mycophenolic-acid and Opportunistic-Infections

Leukopenia and neutropenia (L/N) may affect treatment decisions, potentially resulting in poor clinical and economic outcomes among kidney transplant recipients (KTRs). The burden of L/N is poorly quantified systematically. This systematic literature review aimed to summarize the incidence of, risk factors for, and clinical and economic outcomes associated with L/N post-KT.. We systematically searched MEDLINE, Embase, and the Cochrane Library (from database inception-June 14, 2021) and conferences (past 3 years) to identify observational studies examining epidemiology, risk factors, or outcomes associated with L/N among adult KTRs.. Of 2081 records, 82 studies met inclusion criteria. Seventy-three studies reported the epidemiology of L/N post-KT. Pooled incidence of neutropenia, defined as absolute neutrophil counts (ANC) <1000/μl, ranged from 13% to 48% within 1-year post-transplant; ANC <500/μl ranged from 15% to 20%. Leukopenia, defined as white blood cell counts <3500/μl, was 19% to 83%. Eleven studies reported independent risk factors associated with L/N post-KT. D+/R- cytomegalovirus status, mycophenolic acid (MPA), and tacrolimus use were the most consistent risk factors across studies. Fourteen studies reported L/N-associated clinical outcomes. We noted a trend toward a positive association between neutropenia and acute rejection/opportunistic infections. Mixed findings were noted on the association between L/N and graft failure or mortality. Dosage modifications of valganciclovir, MPA, cotrimoxazole, and anti-thymoglobulin and the need for granulocyte colony-stimulating factor (G-CSF) use were common with L/N.. Findings suggest post-transplant L/N were common and associated with frequent modifications of immunosuppressive agents, requiring G-CSF use, and rejection or opportunistic infections. Findings highlight the need for interventions to reduce risk of L/N post-KT.

Topics: Adult; Anemia; Graft Rejection; Granulocyte Colony-Stimulating Factor; Humans; Immunosuppressive Agents; Kidney Transplantation; Leukopenia; Mycophenolic Acid; Neutropenia; Opportunistic Infections; Transplant Recipients; Valganciclovir

Over the last 4 decades, cardiac transplantation has become the preferred therapy for select patients with end-stage heart disease. Heart transplantation is indicated in patients with heart failure despite optimal medical and device therapy, manifesting as intractable angina, refractory heart failure, or intractable ventricular arrhythmias. This article provides an overview of heart transplantation in the current era, focusing on the evaluation process for heart transplantation, the physiology of the transplanted heart, immunosuppressive regimens, and early and long-term complications.

Topics: Allografts; Azathioprine; Cardiotonic Agents; Contraindications; Graft Occlusion, Vascular; Graft Rejection; Heart; Heart Failure; Heart Transplantation; Humans; Immunosuppressive Agents; Long-Term Care; Mycophenolic Acid; Neoplasms; Opportunistic Infections; Postoperative Care; Steroids

The last 5 years have seen an expansion of knowledge about the gastrointestinal diseases that may present in haematopoietic stem cell transplant (HSCT) patients and also about new gastrointestinal diseases in this patient population.. This article summarizes the recent opinions and findings regarding gastrointestinal graft-versus-host disease, and viral and other opportunistic gastrointestinal infections that can develop in HSCT patients. This article also discusses the more newly described entities of mycophenolate-mofetil-related gastrointestinal injury and cord colitis syndrome.. This review emphasizes the need for comprehensive clinical information when assessing gastrointestinal endoscopic biopsies from HSCT patients. It is crucial that both clinicians and histopathologists are aware of several specific but rare gastrointestinal diseases that may develop in these patients, because several of these diseases have specific treatments.

Topics: Apoptosis; Gastrointestinal Diseases; Gastrointestinal Tract; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Immunosuppressive Agents; Inflammation Mediators; Mycophenolic Acid; Opportunistic Infections

Mycophenolate mofetil (MMF) is one of the most frequently used immunosuppressive drugs in solid organ transplant recipients. MMF is an inhibitor of inosine-5'-monophosphate, and is able to preferentially inhibit B-cell and T-cell function. The immunosuppressive abilities of MMF have made it one of the most successful anti-rejection drugs in transplant patients, but patients also appear to have increased susceptibility to infections, specifically cytomegalovirus and BK virus. Despite its association with an increased risk of infection, MMF has also exhibited antimicrobial activity against pathogens including hepatitis C, Pneumocystis jirovecii, and human immunodeficiency virus. A thorough understanding of the functions of MMF on the immune system and interaction with infectious pathogens could be helpful in implementing preventative strategies against opportunistic infections in transplant patients.

Topics: Animals; Antifungal Agents; Antiviral Agents; B-Lymphocytes; Clinical Trials as Topic; Graft Rejection; Humans; Immunosuppressive Agents; Mice; Mycophenolic Acid; Opportunistic Infections; Organ Transplantation; Pneumocystis; Rats; T-Lymphocytes; Viruses

Evans syndrome is a rare disorder characterized by combined autoimmune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Standard treatments consist of transfusions, corticosteroids, splenectomy, IVIG, anabolic steroids, vincristine, alkylating agents, or cyclosporine. In a patient with refractory disease, an allogeneic hematopoietic stem cell transplant (HSCT) resulted in complete clinical and serologic remission for more than 30 months. Allogeneic HSCT may be the only current curative therapy for Evans syndrome but may also be complicated by significant toxicities.

Topics: Adrenal Cortex Hormones; Adult; Anemia, Hemolytic, Autoimmune; Antibodies, Monoclonal; Autoimmune Diseases; Combined Modality Therapy; Danazol; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Infliximab; Male; Mycophenolic Acid; Opportunistic Infections; Prednisone; Purpura, Thrombotic Thrombocytopenic; Remission Induction; Salvage Therapy; Splenectomy; Syndrome; Thrombocytopenia; Transplantation Conditioning; Transplantation, Homologous; Vincristine

Topics: Critical Care; Drug Interactions; Humans; Immunosuppressive Agents; Mycophenolic Acid; Opportunistic Infections; Transplantation Immunology

Mycophenolic acid (MPA) plasma concentrations are highly variable on standard-dose mycophenolate mofetil therapy. At creatinine clearances below 25 mL/min, MPA clearance increases as a result of a higher nonprotein-bound fraction. Patients with delayed graft function (DGF) after renal transplantation are exposed to low total MPA concentrations, when risk of rejection is highest. This study investigated the influence of DGF on MPA exposure and on clinical outcome.. Adult renal transplantation patients treated with mycophenolate mofetil, corticosteroids, and either microemulsified cyclosporine (n = 459) or tacrolimus (n = 371) participated in a randomized controlled trial (the Fixed-Dose Concentration-Controlled [FDCC] Study). Abbreviated MPA areas under the curve (AUCs) were obtained on Day 3, Day 10, Week 4, and Month 3, to calculate MPA AUC₀₋₁₂. Free MPA AUC values were available for a subgroup of patients (n = 269).. The overall incidence of DGF was 187 of 830 (23%) and did not differ between cyclosporine-treated (24%) and tacrolimus- (21%) treated patients. The incidence of biopsy-proven acute rejection at 12 months was significantly higher in patients with DGF (13.8% versus 21.4%). Patients with DGF had significantly lower dose-corrected MPA AUC on Day 3 and Day 10. Free MPA fraction and dose-corrected free MPA AUC were significantly higher in patients with DGF, from Day 3 until Month 3. The total number of patients with at least one opportunistic infection was significantly higher in patients with DGF (33.2%) compared with patients without DGF (25.8%) (P = 0.048). Patients with DGF developing opportunistic infections did not have higher total MPA AUC nor higher free MPA AUC compared with those without opportunistic infections.. Patients with DGF have significantly lower dose-corrected MPA AUC in the first month after renal transplantation, presumably as a result of enhanced MPA clearance on account of the elevated MPA free fraction. Because patients with DGF have a higher rate of acute rejection and lower MPA exposure, higher dosing of mycophenolate mofetil in such patients may improve outcome. However, the already increased incidence of opportunistic infections in patients with DGF is a concern.

Topics: Adrenal Cortex Hormones; Adult; Area Under Curve; Creatinine; Cyclosporine; Delayed Graft Function; Drug Interactions; Drug Monitoring; Drug Therapy, Combination; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Mycophenolic Acid; Opportunistic Infections; Tacrolimus; Treatment Failure

To compare the efficacy and safety of mycophenolate mofetil (MMF) and intravenous cyclophosphamide (IVC) as induction treatment for lupus nephritis (LN), by race, ethnicity and geographical region.. A total of 370 patients with active Class III-V LN received MMF (target dose 3.0 g/day) or IVC (0.5-1.0 g/m(2)/month), plus tapered prednisone, for 24 weeks. Renal function, global disease activity, immunological complement (C3 and C4) and anti-dsDNA levels are the outcomes that were assessed in this study.. MMF was not superior to IVC as induction treatment (primary objective). There were important pre-specified interactions between treatment and race (P = 0.047) and treatment and region (P = 0.069) (primary endpoint). MMF and IVC response rates were similar for Asians (53.2 vs 63.9%; P = 0.24) and Whites (56.0 vs 54.2%; P = 0.83), but differed in the combined Other and Black group (60.4 vs 38.5%; P = 0.03). Fewer patients in the Black (40 vs 53.9%; P = 0.39) and Hispanic (38.8 vs 60.9%; P = 0.011) groups responded to IVC. Latin American patients had lower response to IVC (32 vs 60.7%; P = 0.003). Baseline disease characteristics were not predictive of response. The incidence of adverse events (AEs) was similar across groups. Serious AEs were slightly more prevalent among Asians.. MMF and IVC have similar efficacy overall to short-term induction therapy for LN. However, race, ethnicity and geographical region may affect treatment response; more Black and Hispanic patients responded to MMF than IVC. As these factors are inter-related, it is difficult to draw firm conclusions about their importance.

Topics: Adolescent; Adult; Aged; Child; Cyclophosphamide; Drug Administration Schedule; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Lupus Nephritis; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Prednisone; Prospective Studies; Treatment Outcome; Young Adult

Topics: Adrenal Cortex Hormones; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Incidence; Mycophenolic Acid; Nephrotic Syndrome; Opportunistic Infections; Respiratory Tract Infections; Risk Factors; Systemic Vasculitis; Treatment Outcome; Urinary Tract Infections

This open-label, randomized study compared the efficacy of a regimen of corticosteroids and tacrolimus (standard therapy group, n = 79) with a regimen of daclizumab induction therapy in combination with mycophenolate mofetil and tacrolimus (modified therapy group, n = 78) in primary liver transplant recipients. The primary endpoint was biopsy-proven acute rejection (BPAR) at 24 weeks. Secondary endpoints included time to rejection and patient and graft survival. The incidence of BPAR was significantly reduced in the modified therapy group compared to the standard therapy group (11.5% versus 26.6%, respectively, P = 0.017). The time to rejection was significantly shorter in the standard therapy group compared with the modified therapy group (P = 0.044). There was no significant difference between groups in patient or graft survival. Hepatitis C virus-positive patients exhibited no differences from hepatitis C virus-negative patients with respect to the incidence of BPAR. A steroid-sparing regimen of daclizumab, mycophenolate mofetil, and tacrolimus was effective and well tolerated in the prevention of BPAR in adult liver transplant recipients in comparison with a standard regimen of tacrolimus and steroids.

