Improved Disease Survival without Increased GVHD Using Low Dose Cyclosporine and Prednisone in Allogeneic Stem Cell Transplantation - a Case Control Study.

Allogeneic stem cell transplantation (HSCT) can cure numerous malignant and non-malignant diseases but this is offset by significant morbidity and mortality from graft versus host disease (GVHD). The standard prophylactic regimen contains cyclosporine, methotrexate and/or prednisone however doses and the timing of tapering remain unclear. Recently Ruutu et al demonstrated reduced GVHD using a prednisone based prophylactic regimen without a survival benefit whereas Baclgalupo et al demonstrated an increased survival benefit with 1mg/kg cyclosporine over 3mg/kg which strongly correlated with cyclosporine levels. Since early 2002 we have adopted both these strategies in an attempt to reduce GVHD in myeloblative HSCT but still maintain disease free survival. Consecutive myeloblative allogeneic HSCT patients (n=47, median age 41 yrs, 28 sibling or family, 19 unrelated) underwent HSCT using cyclosporine 1mg/kg, standard dose methotrexate and prednisone commencing at D14 0.5mg/kg, according to Ruutu et al. All sibling allograft patients underwent conditioning with Bu/Cy whereas unrelated recipients received Cy/TBI. This group was compared with 94 historical controls for age and disease status (median age 36 yrs, 63 sibling or family, 31 unrelated). At a median of 1 year follow up (range 100–600 days), overall and disease free survival is significantly increased in the low dose cyclosporine/prednisone arm (OS: 75% vs 50% at 1 yr, p=0.04). Acute GVHD (II–IV) was similar in both arms at D100 with a trend to less GVHD in the low dose cyclosporine/prednisone arm (20% vs 30%, p=0.1). These results suggest that the low dose cyclosporine/prednisone regimen has controlled GVHD whilst maintaining an adequate GVL effect. Randomised trials using this regimen may be warranted to fully determine its place in allogeneic HSCT prophylaxis.