We evaluated survival after nonmyeloablative, HLA-haploidentical BMT and GVHD prophylaxis incorporating high dose, post-transplantation cyclophosphamide (Cy) for patients with poor risk leukemia or lymphoma who lacked a HLA-matched related donor. The trial enrolled 55 patients from 17 centers and 52 proceeded to transplantation. Their median age was 51 years (range, 7-70); 32 were male, and 42, Caucasian. Diagnoses included acute myeloid (10 in CR1, 13 in CR ≥ 2), acute lymphocytic (3 in CR1, 3 in CR ≥ 2) biphenotypic/undifferentiated leukemia in CR (n = 3) and, relapsed/chemosensitive Hodgkin (n = 8), mantle cell (n = 3), large cell (n = 8), and marginal zone B cell lymphoma (n = 1). Thirty-nine patients had performance status ≥ 90%, and 12 patients had failed prior autologous SCT. Median donor age was 43 years and the median mismatch, 5/10 HLA alleles in the graft-versus-host direction and 4/10 alleles in the host-versus-graft direction. Patients were conditioned with Cy (14.5 mg/kg IV, day -6, -5), fludarabine (30 mg/m2 IV, day -6 to -2), total body irradiation (200 cGy, day -1) followed by infusion of T-cell replete bone marrow. GVHD prophylaxis consisted of Cy 50 mg/kg IV on day +3 and +4, mycophenolate mofetil, day +5 to +35, and tacrolimus, day +5 to +180. Filgrastim was given from day +5 until neutrophil recovery. The median times to > 0.5 × 109/L neutrophils and platelets ≥ 20 × 109/L, were 16 and 21 days, respectively. The median donor chimerism in marrow/blood at day +28 was 100% (range, 70-100%), and T cell chimerism, 100%. One patient experienced primary graft failure and none, secondary graft failure. The day +56 incidence of acute grade II GVHD was 31% (95% CI, 18-44%) and day +180 chronic GVHD, 11% (95% CI, 1-22%). No patient experienced grade III-IV acute GVHD. The day +180 incidences of relapse/progression and non-relapse mortality were 19% (95% CI, 7-32%) and 5% (95% CI, 0-13%), respectively. Ten patients experienced relapse/progression and there were 13 deaths: relapse/progression (n = 8); infection (n = 2); graft failure (n = 1); unknown (n = 2). With a median follow-up of surviving patients of 294 days (range 76-650), the 6-month probabilities of overall and event-free survival are 82% (95% CI, 65-91%) and 75% (95% CI, 59-86%), respectively. These results confirm nonmyeloablative, HLA-haploidentical BMT is feasible, associated with low toxicity and these data may be used to plan multi-center trials to identify the optimal alternative donor.