Topics: Acute Disease; Adolescent; Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Daclizumab; Drug Therapy, Combination; Female; Graft Rejection; Humans; Immunoglobulin G; Immunosuppressive Agents; Incidence; Kaplan-Meier Estimate; Liver Transplantation; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Prospective Studies; Steroids; Tacrolimus; Young Adult

Immunosuppressive regimens with the fewest possible toxic effects are desirable for transplant recipients. This study evaluated the efficacy and relative toxic effects of four immunosuppressive regimens.. We randomly assigned 1645 renal-transplant recipients to receive standard-dose cyclosporine, mycophenolate mofetil, and corticosteroids, or daclizumab induction, mycophenolate mofetil, and corticosteroids in combination with low-dose cyclosporine, low-dose tacrolimus, or low-dose sirolimus. The primary end point was the estimated glomerular filtration rate (GFR), as calculated by the Cockcroft-Gault formula, 12 months after transplantation. Secondary end points included acute rejection and allograft survival.. The mean calculated GFR was higher in patients receiving low-dose tacrolimus (65.4 ml per minute) than in the other three groups (range, 56.7 to 59.4 ml per minute). The rate of biopsy-proven acute rejection was lower in patients receiving low-dose tacrolimus (12.3%) than in those receiving standard-dose cyclosporine (25.8%), low-dose cyclosporine (24.0%), or low-dose sirolimus (37.2%). Allograft survival differed significantly among the four groups (P=0.02) and was highest in the low-dose tacrolimus group (94.2%), followed by the low-dose cyclosporine group (93.1%), the standard-dose cyclosporine group (89.3%), and the low-dose sirolimus group (89.3%). Serious adverse events were more common in the low-dose sirolimus group than in the other groups (53.2% vs. a range of 43.4 to 44.3%), although a similar proportion of patients in each group had at least one adverse event during treatment (86.3 to 90.5%).. A regimen of daclizumab, mycophenolate mofetil, and corticosteroids in combination with low-dose tacrolimus may be advantageous for renal function, allograft survival, and acute rejection rates, as compared with regimens containing daclizumab induction plus either low-dose cyclosporine or low-dose sirolimus or with standard-dose cyclosporine without induction. (ClinicalTrials.gov number, NCT00231764 [ClinicalTrials.gov].).

Topics: Adrenal Cortex Hormones; Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Calcineurin Inhibitors; Cyclosporine; Daclizumab; Diabetes Mellitus; Drug Therapy, Combination; Enzyme Inhibitors; Female; Glomerular Filtration Rate; Graft Rejection; Humans; Immunoglobulin G; Immunosuppressive Agents; Kaplan-Meier Estimate; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Prednisone; Sirolimus; Tacrolimus; Treatment Failure

Daclizumab, a humanized monoclonal antibody against the interleukin-2 receptor, reduced the risk of rejection without increasing the risk of infection among renal-transplant recipients and, in a single-center trial, among cardiac-transplant recipients. We conducted a multicenter, placebo-controlled, double-blind study to confirm these results in cardiac-transplant patients.. We randomly assigned 434 recipients of a first cardiac transplant treated with standard immunosuppression (cyclosporine, mycophenolate mofetil, and corticosteroids) to receive five doses of daclizumab or placebo. The primary end point was a composite of moderate or severe cellular rejection, hemodynamically significant graft dysfunction, a second transplantation, or death or loss to follow-up within six months.. By six months, 104 of 218 patients in the placebo group had reached the primary end point, as compared with 77 of the 216 patients in the daclizumab group (47.7 percent vs. 35.6 percent, P=0.007), a 12.1 percent absolute risk reduction and a 25 percent relative reduction. The rate of rejection was lower in the daclizumab group than in the placebo group (41.3 percent vs. 25.5 percent). Among patients reaching the primary end point, the median time to the end point was almost three times as long in the daclizumab group as in the placebo group during the first 6 months (61 vs. 21 days) and at 1 year (96 vs. 26 days). More patients in the daclizumab group than in the placebo group died of infection (6 vs. 0) when they received concomitant cytolytic therapy.. Daclizumab was efficacious as prophylaxis against acute cellular rejection after cardiac transplantation. Because of the excess risk of death, concurrent or anticipated use of cytolytic therapy with daclizumab should be avoided.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Cyclosporine; Daclizumab; Double-Blind Method; Drug Therapy, Combination; Female; Graft Rejection; Heart Transplantation; Humans; Immunoglobulin G; Immunosuppressive Agents; Logistic Models; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Survival Analysis

In an attempt to decrease toxicity in high-risk patients undergoing unrelated donor hematopoietic stem cell transplantation (URD HSCT), we tested a combination of cyclosporine (CSP) and mycophenolate mofetil (MMF) as graft-versus-host disease (GVHD) prophylaxis with the reduced-intensity conditioning regimen fludarabine/melphalan (Flu/Mel). A total of 22 adult patients with advanced myeloid (n=15) and lymphoid (n=7) malignancies were treated. All patients received Flu 25 mg/m2 for 5 days and Mel 140 mg/m2, with CSP 3 mg/kg daily and MMF 15 mg/kg three times a day. The median age was 49 years (range 18-66). Durable engraftment was seen in all but one patient with myelofibrosis. The 1-year nonrelapse mortality was 32%, 27% from GVHD. The cumulative incidence of acute GVHD grade 2-4 and 3-4 was 63 and 41%, respectively. With a median follow-up of 18 months, the disease-free survival (DFS) and overall survival (OS) are 55 and 59%, respectively. For patients with AML and MDS (n=14), the DFS and OS is 71%. For patients undergoing a second transplant (n=14), the DFS and OS is 57%. In conclusion, this regimen is associated with acceptable toxicity but high rates of GVHD in high-risk patients undergoing URD HSCT. Encouraging disease control for patients with advanced myeloid malignancies was observed.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclosporine; Female; Graft Survival; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Premedication; Prospective Studies; Survival Analysis; Tissue Donors; Transplantation Conditioning; Treatment Outcome; Vidarabine

Kidney grafts from suboptimal donors are more likely to suffer the nephrotoxic side-effects of cyclosporine than kidneys from standard donors. In an attempt to avoid the use of cyclosporine, we carried out a prospective study in low-immunological risk recipients of suboptimal kidneys, using an immunosuppressive protocol combining Thymoglobuline in induction with a bi-therapy of mycophenolate mofetil (MMF) and steroids. Patients with panel reactive antibodies (PRA) <50% receiving a first renal transplant from a suboptimal donor (age >or=50, non heart beating, arterial hypertension, or acute renal failure) or a kidney at risk of delayed graft function (DGF) because of a prolonged cold ischaemia time (CIT) of 24 h or more, were eligible for this trial. Between September 1996 and December 1999, 30 patients were enrolled for the trial and treated with MMF 2 g orally, pre-operatively, and 3 g daily, post-operatively; Thymoglobuline 2 mg/kg IV pre-operatively, 1.5 mg/kg IV the next day, and for doses of 1 mg/kg IV given on alternate days; and prednisolone 0.25 mg/kg per day, reduced progressively from the end of the first month to 0.1 mg/kg per day by 3 months post-transplant. Cyclosporine was added only if rejection grade II or higher, or a reduction in MMF below 1 g daily, occurred. Ten patients (30%) suffered from DGF, and one kidney suffered primary non function. Seven patients (24%) suffered acute rejection (six were biopsy proven, 3 grade I and 3 grade II). MMF dosage was reduced in 28 patients because of adverse events, and calcineurin inhibitors were introduced in 16 patients. There were 14 episodes of opportunistic infection (cytomegalovirus (CMV 10), Herpes zoster 2, Listeria monocytogenes 1, Pseudomonas aeuruginosa 1), and 7 malignancies (skin 2, thyroid 1, lung 1, Kaposi's sarcoma 2, post-transplantation lymphoproliferative disorder 1). Mean serum creatinine was 178, 199, 213, and 218 micromol/l at 1, 2, 3 and 5 years after transplantation, respectively. Actuarial patient and graft (after censoring for death) survival was 94% and 83% after 1 year and 79% and 65% after 5 years, respectively. These results show that with the combination of MMF, Thymoglobuline and steroids the use of cyclosporine can be delayed, and in a few cases completely avoided, with good efficacy in terms of prevention of rejection and recovery of renal function. Regardless of acceptable patient and graft survival, side-effects of MMF at the doses used in this protocol were common

Topics: Adult; Aged; Antilymphocyte Serum; Cadaver; Calcineurin Inhibitors; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Neoplasms; Opportunistic Infections; Prospective Studies; Survival Analysis; Tissue Donors

Differences in the incidence, etiology, type, and outcome of infections occurring during the first 6 months after transplantation were evaluated in two consecutive cohorts of kidney recipients who received immunosuppressive regimens based on either azathioprine (plus antilymphocyte globulin, cyclosporine A, and prednisone) (ATG-AZA cohort) or mycophenolate-mofetil (plus cyclosporine A and prednisone) (MMF cohort). The overall incidence of infections in the two cohorts was similar (0.99+/-1.06 infections/patient in the MMF cohort and 1.04+/-0.99 in the ATG-AZA cohort, P=0.3), as was the incidence of bacterial and fungal infections. In patients who received mycophenolate, cytomegalovirus disease occurred at a higher incidence (0.3+/-0.54 vs. 0.1+/-0.34 episodes/patient, P=0.005) and affected the upper gastrointestinal tract more frequently (0.21+/-0.48 vs. 0.025+/-0.16 episodes of cytomegalovirus ulcerative esophagitis, gastritis, or duodenitis per patient; P=0.001). A nonsignificant trend toward a higher recipient survival for patients receiving mycophenolate was noted (100% vs. 95%, P=0.07). In multivariate analysis, the following factors were independently associated with a higher risk of cytomegalovirus disease: the serostatus R-/D+ (seronegative recipients who received a kidney from a seropositive donor) (RR=35.7 [95%CI, 7.4-166.7]), treatment with mycophenolate (RR=10.4 [95%CI, 2.7-38.4]), and the development of any episodes of acute rejection (RR=10.1 [95%CI, 2.5-41.6]). These data show that kidney recipients receiving mycophenolate have a higher incidence of cytomegalovirus disease, mainly affecting the upper gastrointestinal tract, compared to those receiving azathioprine-based immunosuppression.

Topics: Adult; Azathioprine; Bacterial Infections; Cohort Studies; Drug Therapy, Combination; Female; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Mycoses; Opportunistic Infections; Prospective Studies; Treatment Outcome; Virus Diseases

Topics: Adrenal Cortex Hormones; Age Factors; Creatinine; Drug Therapy, Combination; Female; Follow-Up Studies; Graft Rejection; Humans; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Postoperative Complications; Prednisone; Tacrolimus; Time Factors; Transplantation, Homologous

Acute rejection episodes (ARE) of kidney transplants are considered as risk factor in the development of chronic rejection. In adult renal transplantation (RTx), ARE have been significantly reduced by mycophenolate mofetil (MMF) in combination with cyclosporin (CyA) and steroids (Pred). Reports of pediatric RTx on a maintenance immunosuppression with MMF are restricted to patients (P) after antibody induction therapy.. The efficacy and safety of MMF combined with CyA and Pred in pediatric RTx without induction therapy were evaluated in an open-labeled multicenter study.. From 10/1996 to 6/1999, 65 pediatric P (MMF group) were followed for at least 6 months, 58 of 65 for 12 months. These P were compared with 54 retrospectively analyzed pediatric P who were transplanted between 1990 and 1996 and had received CyA, Pred, and azathioprine for immunosuppression (historic AZA group). Within the first 6 months after RTx, 18 of 65 (MMF group) and 32 of 54 (historic AZA group) P showed clinical signs of acute rejection (P<0.01). Thereafter only one further P in the MMF group developed a first ARE. Graft loss due to rejection occurred in one MMF- and seven AZA-treated P (P<0.05). The creatinine-clearance 3 and 6 months after RTx was higher in the MMF group. Major adverse events (MMF group) included infections of the urinary and the upper respiratory tract, diarrhea, and leukopenia. Cytomegalovirus-infection occurred in 13 P and 2 P developed cytomegalovirus disease. One P developed PTLD 10 months after RTx and recovered after the reduction of immunosuppression.. The combination of MMF, CyA, and Pred reduced ARE in pediatric RTx without incurring major side effects.

