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Synergism Between Mycophenolate Mofetil and Cyclosporine
in Preventing Graft-Versus-Host Disease Among Lethally Irradiated
Dogs Given DLA-Nonidentical Unrelated Marrow Grafts
Cong Yu,
Kristy Seidel,
Richard A. Nash,
H. Joachim Deeg,
Brenda
M. Sandmaier,
Alexander Barsoukov,
Erlinda Santos, and
Rainer Storb
From the Clinical and Public Health Sciences Divisions of the Fred
Hutchinson Cancer Research Center, Seattle, WA; and the University of
Washington, Seattle, WA.
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.
Blood, Vol. 91 No. 7 (April 1), 1998:
pp. 2581-2587
© 1998 by The American Society of Hematology.
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