Sequential allogeneic and autologous CAR-T–cell therapy to treat an immune-compromised leukemic patient by Jian-Ping Zhang, Rui Zhang, Shih-Ting Tsao, Yu-Chen Liu, Xiaochuan Chen, Dao-Pei Lu, Paul Castillo, and Lung-Ji Chang BloodAdv Volume 2(14):1691-1695 July 24, 2018 © 2018 by The American Society of Hematology

The time line and key events of the allogeneic/autologous CAR-T treatment regimen. The time line and key events of the allogeneic/autologous CAR-T treatment regimen. The patient was diagnosed with ALL on day −1277 (−42.5 months) and received extensive chemotherapy but developed refractory relapses with lung infections. Maternal source CD19 CAR-T cells were prepared based on a 5- to 7-day CAR-T–cell preparation protocol as illustrated on the top. Allo–CAR-T cells were infused on days 0, 3, and 7, after conditioning chemotherapy. The patient achieved a partial response (PR) in 50 days and received an auto–CAR-T infusion on day 56 after conditioning chemotherapy. CR was achieved on day 77. Jian-Ping Zhang et al. Blood Adv 2018;2:1691-1695 © 2018 by The American Society of Hematology

Biochemical and immunological kinetics after allo–/auto–CAR-T-cell infusions. Biochemical and immunological kinetics after allo–/auto–CAR-T-cell infusions. (A) Kinetics of hematologic correlates and body temperature. After allo–CAR-T-cell infusions, the body temperature (Temp.) and white blood cell (WBC) count fluctuated continuously, and the platelet count increased gradually. The hemoglobin (HGB) remained steady, and lactate dehydrogenase (LDH) went up correlated with inflammatory response and tumor reduction. (B) The kinetics of IgA and IgM. (C) The kinetics of inflammatory cytokines. The plasma levels of various cytokines were determined by CBA bead array. (D) The kinetics of BM lymphocytes (BM%) and CAR-T cells (CART%). After allo–CAR-T and auto–CAR-T infusions, BM lymphocytes rapidly dropped as did leukemic cell burden, which elicited PR and CR, respectively. The reduction of leukemic cells correlated with CAR-T–cell expansion. Jian-Ping Zhang et al. Blood Adv 2018;2:1691-1695 © 2018 by The American Society of Hematology

CT scans of the chest before and after allo–/auto–CAR-T infusions. CT scans of the chest before and after allo–/auto–CAR-T infusions. Before CAR-T treatment, CT scans revealed severe infections (day −9), which gradually resolved after allo– and auto–CAR-T infusions (days 22, 52, and 83). Jian-Ping Zhang et al. Blood Adv 2018;2:1691-1695 © 2018 by The American Society of Hematology