A Prospective Randomized Trial of Mycophenolate Mofetil With Neoral or Tacrolimus After Orthotopic Liver Transplantation1,2

Fisher, Robert A.; Ham, J. M.; Marcos, Amadeo; Shiffman, Mitchell L.; Luketic, Velimir A.; Kimball, Pam; Sanyal, Arun J.; Wolfe, Luke; Chodorov, Amy; Posner, Marc P.

doi:10.1097/00007890-199812270-00008

Cited by 83 publications

(50 citation statements)

References 16 publications

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“…Another study also confirmed that allograft rejection is linked to the indirect pathway of allorecognition (36). MMF has been shown to attenuate chronic rejection of transplants in rats and humans (37)(38)(39). In addition, graft rejection by DTH-like reactions by Th1 cells has been inferred as playing a role in chronic rejection (1,40).…”

Section: Discussionmentioning

confidence: 78%

Mycophenolate Mofetil Impairs the Maturation and Function of Murine Dendritic Cells

Mehling

Grabbe

Voskort

et al. 2000

The Journal of Immunology

168

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The immunosuppressive drug, mycophenolate mofetil (MMF), has been successfully introduced in allogeneic transplantation medicine and, more recently, in the treatment of autoimmune skin disorders. MMF inhibits lymphocyte proliferation via a blockade of the enzyme inosine 5′-monophosphate dehydrogenase, an enzyme on which lymphocytes solely depend to generate the purines necessary for DNA/RNA synthesis. To investigate the effects of MMF on cutaneous immune responses, a murine model of contact hypersensitivity (CHS) was used, with oxazolone or trinitrochlorobenzene as a contact allergen. Compared with the respective vehicle, i.p. applied MMF significantly inhibited the elicitation and, surprisingly, the induction of CHS responses. This prompted further studies into the effects of MMF on Ag presentation. Bone marrow-derived dendritic cells (DC) were cultured with GM-CSF and IL-4 in the presence of MMF and were tested for their Ag-presenting capacity. Sensitization and elicitation of CHS and delayed-type hypersensitivity responses by s.c. injected haptenated DC were reduced upon preincubation of DC with MMF. CHS responses were not impaired upon resensitization, indicating that MMF does not induce hapten-specific immunotolerance. In addition, MMF decreased the ability of DC to stimulate allogeneic T cells in MLR assays. Accordingly, flow cytometric analyses revealed a dose-dependent reduction of the expression of CD40, CD80, CD86, I-A, and ICAM-1 on DC with a concurrent reduction of IL-12 production. These data suggest that MMF, in addition to affecting T lymphocytes, directly affects APC, resulting in an impairment of immune responses. They furthermore point to a possible role of inosine 5′-monophosphate dehydrogenase in the maturation of DC.

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Section: Discussionmentioning

confidence: 78%

Mycophenolate Mofetil Impairs the Maturation and Function of Murine Dendritic Cells

Mehling

Grabbe

Voskort

et al. 2000

The Journal of Immunology

168

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“…These factors that limit the ability to use MMF are not usually seen in kidney transplant patients and explain the differences in dropout rates. Fisher et al reported in their randomized trial of MMF with Neoral versus TAC, that gastrointestinal toxicity and bone marrow suppression were not notable, although the study was limited to a 6-month follow-up, and target dose of MMF at 6 month was 1 g/day (24). This study was not designed to evaluate steroid withdrawal after L Tx, although there appeared to be a slightly higher number of patients in the MMF group that were steroid free.…”

Section: Hematologymentioning

confidence: 96%

A Prospective Randomized Trial of Tacrolimus and Prednisone Versus Tacrolimus, Prednisone and Mycophenolate Mofetil in Primary Adult Liver Transplantation: A Single Center Report1

et al. 2001

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“…[4][5][6][7] In addition, recent studies of liver transplant recipients suggest that MMF may prevent acute rejection in patients who are unable to tolerate calcineurin inhibitors and may be effective in treating unresponsive episode hepatic allograft rejection. [8][9][10] Patient and graft survival rates at 1 year after liver transplantation continue to improve and presently are approaching 85% and 80% at major liver transplant centers in the United States, respectively. Despite these encouraging results, recent reports noted that acute hepatic allograft rejection still occurs in up to 40% to 50% of liver transplant recipients.…”

mentioning

confidence: 99%

A randomized double-blind comparative study of mycophenolate mofetil and azathioprine in combination with cyclosporine and corticosteroids in primary liver transplant recipients

Wiesner

2001

Liver Transplantation

259

152

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Acute hepatic allograft rejection occurs in approximately 50% to 60% of the patients undergoing liver transplantation. In this study, we compared the rate of acute rejection in liver transplant recipients randomized in a doubleblind comparative study to treatment with mycophenolate mofetil (MMF) or azathioprine (AZA), both in combination with cyclosporine and corticosteroids. Five hundred sixty-five primary liver transplant recipients were randomly assigned to treatment with MMF, 1 g twice daily intravenously followed by 1.5 g twice daily orally (n ‫؍‬ 278), or AZA, 1.0 to 2.0 mg/kg/d intravenously followed by oral administration (n ‫؍‬ 287), in combination with cyclosporine and corticosteroids. Patients were followed up for at least 1 year, and efficacy analysis was based on intent-to-treat methods. Acute rejection was defined according to the Banff histological criteria. The two study groups were balanced for demographic and clinical baseline characteristics. The incidence of acute rejection or graft loss was 47.7% in the AZA patients and 38.5% in the MMF patients (P < .03). The incidence of biopsyproven and treated rejection censoring for graft loss was 40.0% in the AZA group versus 31.0% in the MMF group (P < .06). Steroid-resistant rejection requiring treatment with either OKT3 or antithymocyte globulin occurred in 8.2% of AZA patients versus 3.8% in MMF patients (P < .02). Patient and graft survival rates at 1 year posttransplantation were 85.4% in the AZA group and 85.3% in the MMF group (P ‫؍‬ not significant). MMF was superior to AZA in preventing acute rejection in the first 6 months posttransplantation. MMF and AZA were equivalent in preventing graft loss at 1 year, and the safety profiles between the two immunosuppressive agents were similar. (Liver Transpl 2001;7:442-450.)

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A Prospective Randomized Trial of Mycophenolate Mofetil With Neoral or Tacrolimus After Orthotopic Liver Transplantation1,2

Abstract: The use of Mycophenolate Mofetil with N or FK and an identical steroid taper after orthotopic liver transplantation is associated with excellent graft and patient survival, and at 6 months, only 191% of the patients experienced rejection, with a 48% overall infection rate.

Cited by 83 publications

References 16 publications

Mycophenolate Mofetil Impairs the Maturation and Function of Murine Dendritic Cells

Mycophenolate Mofetil Impairs the Maturation and Function of Murine Dendritic Cells

A Prospective Randomized Trial of Tacrolimus and Prednisone Versus Tacrolimus, Prednisone and Mycophenolate Mofetil in Primary Adult Liver Transplantation: A Single Center Report1

A randomized double-blind comparative study of mycophenolate mofetil and azathioprine in combination with cyclosporine and corticosteroids in primary liver transplant recipients

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