mycophenolic-acid and Communicable-Diseases

There are limited data as to the effectiveness of mycophenolate mofetil (MMF) plus high-dose corticosteroids for the treatment of acute graft-versus-host disease (aGVHD), and even less data regarding the pharmacokinetic disposition and exposure-response relationship of MMF in individuals with GVHD. MMF pharmacokinetics were studied in a multicenter Blood and Marrow Transplant Clinical Trials Network randomized phase II trial evaluating the effectiveness of MMF as one of 4 agents added to corticosteroids as treatment of aGVHD. Thirty-two of the patients randomized to receive MMF underwent pharmacokinetic sampling in weeks 1 and 2 were studied. Mean age was 41 +/- 13.6 years. Twenty one (65.6%), 5 (15.6%), 6 (18.8%) patients had a complete response (CR), partial response (PR) or lesser response by day 28, respectively. Twenty-five (78.1%), 2 (6.3%), 5 (15.6%) patients had a CR, PR, or other response by day 56 to treatment, respectively. Mycophenolic acid (MPA) pharmacokinetic measurements from weeks 1 and 2 did not correlate with CR at either day 28 or day 56 (P > .07); however, if the mean of weeks 1 and 2 total MPA troughs was >0.5 microg/mL or that of an unbound trough was >0.015 microg/mL, then a significantly greater proportion achieved CR + PR at days 28 and 56. CR + PR at day 28 was observed in 19 of 19 patients (100%) with a mean total trough >0.5 mg/mL, but in only 7 of 13 (54%) with a mean total trough < or =0.5 microg/mL (P = .002). Similarly, CR + PR at day 28 was seen in 15 of 15 patients (100%) with an unbound trough concentration >0.015 microg/mL, but in only 11 of 17 (65%) with an unbound trough concentration < or =0.015 microg/mL (P = .02). There was no association between the pharmacokinetic measures and risk of infection by day 90 or overall survival (OS) at day 180 postrandomization. About one-half of subjects did not achieve the favorable MPA total and unbound trough concentrations. The current practice of MMF 1 gm twice daily dosing provides low plasma concentrations in many patients. Higher doses may improve the efficacy of MMF as aGVHD therapy.

Topics: Adrenal Cortex Hormones; Adult; Area Under Curve; Communicable Diseases; Drug Therapy, Combination; Glucuronides; Graft vs Host Disease; Humans; Immunosuppressive Agents; Liver; Lower Gastrointestinal Tract; Middle Aged; Mycophenolic Acid; Remission Induction; Skin; Survival Analysis; Treatment Outcome

Conventional antibody induction therapy is currently used in heart transplantation despite safety concerns. This 6-month, prospective, randomized, multicenter, open-label study examined whether basiliximab offers a tolerability benefit compared with anti-thymocyte globulin (ATG) while maintaining similar efficacy in de novo heart transplant recipients.. Adult heart transplant recipients were randomized to receive basiliximab (20 mg on Day 0 and Day 4) or ATG (2.5 mg/kg/day for 3 to 5 days) with cyclosporine, mycophenolate mofetil and steroids. The primary safety end-point was a composite of serum sickness, fever, cutaneous rash, anaphylaxis, infection, thrombocytopenia, leukopenia and post-transplant proliferative disease. Efficacy was assessed by a composite end-point of death, graft loss, acute rejection Grade > 1B, acute rejection associated with hemodynamic compromise or treated with antibody therapy, or loss to follow-up, whichever occurred first.. Eighty patients were randomized and analyzed. By Month 6, the incidence of the composite safety end-point was significantly lower with basiliximab than with ATG (50.0% vs 78.6%, p = 0.01), and infectious death was less frequent in the basiliximab group (0 of 38 vs 6 of 42, p = 0.027). The composite efficacy end-point occurred in 24 patients (63.2%) in the basiliximab arm vs 28 patients (66.7%, p = not significant [NS]) receiving ATG. Acute rejection episodes of Grade > or = 1B were reported with similar frequency (50% with basiliximab vs 45.2% with ATG, p = NS); 7 patients (18.4%) in the basiliximab group and 3 (7.1%) in the ATG group had rejection Grade > or = 3A.. These results suggest that basiliximab offers improved tolerability with similar efficacy compared with current polyclonal antibody induction therapy in de novo heart transplant patients.

Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal; Antilymphocyte Serum; Basiliximab; Communicable Diseases; Cyclosporine; Drug Therapy, Combination; Endpoint Determination; Female; Graft Rejection; Heart Transplantation; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Prospective Studies; Recombinant Fusion Proteins; Risk Factors; Steroids; Transplantation Immunology; Treatment Outcome

Topics: Adolescent; Adult; Aged; Antilymphocyte Serum; CD3 Complex; Child; Communicable Diseases; Cyclosporine; Drug Therapy, Combination; Female; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Muromonab-CD3; Mycophenolic Acid; Postoperative Complications; Prospective Studies; Survival Rate; T-Lymphocyte Subsets; Tacrolimus

Topics: Communicable Diseases; Follow-Up Studies; Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Liver Transplantation; Mycophenolic Acid; Postoperative Complications; Prednisone; Tacrolimus

Topics: Adolescent; Adult; Aged; Antilymphocyte Serum; Azathioprine; Communicable Diseases; Cyclosporine; Drug Therapy, Combination; Female; Graft Rejection; Humans; Immunosuppressive Agents; Lung Transplantation; Male; Middle Aged; Mycophenolic Acid; Postoperative Complications; Respiratory Tract Infections; Survival Rate

