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Acute lymphoblastic leukemia

Unmanipulated haploidentical hematopoietic stem cell transplantation is an excellent option for children and young adult relapsed/refractory Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia after CAR-T-cell therapy

Leukemia volume 35, pages 3092–3100 (2021)Cite this article

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Abstract

Although chimeric antigen receptor T-cell (CAR-T) therapy produces a high complete remission rate among patients with relapsed/refractory B-cell acute lymphoblastic leukemia, relapse remains an urgent issue. It is uncertain whether consolidative haploidentical-allogeneic hematopoietic stem cell transplantation (haplo-HSCT) is suitable for achieving sustainable remission. Therefore, we aimed to assess the efficacy and safety of bridging CAR-T therapy to haplo-HSCT. Fifty-two patients with relapsed/refractory Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia who underwent haplo-HSCT after CAR-T therapy were analyzed. The median time from CAR-T therapy to haplo-HSCT was 61 days. After a median follow-up of 24.6 months, the 1-year probabilities of event-free survival, overall survival, and cumulative incidence of relapse were 80.1% (95% confidence interval (CI), 69.0–90.9), 92.3% (95% CI, 85.0–99.5), and 14.1% (95% CI, 10.7–17.4), respectively, while the corresponding 2-year probabilities were 76.0% (95% CI, 64.2–87.7), 84.3% (95% CI, 74.3–94.3), and 19.7% (95% CI, 15.3–24.0), respectively. No increased risk of 2-year cumulative incidence of graft-versus-host disease, treatment-related mortality, or infection was observed. A pre-HSCT measurable residual disease-positive status was an independent factor associated with poor overall survival (hazard radio: 4.201, 95% CI: 1.034–17.063; P = 0.045). Haplo-HSCT may be a safe and effective treatment strategy to improve event-free survival and overall survival after CAR-T therapy.

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Fig. 1: Diagram of patients enrolled in this study.
Fig. 2: Outcome of haploidentical allogeneic stem cell transplantations in patients with relapsed/refractory Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia.

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Acknowledgements

The authors thank all the doctors at the institute who participated in this study for providing the follow-up samples and information.

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Author notes

  1. These authors contributed equally: Guan-Hua Hu, Xiang-Yu Zhao, Ying-Xi Zuo

Authors and Affiliations

  1. Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking-Tsinghua Center for Life Science, Research Unit of Key Technique for Diagnosis and Treatment of Hematologic Malignancies, Chinese Academic of Medical Sciences, Beijing, China

    Guan-Hua Hu, Xiang-Yu Zhao, Ying-Jun Chang, Pan Suo, Jun Kong, Chen-Hua Yan, Lan-Ping Xu, Xiao-Hui Zhang, Kai-Yan Liu, Yi-Fei Cheng, Yu Wang & Xiao-Jun Huang

  2. Department of Pediatrics, Peking University People’s Hospital, Peking University, Beijing, China

    Ying-Xi Zuo, Jun Wu, Yue-Ping Jia, Ai-Dong Lu & Le-Ping Zhang

  3. Beijing Yongtai Reike Biotechnology Company Ltd, Beijing, China

    Ying-Chun Li & Yu Wang

  4. Chinese People Liberation Army (PLA) General Hospital, Beijing, China

    Shun-Chang Jiao

  5. Shenzhen Geno-immune Medical Institute, Shenzhen, China

    Long-Ji Zhang

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Correspondence to Yi-Fei Cheng or Yu Wang.

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Hu, GH., Zhao, XY., Zuo, YX. et al. Unmanipulated haploidentical hematopoietic stem cell transplantation is an excellent option for children and young adult relapsed/refractory Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia after CAR-T-cell therapy. Leukemia 35, 3092–3100 (2021). https://doi.org/10.1038/s41375-021-01236-y

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