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British Journal of Haematology Apr 2012Aplastic anaemia (AA) is a rare heterogeneous condition in children. 15-20% of cases are constitutional and correct diagnosis of these inherited causes of AA is... (Review)
Review
Aplastic anaemia (AA) is a rare heterogeneous condition in children. 15-20% of cases are constitutional and correct diagnosis of these inherited causes of AA is important for appropriate management. For idiopathic severe aplastic anaemia, a matched sibling donor (MSD) haematopoietic stem cell transplant (HSCT) is the treatment of choice. If a MSD is not available, the options include immunosuppressive therapy (IST) or unrelated donor HSCT. IST with horse anti-thymocyte globulin (ATG) is superior to rabbit ATG and has good long-term results. In contrast, IST with rabbit ATG has an overall response of only 30-40%. Due to improvements in outcome over the last two decades in matched unrelated donor (MUD) HSCT, results are now similar to that of MSD HSCT. The decision to proceed with IST with ATG or MUD HSCT will depend on the likelihood of finding a MUD and the differing risks and benefits that each therapy provides.
Topics: Adolescent; Anemia, Aplastic; Animals; Antilymphocyte Serum; Child; Child, Preschool; Female; Hematopoietic Stem Cell Transplantation; Horses; Humans; Immunosuppressive Agents; Infant; Living Donors; Male; Rabbits; Siblings; Transplantation, Homologous
PubMed: 22348483
DOI: 10.1111/j.1365-2141.2012.09058.x -
Jornal Brasileiro de Nefrologia 2015The combination of immunosuppressive drugs is part of the treatment regimen of patients undergoing kidney transplantation (RT). Thymoglobulin®, a rabbit immunoglobulin... (Review)
Review
The combination of immunosuppressive drugs is part of the treatment regimen of patients undergoing kidney transplantation (RT). Thymoglobulin®, a rabbit immunoglobulin directed against human thymocytes, is the most commonly agent used for induction therapy in RT in the US. In Brazil, Thymoglobulin® is approved by ANVISA for the use in patients who underwent kidney transplantation and despite being widely used, there are controversies regarding the drug administration. We prepared a systematic review of the literature, evaluating studies that used Thymoglobulin® for induction and for acute rejection treatment in patients undergoing RT. The review used the computadorized databases of EMBASE, LILACS and MedLine. Data were extracted from the studies concerning general features, methodological characteristics and variables analyzed in each study. From the results, a practical guide was prepared analyzing various aspects on the use of Thymoglobulin® in patients submitted to RT.
Topics: Antilymphocyte Serum; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Practice Guidelines as Topic
PubMed: 26154644
DOI: 10.5935/0101-2800.20150036 -
Nonmyeloablative conditioning with total lymphoid irradiation and antithymocyte globulin: an update.Current Opinion in Hematology Nov 2009The immune modulatory effects of total lymphoid irradiation (TLI) for graft-versus-host disease (GVHD) protection and transplantation tolerance following allogeneic bone... (Review)
Review
PURPOSE OF REVIEW
The immune modulatory effects of total lymphoid irradiation (TLI) for graft-versus-host disease (GVHD) protection and transplantation tolerance following allogeneic bone marrow and organ transplantation have been studied for years in animal models. In preclinical models nonmyeloablative TLI conditioning alters residual host T cell subsets to favor regulatory natural killer T cells that suppress GVHD and prevent organ allograft rejection. These preclinical models have been recently adapted to human transplantation.
RECENT FINDINGS
Patients receiving allogeneic hematopoietic cell transplantation for hematological malignancies conditioned with TLI and depletive T cell antibodies showed sustained donor chimerism, a reduced incidence of acute GVHD yet retained graft antitumor activity. As in the preclinical models, nonmyeloablative TLI conditioning significantly altered residual host T cell subsets favoring natural killer T cells, and the low incidence of GVHD was associated with increased IL-4 secretion by chimeric donor T cells. The TLI regimen used in cancer patients was modified to determine conditions for stable mixed chimerism and tolerance induction following combined hematopoietic cell and kidney transplantation.
SUMMARY
This review summarizes the evolution of the preclinical TLI protocols and their recent translation to clinical trials, and discusses the mechanisms involved in protection from GVHD and the induction of tolerance following mixed chimerism.
Topics: Animals; Antilymphocyte Serum; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Lymphatic Irradiation; Transplantation Conditioning
PubMed: 19812489
DOI: 10.1097/MOH.0b013e3283319e8f -
Annals of the Royal College of Surgeons... Nov 1996
Review
Topics: Antilymphocyte Serum; Cost-Benefit Analysis; Drug Monitoring; Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; T-Lymphocyte Subsets
PubMed: 8943640
DOI: No ID Found -
Transactions of the American Clinical... 1997
Review
Topics: Antibody Specificity; Antilymphocyte Serum; Autoantibodies; Epitopes; Humans; Immunoglobulin M; Leukocyte Common Antigens; Lupus Erythematosus, Systemic; T-Lymphocyte Subsets
PubMed: 9108672
DOI: No ID Found -
Blood Nov 2013Refractory aplastic anemia (AA) is defined as a lack of response to first-line immunosuppressive therapy (IST) with antithymocyte globulin and cyclosporin and is... (Review)
Review
Refractory aplastic anemia (AA) is defined as a lack of response to first-line immunosuppressive therapy (IST) with antithymocyte globulin and cyclosporin and is manifested as persistence of severe cytopenias at 6 months after IST. Although supportive care is critical for AA patients, it is of paramount importance for refractory disease in view of the longer duration of pancytopenia and susceptibility to life-threatening infections due to IST. Improvements in supportive care have largely contributed to better outcome over the past 2 decades, with 5-year overall survival reaching 57% during 2002 to 2008 for patients with AA unresponsive to initial IST. Exclusion of hypocellular myelodysplastic syndrome and constitutional BM failure masquerading as apparent idiopathic AA should be done in conjunction with centers of excellence. Hematopoietic stem cell transplantation is indicated if refractory AA patients are fit and have a suitably matched donor, either a sibling (>40-50 years) or unrelated donor. Patients lacking a fully matched donor should be considered for a second course of antithymocyte globulin plus cyclosporin, although response in the refractory setting is only ∼30% to 35%. Response may also occur with alemtuzumab or the thrombopoietin mimetic eltrombopag in refractory AA. The emerging data for alternate donor (cord or haploidentical) transplantation in AA has provided additional therapeutic choices to consider in refractory disease.
