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Liver Transplantation and Surgery :... Jul 1999Polyclonal and monoclonal antilymphocyte agents (antilymphocyte globulin, antithymocyte globulin, OKT3, anti-interleukin-2 receptor antibody) are potent... (Review)
Review
Polyclonal and monoclonal antilymphocyte agents (antilymphocyte globulin, antithymocyte globulin, OKT3, anti-interleukin-2 receptor antibody) are potent immunosuppressive agents that differ fundamentally in their mechanisms of action from cyclosporine- and tacrolimus-based induction therapy. Clinical trials and retrospective studies show low rates of acute rejection can be obtained when biological antilymphocyte agents are used for induction immunosuppression in liver transplant recipients. Infectious complications are similar to those of conventional induction regimens, and the incidence of posttransplant lymphoproliferative disease is acceptably low when excessive doses are not used. Published series of liver transplant recipients have so far not shown the clear superiority of antilymphocyte induction therapy, in terms of patient and graft survival, compared with standard therapy (cyclosporine or tacrolimus plus steroids and azathioprine). At present, there is no ideal induction regimen recommended for all patients.
Topics: Acute Disease; Antilymphocyte Serum; Graft Rejection; Graft Survival; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Liver Transplantation; Postoperative Complications
PubMed: 10431019
DOI: 10.1053/JTLS005s00064 -
Frontiers in Immunology 2023Transfusion-dependent non-severe aplastic anemia (TD-NSAA) is a rare condition of bone marrow failure that can persist for a long time or develop into severe aplastic...
Transfusion-dependent non-severe aplastic anemia (TD-NSAA) is a rare condition of bone marrow failure that can persist for a long time or develop into severe aplastic anemia (SAA). Little is known about the clinical and laboratory characteristics, and disease prognosis and outcomes in TD-NSAA patients. The clinical and laboratory data of 124 consecutive TD-NSAA patients in the Chinese Eastern Collaboration Group of Anemia from December 2013 and January 2017 were analyzed retrospectively. In 124 TD-NSAA patients, the median age was 32 years (range: 3-80) and the median disease course was 38 months (range: 3-363). Common complications were iron overload (53/101, 52.5%), liver and kidney dysfunction (42/124, 33.9%), diabetes mellitus/impaired glucose tolerance (24/124, 19.4%), and severe infection (29 cases, 23.4%). 58% of patients (57/124) developed severe aplastic anemia with a median progression time of 24 months (range: 3-216). Patients with absolute neutrophil count (ANC) <0.5×10/L, severe infection, or iron overload had a higher probability of progression to SAA (P=0.022, P=0.025, P=0.001). Patients receiving antithymocyte globulin (ATG) plus Cyclosporin A (CsA) had a higher overall response rate compared to those receiving CsA alone (56.7% vs 19.3%, P < 0.001). The addition of ATG was the favorable factor for efficacy (P=0.003). Fourteen patients developed secondary clonal hematologic disease: eleven patients with paroxysmal nocturnal hemoglobinuria, two patients with myelodysplastic syndromes, and one patient with acute myeloid leukemia, respectively. Ten patients (8.1%) died with a median follow-up of 12 months (range: 3- 36 months). Patients with TD-NSAA usually have a prolonged course of disease, and are prone to be complicated with important organ damage and disease progression to SAA. Intensive immunosuppressive therapy based on ATG might be an appropriate approach for TD-NSAA. http://www.chictr.org.cn/edit.aspx?pid=125480&htm=4, identifier ChiCTR2100045895.
Topics: Humans; Adult; Anemia, Aplastic; Retrospective Studies; Cyclosporine; Antilymphocyte Serum; Iron Overload
PubMed: 37497227
DOI: 10.3389/fimmu.2023.1197982 -
Immunotherapy Jul 2011Monoclonal antibodies are applied in various settings in renal transplantation. Depleting T-cell antibodies are used for treatment of steroid-resistant acute rejection... (Review)
Review
Monoclonal antibodies are applied in various settings in renal transplantation. Depleting T-cell antibodies are used for treatment of steroid-resistant acute rejection and as induction therapy to reduce the intensity of concomitant immunosuppressive drug therapy. Induction therapy with the nondepleting IL-2 receptor antagonists basiliximab and daclizumab, added to cyclosporine-based regimens, reduces the incidence of acute rejection without side effects. However, an increase in long-term graft and patient survival has not been demonstrated yet. The B-cell-targeting antibody rituximab is used in blood group ABO-incompatible transplantation, in desensitization protocols, and for treatment of antibody-mediated rejection. Eculizumab interrupts the complement pathway and is a promising tool for the treatment of antibody-mediated rejection and post-transplant hemolytic-uremic syndrome. Future options are monoclonal antibodies with new molecular targets and antibodies that can be used for maintenance immunosuppression in order to avoid the toxicity of existing drugs. However, in several cases, the development of new monoclonal antibodies has been hampered by safety issues.
