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1.
Outcomes at 3 years of a prospective pilot study of Campath-1H and sirolimus immunosuppression for renal transplantation 总被引:2,自引:0,他引:2
Rolf N. Barth Christina A. Janus Christine A. Lillesand Nancy A. Radke John D. Pirsch Bryan N. Becker Luis A. Fernandez L. Thomas Chin Yolanda T. Becker Jon S. Odorico Anthony M. D''Alessandro Hans W. Sollinger Stuart J. Knechtle 《Transplant international》2006,19(11):885-892
Campath-1H (alemtuzumab) induction was used for renal transplantation in combination with sirolimus as immunosuppression. We previously reported a high (28%) rate of early rejection with this regimen, and now report 3-year outcomes. Twenty-nine patients were recipients of either deceased donor or non-HLA (Human Leukocyte Antigen) identical living donor primary renal allografts. Clinical parameters including infection, malignancy, kidney function, and kidney histology were followed prospectively for 3 years. Three-year cumulative graft and patient survival were 96% and 100%, respectively. Twenty patients were maintained on steroid-free immunosuppressive regimens, and 15 patients were maintained on monotherapy for immunosuppression (12 on sirolimus). No serious infectious complications were observed and two patients developed basal cell skin cancer. The 3-year results of our initial pilot study demonstrate good graft (96%) and patient (100%) outcomes. Campath-1H induction has yielded a high proportion of patients maintained on immunosuppressive monotherapy (57%) without serious infectious- and no malignancy-related complications. The reported regimen yielded novel insights into both Campath-1H and sirolimus therapy in renal transplantation. Because of the higher incidence of early rejection, we recommend a modified strategy of immunosuppression including a brief course of a calcineurin inhibitor. 相似文献
2.
The greatest benefit of immunosuppression minimization for children may lie in improving patient morbidity, by the elimination of the inherent side effects of steroid and calcineurin inhibitors (CNI). The newer generation of powerful induction and maintenance immunosuppressants offers an option for selected immunosuppression minimization strategies, some of which have been shown to also reduce graft morbidity. Steroid minimization and avoidance in single-center uncontrolled trials have shown early promise and the availability of data from an ongoing randomized, prospective, controlled trial of steroid avoidance in children will provide necessary data to support a practice change for steroid elimination in children. Calcineurin inhibitor minimization and addition of mycophenolate mofetil (MMF) or sirolimus have shown variable improvements in renal function, though suboptimal efficacy and safety with the currently proposed regimes have limited their application. Randomized, prospective studies of steroid and calcineurin inhibitor minimization and/or avoidance are warranted to clearly confirm the short and long-term safety and efficacy of alternative immunosuppression combinations. Linked pharmacokinetic and mechanistic studies within these trials will allow for optimizing drug dosing and monitoring. This article reviews published experience to date with steroid and calcineurin minimization in pediatric renal transplantation and discusses the risks and benefits of these approaches. 相似文献
3.
Michael Robson Isabelle Côte Ian Abbs Geoffrey Koffman David Goldsmith 《American journal of transplantation》2003,3(3):324-327
Thrombotic microangiopathy is a rare but important finding in the context of organ transplantation. Acute renal insufficiency in the setting of hemolysis and thrombocytopenia, a triad that constitutes 'hemolytic uremic syndrome', can be associated with, or triggered by, conditions such as verocytotoxin-producing Escherichia coli, viral infections, malignant hypertension, scleroderma, allograft rejection, lupus erythematosus, pregnancy, and medications including mitomycin C, calcineurin inhibitors, and oral contraceptives. After renal transplantation, it can occur, as either a de novo episode, or recurrent disease. Calcineurin inhibitors have long been associated with post-transplantation thrombotic microangiopathy. Sirolimus has been used as a primary immunosuppressant in patients transplanted with a history of earlier hemolytic-uremic syndrome, and also as rescue therapy in patients with calcineurin-inhibitor-associated thrombotic microangiopathy. We describe four cases where there was significant thrombotic microangiopathy in the context of contemporaneous or contiguous calcineurin inhibitor and sirolimus usage. As the intrarenal cyclosporin concentration is thought to be significantly elevated when cyclosporin and sirolimus are used together, this may explain these findings, and mandates caution in their co-administration. 相似文献
4.