Topics: Adolescent; Child; Cyclosporine; Drug Therapy, Combination; Female; Glucocorticoids; Graft Rejection; Humans; Immunosuppressive Agents; Incidence; Kidney; Kidney Transplantation; Male; Mycophenolic Acid; Opportunistic Infections; Patient Dropouts; Prednisone; Prospective Studies; Survival Analysis; Treatment Outcome

Topics: Adrenal Cortex Hormones; Cyclosporine; Diabetes Mellitus; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Infections; Kidney Transplantation; Leukopenia; Male; Mycophenolic Acid; Opportunistic Infections; Postoperative Complications; Prednisolone; Survival Rate

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).

Topics: Adolescent; Adrenal Cortex Hormones; Bone Marrow Transplantation; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Combined Modality Therapy; Cyclosporine; Drug Resistance; Female; Gastrointestinal Diseases; Graft vs Host Disease; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Opportunistic Infections; Prodrugs; PUVA Therapy; Safety; Transplantation, Homologous; Treatment Outcome

In simultaneous kidney-pancreas (SPK) transplantation, manifestations of renal allograft rejection typically become evident before those of pancreatic rejection. This study compared mycophenolate mofetil (MMF) and azathioprine (AZA) in prevention of renal rejection after primary SPK transplantation.. In an open-label, randomized, multicenter study, patients received MMF 1.5 g twice daily (n=74) or AZA 1-3 mg/kg daily (n=76) for 1 year after transplantation. The incidence of rejection was assessed at 6 months. Adverse events were tracked through 1 year. Survival data are reported through 2 years.. At 6 months, efficacy results for MMF vs. AZA patients, respectively, were the following: rejection (27% vs. 39%); rejection or death (34% vs. 42%); rejection, graft loss, death, or premature withdrawal (i.e., treatment failure; 41% vs. 55%). Six-month efficacy trends favored MMF, and time to rejection or treatment failure was significantly longer when compared with AZA (P=0.049). One-year efficacy results for MMF vs. AZA patients, respectively, were the following: treatment of renal rejection (35% vs. 47%); renal allograft loss or death (9% vs. 12%); pancreas allograft loss or death (15% vs. 14%). Five MMF patients (7%) and four (5%) in the AZA group died. More MMF than AZA patients developed opportunistic infections (54% vs. 38%), but the pathogens did not differ.. Trends for most efficacy parameters favored MMF over AZA, and time to renal allograft rejection or treatment failure was statistically significantly longer for MMF. The use of MMF in the treatment of SPK recipients is a useful advance.

Topics: Acute Disease; Azathioprine; Biopsy; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid; Opportunistic Infections; Pancreas Transplantation; Prospective Studies; Transplantation, Homologous

Topics: Adrenal Cortex Hormones; Biopsy; Cyclosporine; Drug Therapy, Combination; Female; Gastrointestinal Diseases; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Leukopenia; Male; Mycophenolic Acid; Opportunistic Infections; Postoperative Complications; Prednisolone; Thrombocytopenia

This report extends the randomized, double-blind, multicenter trial at 14 centers in the United States that compared triple-therapy regimens containing mycophenolate mofetil (MMF), 2 or 3 g, with a similar regimen containing azathioprine (AZA) in recipients of cadaveric renal allografts. We investigated the continued long-term use of MMF with respect to graft and patient survival, graft function, and safety. All patients who received the study drug (MMF, 2 g, n = 165; MMF, 3 g, n = 166; AZA, n = 164) were included in the 3-year intent-to-treat evaluation of graft and patient survival. At 3 years posttransplantation, the weighted pairwise difference was 6.5%, and 95% confidence interval in graft and patient survival (ie, patients alive with a functioning graft) was -2.1 to 15.1 (P = 0.17) numerically in favor of MMF, 2 g, compared with AZA. Similar to the 1-year data, the principal adverse events were limited to the gastrointestinal and hematologic systems. Although cytomegalovirus (CMV) tissue-invasive disease occurred more often in the MMF-treated groups, most instances occurred during the first year posttransplantation. One patient in the AZA group and one patient in the MMF 2-g group developed lymphoma, whereas three patients in the MMF 3-g group developed lymphoma at 3 years posttransplantation. In conclusion, although the design of the study did not afford adequate statistical power to address survival end points, at 3 years posttransplantation, graft survival, patient survival, renal function, and safety were similar among the AZA, MMF 2-g, and MMF 3-g groups. There was an increased incidence of infection caused by invasive CMV and Aspergillus spp and mucormycosis seen in the MMF groups, but the long-term data confirm MMF is a safe and valuable addition to the range of drugs available to prevent rejection.

Topics: Azathioprine; Cadaver; Double-Blind Method; Follow-Up Studies; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid; Opportunistic Infections; Survival Rate

Adding a fixed dose of 1 g b.i.d. of mycophenolate mofetil (MMF) to an immunosuppressive regimen consisting of cyclosporine and prednisone results in a 50% reduction in the incidence of acute rejection after kidney transplantation. This study was designed to investigate the relationship between pharmacokinetic data (mycophenolic acid area under the curve; MPA AUC) and the prevention of rejection after kidney transplantation.. A total of 154 adult recipients of a primary or secondary cadaveric kidney graft were randomly allocated, in this double-blind trial, to receive MMF treatment aimed at three predefined target MPA AUC values (16.1, 32.2, and 60.6 microg x hr/ml). During the first 6 months after transplantation, plasma samples for nine AUCs were collected. After analysis of the samples, a coded dose adjustment advice was generated using a Bayesian algorithm, maintaining the double blinding. Immunosuppressive therapy further consisted of cyclosporine and prednisone. The primary end point of this study was the occurrence of biopsy-proven acute rejection within the 6-month study period.. A total of 150 patients were eligible for analysis. Although after day 21, the mean MMF dose was reduced, the mean MPA AUC gradually increased and target MPA AUC values were exceeded in all three groups. The incidences of biopsy-proven acute rejection in the low, intermediate, and high target MPA AUC groups were 14 of 51 (27.5%), 7 of 47 (14.9%), and 6 of 52 (11.5%), respectively. The incidences of premature withdrawal from the study due to adverse events in the three groups were 4 of 51 (7.8%), 11 of 47 (23.4%), and 23 of 52 (44.2%), respectively. Logistic regression analysis showed a highly statistically significant relationship between median ln(MPA AUC) and the occurrence of a biopsy-proven rejection (P<0.001). The logistic regression using median ln(Cpredose) was also statistically significant for this relationship (P=0.01), whereas it was not when using mean MMF dose (P=0.082). In contrast, the logistic regression using mean MMF dose for comparison of patients who successfully completed the study versus patients experiencing premature withdrawal due to adverse events was highly significant (P<0.001), whereas this was not significant when using median ln(Cpredose) (P=0.512) or median ln(MPA AUC) (P=0.434).. MPA Cpredose and MPA AUC are significantly related to the incidence of biopsy-proven rejection after kidney transplantation, whereas MMF dose is significantly related to the occurrence of adverse events.

Topics: Acute Disease; Administration, Oral; Adult; Cyclosporine; Drug Therapy, Combination; Female; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Incidence; Kidney; Kidney Transplantation; Logistic Models; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Pharmacokinetics; Pharmacology; Prednisone; Severity of Illness Index; Survival Rate

Mycophenolate mofetil (MMF) prolongs allograft survival in experimental animals, prevents acute rejection in humans, and has recently been approved for use in renal transplantation in combination with cyclosporine. Tacrolimus (Prograf) has been shown to be effective for the prevention and treatment of allograft rejection in liver transplantation. However, there has been limited experience with the combination of tacrolimus and MMF in liver transplantation.. This retrospective pilot study examined the results in 130 primary, consecutive, adult liver transplants under two separate immunosuppressive protocols. Patients in the study group received MMF (1 g p.o. b.i.d.), tacrolimus (0.1 mg/kg p.o. b.i.d.), and a standard steroid taper. MMF was also tapered and then discontinued within 3 months of transplantation. A historical control received tacrolimus (0.15 mg/kg p.o. b.i.d.) and the same steroid taper.. Pretransplant demographics, including creatinine, were not significantly different between the groups. The 6-month patient and graft survivals of 96.3% (control) versus 92.0% (study) were not significantly different. The incidence of acute rejection was 45.0% in the control group versus 26.0% in the study group (P = 0.03). The study group had a lower incidence of rejection (mean episodes/patient +/- SEM): 0.28+/-0.07 vs. 0.61+/-0.10 (P = 0.007). All of the study group members responded to high-dose steroids. In the control group, three patients required monoclonal antibody therapy and two patients required the addition of MMF. The incidence of cytomegalovirus was similar in the study group and the control group (13.8% vs. 10.0%, P = NS). Early renal function was better preserved in the tacrolimus/MMF group (mean creatinine +/- SEM): 1.09 mg/dl +/- 0.05 vs. 1.51 mg/dl +/- 0.08 at 30 days, P = 0.0001. The study design required dosing with less tacrolimus (mean mg/day +/- SEM), which was achieved at 1 week (23.2+/-0.7 vs. 13.5+/-0.5); 1 month (18.7+/-0.8 vs. 11.4+/-0.5); 3 months (14.5+/-0.6 vs. 9+/-0.5); and 6 months (11.6+/-0.6 vs. 8.2+/-0.6); P = 0.0001, for all time points.. Combination therapy with tacrolimus and MMF may significantly reduce the incidence of acute liver allograft rejection, allow a significant reduction in tacrolimus dosage, and decrease the incidence of nephrotoxicity. Long-term analysis will be necessary to assess any increased risk of opportunistic infections.

Topics: Drug Therapy, Combination; Female; Glucocorticoids; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Methylprednisolone; Middle Aged; Muromonab-CD3; Mycophenolic Acid; Opportunistic Infections; Pilot Projects; Retrospective Studies; Survival Analysis; Tacrolimus; Transplantation Immunology

Topics: Adrenal Cortex Hormones; Antilymphocyte Serum; Cyclosporine; Drug Therapy, Combination; Graft Rejection; Humans; Immunosuppressive Agents; Incidence; Kidney Transplantation; Living Donors; Muromonab-CD3; Mycophenolic Acid; Opportunistic Infections; Prospective Studies; Transplantation, Homologous

Mycophenolate mofetil (MMF) has been shown to reduce the incidence of acute graft rejection in three controlled trials of cadaveric renal transplantation. In a U.S. trial using quadruple sequential induction therapy as control, the MMF 2-g treatment group had an acute rejection rate 40.6% lower than control in the first posttransplant year (27.9% MMF-treated versus 47.0% control). The purpose of this analysis is to evaluate the economic implications of these clinical differences. The analysis relies on resource use data from the trial and other sources. Medical costs were estimated using a societal perspective and excluded the cost of the transplant procedure and organ acquisition. The two groups were compared in terms of treatment for acute rejection and opportunistic infection, graft survival, dialysis use, and maintenance immunosuppression. The results suggest that, on average, when compared with standard therapy, patients treated with MMF are likely to have lower rejection-related treatment costs because of a lower incidence of rejection ($6237 versus $3702), lower dialysis and graft failure costs because of improved graft survival ($20,104 versus $16,972), no difference in opportunistic infection treatment costs ($1962 versus $1962), and higher additional immunosuppression costs ($855 versus $5170). Taken together, these results suggest that patients treated with MMF are, on average, likely to have slightly lower first-year costs ($29,158 versus $27,807) compared with control, indicating that MMF treatment is cost-effective in the first year. These results remained stable under sensitivity analyses, with plausible variation in the rates of acute rejection, graft survival, and infection.

