Peripheral leukemia burden at time of apheresis negatively affects the clinical efficacy of CART19 in refractory or relapsed B-ALL
Our previous clinical study achieved complete remission (CR) rates of >90% following chimeric antigen receptor T cells targeting CD19 (CART19) treatment of refractory/relapsed B cell acute lymphoblastic leukemia (r/r B-ALL); however, the influence of the leukemia burden in peripheral blood (PB) b...
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2021
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oai:doaj.org-article:8a5d1e95aae845aaab269d3ee1c2bab72021-12-02T05:01:47ZPeripheral leukemia burden at time of apheresis negatively affects the clinical efficacy of CART19 in refractory or relapsed B-ALL2329-050110.1016/j.omtm.2021.10.006https://doaj.org/article/8a5d1e95aae845aaab269d3ee1c2bab72021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2329050121001637https://doaj.org/toc/2329-0501Our previous clinical study achieved complete remission (CR) rates of >90% following chimeric antigen receptor T cells targeting CD19 (CART19) treatment of refractory/relapsed B cell acute lymphoblastic leukemia (r/r B-ALL); however, the influence of the leukemia burden in peripheral blood (PB) blasts remains unclear. Here, we retrospectively analyzed 143 patients treated with CART19 (including 36 patients with PB blasts) to evaluate the effect of peripheral leukemia burden at the time of apheresis. One hundred seventeen patients with high disease burdens achieved 91.5% CR or incomplete count recovery CR and 86.3% minimal residual disease-negative CR, and 26 patients with low disease burdens obtained 96.2% MRD− CR. Collectively, 9 of 36 (25%) patients with PB blasts and 2 of 107 (1.87%) patients without PB blasts did not respond to CART19 therapy. The leukemia burden in PB negatively influenced ex vivo cell characteristics, including the transduction efficiency of CD3+ T cells and their fold expansion, and in vivo cell dynamics, including peak CART19 proportion and absolute count, fold expansion, and persistence duration. Further studies showed that these patients had higher programmed death-1 expression in CART19 products. Our data imply that PB blasts negatively affected CART19 production and the clinical efficacy of CART19 therapy in patients with r/r B-ALL.Biping DengJing PanZhaoli LiuShuangyou LiuYunlong ChenXiaomin QuYu'e ZhangYuehui LinYanlei ZhangXinjian YuZhongxin ZhangXuansha NiuRong LuanMing MaXiaomei LiTingting LiuXi'ai WuHuan NiuAlex H. ChangChunrong TongElsevierarticleCAR-T cellsCART19B-cell acute lymphoblastic leukemiaPB blastsleukemia burden in peripheral bloodtime of apheresisGeneticsQH426-470CytologyQH573-671ENMolecular Therapy: Methods & Clinical Development, Vol 23, Iss , Pp 633-643 (2021) |
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DOAJ |
| collection |
DOAJ |
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EN |
| topic |
CAR-T cells CART19 B-cell acute lymphoblastic leukemia PB blasts leukemia burden in peripheral blood time of apheresis Genetics QH426-470 Cytology QH573-671 |
| spellingShingle |
CAR-T cells CART19 B-cell acute lymphoblastic leukemia PB blasts leukemia burden in peripheral blood time of apheresis Genetics QH426-470 Cytology QH573-671 Biping Deng Jing Pan Zhaoli Liu Shuangyou Liu Yunlong Chen Xiaomin Qu Yu'e Zhang Yuehui Lin Yanlei Zhang Xinjian Yu Zhongxin Zhang Xuansha Niu Rong Luan Ming Ma Xiaomei Li Tingting Liu Xi'ai Wu Huan Niu Alex H. Chang Chunrong Tong Peripheral leukemia burden at time of apheresis negatively affects the clinical efficacy of CART19 in refractory or relapsed B-ALL |
| description |
Our previous clinical study achieved complete remission (CR) rates of >90% following chimeric antigen receptor T cells targeting CD19 (CART19) treatment of refractory/relapsed B cell acute lymphoblastic leukemia (r/r B-ALL); however, the influence of the leukemia burden in peripheral blood (PB) blasts remains unclear. Here, we retrospectively analyzed 143 patients treated with CART19 (including 36 patients with PB blasts) to evaluate the effect of peripheral leukemia burden at the time of apheresis. One hundred seventeen patients with high disease burdens achieved 91.5% CR or incomplete count recovery CR and 86.3% minimal residual disease-negative CR, and 26 patients with low disease burdens obtained 96.2% MRD− CR. Collectively, 9 of 36 (25%) patients with PB blasts and 2 of 107 (1.87%) patients without PB blasts did not respond to CART19 therapy. The leukemia burden in PB negatively influenced ex vivo cell characteristics, including the transduction efficiency of CD3+ T cells and their fold expansion, and in vivo cell dynamics, including peak CART19 proportion and absolute count, fold expansion, and persistence duration. Further studies showed that these patients had higher programmed death-1 expression in CART19 products. Our data imply that PB blasts negatively affected CART19 production and the clinical efficacy of CART19 therapy in patients with r/r B-ALL. |
| format |
article |
| author |
Biping Deng Jing Pan Zhaoli Liu Shuangyou Liu Yunlong Chen Xiaomin Qu Yu'e Zhang Yuehui Lin Yanlei Zhang Xinjian Yu Zhongxin Zhang Xuansha Niu Rong Luan Ming Ma Xiaomei Li Tingting Liu Xi'ai Wu Huan Niu Alex H. Chang Chunrong Tong |
| author_facet |
Biping Deng Jing Pan Zhaoli Liu Shuangyou Liu Yunlong Chen Xiaomin Qu Yu'e Zhang Yuehui Lin Yanlei Zhang Xinjian Yu Zhongxin Zhang Xuansha Niu Rong Luan Ming Ma Xiaomei Li Tingting Liu Xi'ai Wu Huan Niu Alex H. Chang Chunrong Tong |
| author_sort |
Biping Deng |
| title |
Peripheral leukemia burden at time of apheresis negatively affects the clinical efficacy of CART19 in refractory or relapsed B-ALL |
| title_short |
Peripheral leukemia burden at time of apheresis negatively affects the clinical efficacy of CART19 in refractory or relapsed B-ALL |
| title_full |
Peripheral leukemia burden at time of apheresis negatively affects the clinical efficacy of CART19 in refractory or relapsed B-ALL |
| title_fullStr |
Peripheral leukemia burden at time of apheresis negatively affects the clinical efficacy of CART19 in refractory or relapsed B-ALL |
| title_full_unstemmed |
Peripheral leukemia burden at time of apheresis negatively affects the clinical efficacy of CART19 in refractory or relapsed B-ALL |
| title_sort |
peripheral leukemia burden at time of apheresis negatively affects the clinical efficacy of cart19 in refractory or relapsed b-all |
| publisher |
Elsevier |
| publishDate |
2021 |
| url |
https://doaj.org/article/8a5d1e95aae845aaab269d3ee1c2bab7 |
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