Edwin H. Preston He Xu Kiran K. Dhanireddy Jonathan P. Pearl Frank V. Leopardi Matthew F. Starost Douglas A. Hale Allan D. Kirk 《American journal of transplantation》2005,5(5):1032-1041
CD154-specific antibody therapy prevents allograft rejection in many experimental transplant models. However, initial clinical transplant trials with anti-CD154 have been disappointing suggesting the need for as of yet undetermined adjuvant therapy. In rodents, donor antigen (e.g., a donor blood transfusion), or mTOR inhibition (e.g., sirolimus), enhances anti-CD154's efficacy. We performed renal transplants in major histocompatibility complex-(MHC) mismatched rhesus monkeys and treated recipients with combinations of the CD154-specific antibody IDEC-131, and/or sirolimus, and/or a pre-transplant donor-specific transfusion (DST). Therapy was withdrawn after 3 months. Triple therapy prevented rejection during therapy in all animals and led to operational tolerance in three of five animals including donor-specific skin graft acceptance in the two animals tested. IDEC-131, sirolimus and DST are highly effective in preventing renal allograft rejection in primates. This apparently clinically applicable regimen is promising for human renal transplant trials. 相似文献
5.
J. A. Kobashigawa L. W. Miller S. D. Russell G. A. Ewald M. J. Zucker L. R. Goldberg H. J. Eisen K. Salm D. Tolzman J. Gao W. Fitzsimmons R. First 《American journal of transplantation》2006,6(6):1377-1386
The most advantageous combination of immunosuppressive agents for cardiac transplant recipients has not yet been established. Between November 2001 and June 2003, 343 de novo cardiac transplant recipients were randomized to receive steroids and either tacrolimus (TAC) + sirolimus (SRL), TAC + mycophenolate mofetil (MMF) or cyclosporine (CYA) + MMF. Antilymphocyte induction therapy was allowed for up to 5 days. The primary endpoint of >/=3A rejection or hemodynamic compromise rejection requiring treatment showed no significant difference at 6 months (TAC/MMF 22.4%, TAC/SRL 24.3%, CYA/MMF 31.6%, p = 0.271) and 1 year (p = 0.056), but it was significantly lower in the TAC/MMF group when compared only to the CYA/MMF group at 1 year (23.4% vs. 36.8%; p = 0.029). Differences in the incidence of any treated rejection were significant (TAC/SRL = 35%, TAC/MMF = 42%, CYA/MMF = 59%; p < 0.001), as were median levels of serum creatinine (TAC/SRL = 1.5 mg/dL, TAC/MMF = 1.3 mg/dL, CYA/MMF = 1.5 mg/dL; p = 0.032) and triglycerides (TAC/SRL = 162 mg/dL, TAC/MMF = 126 mg/dL, CYA/MMF = 154 mg/dL; p = 0.028). The TAC/SRL group encountered fewer viral infections but more fungal infections and impaired wound healing. These secondary endpoints suggest that the TAC/MMF combination appears to offer more advantages than TAC/SRL or CYA/MMF in cardiac transplant patients, including fewer >/=3A rejections or hemodynamic compromise rejections and an improved side-effect profile. 相似文献
6.
Calcineurin Inhibitor Withdrawal from Sirolimus-Based Therapy in Kidney Transplantation: A Systematic Review of Randomized Trials 总被引:4,自引:0,他引:4
Atul V. Mulay Naser Hussain Dean Fergusson Greg A. Knoll 《American journal of transplantation》2005,5(7):1748-1756
Calcineurin inhibitor (CNI) withdrawal has been used as a strategy to improve renal allograft function, however, it also carries risk of acute rejection. We conducted a systematic review of randomized trials that involved CNI withdrawal from a sirolimus-based immunosuppressive regimen. The search strategy yielded six trials (n = 1047 patients) reported in eight publications. CNI withdrawal from sirolimus-based therapy, was associated with an increased risk of acute rejection (risk difference, 6%; 95% CI 2-10%, p = 0.002) but a higher creatinine clearance (mean difference, 7.49 mL/min; 95% CI 5.08-9.89 mL/min, p < 0.00001) at 1 year compared to continued CNI and sirolimus therapy. Graft loss (relative risk, 0.87; 95% CI 0.46-1.64, p = 0.66) and death (relative risk, 0.88; CI 0.40-1.96, p = 0.76) were similar in both groups at 1 year. Hypertension was significantly reduced in the CNI withdrawal group (relative risk, 0.56; 95% CI 0.40-0.78, p = 0.0006). CNI withdrawal from sirolimus-based therapy is associated with an increased risk of acute rejection in the short term with a significant improvement in renal function and a reduction in hypertension. Longer follow-up is needed to determine if these changes will result in a significant improvement in patient and graft survival. 相似文献
7.