Topics: Acute Disease; Azathioprine; Cadaver; Cost-Benefit Analysis; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid; Opportunistic Infections; Time Factors

Topics: Adrenal Cortex Hormones; Adult; Aged; Biopsy, Needle; Cyclosporine; Drug Therapy, Combination; Europe; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Postoperative Complications; Survival Rate; Transplantation, Homologous; Treatment Failure

Mycophenolate mofetil (MMF) is a new immunosuppressive drug that selectively inhibits de novo purine synthesis. It has been tested in three large double-blind controlled trials for the prevention of rejection in renal transplant patients. These studies indicate that the use of MMF dramatically decreases the incidence of biopsy-proven rejection, the use of multiple courses of steroids for rejection, and the use of antilymphocyte preparations for treatment of rejection. The drug was well tolerated with an acceptable safety profile. The main side effects were gastrointestinal (nausea, vomiting, diarrhea), but seldom resulted in the cessation of drug therapy. Hematologic side effects similar to those with azathioprine occurred and were reversible. There was a slight increase in CMV-invasive disease with the use of MMF, but no deaths. Rates of malignancy were within published ranges for transplant recipients. Mycophenolate mofetil is a safe and efficacious drug for prevention of rejection in kidney transplant recipients.

Topics: Antilymphocyte Serum; Azathioprine; Cytomegalovirus Infections; Diarrhea; Double-Blind Method; Graft Rejection; Humans; Immunosuppressive Agents; Incidence; Kidney Transplantation; Mycophenolic Acid; Nausea; Neoplasms; Opportunistic Infections; Placebos; Purines; Safety; Steroids; Vomiting

Immunoglobulin replacement therapy is recommended in case of severe hypogammaglobulinemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the supposed increased risk of infection in case of hypogammaglobulinemia has not been confirmed in allo-HSCT. In this study, we assessed the relationship between the gamma globulin level and the risk of infection during the 100 days following the allo-HSCT.. We gathered the weekly laboratory tests from day 7 to day 100 of 76 allograft patients, giving a total of 1 044 tests. 130 infections were documented clinically, by imaging, or microbiologically.. Average gamma globulin levels between D-7 and D100 did not differ between patients with or without infection (642 ± 232 and 671 ± 246 mg/dL, respectively, P = .65). Gamma globulin level <400 mg/dl was not associated with the occurrence of infection between the test studied and the next one (aOR 1.33 [0.84-2.15], P = .24). The gamma globulin level was not predictive of bacterial or fungal infections (AUC 0.54 [95%CI: 0.47-0.61]) nor of viral reactivations (AUC 0.51 [95%CI: 0.43-0.60]).. This confirmed that the humoral deficiency is a minor part of the immune deficiency in the 100 days post-transplant. This questions the relevance of the indications of immunoglobulin substitution during this period.

Topics: Aged; Bacterial Infections; Cyclosporine; Female; gamma-Globulins; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulins, Intravenous; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Leukemia; Lymphoma; Male; Middle Aged; Mycophenolic Acid; Mycoses; Myeloablative Agonists; Myelodysplastic Syndromes; Opportunistic Infections; Prognosis; ROC Curve; Transplantation Conditioning; Transplantation, Homologous; Virus Activation

The efficacy and safety of minimisation of immunosuppression including early steroid withdrawal in kidney transplant recipients treated with Basiliximab induction remains unclear.. This retrospective cohort study reports the outcomes from 298 consecutive renal transplants performed since 1st July 2010-June 2013 treated with Basiliximab induction and early steroid withdrawal in low immunological risk patients using a simple immunological risk stratification and 3-month protocol biopsy to optimise therapy. The cohort comprised 225 low-risk patients (first transplant or HLA antibody calculated reaction frequency (CRF ≤50% with no donor specific HLA antibodies) who underwent basiliximab induction, steroid withdrawal on day 7 and maintenance with tacrolimus and mycophenolate mofetil (MMF), and 73 high-risk patients who received tacrolimus, MMF and prednisolone for the first 3 months followed by long term maintenance immunosuppression with tacrolimus and prednisolone. High-risk patients not undergoing 3-month protocol biopsy were continued on triple immunosuppression.. Steroid withdrawal could be safely achieved in low immunological risk recipients with IL2 receptor antibody induction. The incidence of biopsy-proven acute rejection was 15.1% in the low-risk and 13.9% in the high-risk group (including sub-clinical rejection detected at protocol biopsy). One- year graft survival was 93.3% and patient survival 98.5% in the low-risk group, and 97.3 and 100% respectively in the high-risk group. Graft function was similar in each group at 1 year (mean eGFR 61.2 ± 23.4 mL/min low-risk and 64.6 ± 19.2 mL/min high-risk).. Immunosuppression regimen comprising basiliximab induction, tacrolimus, MMF and prednisolone with early steroid withdrawal in low risk patients and MMF withdrawal in high risk patients following a normal 3-month protocol biopsy is effective in limiting acute rejection episodes and produces excellent rates of patient survival, graft function and complications.

Topics: Adult; Aged; Azathioprine; Basiliximab; Drug Administration Schedule; Female; Glucocorticoids; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Postoperative Care; Postoperative Complications; Prednisolone; Receptors, Interleukin-2; Renal Insufficiency, Chronic; Retrospective Studies; Risk Assessment; Tacrolimus; Young Adult

The clinical course and outcomes of immunocompromised patients, such as transplant recipients, with COVID-19 remain unclear. It has been postulated that a substantial portion of the disease burden seems to be mediated by the host immune activation to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, we present a simultaneous heart-kidney transplant (SHKT) recipient who was hospitalized for the management of respiratory failure from volume overload complicated by failure to thrive, multiple opportunistic infections, and open non-healing wounds in the setting of worsening renal dysfunction weeks prior to the first case of SARS-CoV-2 being detected in the state of Connecticut. After his third endotracheal intubation, routine nucleic acid testing (NAT) for SARS-CoV-2, in anticipation of a planned tracheostomy, was positive. His hemodynamics, respiratory status, and ventilator requirements remained stable without any worsening for 4 weeks until he had a negative NAT test. It is possible that the immunocompromised status of our patient may have prevented significant immune activation leading up to clinically significant cytokine storm that could have resulted in acute respiratory distress syndrome and multisystem organ failure.

Topics: Antibiotics, Antineoplastic; Bacteremia; BK Virus; Cardiomyopathy, Dilated; Cardiotoxicity; COVID-19; COVID-19 Nucleic Acid Testing; Doxorubicin; Graft Rejection; Gram-Positive Bacterial Infections; Heart Transplantation; Humans; Immunocompromised Host; Immunosuppressive Agents; Incidental Findings; Kidney Failure, Chronic; Kidney Transplantation; Male; Malnutrition; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Polyomavirus Infections; Postoperative Complications; Prednisone; Renal Dialysis; SARS-CoV-2; Staphylococcal Infections; Surgical Wound Infection; Tacrolimus; Tracheostomy; Tumor Virus Infections; Vancomycin-Resistant Enterococci; Viremia; Water-Electrolyte Imbalance

Since there are only a few reports on pediatric systemic lupus erythematosus (pSLE) in Chinese populations, therefore we retrospectively report the clinical and immunological features as well as renal outcome in Chinese pSLE.. Patients diagnosed with pSLE at Shanghai Children's Medical Center between 2001 and 2016 were evaluated and clinical data were retrospectively collected.. A total of 102 pSLE patients were analyzed. Renal disorder including proteinuria (81.37%) and hematuria (65.69%) were most commonly identified. Class IV was the most common finding on renal biopsy. In lupus nephritis (LN), 67.21%, 78.0%, 86.0% and 94.55% achieved complete remission within 6, 12, 18 and 24 months, respectively. Furthermore, 16.67% of LN patients suffered at least one renal flare. Antinuclear antibodies were detected in nearly all patients (97.62%), followed by anti-double-stranded DNA (anti-dsDNA) antibodies (70.0%) and anti-Sjögren's syndrome A (anti-SSA) antibodies (60.64%). Oral corticosteroid (93.14%) and mycophenolate mofetil (64.71%) was used in the majority of patients. Infection (32.35%) was the main side effect caused by the medications.. Our population-based pSLE cohort indicated that compared to other international cohorts, there was a higher prevalence of LN in Chinese pSLE. Proteinuria was the most frequent manifestation both at disease onset and during the entire clinical course. Class IV LN was the dominant renal pathological type. Nevertheless, there was a favorable renal remission rate and relatively low incidence of renal flare in our cohort. Apart from antinuclear antibodies and anti-dsDNA antibodies, anti-SSA antibodies were most frequently detected. Infection was the leading complication caused by the medications.

Topics: Adolescent; Adrenal Cortex Hormones; Age of Onset; Antibodies, Antinuclear; Biomarkers; Child; China; Female; Hematuria; Humans; Immunocompromised Host; Incidence; Lupus Erythematosus, Systemic; Lupus Nephritis; Male; Mycophenolic Acid; Opportunistic Infections; Prevalence; Proteinuria; Remission Induction; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome

The immunosuppressant agents in kidney transplantation (KT) may lead to various complications such as opportunistic infections and malignancies. BK virus associated nephropathy is a significant complication following KT, and it can result in graft failure. BK virus causes tubulointerstitial nephritis, ureter stenosis, and even graft failure in KT recipients with impaired immune system. We described a 63-year-old woman, who was a hepatitis C carrier and on dialysis for 22 years before KT, who received cadaveric-donor KT 2 years previously. She reported decreasing urine output and general weakness. The serum creatinine level was slightly increased from 2.94 to 4.38 mg/dL.. Immunosuppressant medications including prednisolone, everolimus, cyclosporin, and mycophenolate sodium were continued as maintenance therapy post KT. Kidney biopsy was performed due to deterioration of graft function.. The kidney biopsy showed consistent results with early-stage polyomavirus nephropathy, characterized by focal viral cytopathic changes with positive immunohistochemical signals and mesangial proliferative glomerulonephritis, immune-complex-mediated (Fig 1 and Fig 2). Negative C4d staining at peritubular capillary was reported. The dosage of mycophenolate sodium was tapered from 720 to 360 mg daily and that of everolimus increased from 0.5 to 1.0 mg daily due to BK viral infection with BK nephropathy. The serum creatinine level was 2.75 mg/dL after treatment.. Early detection of BK nephropathy and decreasing immunosuppressant agents are the mainstay of treatment. Substituting leflunomide for mycophenolate sodium and increasing dosage of everolimus has been proposed to solve BK nephropathy. We presented that the use of leflunomide in such situation is in a timely manner.

