Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Giaccone, L. et al.

Pharmacodynamics of mycophenolate mofetil after nonmyeloablative conditioning and unrelated donor hematopoietic cell transplantation.

The immunosuppressive drug mycophenolate mofetil (MMF) is used after nonmyeloablative hematopoietic cell transplantation (HCT); however, limited pharmacodynamic data are available. We evaluated plasma concentrations of mycophenolic acid (MPA), the active metabolite of MMF, and outcomes in 85 patients with hematologic malignancies conditioned with fludarabine and 2 Gy total body irradiation followed by HLA-matched unrelated-donor HCT and postgrafting cyclosporine and MMF. The first 38 patients received MMF 15 mg/kg twice daily; the next 47 patients received MMF 3 times daily. MPA pharmacokinetics were determined on days 7 and 21. Comparing the twice-daily and 3-times-daily MMF groups, the mean total MPA concentration steady state (Css) was 1.9 and 3.1 microg/mL; the unbound Css was 18 and 36 ng/mL, respectively (P < .001). Sixteen patients with a total MPA Css less than 3 microg/mL had low (< 50%) donor T-cell chimerism (P = .03), and 6 patients with MPA Css less than 2.5 microg/mL had graft rejection. An elevated unbound Css was associated with cytomegalovirus reactivation (P = .03). There were no significant associations between MPA pharmacokinetics and acute graft-versus-host disease (GVHD) or relapse. We conclude that increased MPA Css's predicted higher degrees of donor T-cell chimerism after unrelated donor nonmyeloablative HCT and suggest that targeting MPA Css's greater than 2.5 microg/mL could prevent graft rejection.[1]

References

Pharmacodynamics of mycophenolate mofetil after nonmyeloablative conditioning and unrelated donor hematopoietic cell transplantation. Giaccone, L., McCune, J.S., Maris, M.B., Gooley, T.A., Sandmaier, B.M., Slattery, J.T., Cole, S., Nash, R.A., Storb, R.F., Georges, G.E. Blood (2005) [Pubmed]

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