Yazarlar : Peccatori J, Forcina A, Clerici D et al

Yayın : Leukemia

Yayın Yılı : 2014

Pubmed Linki : http://www.docguide.com/sirolimus-based-graft-versus-host-disease-prophylaxis-promotes-vivo-expansion-regulatory-t-cells-and?tsid=5

Konu : Lösemi

Literatür İçeriği :  Hematopoietic Stem Cell Transplantation (HSCT) from HLA haploidentical family donors is a promising therapeutic option for high-risk hematologic malignancies. Here we explored in 121 patients, mostly with advanced stage diseases, a sirolimus-based, calcineurin-inhibitor-free prophylaxis of Graft-versus-Host Disease (GvHD) to allow the infusion of unmanipulated peripheral blood stem cell (PBSC) grafts from partially HLA-matched family donors (TrRaMM study, Eudract 2007-5477-54). Conditioning regimen was based on treosulfan and fludarabine; GvHD prophylaxis on anti-thymocyte globulin Fresenius (ATG-F), rituximab, and oral administration of sirolimus and mycophenolate. Neutrophil and platelet engraftment occurred in median at 17 and 19 days after HSCT, respectively, and full donor chimerism was documented in patients' bone marrow since the first post-transplant evaluation. T cell immune reconstitution was rapid, and high frequencies of circulating functional T-regulatory cells (Treg) were documented during sirolimus prophylaxis. Incidence of acute GvHD grade II-IV was 35%, and occurrence and severity correlated negatively with Treg frequency. Chronic GvHD incidence was 47%. At three years after HSCT Transpant-Related Mortality was 31%, relapse incidence 48% and overall survival 25%. In conclusion, GvHD prophylaxis with sirolimus-mycophenolate-ATG-F-rituximab promotes a rapid immune reconstitution skewed towards Tregs, allowing the infusion of unmanipulated haploidentical PBSC grafts.Leukemia accepted article preview online, 4 June 2014; doi:10.1038/leu.2014.180.

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