Four-Year Follow-Up of Mycophenolate Mofetil for Graft Rescue in Liver Allograft Recipients1

Hébert, Mary F.; Ascher, Nancy L.; Lake, John R.; Emond, Jean; Nikolai, B.; Linna, T. Juhani; Roberts, John P.

doi:10.1097/00007890-199903150-00011

Cited by 109 publications

(55 citation statements)

References 7 publications

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“…9,10 Orally administered MMF is hydrolyzed by esterases to mycophenolic acid, its biologically active component. 11 This reversibly inhibits eukaryotic inosine monophophate dehydroxygenase, blocking the de novo synthesis of the purine guanosine, the effect of which is selective depletion of guanine nucleotide pools.…”

Section: Discussionmentioning

confidence: 99%

Mycophenolate mofetil (MMF) as therapy for refractory chronic GVHD (cGVHD) in children receiving bone marrow transplantation

Busca

Saroglia

Lanino

et al. 2000

Bone Marrow Transplant

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Summary:Mycophenolate mofetil (MMF) is an alternative immunosuppressant which inhibits the proliferation of T and B lymphocytes. The purpose of the present study was to evaluate the safety and efficacy of MMF as salvage therapy for chronic GVHD (cGVHD) in children receiving allogeneic bone marrow transplantation. Fifteen children, 3-16 years of age, who had received grafts from HLA-compatible siblings (n ‫؍‬ 8), partially matched related donors (n ‫؍‬ 2) or matched unrelated donors (n ‫؍‬ 5), developed extensive cGVHD which had proved unresponsive to standard immunosuppressive therapy. Patients were treated with MMF at the dose of 15-40 mg/kg/day in combination with other immunosuppressive therapy for a median of 4 months (range 1-15 months). The overall response rate (complete or partial response) was 60%. Thirteen percent had only minor responses, whereas 27% of patients had progressive disease. Best responses were seen in patients with GI tract (60% of complete responses) or mouth (33% of complete responses) cGVHD and skin involvement (43% of complete responses) that did not include sclerodermatous manifestations. Once MMF was started, improvements in the clinical manifestations of cGVHD allowed a significant reduction of steroids in 45% of patients and discontinuation in 27% of cases. Six patients (40%) experienced adverse events, with gastrointestinal symptoms predominating. Five patients experienced opportunistic infections. MMF was discontinued after 35-180 days in six patients for the following reasons: parents choice (n ‫؍‬ 2), liver toxicity (n ‫؍‬ 1), poor compliance (n ‫؍‬ 2), and no response (n ‫؍‬ 1). In conclusion, these preliminary results suggest that MMF in combination with other immunosuppressive agents may have a role to play in patients with cGVHD. Prospective clinical trials are needed to establish exact indications for therapy and dosage scheduling. Bone Marrow Transplantation (2000) 25, 1067-1071.

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Section: Discussionmentioning

confidence: 99%

Mycophenolate mofetil (MMF) as therapy for refractory chronic GVHD (cGVHD) in children receiving bone marrow transplantation

Busca

Saroglia

Lanino

et al. 2000

Bone Marrow Transplant

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“…77 Persistent cholestasis may be managed by conversion to an alternative immunosuppressive agent, such as mycophenolate mofetil or sirolimus (Table 2). 78,79 Azathioprine Azathioprine is a purine analogue that is metabolized in the liver to 6-mercaptopurine by the enzyme glutathione S-transferase. Azathioprine causes inhibition of nucleic acid synthesis during the S-phase of the cell cycle.…”

Section: Tacrolimusmentioning

confidence: 99%

Intrahepatic cholestasis after liver transplantation

Ben‐Ari

Pappo

Mor

2003

Liver Transplantation

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Cholestasis is a common sequela of liver transplantation. Although the majority of cases remain subclinical, severe cholestasis may be associated with irreversible liver damage, requiring retransplantation. Therefore, it is essential that clinicians be able to identify and treat the syndromes associated with cholestasis. In this review, we consider causes of intrahepatic cholestasis. These may be catego-

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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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Four-Year Follow-Up of Mycophenolate Mofetil for Graft Rescue in Liver Allograft Recipients1

Abstract: MMF seems to be an effective alternative immunosuppressive in patients failing CsA-based conventional therapy. MMF may be of particular benefit in patients who do not tolerate CsA or tacrolimus. The long-term safety profile is similar to that of other immunosuppressives.

Cited by 109 publications

References 7 publications

Mycophenolate mofetil (MMF) as therapy for refractory chronic GVHD (cGVHD) in children receiving bone marrow transplantation

Mycophenolate mofetil (MMF) as therapy for refractory chronic GVHD (cGVHD) in children receiving bone marrow transplantation

Intrahepatic cholestasis after liver transplantation

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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