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

摘要

BackgroundConsolidative 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.MethodsA 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.ResultsCompared 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).ConclusionHaploidentical 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.