Cai Bo, Guo Mei, Wang Yao, Zhang Yajing, Yang Jun, Guo Yelei, Dai Hanren, Yu Changlin, Sun Qiyun, Qiao Jianhui, Hu Kaixun, Zuo Hongli, Dong Zheng, Zhang Zechuan, Feng Mingxing, Li Bingxia, Sun Yujing, Liu Tieqiang, Liu Zhiqing, Wang Yi, Huang Yajing, Yao Bo, Han Weidong, Ai Huisheng
Department of Hematology and Transplantation, Affiliated Hospital of Academy of Military Medical Sciences, 8 Dongdajie, Beijing, 100071, China.
Department of Immunology/Department of Bio-therapeutic, Institute of Basic Medicine, School of Life Sciences, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China.
J Hematol Oncol. 2016 Nov 25;9(1):131. doi: 10.1186/s13045-016-0357-z.
Elderly patients with relapsed and refractory acute lymphoblastic leukemia (ALL) have poor prognosis. Autologous CD19 chimeric antigen receptor-modified T (CAR-T) cells have potentials to cure patients with B cell ALL; however, safety and efficacy of allogeneic CD19 CAR-T cells are still undetermined.
We treated a 71-year-old female with relapsed and refractory ALL who received co-infusion of haplo-identical donor-derived CD19-directed CAR-T cells and mobilized peripheral blood stem cells (PBSC) following induction chemotherapy. Undetectable minimal residual disease by flow cytometry was achieved, and full donor cell engraftment was established. The transient release of cytokines and mild fever were detected. Significantly elevated serum lactate dehydrogenase, alanine transaminase, bilirubin and glutamic-oxalacetic transaminase were observed from days 14 to 18, all of which were reversible after immunosuppressive therapy.
Our preliminary results suggest that co-infusion of haplo-identical donor-derived CAR-T cells and mobilized PBSCs may induce full donor engraftment in relapsed and refractory ALL including elderly patients, but complications related to donor cell infusions should still be cautioned.
Allogeneic CART-19 for Elderly Relapsed/Refractory CD19+ ALL. NCT02799550.
复发难治性急性淋巴细胞白血病(ALL)老年患者预后较差。自体CD19嵌合抗原受体修饰的T(CAR-T)细胞有治愈B细胞ALL患者的潜力;然而,同种异体CD19 CAR-T细胞的安全性和疗效仍未确定。
我们治疗了一名71岁复发难治性ALL女性患者,在诱导化疗后接受了单倍体相合供者来源的CD19导向CAR-T细胞与动员外周血干细胞(PBSC)的联合输注。通过流式细胞术实现了不可检测的微小残留病,并建立了完全供体细胞植入。检测到细胞因子的短暂释放和轻度发热。在第14至18天观察到血清乳酸脱氢酶、丙氨酸转氨酶、胆红素和谷草转氨酶显著升高,所有这些在免疫抑制治疗后均可逆转。
我们的初步结果表明,单倍体相合供者来源的CAR-T细胞与动员的PBSC联合输注可能在包括老年患者在内的复发难治性ALL中诱导完全供体植入,但仍应警惕与供体细胞输注相关的并发症。
老年复发/难治性CD19+ ALL的同种异体CART-19。NCT02799550。