Topics: Animals; Antibodies, Monoclonal; Antilymphocyte Serum; B-Lymphocytes; Cyclosporine; Graft Rejection; Hemolytic-Uremic Syndrome; Humans; Immunoglobulin G; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Mice; Rats; Receptors, Interleukin-2
PubMed: 21751955
DOI: 10.2217/imt.11.72 -
Annals of Transplantation May 2018Pediatric heart transplantation (pHTx) represents only a small proportion of cardiac transplants. Due to these low numbers, clinical data relating to induction therapy... (Review)
Review
Pediatric heart transplantation (pHTx) represents only a small proportion of cardiac transplants. Due to these low numbers, clinical data relating to induction therapy in this special population are far less extensive than for adults. Induction is used more widely in pHTx than in adults, mainly because of early steroid withdrawal or complete steroid avoidance. Antithymocyte globulin (ATG) is the most frequent choice for induction in pHTx, and rabbit antithymocyte globulin (rATG, Thymoglobulin®) (Sanofi Genzyme) is the most widely-used ATG preparation. In the absence of large, prospective, blinded trials, we aimed to review the current literature and databases for evidence regarding the use, complications, and dosages of rATG. Analyses from registry databases suggest that, overall, ATG preparations are associated with improved graft survival compared to interleukin-2 receptor antagonists. Advantages for the use of rATG have been shown in low-risk patients given tacrolimus and mycophenolate mofetil in a steroid-free regimen, in sensitized patients with pre-formed alloantibodies and/or a positive donor-specific crossmatch, and in ABO-incompatible pHTx. Registry and clinical data have indicated no increased risk of infection or post-transplant lymphoproliferative disorder in children given rATG after pHTx. A total rATG dose in the range 3.5-7.5 mg/kg is advisable.
Topics: ABO Blood-Group System; Animals; Antilymphocyte Serum; Child; Graft Survival; Heart Transplantation; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Infections; Lymphoproliferative Disorders; Rabbits; Receptors, Interleukin-2; Registries; Retrospective Studies; Steroids; T-Lymphocytes
PubMed: 29760372
DOI: 10.12659/AOT.908243 -
Transplant International : Official... Jul 2013Currently available immunosuppressive agents can be classified into three categories: induction agents, maintenance therapy, and treatment for rejection. This review... (Review)
Review
Currently available immunosuppressive agents can be classified into three categories: induction agents, maintenance therapy, and treatment for rejection. This review article will focus on induction immunosuppression. There are three antibodies which are used for induction therapy: the lymphocyte-depleting agents - anti-thymocyte globulin and alemtuzumab, and basiliximab which is nondepleting. Historically, immunosuppressant selection was solely based on efficacy for prevention of rejection. In the current era of transplantation, it is now common practice in the transplant community to select induction therapy on the basis of risk-benefit considerations for each patient. This article will focus on the efficacy of available induction agents and the selection of induction agent based on donor and recipient risk factors.
Topics: Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antilymphocyte Serum; Basiliximab; Delayed Graft Function; Humans; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Recombinant Fusion Proteins
PubMed: 23279211
DOI: 10.1111/tri.12043 -
Frontiers in Immunology 2023This study developed and validated the Early Death Risk Score Model for early identification of emergency patients with very severe aplastic anemia (VSAA). All 377...
This study developed and validated the Early Death Risk Score Model for early identification of emergency patients with very severe aplastic anemia (VSAA). All 377 patients with VSAA receiving first-line immunosuppressive therapy (IST) were categorized into training (n=252) and validation (n=125) cohorts. In the training cohort, age >24 years, absolute neutrophil count ≤0.015×10/L, serum ferritin >900ng/mL and times of fever before IST >1 time were significantly associated with early death. Covariates were assigned scores and categorized as: low (score 0-4), medium (score 5-7) and high (score ≥8) risk. Early death rate was significantly different between risk groups and the validation cohort results were consistent with those of the training cohort. The area under the receiver operating characteristic curve for the model was 0.835 (0.734,0.936) in the training cohort and 0.862 (0.730,0.994) in the validation cohort. The calibration plots showed high agreement, and decision curve analysis showed good benefit in clinical applications. The VSAA Early Death Risk Score Model can help with early identification of emergency VSAA and optimize treatment strategies. Emergency VSAA with high risk is associated with high early death rate, and alternative donor hematopoietic stem cell transplantation could be a better treatment than IST even without HLA-matching.