Topics: Anemia, Aplastic; Anemia, Refractory; Antilymphocyte Serum; Blood Transfusion; Cord Blood Stem Cell Transplantation; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Infection Control; Treatment Outcome; Unrelated Donors
PubMed: 24052548
DOI: 10.1182/blood-2013-05-498279 -
British Medical Journal Apr 1970
Topics: Antilymphocyte Serum; Female; Glomerulonephritis; Humans; Immunosuppressive Agents; Male
PubMed: 5440581
DOI: 10.1136/bmj.2.5700.4 -
American Journal of Nephrology 2013Thymoglobulin (Thymoglobulin®; Genzyme, Cambridge, Mass., USA) is a polyclonal antibody which has been used in the field of transplantation over the last four decades.... (Review)
Review
Thymoglobulin (Thymoglobulin®; Genzyme, Cambridge, Mass., USA) is a polyclonal antibody which has been used in the field of transplantation over the last four decades. With an initial hesitancy, it is widely used now in the prevention and treatment of rejection following renal transplantation. Thymoglobulin's lack of nephrotoxic properties (unlike calcineurin inhibitors) may potentiate it to be a very useful induction therapy during the early days following transplantation, particularly in a donation after circulatory death programme. More recently its role in conjunction with inhibitors of terminal complement activation has been shown to be beneficial in cross-match-positive transplantation. This review article consolidates up-to-date available evidence to address the therapeutic role of thymoglobulin in immunological tolerance, ischemia perfusion, live donor transplantation, delayed graft function, prevention and treatment of rejection, graft survival and post-transplant lymphoproliferative disorder following renal transplantation.
Topics: Antilymphocyte Serum; Graft Rejection; Graft Survival; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Transplantation Tolerance
PubMed: 23774740
DOI: 10.1159/000351643 -
American Journal of Hematology Jun 2023Immune severe aplastic anemia (SAA) is characterized by pancytopenia and immune-mediated bone marrow destruction. SAA may be treated with hematopoietic stem cell...
Immune severe aplastic anemia (SAA) is characterized by pancytopenia and immune-mediated bone marrow destruction. SAA may be treated with hematopoietic stem cell transplantation (HSCT) or immunosuppressive therapy (IST). However, 30% of patients treated with IST relapse. We previously reported a clinical trial of alemtuzumab in which more than half of 25 relapsed SAA patients (56%) responded hematologically. Here, we present long-term results of a total of 42 patients. Participants with SAA who had previously completed antithymocyte globulin (ATG)-based IST, but had relapsed, were enrolled on this study. Alemtuzumab was administered intravenously (IV) (n = 28) or subcutaneously (SC) (n = 14). The primary endpoint was hematologic response at 6 months. Secondary endpoints included relapse, clonal evolution, and survival. This trial was registered at clinicaltrials.gov (NCT00195624). Patients were enrolled over 9 years, with median follow-up of 6 years. Median age was 32 years, with 57% being female. At 6 months, 18 patients (43%) achieved response; 15 (54%) of those who received IV compared with 3 (21%) who received SC therapy. Six patients (14%) had durable long-term response without need for subsequent AA-directed therapy or HSCT at last follow-up. Nine patients had clonal evolution, with high-risk evolution occurring in 6. Overall survival was 67% at median follow-up of 6 years. Prolonged iatrogenic immunosuppression was observed as long as 2 years after alemtuzumab administration. Alemtuzumab induces responses in relapsed SAA, some of which are durable long-term. However, immunosuppression can persist for years, requiring long-term monitoring.
Topics: Humans; Female; Adult; Male; Immunosuppressive Agents; Cyclosporine; Alemtuzumab; Anemia, Aplastic; Treatment Outcome; Antilymphocyte Serum; Recurrence
PubMed: 37021397
DOI: 10.1002/ajh.26924 -
Experimental and Clinical... Dec 2003The induction of immunological tolerance to solid organ allograft is currently a subject of major investigation due to the morbidity and mortality related to... (Review)
Review
The induction of immunological tolerance to solid organ allograft is currently a subject of major investigation due to the morbidity and mortality related to immunosuppressive therapy. Immunosuppression induction by recipient treatment may allow to tailoring the timing and dosage of standard therapy not only reducing adverse reactions but also improving the graft outcome. Depletion of recipient T cells with polyclonal antithymocyte globulins is one of the methods nowadays investigated both in experimental and clinical procedures, demonstrating a better outcome of organ engraftment. Our intention is to give an overview of the literature about the mechanisms of action of polyclonal ATGs, the status of induction treatment in clinical and experimental transplantation as well as of the possible pathophysiological relationships with acquired tolerance, delayed graft failure and ischemia-reperfusion injury.
Topics: Animals; Antilymphocyte Serum; Humans; Immunosuppressive Agents; Organ Transplantation
PubMed: 15859913
DOI: No ID Found