The combination of sirolimus plus tacrolimus improves outcome after reduced-intensity conditioning, unrelated donor hematopoietic stem cell transplantation compared with cyclosporine plus mycofenolate
Por:
Perez-Simon, JA, Martino, R, Parody, R, Cabrero, M, Lopez-Corral, L, Valcarcel, D, Martinez, C, Solano, C, Vazquez, L, Marquez-Malaver, FJ, Sierra, J, Caballero, D
Publicada:
1 abr 2013
Resumen:
Different types of graft-versus-host disease prophylaxis have been proposed in the setting of reduced intensity and non-myeloablative allogeneic stem cell transplantation. An alternative combination with sirolimus and tacrolimus has recently been tested although comparative studies against the classical combination of a calcineurin inhibitor and mycophenolate mofetil or methotrexate are lacking. We describe the results of a prospective, multicenter trial using sirolimus + tacrolimus as immunoprophylaxis, and compare this approach with our previous experience using cyclosporine + mycophenolate in the setting of unrelated donor transplantation setting after reduced-intensity conditioning. Forty-five patients received cyclosporine + mycophenolate between 2002 and mid-2007, while the subsequent 50 patients, who were transplanted from late 2007, were given sirolimus + tacrolimus. No significant differences were observed in terms of hematopoietic recovery or acute graft-versus-host disease overall, although gastrointestinal acute graft-versus-host disease grade >= 2 was more common in the cyclosporine + mycophenolate group (55% versus 21%, respectively, P=0.003). The 1-year cumulative incidence of chronic graft-versus-host disease was 50% versus 90% for the patients treated with the sirolimus- versus cyclosporine-based regimen, respectively (P<0.001), while the incidence of extensive chronic disease was 27% versus 49%, respectively (P=0.043). The 2-year non-relapse mortality rate was 18% versus 38% for patients receiving the sirolimus-versus the cyclosporine-based regimen, respectively (P=0.02). The event-free survival and overall survival at 2 years were 53% versus 29% (P=0.028) and 70% versus 45% (P=0.018) among patients receiving the sirolimus-versus the cyclosporine-based regimen, respectively. In conclusion, in the setting of reduced intensity transplantation from an unrelated donor, promising results can be achieved with the combination of sirolimus + tacrolimus, due to a lower risk of chronic graft-versus-host disease and non-relapse mortality, which translates into better event-free and overall survival rates, in comparison with those achieved with cyclosporine + mycophenolate.
Filiaciones:
Perez-Simon, JA:
Hosp Clin Univ, Salamanca, Spain
Martino, R:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Cabrero, M:
Hosp Clin Univ, Salamanca, Spain
Lopez-Corral, L:
Hosp Clin Univ, Salamanca, Spain
Valcarcel, D:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Martinez, C:
Hosp Clin Barcelona, Barcelona, Spain
Solano, C:
Hosp Clin, Valencia, Spain
Vazquez, L:
Hosp Clin Univ, Salamanca, Spain
Sierra, J:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Caballero, D:
Hosp Clin Univ, Salamanca, Spain
Gold, Green Published
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