Background: Immunosuppression to prevent graft rejection and GVHD is associated with an increased incidence of PTLD in the first year after alloBMT. AlloBMTs using partially HLA-mismatched or unrelated donor grafts, particularly when coupled with selective T-cell depletion approaches and/or anti-thymocyte globulin therapy, are associated with PTLD rates of 4-8%. The incidence of PTLD after umbilical cord blood alloBMT ranges from 2-7%. We evaluated the incidence of PTLD associated with the use of PT-Cy as GVHD prophylaxis at Johns Hopkins Hospital. Methods: After IRB approval, the Blood and Marrow Transplant Research database was queried for adult patients (age > 18) who received PT-Cy as GVHD prophylaxis. Medical records from the first year after alloBMT, including clinical notes, pathology reports, and laboratory assays for Epstein-Barr virus (EBV), were reviewed. Results: From 2000-2011, 765 alloBMT patients received PT-Cy (50 mg/kg/day on days 3 and 4 after alloBMT) as GVHD prophylaxis. Of these, 734 patients had 1-year follow-up or death. In patients receiving myeloablative conditioning and HLA-matched grafts (n=289, 117 unrelated donors), PT-Cy was the sole GVHD prophylaxis. Other patients undergoing alloBMT received mycophenolate mofetil and tacrolimus in addition to PT-Cy. These included recipients of HLA-matched (n=63) or haploidentical (n=352) grafts who were conditioned with reduced intensity regimens, as well as recipients of HLA-haploidentical grafts who received myeloablative regimens (n=30). Forty-one patients with CD20(+) tumors received rituximab after alloBMT as part of a clinical protocol. There were no cases of PTLD. Conclusions: The absence of PTLD in this series, even among high-risk recipients of haploidentical or unrelated donor grafts, suggests that PT-Cy is less associated with PTLD than other GVHD prophylaxis strategies. We hypothesize that multiple mechanisms may account for the lack of PTLD with PT-Cy, including destruction of B cells that harbor EBV, sparing of EBV-specific memory T cells, and rapid immune reconstitution.