Synergistic mechanisms by which sirolimus and cyclosporin inhibit rat heart and kidney allograft rejection 总被引:3,自引:0,他引:3 下载免费PDF全文
S M STEPKOWSKI L TIAN K L NAPOLI R GHOBRIAL M E WANG T C CHOU B D KAHAN 《Clinical and experimental immunology》1997,108(1):63-68
The studies presented herein examined the mechanism(s) whereby sirolimus (SRL) and cyclosporin (CsA) act synergistically to block allograft rejection. Combination index (CI=1 reflects additive, CI<1 antagonistic, and CI<1 synergistic, effects) analysis documented potent synergism between SRL and CsA to block allograft rejection. Combinations of the two drugs produced synergistic prolongation of heart (CI=0.001–0.2) or kidney (CI=0.03–0.5) allograft survival at SRL/CsA ratios ranging from 1:12.5 to 1:200. Pharmacokinetic analysis of the individual drugs showed that CsA does not affect the blood levels of SRL, and SRL mildly increases the levels of CsA in SRL/CsA-treated rats. Quantitative polymerase chain reaction analysis was used to document that both subtherapeutic (1.0 mg/kg) and therapeutic (2.0 or 4.0 mg/kg) CsA doses inhibited the expression of interferon-gamma (IFN-γ) (P<0.03) and IL-2 (P<0.003) mRNA produced by T helper (Th) 1 cells, as well as IL-10 (P<0.001), but not IL-4 (NS) mRNA produced by Th2 cells. Contrariwise, all tested SRL doses (0.02, 0.04 or 0.08 mg/kg) did not affect cytokine mRNA expression. However, heart allografts from rat recipients treated with synergistic SRL/CsA doses displayed reduced levels of IFN-γ (P<0.01), IL-2 (P<0.001) and IL-10 (P<0.001) mRNA. Thus, because subtherapeutic doses of CsA reduce Th1/Th2 activity, thereby facilitating the inhibition of signal transduction by low does of SRL, the two agents act synergistically to inhibit allograft rejection. 相似文献
8.
9.
Epstein–Barr virus–associated smooth‐muscle tumors (EBV‐SMTs) are unique and rare neoplasms described in immunocompromised patients. The case describes a nine‐year‐old female with a history of acute lymphoblastic leukemia with relapse and subsequent allogeneic bone marrow transplantation who presented with multiple EBV‐SMTs of the liver. EBV utilizes the mammalian target of rapamycin (mTOR) pathway for tumor growth, and sirolimus, a mTOR inhibitor, has shown to result in a short‐term response. We now report an extended treatment response with sirolimus in a pediatric patient with an EBV‐SMT. 相似文献
10.
Sirolimus for the treatment of progressive kaposiform hemangioendothelioma: A multicenter retrospective study 下载免费PDF全文
Yi Ji Siyuan Chen Bo Xiang Kai Li Zhicheng Xu Wei Yao Guoyan Lu Xingtao Liu Chuncao Xia Qi Wang Yanan Li Chuan Wang Kaiying Yang Gang Yang Xueyang Tang Ting Xu Hao Wu 《International journal of cancer. Journal international du cancer》2017,141(4):848-855
Kaposiform hemangioendothelioma (KHE) is an aggressive disease with high morbidity and mortality. The aim of this study was to retrospectively evaluate the efficacy and safety of sirolimus for the treatment of progressive KHE. A multicenter, retrospective cohort study was conducted in patients with progressive KHE treated with sirolimus. A total of 52 patients were analyzed. Thirty‐seven (71%) patients exhibited Kasabach‐Merritt phenomenon (KMP) and were significantly younger than the patients without KMP [95% confidence interval (CI), 14.39–41.61; p < 0.001]. Patients without KMP were all treated with sirolimus alone, whereas 21 KMP patients with severe symptoms received short‐term combination therapy with prednisolone. Overall, 96% and 98% of patients showed improved relief of notable symptoms and/or improved complications at 6 and 12 months after treatment, respectively. After sirolimus treatment, significant decreases in mean severity scores occurred at 6 months (95% CI, 2.23–2.54, p < 0.001) and 12 months (95% CI, 1.53–1.90, p < 0.001). Compared to KMP patients, patients without KMP showed a response that was similar to but less pronounced during the 12 months of treatment (95% CI, 40.87–53.80; p < 0.001). For subgroup analysis of KMP patients, there were no significant differences in tumor shrinkage between those treated with combination therapy and those receiving sirolimus alone (95% CI, 18.11–25.02; p > 0.05). No patients permanently discontinued treatment due to toxicity‐related events, and no drug‐related deaths occurred. Sirolimus was effective and safe for the treatment of progressive KHE. Sirolimus may be considered as a first‐line therapy or as part of a multidisciplinary approach for the treatment of KHE. 相似文献