Original Article

Leukemia advance online publication 23 June 2017; doi: 10.1038/leu.2017.145

High efficacy and safety of low-dose CD19-directed CAR-T cell therapy in 51 refractory or relapsed B acute lymphoblastic leukemia patients

J Pan1, J F Yang1, B P Deng2, X J Zhao3, X Zhang1, Y H Lin1, Y N Wu2, Z L Deng2, Y L Zhang3, S H Liu3, T Wu4, P H Lu1, D P Lu4, A H Chang3 and C R Tong1

  1. 1Department of Hematology, Hebei Yanda Lu Daopei Hospital, Yanjiao Economic and Technological Development Zone, Langfang, China
  2. 2Department of Immunotherapy, Hebei Yanda Lu Daopei Hospital, Langfang, China
  3. 3Clinical Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
  4. 4Department of Bone Marrow Transplantation, Hebei Yanda Lu Daopei Hospital, Langfang, China

Correspondence: Professor C Tong, Department of Hematology, Hebei Yanda Lu Daopei Hospital, Yanjiao Economic and Technological Development Zone, Si Pu Lan South Road, Langfang, Hebei 065201, China. E-mail: tongcr.21@163.com; Dr AH Chang, Clinical Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 1600 Guo Quan Bei Road Building A8, Rm 204, Shanghai 100438, China. E-mail: alexhchang@yahoo.com

Received 23 January 2017; Revised 25 April 2017; Accepted 4 May 2017
Accepted article preview online 15 May 2017; Advance online publication 23 June 2017

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Abstract

Refractory or relapsed B lymphoblastic leukemia (B-ALL) patients have a dismal outcome with current therapy. We treated 42 primary refractory/hematological relapsed (R/R) and 9 refractory minimal residual disease by flow cytometry (FCM-MRD+) B-ALL patients with optimized second generation CD19-directed CAR-T cells. The CAR-T-cell infusion dosages were initially ranged from 0.05 to 14 × 105/kg and were eventually settled at 1 × 105/kg for the most recent 20 cases. 36/40 (90%) evaluated R/R patients achieved complete remission (CR) or CR with incomplete count recovery (CRi), and 9/9 (100%) FCM-MRD+ patients achieved MRD. All of the most recent 20 patients achieved CR/CRi. Most cases only experienced mild to moderate CRS. 8/51 cases had seizures that were relieved by early intervention. Twenty three of twenty seven CR/CRi patients bridged to allogeneic hematopoietic stem cell transplantation (allo-HCT) remained in MRD with a median follow-up time of 206 (45–427) days, whereas 9 of 18 CR/CRi patients without allo-HCT relapsed. Our results indicate that a low CAR-T-cell dosage of 1 × 105/kg, is effective and safe for treating refractory or relapsed B-ALL, and subsequent allo-HCT could further reduce the relapse rate.

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