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Allogeneic haematopoietic stem cell transplantation improves outcome of adults with relapsed/refractory Philadelphia chromosome-positive acute lymphoblastic leukemia entering remission following CD19 chimeric antigen receptor T cells

Bone Marrow Transplantation volume 56, pages 91–100 (2021)Cite this article

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Abstract

Relapsed/refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (r/r Ph+ ALL) has an extremely poor prognosis. Chimeric antigen receptor T-cell (CART) therapy has acquired unprecedented efficacy in B-cell malignancies, but its role in the long-term survival of r/r Ph+ ALL patients is unclear. We analyzed the effect of CART on 56 adults with r/r Ph+ ALL who accepted split doses of humanized CD19-targeted CART after lymphodepleting chemotherapy. 51/56 (91.1%) achieved complete remission (CR) or CR with inadequate count recovery (CRi), including 38 patients with negative minimal residual disease (MRD) tested by bone marrow BCR-ABL1 copies. Subsequently, 30/51 CR/CRi patients accepted consolidative allogeneic haematopoietic stem cell transplantation (alloHSCT). Their outcomes were compared with those of 21/51 contemporaneous patients without alloHSCT. The 2-year overall survival (OS) and leukemia-free survival (LFS) of CR/CRi patients with alloHSCT were significantly superior to those without alloHSCT (58.9%, CI 49.8–68.0% vs. 22.7%, CI 12.7–32.7%, p = 0.005; 53.2%, CI 43.6–62.8% vs. 18.8%, CI 9.2–28.4%, p = 0.000, respectively). Multivariate analysis revealed that alloHSCT and MRD-negative post-CART were the independent prognostic factors for OS and LFS. CART therapy is highly effective for r/r Ph+ ALL patients, and consolidative alloHSCT could prolong their OS and LFS.

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Fig. 1: Flow diagram of the patients.
Fig. 2: The persistence and quantity of CART.
Fig. 3: Survival outcome of the 51 r/r Ph+ ALL patients who achieved CR/CRi post-CART.
Fig. 4: Effect of minimal residual disease (MRD) assessed by bone marrow BCR/ABL1 levels on subgroup patients.

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Acknowledgements

This work was supported by National Natural Science Foundation of China (81730003 and 81700204), Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), Jiangsu Medical Outstanding Talents Project (JCRCA2016002), Jiangsu Provincial Key Medical Center (YXZXA2016002), Innovation Capability Development Project of Jiangsu Province (BM2015004), and National Key R&D Program of China (2017YFA0104502, 2017ZX09304021).

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  1. These authors contributed equally: Bin Gu, Bing-Yu Shi, Xiang Zhang

Authors and Affiliations

  1. National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China

    Bin Gu, Bing-Yu Shi, Xiang Zhang, Shi-Yuan Zhou, Jian-Hong Chu, Xiao-Jin Wu, Cheng-Cheng Fu, Hui-Ying Qiu, Yue Han, Su-Ning Chen, Xiao Ma & De-Pei Wu

  2. Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215006, China

    Bin Gu, Bing-Yu Shi, Xiang Zhang, Shi-Yuan Zhou, Jian-Hong Chu, Xiao-Jin Wu, Cheng-Cheng Fu, Hui-Ying Qiu, Yue Han, Su-Ning Chen, Xiao Ma & De-Pei Wu

  3. Key Laboratory of Stem Cells and Biomedical Materials of Jiangsu Province and Chinese Ministry of Science and Technology, Suzhou, 215006, China

    Bin Gu, Bing-Yu Shi, Xiang Zhang, Shi-Yuan Zhou, Jian-Hong Chu, Xiao-Jin Wu, Cheng-Cheng Fu, Hui-Ying Qiu, Yue Han, Su-Ning Chen, Xiao Ma & De-Pei Wu

  4. Shanghai Unicar-Therapy Bio-medicine Technology Co. Ltd, Shanghai, 201203, China

    Lei Yu

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Contributions

Conception and design: BG, XM, DPW. Collection and assembly of data: BYS, XZ. Patient care: all coauthors. Data analysis and interpretation: BG, BYS, XZ, XM, DPW. Paper writing: BG, DPW. Final approval of paper: all coauthors.

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Correspondence to Xiao Ma or De-Pei Wu.

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Gu, B., Shi, BY., Zhang, X. et al. Allogeneic haematopoietic stem cell transplantation improves outcome of adults with relapsed/refractory Philadelphia chromosome-positive acute lymphoblastic leukemia entering remission following CD19 chimeric antigen receptor T cells. Bone Marrow Transplant 56, 91–100 (2021). https://doi.org/10.1038/s41409-020-0982-6

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