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CD19 chimeric antigen receptor T-cell therapy as a bridge therapy for allogeneic hematopoietic stem cell transplantation in patients with relapsed Philadelphia chromosome-positive acute lymphoblastic leukemia

Bone Marrow Transplantation volume 58, pages 103–105 (2023)Cite this article

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The incorporation of tyrosine kinase inhibitors (TKIs) into first-line treatment with chemotherapy has significantly improved the overall outcome of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), but these patients are still at high risk of relapse [1]. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is strongly recommended as a potential curative treatment for relapsed patients, and achieving second remission at transplant is a prerequisite for a favorable outcome [1, 2]. Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has shown remarkable early complete responses in patients with relapsed/refractory (r/r) B-cell ALL, including Ph + ALL [3, 4]. Nevertheless, relapse post CAR T-cell therapy is still an unresolved clinical challenge [3,4,5]. Therefore, CAR T-cell therapy as a bridge before allo-HSCT seems to be a promising therapeutic strategy for relapsed Ph+ ALL [5, 6], but its clinical impact on survival after allo-HSCT compared with traditional salvage therapy (TST), most often a change to a more potent TKI combined with chemotherapy, remains undetermined.

Herein, from a phase 2 study of CD19-specific CAR T-cell therapy for r/r ALL, we report the results for 17 relapsed Ph + ALL patients treated with CAR T-cell therapy and subsequent allo-HSCT compared with a historical cohort of 23 patients treated with TST.

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Fig. 1: Study screening flowchart and outcomes for patients.

Data availability

The data are available from the corresponding author upon reasonable request.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (81670164, 81730003), the National Clinical Research Center for Hematologic Disease (2020WSC04, 2020WSB10, H220559), the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), and the National Key Research and Development Program (2017YFA0104502, 2019YFC0840604). All the samples were from Jiangsu Biobank of Clinical Resources.

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  1. These authors contributed equally: Zhenzhen Yao, Bin Gu, Yanming Zhang.

Authors and Affiliations

  1. National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China

    Zhenzhen Yao, Bin Gu, Jiaqian Qi, Jia Chen, Yang Xu, Feng Chen, Xiao Ma, Miao Miao, Shengli Xue, Huiying Qiu, Xiaowen Tang, Yue Han, Suning Chen, Aining Sun, Depei Wu & Ying Wang

  2. Department of Hematology, The Affiliated Huai’an Hospital of Xuzhou Medical University and The Second People’s Hospital of Huai’an, No 62, Huaihai Road (S.), Huai’an, China

    Yanming Zhang

  3. Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China

    Jia Chen, Yang Xu, Shengli Xue, Huiying Qiu, Xiaowen Tang, Yue Han, Suning Chen, Aining Sun, Depei Wu & Ying Wang

  4. Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Suzhou, China

    Yang Xu, Xiaowen Tang, Yue Han, Suning Chen, Depei Wu & Ying Wang

  5. Shanghai Unicar-Therapy Bio-medicine Technology Co., Ltd, Shanghai, China

    Lei Yu

  6. State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China

    Depei Wu

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  1. Zhenzhen Yao
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Contributions

ZZY, BG, and YMZ interpreted the data and wrote the paper; JQQ, JC, YX, FC, XM, MM, SLX, HYQ, XWT, YH, SNC and ANS collected research data and revised the manuscript. LY performed laboratory examinations. DPW and YW designed the research, analyzed the data and edited the manuscript.

Corresponding authors

Correspondence to Depei Wu or Ying Wang.

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LY is an employee of Shanghai Unicar-Therapy Bio-medicine Technology Co., Ltd. The other authors declare no competing financial interests.

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Yao, Z., Gu, B., Zhang, Y. et al. CD19 chimeric antigen receptor T-cell therapy as a bridge therapy for allogeneic hematopoietic stem cell transplantation in patients with relapsed Philadelphia chromosome-positive acute lymphoblastic leukemia. Bone Marrow Transplant 58, 103–105 (2023). https://doi.org/10.1038/s41409-022-01845-w

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