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Reduced incidence of neurologic complications after allogeneic hematopoietic stem cell transplantation with calcineurin-free graft-versus-host disease prophylaxis
Balaguer-Roselló, A., Gil-Perotín, S., Montoro, J., Bataller, L., Lamas, B., Villalba, M., Facal, A., Guerreiro, M., Chorão, P., Bataller, A., et al
Transplantation and cellular therapy. 2023
Abstract
Calcineurin inhibitors (CNI), including cyclosporine and tacrolimus, are frequently associated with neurological complications after allogeneic hematopoietic stem cell transplantation (HSCT). However, there is a lack of studies comparing the incidence and characteristics of NCs in patients undergoing HSCT based on CNI-free or CNI-based GVHD prophylaxis. This retrospective single-center study analyzed the neurologic complications in two subsequent cohorts of patients undergoing HSCT with either CNI-based GVHD prophylaxis (n=523) or CNI-free prophylaxis with posttransplant cyclophosphamide, sirolimus, and mycophenolate mofetil (n=371). The latter cohort included older patients, received more reduced-intensity conditioning and transplants from matched unrelated and haploidentical donors. The 2-year cumulative incidence of neurologic complications was significantly lower in the CNI-free cohort (6.9% vs. 11.9%; P=0.016), and GVHD prophylaxis was the only statistically significant variable in multivariate analysis (HR, 2.2; 95% confidence interval [CI], 0.25-3.13; P=0.0017). Distribution of neurologic types was similar in both cohorts, with encephalopathy being the most prevalent complication, except for headaches and myopathy, which decreased equally from 15% in the CNI-based group to 4% in the CNI-free group. Neurologic complications negatively impacted on mortality and survival rates, with a significantly higher 2-year cumulative incidence of non-relapse mortality (44% [95%CI, 34-54] vs. 16% [95%CI, 13-18]; P < 0.0001) and inferior overall survival (66% [95%CI, 62-69] vs. 46% [95%CI, 37-58]; P < 0.0001) in patients with neurologic complications. The study suggests that CNI-free GVHD prophylaxis with PTCy, sirolimus and MMF may reduce not only GVHD incidence, but also NCs and NRM rates, leading to improved survival outcomes in patients undergoing HSCT.