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Current Pharmaceutical Design 2022Aplastic anemia (AA) is a hematological disease characterized by pancytopenia and hypofunctional bone marrow hematopoiesis. Patients with AA are treated with either... (Review)
Review
Aplastic anemia (AA) is a hematological disease characterized by pancytopenia and hypofunctional bone marrow hematopoiesis. Patients with AA are treated with either immunosuppressive therapy (IST) using anti-thymocyte globulin (ATG) and cyclosporine (CsA) or hematopoietic stem cell transplantation (HSCT), if a matched donor is available. The standard IST regimen for AA patients results in response rates up to 70% and even higher overall survival. However, primary and secondary failures after IST remain frequent, and to date, all attempts aiming to overcome this problem have been unfruitful. The nontransplant therapeutic options for AA have significantly expanded during the last few years. Here, we review the new trends of nontransplant therapy for AA and summarize the current therapeutic effect of AA.
Topics: Anemia, Aplastic; Antilymphocyte Serum; Cyclosporine; Humans; Immunosuppression Therapy; Immunosuppressive Agents
PubMed: 35440301
DOI: 10.2174/1381612828666220418132432 -
Hematology. American Society of... Nov 2018Allogeneic hematopoietic stem-cell transplantation remains the only curative treatment for patients with acquired severe aplastic anemia (SAA). When a matched sibling is... (Review)
Review
Allogeneic hematopoietic stem-cell transplantation remains the only curative treatment for patients with acquired severe aplastic anemia (SAA). When a matched sibling is not available, one can search for a matched unrelated donor or a cord blood unit (CB) in the international registries or, more recently, for an HLA haploidentical (HAPLO) family member. International guidelines call for a course of antithymocyte globulin (ATG) and cyclosporine before a patient with SAA receives a transplant from a donor other than an HLA identical sibling, but whether this is necessary for patients age <20 years is less clear. Here I will examine the rapid increase in HAPLO transplantations for SAA, showing encouraging early results both in children and young adults. Graft-versus-host disease prophylaxis remains of primary importance in patients with SAA, and in vivo T-cell depletion with either ATG or alemtuzumab offers a significant survival advantage. Finally, I will discuss the strong age effect, which is particularly evident at >40 and 50 years of age for reasons not entirely clear and which should be taken into account when designing a treatment strategy for a given patient.
Topics: Allografts; Anemia, Aplastic; Antilymphocyte Serum; Cyclosporine; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Severity of Illness Index; Unrelated Donors
PubMed: 30504347
DOI: 10.1182/asheducation-2018.1.467 -
Hematology. American Society of... Nov 2018Since the approval of horse antithymocyte globulin (ATG) decades ago, there was a long hiatus in therapies with activity in severe aplastic anemia (SAA). This scenario... (Review)
Review
Since the approval of horse antithymocyte globulin (ATG) decades ago, there was a long hiatus in therapies with activity in severe aplastic anemia (SAA). This scenario changed in 2014 when eltrombopag, a thrombopoietin receptor agonist, was approved for SAA after an insufficient response to initial immunosuppressive therapy (IST). The basis for this approval was the observation of single-agent activity of eltrombopag in this patient population, where 40% to 50% recovered blood counts at times involving >1 lineage. The achievement of transfusion independence confirmed the clinical benefit of this approach. Increase in marrow cellularity and CD34+ cells suggested a recovery to a more functioning bone marrow. Further in its development, eltrombopag was associated with standard horse ATG plus cyclosporine in first line, producing increases in overall (at about 90%) and complete response rates (at about 40%) and leading to transfusion independence and excellent survival. Interestingly, best results were observed when all drugs were started simultaneously. The cumulative incidence of clonal cytogenetic abnormalities to date has compared favorably with the vast experience with IST alone in SAA. Longer follow-up will help in define these long-term risks. In this review, the development of eltrombopag in SAA will be discussed.
Topics: Anemia, Aplastic; Antilymphocyte Serum; Benzoates; Cyclosporine; Disease-Free Survival; Humans; Hydrazines; Pyrazoles; Severity of Illness Index; Survival Rate
PubMed: 30504345
DOI: 10.1182/asheducation-2018.1.450 -
American Journal of Transplantation :... Aug 2020
Topics: Antilymphocyte Serum; Cytomegalovirus Infections; Enzyme-Linked Immunosorbent Assay; Ganciclovir; Humans; Immunity, Cellular; Interferon-gamma Release Tests; Kidney Transplantation; Monitoring, Immunologic
PubMed: 32216014
DOI: 10.1111/ajt.15875 -
International Journal of Hematology Jul 2019HLA 1-locus-mismatched unrelated donors (1MMUD) are often considered as alternative donors in allogeneic hematopoietic stem-cell transplantation (allo-HCT) when an... (Review)
Review
HLA 1-locus-mismatched unrelated donors (1MMUD) are often considered as alternative donors in allogeneic hematopoietic stem-cell transplantation (allo-HCT) when an HLA-matched related or unrelated donor is unavailable. However, HLA mismatch remains a major risk factor for acute and chronic graft-versus-host disease (GVHD). Antithymocyte globulin (ATG) has been used to prevent acute and chronic GVHD, and multiple studies have shown that use of ATG is associated with decreased acute and chronic GVHD, which is associated with improved QOL. However, at high doses, ATG may lead to an increase in fatal infection, relapse, or delayed engraftment. The optimal ATG dose for MMUD remains unclear. The optimal ATG dose should be determined based on a fine balance between the reduction of GVHD and the risk of relapse, fatal infection, and/or delayed engraftment. Interestingly, promising results from some recent Asian studies suggest that a low dose of ATG may improve non-relapse mortality and overall survival without increasing relapse or fatal infection in allo-HCT from an HLA-mismatched unrelated donor. A randomized control trial is expected to confirm these results in Japan. In addition, pharmacokinetic/pharmacodynamic studies may help to identify the personalized optimal ATG dose.