Topics: BK Virus; Everolimus; Female; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Transplantation; Leflunomide; Middle Aged; Mycophenolic Acid; Nephritis, Interstitial; Opportunistic Infections; Polyomavirus Infections; Transplantation, Homologous; Tumor Virus Infections

To study the response of lupus nephritis (LN) patients with persistent proteinuria (≥ 1 g/day after ≥ 6 months corticosteroid and single immunosuppressant treatment, or ≥ 3 g/day after ≥ 3 months of corticosteroid and single immunosuppressant treatment) to corticosteroid combined with two immunosuppressants, and to evaluate associated factors of response within 1 year.. A retrospective study of proteinuria and renal function observed in LN patients with persistent proteinuria after adding a second immunosuppressant at 3, 6, 9 and 12 months.. Twenty-one LN patients (100.0% female) with persistent proteinuria were treated with corticosteroid and two immunosuppressants (mycophenolate mofetil [MMF] plus cyclosporine A [CSA]). Their mean age and duration from first immunosuppressant to initiating a combination therapy were 33.2 ± 10.2 years and 17.5 ± 15.7 months, respectively. Twelve (57.1%) patients had proteinuria levels ≥ 3 g/day. The renal pathology from 18 patients were Classes III or IV in 11 (61.1%). Fifteen patients (71.4%) responded to treatment (complete remission [CR], proteinuria ≤ 0.5 g/day, in seven patients and partial remission [PR], proteinuria reduced > 50%, in eight patients). Changing from a single immunosuppressant to combined immunosuppressants was associated with CR within 1 year (hazards ratio = 0.88; 95% CI = 0.78-0.99). Adverse events consisted of one patient with severe infection, two herpes zoster and one with transient increased serum creatinine level.. Approximately 70% of LN patients with persistent proteinuria responded to MMF plus CSA. However, infection should be a concern with these patients.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Cyclosporine; Drug Therapy, Combination; Female; Humans; Immunocompromised Host; Immunosuppressive Agents; Lupus Nephritis; Male; Mycophenolic Acid; Opportunistic Infections; Proteinuria; Remission Induction; Retrospective Studies; Time Factors; Treatment Outcome; Young Adult

Immunosuppression is a known risk for post-transplant infections. Little data exist on the risk contributions of specific agents for various infections.. A triply robust propensity score-adjusted analysis was performed in a renal transplant cohort between February 2006 and January 2014. The study was performed to identify the incidence and the risk factors for developing a post-transplant infection. After initial bivariate analysis, a triply robust propensity score-adjusted multivariate logistic regression was performed.. The mean age of the 717 renal transplant recipients was 50.0 ± 13.3 years, with the majority being male (61.6%) and 349 (48.7%) experiencing at least 1 post-transplant infection. Neither race, graft type, nor insurance status was associated with an increased incidence or risk of infection. In a fully adjusted regression model, the immunosuppressants mycophenolic acid mofetil (OR 0.38, 95% CI 0.21-0.71; P < .001) and alemtuzumab (OR 0.40, 95% CI 0.19-0.85; P = .020) were protective.. Alemtuzumab and mycophenolic acid mofetil as immunosuppressant agents in a multiagent protocol appear to decrease the incidence of infection. Cytomegalovirus antigenemia was the greatest risk for infection and mycophenolic acid mofetil possessed the greatest protective effect on viral infections.

Topics: Adult; Alemtuzumab; Case-Control Studies; Community-Acquired Infections; Cross Infection; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Infections; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Propensity Score; Retrospective Studies; Risk Factors; Tacrolimus; Virus Diseases

Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection of the central nervous system caused by JC virus. Only ten cases of PML have been reported so far in liver transplant recipients. We present a case of liver posttransplantation PML with characteristic clinical and brain MRI findings, but with an atypical late onset, developed 11 years after transplantation and after single-drug, long-term (8 years), and low-dose (750 mg twice a day) immunosuppression with mycophenolate mofetil (MMF). This is the latest onset of PML associated to liver transplant reported. The present case should help physicians to be aware of PML after transplantation, even in the long term and even under low doses of immunosuppressants, especially MMF.

Topics: Aged; Brain; Female; Humans; Immunocompromised Host; Immunosuppressive Agents; JC Virus; Leukoencephalopathy, Progressive Multifocal; Liver; Liver Transplantation; Magnetic Resonance Imaging; Mycophenolic Acid; Opportunistic Infections

Transplant recipients are treated with immunosuppressive (IS) therapies, which impact host-microbial interactions. We examined the impact of IS drugs on gut microbiota and on the expression of ileal antimicrobial peptides.. Mice were treated for 14 days with prednisolone, mycophenolate mofetil, tacrolimus, a combination of these 3 drugs, everolimus, or water. Feces were collected before and after treatment initiation. Ileal samples were collected after sacrifice. Fecal and ileal microbiota were analyzed by pyrosequencing of 16S rRNA genes and enumeration of selected bacteria by culture, and C-type lectins were assessed in ileal tissues by reverse transcriptase-quantitative polymerase chain reaction.. Prednisolone disrupted fecal microbiota community structure, decreased Bacteroidetes, and increased Firmicutes in the feces. Prednisolone, tacrolimus, and mycophenolate mofetil modified fecal microbiota at the family level in each experimental replicate, but changes were not consistent between the replicates. In ileal samples, the genus Clostridium sensu stricto was dramatically reduced in the prednisolone and combined IS drug groups. These modifications corresponded to an altered ileal expression of C-type lectins Reg3γ and Reg3β, and of interleukin 22. Interestingly, the combined IS treatment enabled a commensal Escherichia coli to flourish, and dramatically increased colonization by uropathogenic E. coli strain 536.. IS treatment alters innate antimicrobial defenses and disrupts the gut microbiota, which leads to overgrowth of indigenous E. coli and facilitates colonization by opportunistic pathogens.

Topics: Animals; Antimicrobial Cationic Peptides; Drug Therapy, Combination; Escherichia coli Infections; Feces; Gastrointestinal Microbiome; Host-Pathogen Interactions; Ileum; Immunocompromised Host; Immunosuppressive Agents; Lectins, C-Type; Mice, Inbred C57BL; Models, Animal; Mycophenolic Acid; Opportunistic Infections; Prednisolone; Reverse Transcriptase Polymerase Chain Reaction; Ribotyping; Tacrolimus; Time Factors; Urinary Tract Infections; Uropathogenic Escherichia coli

This study aimed to retrospectively analyze the long-term outcome of mycophenolate mofetil (MMF) therapy for microscopic polyangiitis (MPA) with mild to moderate renal involvement in Chinese patients. Thirty-four MPA patients (24 females, 10 males, aged 44.7 ± 17 years, BVAS score 13.8 ± 3.2, SCr 2.2 ± 1.1 mg/dl) with SCr < 5 mg/dl and who received glucocorticoids plus MMF therapy for inducing and maintaining remission were included in this study. The remission and relapse rates, patient and renal survival rates and adverse events were retrospectively analyzed. We found that 31 (91.2 %) of 34 patients achieved remission and were continuously treated with glucocorticoids plus MMF for maintaining remission. The median duration of MMF treatment was 24 months (IQR 15-53 months) and follow-up time was 86 months (IQR 29-124 months). During the follow-up, 7 (22.6 %) patients relapsed, one patient died, and one patient progressed into end-stage renal disease. The 5-year patient and renal survival rates were 92.8 and 95.2 %, respectively. 11 (32.4 %) patients suffered 16 adverse events, 13 of which were pulmonary infection. In conclusion, glucocorticoids plus MMF regimen as induction and maintenance therapy could achieve high remission rate and good long-term renal survival in MPA patients with mild to moderate renal involvement. Prospective controlled trials with a large sample size are needed to confirm the efficacy of MMF in this population.

Topics: Adult; China; Disease Progression; Drug Administration Schedule; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Immunocompromised Host; Immunosuppressive Agents; Kaplan-Meier Estimate; Kidney Diseases; Male; Microscopic Polyangiitis; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Remission Induction; Respiratory Tract Infections; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome

Mizoribine (MZR) is an immunosuppressive agent that exhibits a less potent immunosuppressive effect at doses up to 3 mg/kg/d. We investigated whether high-dose MZR is effective and safe for renal transplant patients in conjunction with cyclosporine (CsA), basiliximab, and corticosteroids. Ninety Japanese renal transplant patients were administered MZR (6 mg/kg/d), CsA (7 mg/kg/d), prednisolone (maintenance dose, 10 mg/d), and basiliximab (20 mg/body). They were compared with a control group of 81 renal transplant patients who received mycophenolate mofetil (MMF; 1500 mg/d), CsA, prednisolone, and basiliximab. The 2-year patient and graft survival rates were 98.9% and 97.8% in the MZR group and 98.8% and 97.5% in the MMF group, respectively. The rejection rate within 2 years after transplantation was 21.1% in the MZR group and 16.0% in the MMF group; the difference was nonsignificant. None of the MZR group developed cytomegalovirus (CMV) disease, whereas 12.3% of the MMF group contracted CMV (P < .0001). CMV viremia developed in 28.9% of the MZR group vs 46.9% of the MMF group (P < .0001); their peak antigen levels were 20.4 ± 44.1 and 252.8 ± 527.0 (P < .01). Furthermore, the incidence of gastrointestinal disorder, hyperlipidemia, and blood disorder was significantly lower in the MZR group than in the MMF group. The combination of high-dose MZR with CsA, basiliximab, and corticosteroids not only provides satisfactory immunosuppression but is also associated with a low incidence of CMV infection and gastrointestinal and blood disorders.

Topics: Adult; Aged; Anemia; Antibodies, Monoclonal; Basiliximab; Case-Control Studies; Cyclosporine; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Gastrointestinal Diseases; Glucocorticoids; Humans; Immunosuppressive Agents; Japan; Kidney Transplantation; Leukopenia; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Prednisolone; Recombinant Fusion Proteins; Ribonucleosides; Viremia; Young Adult

Although rabbit anti-thymocyte globulin (rATG) is commonly used as induction therapy for kidney transplantation, dosing is not standardized. Recently available findings suggest that even subtle differences in the cumulative dose of rATG induction may have an impact on acute rejection rates for patients receiving steroid-minimization maintenance immunosuppression. This investigation evaluated the potential consequences of rounding and capping rATG doses in patients receiving steroid-containing maintenance immunosuppression when calculating the dose based on actual body weight.. Single-center retrospective cohort study.. A large academic medical center.. A total of 261 adult kidney transplant recipients between July 1, 2010, and December 31, 2012, who received rATG induction and were maintained on tacrolimus, mycophenolate, and prednisone.. Incidences of biopsy-confirmed acute rejection, opportunistic infections and hematologic effects within 12 months posttransplant were assessed for patients receiving a cumulative rATG dose of 5 mg/kg or higher (5.2 ± 0.2 mg/kg, n=138) compared with those who received a cumulative rATG dose lower than  5 mg/kg (4.5 ± 0.6 mg/kg, n=123). The groups had similar baseline characteristics, immunologic risk, and indications for rATG induction. The incidence of clinically relevant biopsy-confirmed acute rejection was low and similar between the groups (8.7% for rATG of 5 mg/kg or higher vs 8.9% for rATG lower than  5 mg/kg, p=0.944). Patient survival, all-cause graft survival, and graft function did not differ between the groups. Incidences of cytomegalovirus and BK virus infection as well as the extent and duration of lymphopenia were also similar between the groups.. In combination with triple maintenance immunosuppression consisting of tacrolimus, mycophenolate, and prednisone, modest differences in the cumulative rATG dose were not associated with increased risk of acute rejection. Measures to optimize rATG utilization present opportunities for cost-saving without sacrificing efficacy in this patient population.

