2022-02-092022-02-092013Pérez Simón, J.A., Martino, R., Parody, R., Cabrero, M., López Corral, L., Valcárcel, D.,...,Caballero, D. (2013). The combination of sirolimus plus tacrolimus improves outcome after reduced-intensity conditioning, unrelated donor hematopoietic stem cell transplantation compared with cyclosporine plus mycofenolate. Haematologica, 98 (4), 526-532.0390-60781592-8721https://hdl.handle.net/11441/129798Different 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 graftversus-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 over all survival rates, in comparison with those achieved with cyclosporine + mycophenolate.application/pdf7engAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/Antineoplastic Combined Chemotherapy Protocols / adverse effectsAntineoplastic Combined Chemotherapy Protocols / therapeutic useCombined Modality TherapyCyclosporine / administration & dosageCyclosporine / adverse effectsDisease-Free SurvivalGastrointestinal Diseases / chemically inducedGraft vs Host Disease / etiologyGraft vs Host Disease / prevention & controlHematologic Neoplasms / mortalityHematologic Neoplasms / therapyHematopoietic Stem Cell Transplantation / adverse effectsHematopoietic Stem Cell Transplantation / methodsInfections / chemically inducedMycophenolic Acid / administration & dosageMycophenolic Acid / adverse effectsMycophenolic Acid / analogs & derivativesProspective StudiesSirolimus / administration & dosageSirolimus / adverse effectsSurvival RateTacrolimus / administration & dosageTacrolimus / adverse effectsTime FactorsTransplantation Conditioning / adverse effectsTransplantation Conditioning / methodsTransplantation, HomologousTreatment OutcomeUnrelated Donorsinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccess10.3324/haematol.2012.065599