 1×106/kg to 1×107/kg. Results: The 2 ALL patients received prior allogenic HSCT; one relapsed with isolated testicular ALL, the other with mammary/axillary lymph node ALL with 15% blast cells in the bone marrow. The other two patients relapsed with DLBCL. After CART19 therapy, all patients achieved complete remission (CR) within a median of 30d (range 29~52d). With a median follow up of 53.5d (range 52~153d), the 2 DLBCL patients remained in CR; the testicular B-LBL patient relapsed with isolated testicular involvement on +153d and received a second CART19; the other B-LBL patient relapsed with isolated bilateral mammary glands involvement on +52d and remained in stable disease. Grade 2 cytokine release syndrome (CRS) were observed in the 2 DLBCL patients (50%). CRS self-resolved within 10d without treatment. Conclusions: CART19 was effective and safe against mass lesions such as relapsed extramedullary ALL and DLBCL with high CR rate. CART19 can induce rapid remission in lymphoma patients around one month.
Immunophenotypic changes in leukemic blasts in children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia after treatment with CD19-directed chimeric antigen receptor (CAR)-expressing T-cells