Treatment of Testicular Relapse of B-cell Acute Lymphoblastic Leukemia With CD19-specific Chimeric Antigen Receptor T Cells

We report the outcomes of 7 boys with isolated testicular relapse of B-cell acute lymphoblastic leukemia who were treated with CD19-specific chimeric antigen receptor T cells. The treatment eradicated testicular leukemia in 6 patients, who remained in second remission for 5 to 23 months (median, 14 months). Chimeric antigen receptor T-cell therapy may replace local irradiation for the treatment of testicular relapse. Background: Irradiation has been a standard treatment for testicular relapse but is associated with severe hypogonadism. Because CD19-specific chimeric antigen receptor T (CAR-T) cells can eradicate leukemic blasts in cerebrospinal fluid, a pharmacologic sanctuary site, we tested the efficacy of this therapy in 7 boys with isolated testicular relapse of B-cell acute lymphoblastic leukemia. Patients and Methods: CD19-specific CAR-T cells were generated with the use of autologous T cells transduced with a lentiviral vector to express a CAR molecule containing anti-CD19 scFv derived from the HI19 alpha murine monoclonal antibody, human CD8 alpha hinge, and human 4-1BB (CD137) and CD3 zeta costimulatory signaling transmembrane domains. After the conditioning regimen, which consisted of intravenous fludarabine and intravenous cyclophosphamide, 7 patients with a median age of 9 years (range, 2-10 years) with isolated testicular relapse received a single infusion of CD19 CAR-T cells at a total dose of 5 x 10(6) all T cells per kilogram. Results: All 7 patients achieved complete remission with normal testes. Six patients remained in second remission for 5 to 23 months (median, 14 months), and 1 patient subsequently relapsed in the bone marrow. The probability of event-free survival for all patients at 12 months of follow-up was 83.3% +/- 15.2% (standard error). The treatment was well-tolerated, with grade 1 cytokine-release syndrome developing in 5 patients. Conclusion: These results suggest that CAR-T cell therapy is a treatment option for patients with testicular relapse. (C) 2019 Elsevier Inc. All rights reserved.