Higher risk of platelet engraftment failure and chronic graft-versus-host disease after allogeneic haematopoietic stem cell transplantation following chimeric antigen receptor T-cell therapy compared to chemotherapy: A propensity score-matched analysis

Abstract

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) has been reported to further sustain long-term leukaemia-free survival following chimeric antigen receptor T-cell (CAR-T) therapy. It remains unclear whether bridging CAR-T to allo-HSCT results in higher treatment-related toxicity and mortality. We conducted a retrospective study to compare outcomes between allo-HSCT after CAR-T or conventional chemotherapy. After propensity score matching, 62 patients with prior CAR-T therapy and 124 patients with chemotherapy were ultimately included. Patients in the CAR-T cohort had a longer duration time from diagnosis to transplant (p < 0.001) and more advanced disease status before HSCT (p < 0.001) than that of the chemotherapy cohort. Patients with prior CAR-T cell therapy had a lower 28-day platelet engraftment rates [Hazard Rate (HR) = 1.38, 95% Confidence Interval (CI), 1.02–1.87, p = 0.037]. Multivariate analysis revealed that CAR-T therapy increased the risk of moderate to severe chronic graft-versus-host disease (cGVHD) (HR = 2.5, 95% CI, 1.01–6.19, p = 0.048). Compared with patients in the chemotherapy cohort, those in the CAR-T cell cohort experienced a higher incidence of transplantation-associated thrombotic microangiopathy (6.5% vs. 0.8%, p = 0.03) and probable/possible invasive fungal disease (10.0% vs. 3.3%, p = 0.08). The relapse rate, non-relapse mortality, and survival were comparable between cohorts. Caution should be exercised in allo-HSCT following CAR-T therapy because of the higher risk of platelet engraftment failure and cGVHD compared to chemotherapy.