Synergism Between Mycophenolate Mofetil and Cyclosporine in Preventing Graft-Versus-Host Disease Among Lethally Irradiated Dogs Given DLA-Nonidentical Unrelated Marrow Grafts

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Abstract
Mycophenolate mofetil (MMF) was evaluated either alone or combined with cyclosporine (CSP) for preventing graft-versus-host disease (GVHD) in dogs given 9.2 Gy total body irradiation and DLA-nonidentical unrelated marrow grafts. Marrow autograft studies showed gut toxicity as limiting MMF side effects. Four groups were studied for GVHD prevention: six dogs in group 1 received MMF 10 mg/kg twice daily subcutaneously (SC) on days 0 to 27. They died between 8 to 28 days from infection or GVHD; survival was better than that of 72 controls given no immunosuppression (P = .04), but not different from 19 dogs given CSP. Four dogs in group 2 received MMF as described, along with CSP at 10 to 15 mg/kg twice daily on days 0 to 27. They died at 6 to 98 days from CSP-associated toxicity, weight loss, or infection. Nine dogs in group 3 received MMF SC twice daily 6 mg/kg/d for 3 days, followed by 10 mg/kg twice daily until day 27, along with CSP as described; four died between 7 to 106 days with intussusception, infection, or GVHD, and five became long-term survivors. Six dogs in group 4 received shortened MMF (21 days) and reduced doses of CSP given through day 100. Three died with GVHD or infection between days 38 to 119, and three became long-term survivors. Results support the notion of synergism between MMF and CSP, as evidenced by stable graft-host tolerance in greater than 50% of dogs.