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The role of allogeneic haematopoietic cell transplantation as consolidation after anti-CD19 CAR-T cell therapy in adults with relapsed/refractory acute lymphoblastic leukaemia: a prospective cohort study

Bone Marrow Transplantation volume 57, pages 513–516 (2022)Cite this article

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The prognosis of relapsed/refractory adults acute lymphoblastic leukaemia (r/r ALL) is poor; however, chimeric antigen receptor T (CAR-T) cell therapy has shown promising results: 70–90% of patients achieve complete remission (CR) [1,2,3]. However, after CD19 CAR-T cell therapy, the disease recurrence rate at 1 year is greater than 50% in adults [3, 4]. Although patients have a higher chance of achieving remission following allogeneic haematopoietic stem cell transplantation (allo-HSCT) after CAR-T cell therapy [5] than after other salvage chemotherapy, many investigators have questioned the necessity of consolidative allo-HSCT after CAR-T cell therapy once patients have achieved remission. Therefore, we designed this prospective cohort study to clarify whether bridging to allo-HSCT after achieving CR through CAR-T cell therapy can improve the outcomes of patients with r/r ALL. The study protocol was in accordance with the Declaration of Helsinki and was approved by the local medical ethics committee. The study was registered with the Chinese Clinical Trial Registry (ChiCTR-OOC-16007779).

Between June 2016 and November 2021, a total of 37 patients with r/r ALL were enroled in the study. The patients were divided into two cohorts according to the patients’ willingness to transplant, whether there were suitable donors, and whether the patients had the ability to pay for treatment. Cohort 1 was the HSCT group, comprising 14 people, and cohort 2 was the non-HSCT group, comprising 23 people. After CAR-T cell infusion, 13 people in the transplantation group achieved remission, and 17 people in the nontransplantation group achieved remission (Supplementary Figure 1). Patients in the HSCT group who achieved complete remission (CR) after CAR-T cell therapy subsequently underwent allo-HSCT, while patients in the non-HSCT group continued with follow-up. We compared the baseline and efficacy of patients who achieved complete remission after CAR-T cell therapy in the two groups. The median age in the HSCT group was 26 years (range, 18–52 years) and that in the non-HSCT group was 34 years (range, 19–68 years). The baseline patient information between the two groups, including sex, age, disease status, prior therapies, bone marrow blasts, MRD and disease genetics, is shown in Table 1. The primary study endpoint was median leukaemia-free survival (LFS). In addition, we compared median overall survival (OS), relapse rate, tumour-related mortality and non-relapse-related mortality between the two groups. The research design is shown in Supplementary Fig. 1.

Table 1 Baseline characteristics of the patients.
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Fig. 1: Numbers of relapses and deaths in the two groups after treatments, leukemia-free survival probability, overall survival probability and leukemia-free survival.

References

  1. Kenderian SS, Porter DL, Gill S. Chimeric antigen receptor T cells and hematopoietic cell transplantation: how not to put the CART before the horse. Biol Blood Marrow Transplant. 2017;23:235–246.

    Article  CAS  Google Scholar 

  2. Davila ML, Riviere I, Wang X, Bartido S, Park J, Curran K, et al. Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med. 2014;6:224ra25.

    Article  Google Scholar 

  3. Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA, et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2015;385:517–528.

    Article  CAS  Google Scholar 

  4. Zhang Y, Chen H, Song Y, Tan X, Zhao Y, Liu X, et al. Chimeric antigen receptor T‐cell therapy as a bridge to haematopoietic stem cell transplantation for refractory/relapsed B‐cell acute lymphoblastic leukemia. Br J Haematol. 2020;189:146–152.

    Article  CAS  Google Scholar 

  5. Dholaria B, Savani BN. Allogeneic haematopoietic cell transplantation after CAR T‐cell therapy: safe, effective and contentious. Br J Haematol. 2020;189:21–23.

    Article  Google Scholar 

  6. Tu S, Huang R, Guo Z, Deng L, Song C, Zhou X, et al. Shortening the ex vivo culture of CD19‐specific CAR T‐cells retains potent efficacy against acute lymphoblastic leukemia without CAR T‐cell‐related encephalopathy syndrome or severe cytokine release syndrome. Am J Hematol. 2019;94:E322–E325.

  7. Park JH, Rivière I, Gonen M, Wang X, Sénéchal B, Curran KJ, et al. Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. N Engl J Med. 2018;378:449–459.

    Article  CAS  Google Scholar 

  8. Park JH, Riviere I, Wang X, Bernal Y, Brentjens RJ. Implications of minimal residual disease negative complete remission (MRD-CR) and allogeneic stem cell transplant on safety and clinical outcome of CD19-targeted 19-28z CAR modified T cells in adult patients with relapsed, refractory B-cell ALL. J Clin Oncol. 2015;33:7010–7010.

    Article  Google Scholar 

  9. Jiang H, Li C, Yin P, Guo T, Liu L, Xia L, et al. Anti‐CD19 chimeric antigen receptor‐modified T‐cell therapy bridging to allogeneic hematopoietic stem cell transplantation for relapsed/refractory B‐cell acute lymphoblastic leukemia: an open‐label pragmatic clinical trial. Am J Hematol. 2019;94:1113–1122.

    Article  CAS  Google Scholar 

  10. Zhao H, Wei J, Wei G, Luo Y, Shi J, Cui Q, et al. Pre-transplant MRD negativity predicts favorable outcomes of CAR-T therapy followed by haploidentical HSCT for relapsed/refractory acute lymphoblastic leukemia: a multi-center retrospective study. J Hematol Oncol. 2020;13:42.

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Acknowledgements

The authors thank doctors from the Department of Haematology at Zhujiang Hospital for diagnosis, monitoring and patient care during CAR-T cell therapy. They also thank professors from the Laboratory of Cell Processing for CAR-T cell culture.

Funding

This work was funded by the Frontier Research Program of Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory) [grant number 2018GZR110105014] and the Natural Science Foundation of Guangdong Province, China [grant number 2018B030311042].

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  1. These authors contributed equally: Shi Han, Lijuan Zhou.

Authors and Affiliations

  1. Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, China

    Shi Han, Lijuan Zhou, Youyou Chen, Xuan Zhou, Zhenling Guo, Jilong Yang, Bo Jin, Yuhua Li & Sanfang Tu

  2. Department of Research and Development, Geno-Immune Medical Institute, Shenzhen, China

    Yuchen Liu & Lung-Ji Chang

  3. Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, Guangdong, 510005, PR China

    Yuhua Li

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Contributions

ST and SH designed the research; SH wrote the paper; SH and LZ analyzed the results and constructed the tables and figures; and ST and SH were the associate investigators. The other authors all performed ward duty as attending physicians.

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Correspondence to Yuhua Li or Sanfang Tu.

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Han, S., Zhou, L., Chen, Y. et al. The role of allogeneic haematopoietic cell transplantation as consolidation after anti-CD19 CAR-T cell therapy in adults with relapsed/refractory acute lymphoblastic leukaemia: a prospective cohort study. Bone Marrow Transplant 57, 513–516 (2022). https://doi.org/10.1038/s41409-022-01572-2

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