Topics: Adult; Animals; Antilymphocyte Serum; Blood Cell Count; Drug Therapy, Combination; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Prednisone; Rabbits; Retrospective Studies; Tacrolimus

Polyomavirus nephropathy is commonly seen in the renal allograft setting but is uncommon in native kidneys. This paper describes polyomavirus nephropathy that developed in the native kidneys of a patient following immunosuppressive therapy for rheumatoid arthritis/Sjögren's syndrome associated lung disease. The patient presented with dyspnoea and a slow steady rise in serum creatinine. Owing to chronic immunosuppression, calcineurin-inhibitor toxicity was suspected. However, renal biopsy revealed polyomavirus nephropathy. The treatment of choice, lowered immunosuppression, was complicated by exacerbation of the patient's lung disease. This case highlights features of polyomavirus nephropathy in the native kidney, as well as the difficulty in its treatment when immunosuppressive treatment is necessary for medical comorbidities.

Topics: Arthritis, Rheumatoid; Humans; Immunosuppressive Agents; Kidney Diseases; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Polyomavirus; Polyomavirus Infections; Pulmonary Fibrosis; Tacrolimus

Data on the efficacy and safety of everolimus in pediatric renal transplantation compared to other immunosuppressive regimens are scarce.. We therefore performed a multicenter, observational, matched cohort study over 4 years post-transplant in 35 patients on everolimus plus low-dose cyclosporine, who were matched (1:2) with a control group of 70 children receiving a standard-dose calcineurin-inhibitor- and mycophenolate mofetil-based regimen.. Corticosteroids were withdrawn in 83% in the everolimus vs. 39% in the control group (p<0.001). Patient and graft survival were comparable. The rate of biopsy-proven acute rejection episodes Banff score ≥ IA during the first year post-transplant was 6% in the everolimus vs. 13% in the control group (p = 0.23). The rate of de novo donor-specific HLA antibodies (11% in everolimus, 18% in controls) was comparable (p = 0.55). At 4 years post-transplant, mean eGFR in the everolimus group was 56±33 ml/min per 1.73 m² vs. 63±22 ml/min per 1.73 m² in the control group (p = 0.14). Everolimus therapy was associated with less BK polyomavirus replication (3% vs. 17% in controls; p = 0.04), but with a higher percentage of arterial hypertension and more hyperlipidemia (p<0.001).. In pediatric renal transplantation, an everolimus-based regimen with low-dose cyclosporine yields comparable four year results as a standard regimen, but with a different side effect profile.

Topics: Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Biomarkers; Child; Child, Preschool; Cohort Studies; Drug Therapy, Combination; Everolimus; Female; Graft Rejection; Graft Survival; HLA Antigens; Hospitalization; Humans; Immunosuppressive Agents; Isoantibodies; Kidney Function Tests; Kidney Transplantation; Male; Mycophenolic Acid; Opportunistic Infections; Retrospective Studies; Tissue Donors; Transplant Recipients; Treatment Outcome

Opportunistic infections cause a significant morbidity and mortality in immunocompromised patients. We describe the case of a patient with skin fusariosis and a probable cerebral toxoplasmosis after UCB stem cell transplantation for B-cell acute lymphoblastic leukaemia. Fusarium species (spp) infections are difficult to treat. To date, there has been no consensus on the treatment of fusariosis and the management of its side effects. Given the negative pretransplant Toxoplasma serology in this case, identifying the origin of the Toxoplasma infection was challenging. All usual transmission routes were screened for and ruled out. The patient's positive outcome was not consistent with that of the literature reporting 60% mortality due to each infection.

Topics: Adolescent; Amphotericin B; Cord Blood Stem Cell Transplantation; Dermatomycoses; Diagnosis, Differential; Drug Therapy, Combination; Febrile Neutropenia; Female; Fusariosis; Gibberella; Humans; Mycophenolic Acid; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pyrimethamine; Retreatment; Sulfadiazine; Toxoplasmosis, Cerebral

Topics: Chronic Disease; Diagnosis, Differential; Female; Granuloma, Lethal Midline; Humans; Immunocompromised Host; Leishmania; Leishmaniasis, Cutaneous; Lupus Erythematosus, Systemic; Lymphoma, T-Cell, Cutaneous; Middle Aged; Mycophenolic Acid; Nose Diseases; Opportunistic Infections; Prednisone; Sjogren's Syndrome; Skin Ulcer

The association of Pneumocystis jirovecii pneumonia (PJP) with connective tissue disease (CTD) and mycophenolate mofetil's (MMF) potent activity against PJP have been separately reported. Until now, there have been no papers describing the occurrence of PJP following MMF treatment in CTD patients. The objective of this study was to describe the clinical features, risk factors, outcomes of PJP in patients with CTD and investigates the effects of MMF on the occurrence of PJP in China. In this retrospective cohort study, we performed a chart review, analyzing clinical features, treatment, and outcomes of PJP in patients with CTD in a single hospital. A total of 17 cases met the inclusion criteria of having PJP and a CTD diagnosis: systemic lupus erythematosus; polymyositis; dermatomyositis; rheumatoid arthritis; Wegener's granulomatosis; and microscopic polyangiitis. Sixteen patients were treated with glucocorticoids (GCs) plus immunosuppressive drugs. Only one patient had GCs without immunosuppressive drugs. Ten subjects (62.5 %) received MMF (1-1.5 g/day), and all ten had lymphopenia. The mortality rates of MMF and non-MMF patients were 50 and 14 %, respectively. This study is the first report of PJP following MMF plus GC treatment in patients with CTD. CTD itself may be a risk factor for PJP. When CTD patients receiving MMF therapy have low lymphocyte counts and/or CD4 lymphocyte counts <250/µL, we should be care of occurrence of PJP.

Topics: Adult; Aged; China; Connective Tissue Diseases; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Immunocompromised Host; Immunosuppressive Agents; Lymphocyte Count; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome

Mycophenolate mofetil (MMF) is used for immunosuppression in myasthenia gravis (MG). Although there are numerous data on associated infection and prophylaxis in transplant patients who are on MMF, data in MG remains lacking. We report two elderly seropositive MG patients who developed cytomegalovirus (CMV) enteritis and Epstein-Barr virus (EBV) encephalitis while on MMF for 5months and 1year, respectively. Chronic MMF therapy in MG patients may trigger life-threatening infections including CMV and EBV diseases, especially in the elderly. Similar to the practice in transplant patients, viral serology testing and appropriate prophylactic regimen with antiviral agents should be considered, particularly in older MG patients.

Topics: Aged, 80 and over; Antiviral Agents; Cytomegalovirus Infections; Encephalitis, Viral; Enteritis; Epstein-Barr Virus Infections; Humans; Immunocompromised Host; Immunosuppressive Agents; Myasthenia Gravis; Mycophenolic Acid; Opportunistic Infections

Cytomegalovirus (CMV) infection remains a major problem in recipients with heart transplantation (HTx), because it may play a significant role in the development of cardiac allograft vasculopathy, which is one of the major causes of death after HTx. Valganciclovir (VGC) is effective for the treatment of CMV infection, but is often associated with neutropenia, especially when used with mycophenolate mophetil (MMF). We experienced an HTx recipient with positive CMV antigenemia who suffered progressive neutropenia after administration of VGC. We switched MMF to everolimus (EVL) and assay for CMV antigenemia was constantly negative even after discontinuation of VGC. In all other 14 HTx recipients who received EVL for any reason, we found that assay for CMV antigenemia remained negative throughout the period of EVL administration. Considering the prophylactic effect on CMV, EVL can not only be an alternative to rescue from comorbidity, but might also be indicated earlier especially in CMV-seronegative HTx recipients.

Topics: Adult; Antigens, Viral; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Drug Substitution; Drug Therapy, Combination; Everolimus; Ganciclovir; Heart Transplantation; Heart-Assist Devices; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Neutropenia; Opportunistic Infections; Sirolimus; Valganciclovir

Topics: Antigens, Viral; Colitis; Colonoscopy; Cytomegalovirus; Cytomegalovirus Infections; Diagnosis, Differential; Female; Humans; Immunocompromised Host; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lupus Nephritis; Methylprednisolone; Mycophenolic Acid; Nocardia Infections; Opportunistic Infections; Pneumatosis Cystoides Intestinalis; Respiratory Tract Infections

A 32 year male presented with deafness and other classical symptoms suggestive of SLE. Subsequent serological investigations confirmed the diagnosis. Renal biopsy showed the presence of SLE induced Grade V nephropathy. Patient was started on NIH protocol for lupus nephritis on which he was doing well. After two years, he presented with symptoms of miliary tuberculosis and was started on ATD. Subsequently, he developed ATD induced hepatotoxicity and had to be switched over to Inj. Streptomycin containing regimen. We thought to share this clinical experience, as we found it a challenge to manage tuberculosis in such a setting, where a fine balance had to be maintained between immunosuppression for SLE and therapy of TB, and an ototoxic drug had to be used in a patient with deafness induced by SLE.

Topics: Adult; Antineoplastic Agents; Antitubercular Agents; Biopsy; Hearing Loss, Sensorineural; Humans; Immunosuppression Therapy; Lupus Erythematosus, Systemic; Lupus Nephritis; Male; Mycophenolic Acid; Opportunistic Infections; Prednisolone; Radiography; Treatment Outcome; Tuberculosis, Miliary

Topics: BK Virus; Drug Labeling; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Mycophenolic Acid; Opportunistic Infections; Red-Cell Aplasia, Pure; United States; Virus Activation

Balancing immunosuppression to prevent rejection while minimizing infection or drug toxicity risk is a major challenge in heart transplantation. Therapeutic drug monitoring alone is inadequate to measure the immune response. An immune monitoring (IM) assay (ImmuKnow; Cylex, Columbia, MD) performed on peripheral blood measures adenosine triphosphatase (ATP) release from activated lymphocytes and may predict the immune state. Therefore, we sought to determine the utility of IM in heart transplant recipients.. Between November 2005 and July 2008, 296 heart transplant recipients had a total of 864 IM assays performed at 2 weeks to 10 years post-transplant and were correlated with infection and rejection events that occurred within 1 month after IM testing. All patients received standard triple-drug immunosuppressive therapy with tacrolimus, mycophenolate mofetil and corticosteroids, without induction therapy.. There were 38 infectious episodes and 8 rejection episodes. The average IM score was significantly lower during infection than steady state (187 vs 280 ng ATP/ml, p < 0.001). The average IM score was not significantly different during rejection when compared with steady state (327 vs 280 ng ATP/ml, p = 0.35). Interestingly, 3 of 8 rejection episodes were antibody-mediated rejections and had hemodynamic compromise and, for these, the mean IM score was significantly higher than for steady-state patients (491 vs 280 ng ATP/ml, p < 0.001).. The non-invasive IM test appears to predict infectious risk in heart transplant patients. The association between high IM scores and rejection risk is inconclusive due to the small number of rejection episodes. Further studies with larger sample sizes for rejection episodes are required.

