Journal of Hematology & Oncology (May 2020)

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

  • Houli Zhao,
  • Jieping Wei,
  • Guoqing Wei,
  • Yi Luo,
  • Jimin Shi,
  • Qu Cui,
  • Mingfeng Zhao,
  • Aibin Liang,
  • Qing Zhang,
  • Jianmin Yang,
  • Xin Li,
  • Jing Chen,
  • Xianmin Song,
  • Hongmei Jing,
  • Yuhua Li,
  • Siguo Hao,
  • Wenjun Wu,
  • Yamin Tan,
  • Jian Yu,
  • Yanmin Zhao,
  • Xiaoyu Lai,
  • Elaine Tan Su Yin,
  • Yunxiong Wei,
  • Ping Li,
  • Jing Huang,
  • Tao Wang,
  • Didier Blaise,
  • Lei Xiao,
  • Alex H. Chang,
  • Arnon Nagler,
  • Mohamad Mohty,
  • He Huang,
  • Yongxian Hu

DOI
https://doi.org/10.1186/s13045-020-00873-7
Journal volume & issue
Vol. 13, no. 1
pp. 1 – 13

Abstract

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Abstract Background Consolidative allogeneic hematopoietic stem cell transplantation is a controversial option for patients with relapsed/refractory acute lymphoblastic leukemia after chimeric antigen receptor T cell (CAR-T) therapy. We performed a multicenter retrospective study to assess whether patients can benefit from haploidentical hematopoietic stem cell transplantation after CAR-T therapy. Methods A total of 122 patients after CAR-T therapy were enrolled, including 67 patients without subsequent transplantation (non-transplant group) and 55 patients with subsequent haploidentical hematopoietic stem cell transplantation (transplant group). Long-term outcome was assessed, as was its association with baseline patient characteristics. Results Compared with the non-transplant group, transplantation recipients had a higher 2-year overall survival (OS; 77.0% versus 36.4%; P < 0.001) and leukemia-free survival (LFS; 65.6% versus 32.8%; P < 0.001). Multivariate analysis showed that minimal residual disease (MRD) positivity at transplantation is an independent factor associated with poor LFS (P = 0.005), OS (P = 0.035), and high cumulative incidence rate of relapse (P = 0.045). Pre-transplant MRD-negative recipients (MRD− group) had a lower cumulative incidence of relapse (17.3%) than those in the non-transplant group (67.2%; P < 0.001) and pre-transplant MRD-positive recipients (MRD+ group) (65.8%; P = 0.006). The cumulative incidence of relapse in MRD+ and non-transplant groups did not differ significantly (P = 0.139). The 2-year LFS in the non-transplant, MRD+, and MRD− groups was 32.8%, 27.6%, and 76.1%, respectively. The MRD− group had a higher LFS than the non-transplantation group (P < 0.001) and MRD+ group (P = 0.007), whereas the LFS in the MRD+ and non-transplant groups did not differ significantly (P = 0.305). The 2-year OS of the MRD− group was higher than that of the non-transplant group (83.3% versus 36.4%; P < 0.001) but did not differ from that of the MRD+ group (83.3% versus 62.7%; P = 0.069). The OS in the non-transplant and MRD+ groups did not differ significantly (P = 0.231). Conclusion Haploidentical hematopoietic stem cell transplantation with pre-transplant MRD negativity after CAR-T therapy could greatly improve LFS and OS in patients with relapsed/refractory acute lymphoblastic leukemia. Trial registration The study was registered in the Chinese clinical trial registry ( ChiCTR1900023957 ).

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