Topics: ABO Blood-Group System; Adult; Antilymphocyte Serum; Communicable Diseases; Dose-Response Relationship, Drug; Female; Graft Rejection; Graft Survival; Histocompatibility Testing; Humans; Immunosuppressive Agents; Japan; Kidney Diseases; Kidney Transplantation; Male; Mycophenolic Acid; Pilot Projects; Survival Analysis

Topics: Adult; Communicable Diseases; Cyclosporine; Dose-Response Relationship, Drug; Double-Blind Method; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid

Evidence supporting a starting dose of 2 g/day of mycophenolate mofetil (MMF) in combination with tacrolimus (TAC) for renal transplantation (RT) is still limited, but maintaining a dose of <2 g could result in worse clinical outcomes in terms of acute rejection (AR). This study aimed to determine the association between AR and infectious and noninfectious complications after RT with a dose of 1.5 g vs 2 g of MMF. A prospective cohort study was performed with a 12-month follow-up of recipients of RT from living donors with low (1.5 g/day) or standard (2 g/day) doses of MMF. The association between adverse effects and complications and doses of MMF was examined using Cox proportional hazard models, and survival free of AR, infectious diseases, and noninfectious complications was evaluated using the Kaplan-Meier test. At the end of the follow-up, the incidence of infectious diseases was 52% versus 50% (P = .71) and AR was 5% versus 5% (P = .86), respectively. The survival rate free of gastrointestinal (GI) complications requiring medical attention was higher in the low-dose group than in the standard-dose dose (88% vs 45%, respectively; P < .001). The use of 1.5 g/day of MMF confers a reduction in GI complications without an increase in infectious diseases or the risk of AR.

Topics: Communicable Diseases; Drug Therapy, Combination; Graft Rejection; Graft Survival; Hospitals; Humans; Immunosuppressive Agents; Kidney Transplantation; Mexico; Mycophenolic Acid; Prospective Studies; Tacrolimus

Following liver transplantation, acute kidney injury (AKI) and chronic kidney disease occur in 20%-50% and 30%-90% of patients, respectively. Basiliximab, a chimeric monoclonal antibody, is highly effective to prevent rejection in organ transplant recipients, particularly among patients with renal dysfunction who benefit from delayed introduction of calcineurin inhibitors.. The objective of this study was to measure the immunosuppressive effect of basiliximab and its impact on renal failure, lengths of hospital and intensive care unit (ICU) stays and prevalence of infection.. From January 2010 through December 2011, we performed a controlled, nonrandomized study comparing two different immunosuppressive regimens: Group I, 36 transplantation on 34 patients, tacrolimus and corticosteroids de novo with mycophenolate mofetil in cases of renal failure; and Group II, 33 transplantation in 33 patients, corticosteriods and mycophenolate mofetil de novo with basiliximab on day 0 and day 4, and inception of tacrolimus on day 3.. Basiliximab patients (Group II) showed a significantly lower incidence of renal failure requiring replacement therapy (3.03% vs 25%; P = .014). The incidence of acute cellular rejection episodes treated with corticosteriod boluses was also significantly lower (3.03% vs 25%; P = .014). Bacterial, fungal, and cytomegalovirus infection rates were lower in Group II, although the differences were not significant. Similarly, Group II patients had an insignificantly shorter average stay in the hospital (25.9 vs 40.06 days) and the ICU (5.9 vs 8.17 days).. Basiliximab administration with delayed introduction of calcineurin inhibitors may be an effective strategy to reduce post-liver transplantation AKI requiring renal replacement therapy.

Topics: Acute Kidney Injury; Adrenal Cortex Hormones; Antibodies, Monoclonal; Basiliximab; Calcineurin Inhibitors; Chi-Square Distribution; Communicable Diseases; Drug Therapy, Combination; Female; Graft Rejection; Humans; Immunosuppressive Agents; Incidence; Intensive Care Units; Length of Stay; Liver Transplantation; Logistic Models; Male; Middle Aged; Multivariate Analysis; Mycophenolic Acid; Recombinant Fusion Proteins; Risk Factors; Tacrolimus; Time Factors; Treatment Outcome

Posttransplant infection after lung transplantation is a common feature due to the immunodeficiency induced by the immunosuppressive load.. To assess B-cell subsets in lung transplant recipients suffering at least one episode of infection within the first year posttransplantation.. Twenty-eight lung transplant recipients were enrolled in the study. Their overall mean age was 56.6 ± 10.7 years and 10 were women (35.7%). All recipients were treated with steroids, tacrolimus, and mycophenolate mofetil. B-cell subset levels were measured in peripheral blood before as well as 7, 14, 30, 60, 90, and 180 days posttransplantation.. No difference in the absolute number of B-cell subsets was observed within the first year of follow-up. However, pre-germinal center-activated naïve B cells (Bm2'), defined as IgD(+)CD38(++), were increased among patients displaying infections within the first year. The increased Bm2' subset was accompanied by a decrease in the double negative (CD27(-)IgD(-)) B-cell population.. Infections in lung transplant recipients were associated with an increase in the Bm2' subset even before transplantation. It is possible that Bm2' cells have a role in response to infection in lung transplantation.

Topics: ADP-ribosyl Cyclase 1; Aged; B-Lymphocytes; Biomarkers; Communicable Diseases; Drug Therapy, Combination; Female; Humans; Immunoglobulin D; Immunosuppressive Agents; Lung Transplantation; Lymphocyte Count; Lymphocyte Subsets; Male; Membrane Glycoproteins; Middle Aged; Mycophenolic Acid; Prospective Studies; Steroids; Tacrolimus; Time Factors; Treatment Outcome; Tumor Necrosis Factor Receptor Superfamily, Member 7

Topics: Adolescent; Adult; Aged; Azathioprine; Communicable Diseases; Cyclosporine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Muromonab-CD3; Mycophenolic Acid; Postoperative Complications; Risk Factors