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CD19/CD22 chimeric antigen receptor T-cell therapy for refractory acute B-cell lymphoblastic leukemia with FLT3-ITD mutations

Bone Marrow Transplantation volume 55, pages 717–721 (2020)Cite this article

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Abstract

Treatment of acute lymphoblastic leukemia (ALL) is still a challenge despite years of researching, especially for those of poor prognosis. Zhang and his team recently proved that FLT3 gene mutation was identified in ~5% of ALL and the mutation spectrum is different from AML. Recently, chimeric antigen receptor T cells (CART) therapy presents great efficacy in treating refractory leukemia. We report a case of a refractory ALL patient with FLT3-ITD mutations and unfavorable karyotypes, who failed to respond to chemotherapy and small molecule tyrosine kinase inhibitors, successfully treated by CART therapy. FLT3-ITD mutations were downregulated dramatically into 14.1% positive 3 days after the infusion and remained negative until now. MRD has stayed to be negative from the 10th day. This case suggests that CART-cell therapy might be effective in treating FLT3-ITD positive refractory ALL, implying the possibility to overcome the traditional prognosis scoring system for leukemia and providing a new chance for other leukemia patients with inferior prognosis factors.

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Fig. 1: The patient developed II grade CRS during CART treatment and achieved complete remission with mutations diminished.
Fig. 2: Time line of the patient’s treatment progress.

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Acknowledgements

This work was supported by the grants from 973 Program (2015CB964900) in study designing, the Natural Science Foundation of China (81470341, 81770201, 81730008) in data collection and analysis, Key Project of Science and Technology Department of Zhejiang Province (2018C03016-2, 2015C03G2150011) in deep analysis and paper writing.

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  1. These authors contributed equally: Aiyun Jin, Jingjing Feng

Authors and Affiliations

  1. Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, China

    Aiyun Jin, Jingjing Feng, Guoqing Wei, Wenjun Wu, Luxin Yang, Huijun Xu, Jiazhen Cui, Yongxian Hu & He Huang

  2. Institute of Hematology, Zhejiang University, Hangzhou, China

    Aiyun Jin, Jingjing Feng, Guoqing Wei, Wenjun Wu, Luxin Yang, Huijun Xu, Jiazhen Cui, Yongxian Hu & He Huang

  3. Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China

    Aiyun Jin, Jingjing Feng, Guoqing Wei, Wenjun Wu, Luxin Yang, Huijun Xu, Jiazhen Cui, Yongxian Hu & He Huang

  4. Shanghai YaKe Biotechnology Ltd, Shanghai, China

    Yanlei Zhang & Alex Hongsheng Chang

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Correspondence to Yongxian Hu or He Huang.

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The authors declare that they have no conflict of interest.

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This study was approved by the Medical ethics committee of the First Affiliated Hospital, Zhejiang University School of Medicine.

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The patient and donor have given their written informed consent. This study is registered at ChiCTR1800015575.

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Jin, A., Feng, J., Wei, G. et al. CD19/CD22 chimeric antigen receptor T-cell therapy for refractory acute B-cell lymphoblastic leukemia with FLT3-ITD mutations. Bone Marrow Transplant 55, 717–721 (2020). https://doi.org/10.1038/s41409-020-0807-7

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