Topics: Humans; Young Adult; Adult; Anemia, Aplastic; Cyclosporine; Antilymphocyte Serum; Treatment Outcome; Risk Factors
PubMed: 37153568
DOI: 10.3389/fimmu.2023.1175048 -
Blood Sep 2019
Topics: Antilymphocyte Serum; Cyclophosphamide; Graft vs Host Disease; Humans; Unrelated Donors
PubMed: 31515227
DOI: 10.1182/blood.2019002284 -
Haematologica Oct 2019
Topics: Anemia, Aplastic; Antilymphocyte Serum; Child; Humans; Immunosuppression Therapy; United States
PubMed: 31575670
DOI: 10.3324/haematol.2019.225870 -
Transplantation Reviews (Orlando, Fla.) Dec 2023Recommendations of the use of antibody induction treatments in kidney transplant recipients (KTR) are based on moderate quality and historical studies. This systematic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Recommendations of the use of antibody induction treatments in kidney transplant recipients (KTR) are based on moderate quality and historical studies. This systematic review aims to reevaluate, based on actual studies, the effects of different antibody preparations when used in specific KTR subgroups.
METHODS
We searched MEDLINE and CENTRAL and selected randomized controlled trials (RCT) and observational studies looking at different antibody preparations used as induction in KTR. Comparisons were categorized into different KTR subgroups: standard, high risk of rejection, high risk of delayed graft function (DGF), living donor, and elderly KTR. Two authors independently assessed the risk of bias.
RESULTS
Thirty-seven RCT and 99 observational studies were finally included. Compared to anti-interleukin-2-receptor antibodies (IL2RA), anti-thymocyte globulin (ATG) reduced the risk of acute rejection at two years in standard KTR (RR 0.74, 95%CI 0.61-0.89) and high risk of rejection KTR (RR 0.55, 95%CI 0.43-0.72), but without decreasing the risk of graft loss. We did not find significant differences comparing ATG vs. alemtuzumab or different ATG dosages in any KTR group.
CONCLUSIONS
Despite many studies carried out on induction treatment in KTR, their heterogeneity and short follow-up preclude definitive conclusions to determine the optimal induction therapy. Compared with IL2RA, ATG reduced rejection in standard-risk, highly sensitized, and living donor graft recipients, but not in high DGF risk or elderly recipients. More studies are needed to demonstrate beneficial effects in other KTR subgroups and overall patient and graft survival.
Topics: Humans; Aged; Antilymphocyte Serum; Immunosuppressive Agents; Kidney Transplantation; Alemtuzumab; Antibodies; Graft Rejection; Lymphocytes; Transplant Recipients; Graft Survival
PubMed: 37774445
DOI: 10.1016/j.trre.2023.100795 -
Transplant International : Official... Mar 2015Clinical data relating to rabbit antithymocyte globulin (rATG) induction in heart transplantation are far less extensive than for other immunosuppressants, or indeed for... (Review)
Review
Clinical data relating to rabbit antithymocyte globulin (rATG) induction in heart transplantation are far less extensive than for other immunosuppressants, or indeed for rATG in other indications. This was highlighted by the low grade of evidence and the lack of detailed recommendations for prescribing rATG in the International Society for Heart and Lung Transplantation (ISHLT) guidelines. The heart transplant population includes an increasing frequency of patients on mechanical circulatory support (MCS), often with ongoing infection and/or presensitization, who are at high immunological risk but also vulnerable to infectious complications. The number of patients with renal impairment is also growing due to lengthening waiting times, intensifying the need for strategies that minimize calcineurin inhibitor (CNI) toxicity. Additionally, the importance of donor-specific antibodies (DSA) in predicting graft failure is influencing immunosuppressive regimens. In light of these developments, and in view of the lack of evidence-based prescribing criteria, experts from Germany, Austria, and Switzerland convened to identify indications for rATG induction in heart transplantation and to develop an algorithm for its use based on patient characteristics.
Topics: Animals; Antilymphocyte Serum; Graft Rejection; Heart Transplantation; Humans; Immune Tolerance; Immunosuppression Therapy; Immunosuppressive Agents; Rabbits
PubMed: 25363471
DOI: 10.1111/tri.12480