Atorvastatin for the Prophylaxis of Acute Graft vs. Host Disease (GVHD) in Patients Undergoing HLA-Matched Related Donor Hematopoietic Stem Cell Transplantation (HSCT)

摘要

Statins possess potent immunomodulatory effects that may play a role in preventing acute GVHD (aGVHD) following allogeneic hematopoietic cell transplantation (allo-HCT). We performed a Phase II study of atorvastatin for aGVHD prophylaxis when given to allo-HCT recipients and their HLA-matched sibling donors. Atorvastatin (40mg/day) was administered to sibling donors, beginning 14 days before the anticipated start of stem cell collection. Allo-HCT recipients (n=40) received atorvastatin (40mg/day) in addition to standard aGVHD prophylaxis. The primary endpoint was cumulative incidence of grades 2-4 aGVHD at day 100. Atorvastatin was well tolerated and there were no attributable grade 3-4 toxicities in donors or their recipients. Day 100 and 180 cumulative incidences of grade 2-4 aGVHD were 30% (95% CI 17- 45%) and 40% (95% CI 25-55%), respectively. One-year cumulative incidence of chronic GVHD was 43% (95% CI 32- 69%). One year non-relapse mortality and relapse incidences were 5.5% (95% CI 0.9-16.5%) and 38% (95% CI 18- 47%), respectively. One-year progression-free survival and overall survival were 54% (95% CI 38-71%) and 82% (95% CI 69-94%). One-year GVHD-free, relapse-free survival (GRFS) was 27% (95% CI 16-47%). These results did not differ from our historical controls (N=96). While safe and tolerable, the addition of atorvastatin did not appear to provide any benefit to standard GVHD prophylaxis alone.