Topics: Antilymphocyte Serum; Dose-Response Relationship, Drug; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Histocompatibility; Humans; Precision Medicine; Unrelated Donors
PubMed: 30680666
DOI: 10.1007/s12185-019-02597-y -
Haematologica Jul 2017
Topics: Anemia, Aplastic; Antilymphocyte Serum; Humans; Immunosuppressive Agents
PubMed: 28655810
DOI: 10.3324/haematol.2017.171538 -
British Journal of Hospital Medicine... Jan 2017Advances in the field of immunohistocompatibility and immunogenetics have been crucial for improvements in kidney transplant outcomes. This review provides a practical... (Review)
Review
Advances in the field of immunohistocompatibility and immunogenetics have been crucial for improvements in kidney transplant outcomes. This review provides a practical outline of these important breakthroughs for the general physician, at a time when demand for kidney transplants is increasing.
Topics: Antilymphocyte Serum; Cytotoxicity Tests, Immunologic; Flow Cytometry; HLA Antigens; Histocompatibility Testing; Humans; Immunogenetic Phenomena; Kidney Failure, Chronic; Kidney Transplantation
PubMed: 28067566
DOI: 10.12968/hmed.2017.78.1.32 -
European Journal of Haematology Nov 2023Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporin A is the standard treatment for aplastic anemia (AA). However, the efficacy of repeated...
OBJECTIVES
Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporin A is the standard treatment for aplastic anemia (AA). However, the efficacy of repeated IST with rabbit ATG (rATG) as salvage therapy remains unclear in patients with relapsed or refractory AA.
METHODS
We retrospectively evaluated the efficacy and safety of IST2 with rATG (IST2-rATG) in 19 consecutive patients with relapsed or refractory AA who received first-line IST with rATG in two centers between 2009 and 2020.
RESULTS
The overall 6-month response rate of the patients was 58%. The response rates were similar between patients with relapsed and refractory AA. The presence of glycophosphatidylinositol-deficient blood cells was associated with a better response to IST2-rATG. Despite retreatment with the same rATG, serum disease and severe allergic reactions were not observed.
CONCLUSION
IST2-rATG is effective and safe for the treatment of adult patients with relapsed and refractory AA after receiving first-line IST with rATG.
Topics: Humans; Adult; Antilymphocyte Serum; Anemia, Aplastic; Retrospective Studies; Immunosuppression Therapy; Cyclosporine; Immunosuppressive Agents; Treatment Outcome
PubMed: 37549934
DOI: 10.1111/ejh.14075 -
Jornal Brasileiro de Nefrologia 2015
Topics: Antilymphocyte Serum; Humans; Immunosuppressive Agents; Kidney Transplantation
PubMed: 26154633
DOI: 10.5935/0101-2800.20150025 -
Drug Design, Development and Therapy 2016Aplastic anemia (AA) is a potential life-threatening hematopoietic stem cell (HSC) disorder resulting in cytopenia. The mainstays of treatment for AA are definitive... (Review)
Review
Aplastic anemia (AA) is a potential life-threatening hematopoietic stem cell (HSC) disorder resulting in cytopenia. The mainstays of treatment for AA are definitive therapy to restore HSCs and supportive measures to ameliorate cytopenia-related complications. The standard definitive therapy is HSC transplantation for young and medically fit patients with suitable donors and immunosuppressive therapy (IST) with antithymocyte globulin and cyclosporine for the remaining patients. A significant proportion of patients are refractory to IST or relapse after IST. Various strategies have been explored in these patients, including second course of antithymocyte globulin, high-dose cyclophosphamide, and alemtuzumab. Eltrombopag, a thrombopoietin mimetic, has recently emerged as an encouraging and promising agent for patients with refractory AA. It has demonstrated efficacy in restoring trilineage hematopoiesis, and this positive effect continues after discontinuation of the drug. There are ongoing clinical trials exploring the role of eltrombopag as a first-line therapy in moderate to severe AA and a combination of eltrombopag with IST in severe AA.
Topics: Alemtuzumab; Anemia, Aplastic; Antibodies, Monoclonal, Humanized; Antilymphocyte Serum; Benzoates; Cyclophosphamide; Cyclosporine; Hematopoietic Stem Cells; Humans; Hydrazines; Immunosuppressive Agents; Pyrazoles
PubMed: 27695288
DOI: 10.2147/DDDT.S95715