1.
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.
2.
Cyclosporine A for the Prevention of Ocular Graft versus Host Disease in Allogeneic Hematopoietic Stem Cell Transplant Recipients Is Safe and Feasible
Cantu-Rodriguez, O. G., Vazquez-Mellado, A., Gonzalez-Trevino, J. L., Martinez-Garza, D. M., Gomez-De Leon, A., Hawing-Zarate, J. A., Jaime-Perez, J. C., Gutierrez-Aguirre, C. H., Garza-Acosta, A. C., Mancias-Guerra, C., et al
Acta haematologica. 2019;:1-7
Abstract
PURPOSE To evaluate the safety and efficacy of ocular cyclosporine in the prevention of the development of ocular graft versus host disease (oGVHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (AHSCT) in comparison with historic data. DESIGN We developed a longitudinal, observational, prospective nonrandomized study. We evaluated the feasibility of prophylactic use of topical cyclosporine A (CsA) to prevent or decrease the incidence of oGVHD and compared this with historic data. METHODS Patients undergoing AHSCT were treated with prophylactic topical CsA for 12 months after engraftment, followed by serial ophthalmic evaluations, including the Schirmer test. RESULTS Twenty patients were included. No serious adverse effects were reported. Poor adherence was documented in 15% of patients. In spite of observing extra-ocular GVHD (acute and chronic GVHD incidence of 50 and 45%, respectively), only 1 in 20 patients developed oGVHD over the 20-month follow-up for the entire cohort. No statistically significant difference was observed in the incidence of oGVHD when compared to a historical cohort. CONCLUSIONS Topical CsA as a prophylactic measure for oGVHD, administered over a period of 1 year after grafting, is safe and feasible and may decrease the incidence of ophthalmic manifestations of GVHD. These findings must be confirmed in a randomized trial.