Summary:To determine the effect of two different graft-versushost disease (GVHD) prophylactic regimens -cyclosporine with short course of methotrexate (CYA-MTX) and cyclosporine with prednisone (CYA-PRED) -on the incidence of chronic GVHD (cGVHD), we retrospectively reviewed the outcomes of 196 consecutive allogeneic related blood and marrow transplants performed at our institution utilizing one of these regimens. CYA-PRED was given to patients who were transplanted more recently because of concern about the increased risk of veno-occlusive disease of the liver, increased mucositis, and slower engraftment in patients receiving CYA-MTX. Prophylaxis with CYA-PRED was associated with a higher risk of development of cGVHD (risk ratio (RR) 3.5; 95% confidence intrerval (CI), 2.2-5.4). The proportion of patients with extensive disease among those developing cGVHD was higher in the CYA-PRED group (71%) than in the CYA-MTX group (57%), although this difference was not statistically significant. The cumulative probability of extensive cGVHD at 2 years was higher in the CYA-PRED group (RR 4.2, 95% CI, 2.4-7.4). Development of acute GVHD and cytomegalovirus mismatch were independent predictors of increased risk of cGVHD. We conclude that GVHD prophylaxis with CYA-PRED is associated with a higher overall rate of cGVHD compared to CYA-MTX. The type of GVHD prophylaxis should be considered when comparing the incidence of cGVHD reported in different studies. Bone Marrow Transplantation (2001) 27, 1133-1140. Keywords: allogeneic bone marrow transplantation; CYA; cytomegalovirus; MTX; prednisone; survival The number of allogeneic bone marrow transplantations (BMT) has increased steadily over the past three decades. 1 BMT offers the potential for cure in many hematologic malignancies. Graft-versus-host disease (GVHD), both acute and chronic, is an important complication of allogeneic transplants. Moderate-to-severe GVHD occurs in as many as one-half of the recipients of HLA-identical sibling transplants despite post-transplantation prophylaxis of GVHD. 2 Chronic GVHD develops in a significant number of these patients. For patients who survive the initial 2 to 3 months after transplantation, development of chronic GVHD has the greatest effect on their subsequent quality of life. The incidence of chronic GVHD reported in previous studies varied from 30% to 60%. 3,4 GVHD alone or in combination with infection accounts for a significant number of late transplant-related deaths in patients free of disease.Severe acute GVHD has a high mortality rate, and its prevention remains a cornerstone in the management of patients who have received a transplant. Considerable controversy exists about how best to prevent acute GVHD, and various pharmacologic and nonpharmacologic modalities have been tried. In vitro depletion of T lymphocytes from the marrow has been associated with a decreased incidence of GVHD, but it contributes to a higher rate of relapse and graft failure. 5 Various immunosuppressive drugs, alone or in combination, have been us...