Topics: Adenosine Triphosphate; Adult; Aged; Biopsy; CD4-Positive T-Lymphocytes; Drug Therapy, Combination; Endocardium; Follow-Up Studies; Graft Rejection; Heart Transplantation; Humans; Immunosuppressive Agents; Lymphocyte Activation; Male; Middle Aged; Monitoring, Immunologic; Mycophenolic Acid; Myocardium; Opportunistic Infections; Prednisolone; Proportional Hazards Models; Risk Assessment; Tacrolimus

Mycophenolate mofetil (MMF) is routinely used at a fixed dose, but several factors interact to alter the blood level of mycophenolic acid (MPA), resulting in toxicity or treatment failure.. From January 2007 to December 2008, 85 kidney transplantation patients were given a fixed dose of 1.5 g/d of MMF in 12-hour intervals. MPA trough levels were measured on postoperative 1 week, 1 month, 3 months, 6 months, and 12 months.. Mean age of patients was 41 years. Thirty five cases were deceased donor kidney transplantations and 50 were living donor kidney transplantations. Mean trough levels of MPA were 1.04 microg/mL, 1.09 microg/mL, 1.28 microg/mL, 1.83 microg/mL, and 1.69 microg/mL at postoperative 1 week, 1 month, 3 months, 6 months, and 12 months, respectively. Mean trough levels of the subgroup of patients taking cyclosporine were 0.82 microg/mL, 0.94 microg/mL, 1.01 microg/mL, 1.56 microg/mL, and 1.46 microg/mL (n=36). Mean trough levels of the subgroup of patients taking tacrolimus were 1.19 microg/mL, 1.21 microg/mL, 1.56 microg/mL, 2.13 microg/mL, and 2.20 microg/mL (n=49). At 12 months, 31% of all patients experienced one or more opportunistic infections. Eight patients (9.4%) had cytomegalovirus infections, 14 patients (16.5%) had polyomavirus infections, and four patients (4.7%) had parvovirus infections. Ten patients (11.8%) experienced biopsy-proven acute rejection during the follow-up period.. Mean MPA trough levels of patients on 1.5 g/d of MMF reached 1.0 microg/mL within 1 week. Thirty one percent of patients experienced opportunistic infections, and 11.8% of patients had biopsy-proven acute rejections.

Topics: Adult; Cadaver; Cyclosporine; Female; Follow-Up Studies; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Male; Mycophenolic Acid; Opportunistic Infections; Postoperative Complications; Retrospective Studies; Tacrolimus; Time Factors; Tissue Donors

Topics: Aged; Colitis; Crohn Disease; Cytomegalovirus Infections; Diagnosis, Differential; Diarrhea; Female; Humans; Immunocompromised Host; Immunosuppressive Agents; Mycophenolic Acid; Opportunistic Infections; Weight Loss

The authors report on a 55-year-old female patient after R1 resection of a malignant thymoma with spindle type epithelial cells (WHO type A, Masaoka stage III) referred for further therapy of an ulcerative colitis. At that time, both adjuvant radiation and cytostatic therapy were not applicable due to severe activity of the ulcerative colitis. Under immunosuppressive treatment with azathioprine and steroids, the patient developed cytomegalovirus (CMV) enteritis which was triggered by therapy-induced leukopenia. After a switch from azathioprine to mycophenolatmofetil (MMF) treatment and administration of cidofovir because of nonresponse to ganciclovir and incompatibility of foscarnet sodium (Foscavir), the patient clinically improved. In addition, the patient was treated with immunoglobulins every 3-4 weeks because of antibody deficiency. At present, 3.5 years after R1 resection, the patient still has no clues of a remaining tumor mass under current immunosuppressive therapy. Ulcerative colitis is also in complete remission stage.. This case indicates the very rare features of a syndrome with thymoma and antibody deficiency which was first described by Robert Good. Furthermore, the impact of immunosuppressive therapy and management of opportunistic infections on the course of this disease is obvious.

Topics: Agammaglobulinemia; Antiviral Agents; Azathioprine; Cidofovir; Colitis, Ulcerative; Cytomegalovirus Infections; Cytosine; Enteritis; Female; Humans; Immunization, Passive; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Leukopenia; Middle Aged; Mycophenolic Acid; Neoplasm Staging; Opportunistic Infections; Organophosphonates; Postoperative Complications; Syndrome; Thymectomy; Thymoma; Thymus Neoplasms

Topics: Adult; Aged; Enzyme Inhibitors; Herpes Zoster; Humans; Incidence; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Pemphigus

We have assessed indications, duration and tolerability of treatment with mycophenolate mofetil (MMF) in patients with diffuse cutaneous systemic sclerosis (dcSSc), and compared clinical outcome with a control cohort treated with other immunosuppressive drugs.. The clinical records of 109 patients treated with MMF and 63 control subjects receiving other immunosuppressive drugs were reviewed. Data covering a 5-yr period from commencement of treatment or until last assessment date were collected.. MMF and control groups were well-matched in terms of basic demographic and clinical parameters. Treatment with MMF was very well tolerated. Of all patients, 12% experienced adverse reactions with gastrointestinal (GI) tract disturbances and infections being most frequent. MMF was discontinued due to disease stabilization in 9%, side effects in 8% and no effect on the disease activity in 14% of the patients. There was a significantly lower frequency of clinically significant pulmonary fibrosis in the MMF-treated cohort (P = 0.037) and significantly better 5-yr survival from disease onset and from commencement of treatment (P = 0.027 and P = 0.012, respectively). There was no significant difference between the two groups in terms of modified Rodnan skin score and forced vital capacity (FVC) change.. MMF is very well tolerated and appears to be at least as effective as the other current therapies for dcSSc. Our results provide support for further evaluation of MMF in a prospective trial.

Topics: Adult; Drug Evaluation; Female; Gastrointestinal Diseases; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Retrospective Studies; Scleroderma, Diffuse; Survival Analysis; Treatment Outcome

Acquired red cell aplasia (RCA) is a rare disorder and can be either idiopathic or associated with certain diseases, pregnancy, or drugs. In exceptionally rare cases, it has been reported to co-exist with other autoimmune cytopenias. We report a high incidence of RCA and autoimmune hemolytic anemia (AIHA) in pancreas transplant recipients on alemtuzumab-based maintenance therapy.. Between February 2003 and July 2005, 357 pancreas transplant recipients were treated with immunosuppressive regimens containing the lymphocyte-depleting antibody alemtuzumab, the T-cell activation inhibitor daclizumab, and the anti-metabolite mycophenolate mofetil (MMF). We retrospectively reviewed medical records, blood bank data and bone marrow biopsy specimens of patients with a Transplant Information Services database diagnosis of RCA and AIHA from February 2003 to November 2005.. Severe RCA, AIHA, and idiopathic thrombocytopenic purpura (ITP) occurred independently or in combination, in 20 out of 357 (5.6%) pancreas transplant recipients, 12 to 24 months following the initiation of the aforementioned immunosuppressive regimens. Severe opportunistic infections developed late in 14/20 (70%) of these patients. Atypical morphologic features, including variable dysgranulopoiesis, variable megakaryocytic hyperplasia with normal or low peripheral platelet counts, and atypical lymphoid aggregates were found in bone marrow trephine sections of 11 patients in whom the diagnosis of RCA was made.. We hypothesize that the combination of alemtuzumab, daclizumab and MMF can result in immune dysregulation thereby permitting autoantibody formation. Because the use of these three immune suppressants is becoming increasingly common, it is important to recognize the severe hematologic complications that can arise.

Topics: Adult; Alemtuzumab; Anemia, Hemolytic, Autoimmune; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Autoimmune Diseases; Bone Marrow; Daclizumab; Female; Humans; Immunoglobulin G; Immunosuppressive Agents; Incidence; Kidney Transplantation; Lymphocyte Activation; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Pancreas Transplantation; Pilot Projects; Postoperative Complications; Purpura, Thrombocytopenic, Idiopathic; Red-Cell Aplasia, Pure; Retrospective Studies; T-Lymphocytes

Topics: Diagnosis, Differential; Female; Humans; Immunosuppressive Agents; Meningitis, Listeria; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Pemphigus

The authors report 10 patients with idiopathic dermatomyositis treated with mycophenolate mofetil in combination with corticosteroids. Successful steroid taper without disease relapse was achieved in six patients; however, in three patients, treatment was associated with opportunistic infections, leading to death in one patient. The disproportionately high rate of opportunistic infections in this group is considered.

Topics: Adult; Aged; Bronchopneumonia; Dermatomyositis; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Prednisone

Anemia is a phenomenon frequently observed after kidney transplantation and differential diagnosis is broad.. A 39-year-old woman who had been transplanted a kidney of her father 11 months ago was admitted to the hospital because of severe and worsening anemia (hematocrit [Hct] 0.24). She was under a standard posttransplant immunosuppressive protocol consisting of tacrolimus, mycophenolate mofetil (MMF) and prednisolone. Kidney function was excellent (serum creatinine 118 micromol/l), clinical symptoms of anemia included vertigo, fatigue and low blood pressure. Striking laboratory features were reticulocytopenia (1 per thousand), high ferritin (3,486 microg/l) and low folic acid (4.8 nmol/l), other parameters remained in the normal or therapeutic range. Endoscopic examinations did not reveal any pathologic finding. Bone marrow biopsy, however, showed giant pronormoblasts and the missing of more mature forms as a possible hint to a lack of, e. g., vitamin B(12) (whose serum level was normal, though). After all, the most probable cause of the anemia seemed to be a toxic drug effect and MMF as a possible causative agent was significantly reduced. Nonetheless, the red blood cell count continued to fall (lowest Hct 0.18). On a later outpatient visit all of a sudden positive IgM and IgG antibodies against parvovirus B19 could be detected. Due to a high virus load short-term immunoglobulin treatment was instituted, after which Hct levels rose to normal and virus load decreased to a low degree although still detectable.. An infection with parvovirus B19 should always be taken into account as a possible cause of anemia in immunosuppressed patients. Establishing the diagnosis in the acute stage of the disease can be difficult, as antibodies are often negative in these patients and viremia remains the only proof. In most cases a substantial reduction of immunosuppressive therapy is necessary, the infection's relevance for the development of a potentially life-threatening myocarditis is still a matter of debate.

Topics: Acute Disease; Adult; Anemia; Biopsy; Bone Marrow; Diagnosis, Differential; Erythroblasts; Female; Humans; Immunoglobulin G; Immunoglobulin M; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid; Opportunistic Infections; Parvoviridae Infections; Parvovirus B19, Human; Postoperative Complications; Viral Load

Topics: Aged, 80 and over; Disease Susceptibility; Female; HIV Seronegativity; Humans; Immunocompromised Host; Immunosuppressive Agents; Liver Transplantation; Male; Meningitis, Cryptococcal; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Polyarteritis Nodosa; Postoperative Complications; Prednisone

Topics: Adult; Animals; Azathioprine; Cryptosporidiosis; Cryptosporidium; Cyclosporine; Female; Gastroscopy; Humans; Immunocompromised Host; Immunosuppressive Agents; Intestinal Diseases, Parasitic; Intestinal Mucosa; Kidney Transplantation; Malnutrition; Methylprednisolone; Mycophenolic Acid; Opportunistic Infections; Postoperative Complications; Spiramycin

To study infectious complications in renal transplant recipients receiving mycophenolate mofetil (MMF) for prevention of acute transplant rejection or treatment of chronic allograft nephropathy (CAN).. A group of renal transplant recipients (n=47) receiving 1.0-2.0 g/day MMF with cyclosporine A (CsA) and steroids as maintaining immunosuppression was compared to a group (n=47) taking triple immunosuppressive therapy which included azathioprine (Aza). Separate group of patients (n=9) received MMF for treatment of CAN. In all groups etiology and incidence of infections were evaluated.. During 2 years various posttransplant infections developed in 72.3% patients on MMF and 93.6% on Aza. The incidence of viral infections was 53.2% in MMF and 59.6% in Aza group, the incidence of bacterial infection--55.3 and 70.2%, respectively. Among 9 recipients with CAN the infections occurred in five. There were two cases of active tuberculosis in Aza group, one--in MMF group and one in patients with CAN.. We suggest that MMF in the dose 1-2 g/day does not increase infection rates in renal transplant recipients comparing Aza.

