Mycophenolate mofetil : fully utilizing its benefits for GvHD prophylaxis

• Published in: International journal of hematology Vol. 96; no. 1; pp. 10 - 25
• Main Authors: Minagawa, Kentaro, Yamamori, Motohiro, Katayama, Yoshio, Matsui, Toshimitsu
• Format: Journal Article
• Language: English
• Published: Japan Springer Japan 01.07.2012; Springer; Springer Nature B.V
• Subjects: Biological and medical sciences; Biomarkers - metabolism; Cord Blood Stem Cell Transplantation - adverse effects; Graft Survival - drug effects; Graft vs Host Disease - drug therapy; Graft vs Host Disease - prevention & control; Graft-versus-host disease (GvHD); Hematologic and hematopoietic diseases; Hematology; Hematopoietic Stem Cell Transplantation - adverse effects; Histocompatibility; Humans; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - pharmacokinetics; Immunosuppressive Agents - therapeutic use; Medical sciences; Medicine; Medicine & Public Health; Methotrexate - therapeutic use; Mycophenolate acid (MPA); Mycophenolate mofetil (MMF); Mycophenolic Acid - administration & dosage; Mycophenolic Acid - adverse effects; Mycophenolic Acid - analogs & derivatives; Mycophenolic Acid - metabolism; Mycophenolic Acid - pharmacokinetics; Mycophenolic Acid - therapeutic use; Oncology; Prognosis; Review Article; Therapeutic drug monitoring (TDM); Tissue Donors; Mycophenolate mofetil (MMF); Graft-versus-host disease (GvHD); Therapeutic drug monitoring (TDM); Mycophenolate acid (MPA); Immunopathology; Graft versus host disease; Mycophenolic acid; Hematology; Enzyme; Stem cell; IMP dehydrogenase; Enzyme inhibitor; Hematopoietic cell; Homograft; Prevention; Therapeutic drug monitoring; Graft; Oxidoreductases; Immunosuppressive agent; Mycophenolate mofetil; Inosine monophosphate dehydrogenase inhibitor
• ISSN: 0925-5710; 1865-3774; 1865-3774
• DOI: 10.1007/s12185-012-1086-x

Mycophenolate mofetil (MMF) has been widely used for the prophylaxis of graft-versus-host disease (GvHD) in hematopoietic stem cell transplantation (HSCT), based on clinical evidence established in organ transplantations. MMF is not a cytotoxic, but rather a cytostatic agent, and there have been several reports of significant advantages in engraftment as well as greatly reduced stomatitis compared to methotrexate (MTX). MMF has been preferred for MTX-free immunosuppression, especially in reduced intensity conditioning, but it is suitable for GvHD prophylaxis for any type of HSCT. Some clinicians doubt its effectiveness, due to the lack of advantage over MTX in acute GvHD prophylaxis, especially in myeloablative conditioning. Pharmacokinetics studies of mycophenolic acid (MPA), the active form of MMF, show large inter- and intra-patient variation, which make interpretations of its clinical usefulness difficult. Nevertheless, several studies, including ours, have demonstrated that relatively higher area under the curve (AUC) of the MPA group leads to significant suppression of acute GvHD in prophylactic use. We propose a model algorithm for optimal dose finding using therapeutic drug monitoring (TDM) for MPA. Preemptive strategies depending on plasma MPA levels could yield more effective approaches to GvHD prophylaxis, alternative to MTX.