Reduced incidence of neurologic complications after allogeneic hematopoietic stem cell transplantation with calcineurin-free graft-versus-host disease prophylaxis.

Autores de IIS La Fe

• Aitana Balaguer Roselló

  Autor

• Sara María García Gil-Perotín

  Autor

• Juan Bautista Montoro Gómez

  Autor

• Luís Bataller Alberola

  Autor

• Marta Villalba Montaner

  Autor

• Ana Facal Malvar

  Autor

• Manuel Nuno Direito De Morais Guerreiro

  Autor

• Pedro Miguel Aparicio Chorao

  Autor

• Ana María Bataller Alfonso

  Autor

• Inés Gómez Seguí

  Autor

• Pilar Solves Alcaina

  Autor

• Alberto Louro Iglesias

  Autor

• 

  Javier De La Rubia Comos

  Autor

• Miguel Ángel Sanz Alonso

  Autor

• Jaime Sanz Caballer

  Autor

Participantes ajenos a IIS La Fe

• Lamas, Brais
• Granados, Pablo

Grupos

• Hematología y Hemoterapia

• Investigación en Neuroinmunología y Esclerosis Múltiple

• Patología Neuromuscular y Ataxias

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.

Copyright © 2023. Published by Elsevier Inc.

Keywords

• allogeneic stem cell transplantation; calcineurin inhibitors; graft-versus-host disease; neurologic complications; sirolimus