Mycophenolic acid trough level monitoring: relevance in acute and chronic graft versus host disease and its relation with albumin Mycophenolate mofetil (MMF) has been used effectively in the treatment of acute and chronic GvHD (1–3). Mycophenolic acid (MPA), an active metabolite of MMF, selectively inhibits prolifera- tion of human T and B lymphocytes. The utility of MPA trough level monitoring when MMF is used for the treatment of GvHD is not well established but there is evidence that maintaining therapeutic MPA trough level may improve outcomes by preventing rejection in solid organ transplantation (4–7). To our knowledge, there is only one retro- spective study in the treatment of acute and chronic GvHD that correlated MPA trough levels with clinical response (3). In that study of 21 patients, a trend for a higher mean total MPA trough level was seen in patients responding to MMF. Another study by Jacobson et al. (8) suggested improved outcomes in hematopoietic stem cell transplantation when MMF was used as prophylaxis to prevent acute GvHD. These authors showed that a higher area under the curve of unbound MPA was associated with lower incidence of acute GvHD, and total MPA trough levels of more than 1 mg/L correlated with higher cumulative incidence of engraftment but not with prevention of GvHD. MMF is used as a second line agent with or without cyclosporine (CsA) for treating patients with steroid refractory or dependent GvHD in our center. MPA trough level monitoring is routinely performed in all patients on MMF. Dosage of MMF in patients with hematopoietic stem cell transplant (HSCT) is extrapolated from the phar- macokinetic data in solid organ transplantation but this may not be appropriate as the pharmaco- kinetics of MMF differ with transplant indication (9). Preliminary data from HSCT recipients after standard MMF dosing showed low total MPA Hiwarkar P, Shaw BE, Tredger JM, Brown NW, Kulkarni S, Saso R, Evans S, Treleaven J, Davies FE, Ethell ME, Morgan GJ, Potter MN. Mycophenolic acid trough level monitoring: relevance in acute and chronic graft versus host disease and its relation with albumin. Clin Transplant 2011: 25: 222–227. ª 2010 John Wiley & Sons A/S. Abstract: Mycophenolate mofetil (MMF) is used to treat acute and chronic graft versus host disease (GvHD). There is scant evidence in the literature about mycophenolic acid (MPA) trough level monitoring in GvHD. We therefore reviewed 32 patients treated with MMF for acute (n = 19) or chronic GvHD (n = 13). Twelve (63%) of 19 patients with acute GvHD and nine (69%) of 13 with chronic GvHD showed a good response. In all 21 patients who responded to MMF, their mean total MPA levels were ther- apeutic (1–3.5 mg/L), whereas five of 11 patients who did not respond had sub-therapeutic mean MPA levels (p = 0.002). Sixteen (66%) of 24 steroid refractory or dependent patients responded to MMF. Associations between the mean total MPA level for each patient and the corresponding mean serum albumin concentration showed therapeutic mean total MPA levels for all 23 patients with mean albumin ‡31 g/L but sub-therapeutic mean total MPA levels in five of nine patients with mean albumin <31 g/L (p = 0.0006). In conclusion, MMF is efficacious in steroid refractory and dependent acute or chronic GvHD with statistically significant correlation between therapeutic plasma total MPA trough levels and clinical response. Serum albumin levels should be taken into account when considering MMF dose adjustments. P. Hiwarkar a , B.E. Shaw a,b , J.M. Tredger c , N.W. Brown c , S. Kulkarni a , R. Saso a , S. Evans a , J. Treleaven a , F.E. Davies a , M.E. Ethell a , G.J. Morgan a and M.N. Potter a a Department of Haematology-Oncology, Royal Marsden Hospital, Downs Road, Surrey, b The Anthony Nolan Trust, London and c Institute of Liver Studies, KingÕs College Hospital, Denmark Hill, London, UK Key words: graft versus host disease (GvHD) – mycophenolate mofetil – mycophenolic acid levels – serum albumin Corresponding author: P. Hiwarkar, Department of Haematology-Oncology, Royal Marsden Hos- pital, Downs Road, Surrey SM2 5PT, UK. Tel.: 020 86426011; fax:020 78138265; e-mail: drhprashant@doctors.net.uk Accepted for publication 11 January 2010 Clin Transplant 2011: 25: 222–227 DOI: 10.1111/j.1399-0012.2010.01226.x ª 2010 John Wiley & Sons A/S. 222