Synergism between mycophenolate mofetil and cyclosporine in preventing graft-versus-host disease among lethally irradiated dogs given DLA-nonidentical unrelated marrow grafts.
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.
Yu
C
C
Clinical and Public Health Sciences Divisions of the Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
Seidel
K
K
Nash
R A
RA
Deeg
H J
HJ
Sandmaier
B M
BM
Barsoukov
A
A
Santos
E
E
Storb
R
R
D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology; D016572:Cyclosporine / Q000008:administration & dosage*; D004285:Dogs; D004357:Drug Synergism; D006086:Graft vs Host Disease / Q000517:prevention & control*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006650:Histocompatibility Testing; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007275:Injections, Intravenous; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
D015395:Histocompatibility Antigens Class I; D007166:Immunosuppressive Agents; C039692:histocompatibility antigen DLA; D016572:Cyclosporine; D009173:Mycophenolic Acid