Topics: Acute Disease; Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Incidence; Kidney Transplantation; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Retrospective Studies; Risk Factors; Transplantation, Homologous

The use of mycophenolate mofetil (MMF) for prophylaxis of aGVHD and/or for treatment of acute or chronic GVHD is increasing. However, the benefit of MMF as an alternative to commonly used immunosuppressive agents still needs to be assessed. We ran a retrospective study on 21 consecutive patients (median age, 36 years; range, 20-63) with aGVHD or extensive cGVHD following related (17) or unrelated (4) matched donor SCT (BM, 16; PBSC, 5) who received MMF (2 g/day) because of intolerance to or failure of CsA-containing combinations. Four of the six patients with aGVHD responded, and the response rate was 69% in cGVHD patients. We observed neither significant differences in terms of response rate for skin, liver and bowel nor dissociated response in cases of multiple organ involvement (67% of the patients). Response was the same for lichenoid and sclerodermatous skin cGVHD subtypes. No adverse effects, except diarrhea (three patients), were observed. However, 22 opportunistic or serious viral or bacterial infections occurred in 10 patients. Analysis of trough plasma levels showed a trend for a higher mean MPA concentration in patients responding to MMF. Our study highlights the high risk of infectious complications induced by the administration of MMF, an otherwise efficient and well-tolerated treatment for GVHD.

Topics: Acute Disease; Adult; Anti-Inflammatory Agents, Non-Steroidal; Biotransformation; Bone Marrow Transplantation; Chronic Disease; Drug Evaluation; Female; Graft vs Host Disease; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Peripheral Blood Stem Cell Transplantation; Retrospective Studies; Risk; Treatment Outcome

Infection due to cytomegalovirus (CMV) is the most frequent opportunistic infection following renal transplantation (RT). It is usually asymptomatic. Cytomegalovirus disease causes fever leucopenia, thrombocytopenia and slightly elevated transaminases. The development of severe invasive forms is uncommon nowadays with post-transplantation monitoring, prophylactic regimens in high-risk patients and early treatment with ganciclovir. We report two renal transplant recipients who presented with severe gastrointestinal bleeding as the first manifestation of CMV disease at 9 and 14 weeks after transplantation. In both patients repeated post-transplantation pp65 antigenemia monitoring was negative. One patient developed hypovolemic shock due to severe rectal bleeding; an atypical bleeding ulcer was detected in the ileocecal valve. The other patient presented with upper gastrointestinal hemorrhage from a bleeding duodenal ulcer. Histological and immunohistochemical study confirmed the diagnosis. Both patients were elderly and on triple therapy with tacrolimus, mycophenolate and prednisone. We discuss the role of mycophenolate and the new immunosuppressant agents as factors favoring a state of enhanced immunosuppression, which may facilitate the onset of severe atypical forms of CMV disease.

Topics: Aged; Cytomegalovirus; Cytomegalovirus Infections; Disease Susceptibility; Duodenal Ulcer; Gastrointestinal Hemorrhage; Humans; Ileal Diseases; Ileocecal Valve; Immunocompromised Host; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Postoperative Complications; Prednisone; Shock; Tacrolimus; Ulcer

Topics: BK Virus; Humans; Immunosuppressive Agents; Kidney Diseases; Kidney Transplantation; Mycophenolic Acid; Opportunistic Infections; Polyomavirus Infections; Tacrolimus

Topics: Adult; Azathioprine; Child; Follow-Up Studies; Graft Rejection; Humans; Immunosuppressive Agents; Incidence; Intestines; Muromonab-CD3; Mycophenolic Acid; Opportunistic Infections; Postoperative Complications; Retrospective Studies; Time Factors; Transplantation, Homologous; Treatment Failure; Viscera

Infection with Nocardia spp. is an uncommon but important cause of morbidity and mortality in organ transplant recipients. Cotrimoxazole prophylaxis against urinary tract infection and Pneumocystis carinii pneumonia in these patients usually prevents nocardial infection also. We report the case of a patient on tacrolimus and mycophenolate mofetil who developed drug-induced diabetes mellitus followed by nocardial brain infection. This infection occurred despite conventional cotrimoxazole prophylaxis. Physicians should be aware that newer, more potent and more diabetogenic immunosuppressive regimens may increase the risk of opportunistic infections such as nocardiosis, even in the presence of "adequate" antimicrobial preventive measures.

Topics: Adult; Anti-Bacterial Agents; Brain Abscess; Diabetes Mellitus; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Mycophenolic Acid; Nocardia asteroides; Nocardia Infections; Opportunistic Infections; Tacrolimus; Trimethoprim, Sulfamethoxazole Drug Combination

Intestinal microsporidiosis is a major cause of chronic diarrhea and malabsorption in patients with human immunodeficiency virus. Its occurrence in transplant recipients has exceptionally been reported to date.. We report what we believe are the first two cases of intestinal microsporidiosis in renal transplant recipients. The patients were treated with mycophenolate mofetil.. The clinical presentation was chronic diarrhea with massive weight loss. Stool analysis revealed microsporidian spores, identified as Enterocytozoon bieneusi spores by polymerase chain reaction. The onset of this opportunistic infection in these two patients is believed to be secondary to an increase in immunosuppression after azathioprine replacement by mycophenolate mofetil. The withdrawal of mycophenolate mofetil led to clinical recovery.. The incidence of microsporidiosis will probably increase in transplant recipients treated with powerful immunosuppressants. Therefore, we recommend a systematic search for microsporidian spores in stool specimens in cases of unexplained diarrhea in these patients.

Topics: Adult; Animals; Feces; Humans; Immunosuppressive Agents; Intestines; Kidney Transplantation; Male; Microsporida; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Postoperative Complications; Protozoan Infections

Opportunistic infections are common after renal transplantation because of the use of immunosuppression. Nocardiosis is a rare but important cause of morbidity and mortality among renal transplant recipients. Depending upon the transplant center, the estimated incidence of nocardiosis among renal transplant recipients varies widely from 0 to 20%. We report the first case of nocardiosis in a recently transplanted renal patient maintained on tacrolimus, prednisone, and mycophenolate mofetil. It is likely that the nocardial infection in our patient was related to the development of her diabetes mellitus, and to her early episode of rejection and treatment which included high-dose steroids, and the addition of mycophenolate mofetil. Our case illustrates the importance of maintaining a heightened awareness so that nocardiosis may be diagnosed early and treated successfully.

Topics: Diabetes Complications; Female; Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; IMP Dehydrogenase; Incidence; Kidney Transplantation; Middle Aged; Mycophenolic Acid; Nocardia asteroides; Nocardia Infections; Opportunistic Infections; Prednisone; Risk Factors; Tacrolimus

Three multicenter studies have shown that the addition of mycophenolate mofetil (MMF) to an immunosuppressive regime consisting of cyclosporin A (CSA) and prednisone (PRED) decreases the incidence of acute rejection episodes when compared with azathioprine (AZA) or placebo (1-3). In those patients receiving 3 g/d of MMF, the highest dose used in the studies, there was a trend towards an increased incidence of cytomegaloviral sepsis (CMV). We postulated therefore that MMF may represent an independent risk factor for the development of CMV infection in patients receiving renal allografts and MMF at our institution. Having altered the triple drug regime from CSA, AZA (2-2.5 mg/kg/d) and PRED to CSA, MMF (2 g/d) and PRED in July 1995, we elected to study all patients undergoing kidney transplantation for the 33-month period January 1994-September 1996, by undertaking a case control analysis to determine independent risk factors for the development of CMV infection, as defined by CMV viremia or tissue-invasive CMV. Three CMV disease-free control patients were matched to each case, these patients having been randomly selected from the entire pool of patients in the observation period. There were 31 CMV case patients and 102 control patients. Univariate analysis indicated that gender, a concomitant pancreas transplant, acute rejection and CMV seropositivity in the donor were risk factors. However, multivariate analysis indicated that only acute rejection and donor CMV seropositivity were independently linked (p < 0.05) to CMV disease in this sample. Specifically, the odds ratio (OR) for CMV disease between MMF and AZA was 1.0 (95% confidence interval (CI): 0.46-2.18). Therefore, in this case control study we find no evidence that MMF at a dose of 2 g/d is an independent risk factor for primary CMV viremia or tissue invasion in renal allograft recipients.

Topics: Adult; Azathioprine; Case-Control Studies; Cyclosporine; Cytomegalovirus Infections; Female; Humans; Immunosuppressive Agents; IMP Dehydrogenase; Kidney Transplantation; Male; Mycophenolic Acid; Opportunistic Infections; Prednisone; Risk Factors

Mycophenolate mofetil (MMF; Cell-Cept) is a potent and selective inhibitor of B and T lymphocyte proliferation that has proven effective in reducing the incidence of acute rejection in cadaveric kidney transplant recipients in several randomized, blinded clinical studies. Because the frequency and characteristics of rejection episodes may be different and more severe after combined pancreas-kidney transplantation, we hypothesized that MMF would have a significant impact on pancreas-kidney rejection and graft outcome. Therefore, we compared the efficacy of MMF versus azathioprine (AZA) in cyclosporine-treated simultaneous pancreas-kidney transplantations.. A retrospective comparison of 358 consecutive primary SPK transplantations performed from 1990 to 1997 was conducted. Patients received either MMF (n=109, 3 g/day) or AZA (n=249, 2 mg/kg q.d.) in combination with cyclosporine-based immunosuppression. All patients received a quadruple-drug sequential induction protocol with either OKT3 or Atgam. Several outcome parameters, including patient and graft survival rates and frequency of rejection, were analyzed.. MMF-treated patients demonstrated a markedly reduced rate of biopsy-proven kidney rejection (31 vs. 75% AZA, P=0.0001), clinically significant pancreas rejection (7 vs. 24% AZA; P=0.003), and steroid-refractory rejection (15 vs. 52% AZA; P=0.01). As a result, kidney and pancreas allograft survival was significantly better in MMF patients compared with AZA patients (2-year survival rates: kidney, 95 vs. 86%; and pancreas, 95 vs. 83%). Although surgical infections after transplantation were more frequent in MMF patients, MMF patients were more likely to have undergone enteric drainage. Importantly, we did not observe an increased incidence of any of the bacterial, fungal, or viral infections that typically plague immunosuppressed transplant recipients.. This retrospective study demonstrates that MMF is a highly effective immunosuppressant in SPK transplantation. It is not associated with an increased risk of opportunistic infections when a balanced immunosuppressive management approach is used. MMF strikingly reduces the frequency of acute cellular and steroid-resistant rejection. As a result of this combined experience, it is not unexpected then that we observe significantly improved graft survival rates in MMF-treated SPK patients compared with patients receiving a more traditional immunosuppressive regimen.

Topics: Acute Disease; Adult; Azathioprine; Female; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Pancreas Transplantation; Retrospective Studies; Transplantation, Homologous