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 6.4x10(6)/kg CD34+ cells, mean 2.0 x10(8)/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.