In a multi-center collaboration, we carried out T-replete, peripheral blood stem cell (PBSC) transplants from related, HLA-haploidentical donors with reduced-intensity conditioning (RIC) and post-transplant cyclophosphamide (Cy) as GvHD prophylaxis in 55 patients with high-risk hematologic disorders. Patients received 2 doses of Cy 50mg/kg IV on days 3 and 4 post-infusion of PBSC (mean 6.4×106/kg CD34+ cells, mean 2.0 ×108/kg CD3+ cells). The median times to neutrophil (500/mcL) and platelet (>20,000/mcL) recovery were 17 and 21 days respectively. All but two of the patients achieved full engraftment. The one-year cumulative incidences of grade II and grade III acute GVHD were 53% and 8% respectively. There were no cases of grade IV GvHD. The two-year cumulative incidence of chronic GHVD was 18%. With a median follow up of 509 days, overall survival (OS) and event free survival (EFS) at two years were 48% and 51%, respectively. The two-year cumulative incidences of non-relapse mortality (NRM) and relapse were 23% and 28% respectively. Our results suggest that PBSC can be substituted safely and effectively for bone marrow (BM) as the graft source for haploidentical transplantation following reduced intensity conditioning.

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The FOXP3 gene encodes for a protein (Foxp3) involved in the development and functional activity of regulatory T cells (CD4+/CD25+/Foxp3+), which exert regulatory and suppressive roles over the immune system. After allogeneic stem cell transplantation, regulatory T cells are known to mitigate graft versus host disease while probably maintaining a graft versus leukemia effect. Short alleles (≤(GT)15) for the (GT)n polymorphism in the promoter/enhancer of FOXP3 are associated with a higher expression of FOXP3, and hypothetically with an increase of regulatory T cell activity. This polymorphism has been related to the development of auto- or alloimmune conditions including type 1 diabetes or graft rejection in renal transplant recipients. However, its impact in the allo-transplant setting has not been analyzed. In the present study, which includes 252 myeloablative HLA-identical allo-transplants, multivariate analysis revealed a lower incidence of grade III-IV acute graft versus host disease (GVHD) in patients transplanted from donors harboring short alleles (OR = 0.26, CI 0.08–0.82, p = 0.021); without affecting chronic GVHD or graft versus leukemia effect, since cumulative incidence of relapse, event free survival and overall survival rates are similar in both groups of patients.

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