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The New England Journal of Medicine Oct 2018
Review
Topics: Adult; Algorithms; Anemia, Aplastic; Benzoates; Bone Marrow Transplantation; Child; Hematopoietic Stem Cell Transplantation; Humans; Hydrazines; Immunosuppressive Agents; Pyrazoles; Receptors, Thrombopoietin; Transplantation, Homologous
PubMed: 30354958
DOI: 10.1056/NEJMra1413485 -
Current Treatment Options in Oncology Nov 2017Acquired aplastic anemia (AA) is a rare, life-threatening bone marrow failure (BMF) disorder that affects patients of all ages and is caused by lymphocyte destruction of... (Review)
Review
Acquired aplastic anemia (AA) is a rare, life-threatening bone marrow failure (BMF) disorder that affects patients of all ages and is caused by lymphocyte destruction of early hematopoietic cells. Diagnosis of AA requires a comprehensive approach with prompt evaluation for inherited and secondary causes of bone marrow aplasia, while providing aggressive supportive care. The choice of frontline therapy is determined by a number of factors including AA severity, age of the patient, donor availability, and access to optimal therapies. For newly diagnosed severe aplastic anemia, bone marrow transplant should be pursued in all pediatric patients and in younger adult patients when a matched sibling donor is available. Frontline therapy in older adult patients and in all patients lacking a matched sibling donor involves immunosuppressive therapy (IST) with horse antithymocyte globulin and cyclosporine A. Recent improvements in upfront therapy include encouraging results with closely matched unrelated donor transplants in younger patients and the emerging benefits of eltrombopag combined with initial IST, with randomized studies underway. In the refractory setting, several therapeutic options exist, with improving outcomes of matched unrelated donor and haploidentical bone marrow transplantation as well as the addition of eltrombopag to the non-transplant AA armamentarium. With the recent appreciation of frequent clonal hematopoiesis in AA patients and with the growing use of next-generation sequencing in the clinic, utmost caution should be exercised in interpreting the significance of somatic mutations in AA. Future longitudinal studies of large numbers of patients are needed to determine the prognostic significance of somatic mutations and to guide optimal surveillance and treatment approaches to prevent long-term clonal complications.
Topics: Anemia, Aplastic; Bone Marrow Diseases; Bone Marrow Transplantation; Cyclosporine; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppression Therapy; Siblings; Tissue Donors
PubMed: 29143887
DOI: 10.1007/s11864-017-0511-z -
Blood Advances Jun 2021Establishing a diagnosis of aplastic anemia (AA) can be challenging, but it is absolutely critical to appropriate management, especially differentiating between acquired... (Review)
Review
Establishing a diagnosis of aplastic anemia (AA) can be challenging, but it is absolutely critical to appropriate management, especially differentiating between acquired and inherited forms of the disease. The hematology field requires updated diagnostic guidelines to ensure that appropriate clinical pathways are pursued for patients and their safety. There are increasing clinical options for patients with immunosuppressive therapy and transplant once the diagnosis is made. In a case-based format, this review emphasizes the newer data on molecular (somatic and germline) findings in AA and how they are (or are not) helpful during diagnosis. There are key details on somatic mutation profiles and stated evidence where available for prognostic and treatment indications. Germline details of newer syndromes are also outlined, which make this review modern and reflect areas of uncertainty for clinicians.
Topics: Anemia, Aplastic; Humans; Immunosuppression Therapy
PubMed: 34156438
DOI: 10.1182/bloodadvances.2021004345 -
Pediatric Clinics of North America Dec 2013This article provides a practice-based and concise review of the etiology, diagnosis, and management of acquired aplastic anemia in children. Bone marrow... (Review)
Review
This article provides a practice-based and concise review of the etiology, diagnosis, and management of acquired aplastic anemia in children. Bone marrow transplantation, immunosuppressive therapy, and supportive care are discussed in detail. The aim is to provide the clinician with a better understanding of the disease and to offer guidelines for the management of children with this uncommon yet serious disorder.
Topics: Anemia, Aplastic; Bone Marrow Transplantation; Child; Humans; Immunosuppressive Agents; Survival Rate; Treatment Outcome
PubMed: 24237973
DOI: 10.1016/j.pcl.2013.08.011 -
Blood Advances Aug 2018Treatment of severe aplastic anemia has improved significantly over the past 4 decades. This review will summarize the key areas of progress in the use of allogeneic... (Review)
Review
Treatment of severe aplastic anemia has improved significantly over the past 4 decades. This review will summarize the key areas of progress in the use of allogeneic hematopoietic cell transplantation and nontransplant immunosuppressive therapy (IST) for the treatment of aplastic anemia and then summarize the recommendations for first-line treatment. Based on recent data, we argue that guidelines for the initial treatment of patients with newly diagnosed severe aplastic anemia require revision. At the time of diagnosis, before beginning treatment, HLA typing should be done to identify a marrow donor among family members or in the unrelated donor registries, and a marrow transplant should be considered first-line therapy. The priority order of donor source for bone marrow transplantation is: (1) HLA-identical sibling, (2) HLA-matched unrelated donor, and (3) HLA-haploidentical donor if an HLA-matched unrelated donor is not rapidly available. Each of these donor marrow sources may be preferable to nontransplant IST. We make this recommendation because of the long-term persistent risk for disease relapse and secondary myelodysplastic syndrome or acute myeloid leukemia with the use of nontransplant IST for patients with aplastic anemia. In contrast, marrow transplantation is associated with high cure rates of aplastic anemia and a relatively low risk for graft-versus-host disease, with many patients now living for decades without the risk for disease recurrence or the development of clonal disorders. Implementation of this first-line treatment strategy will provide patients with severe aplastic anemia the best chance of long-term disease-free survival.
Topics: Allografts; Anemia, Aplastic; Bone Marrow Transplantation; Donor Selection; Histocompatibility Testing; Humans; Unrelated Donors
PubMed: 30108110
DOI: 10.1182/bloodadvances.2018021162 -
Hematology/oncology Clinics of North... Aug 2018Idiopathic acquired aplastic anemia is a rare, life-threatening bone marrow failure syndrome characterized by cytopenias and hypocellular bone marrow. The... (Review)
Review
Idiopathic acquired aplastic anemia is a rare, life-threatening bone marrow failure syndrome characterized by cytopenias and hypocellular bone marrow. The pathophysiology is unknown; the most favored model is of a dysregulated immune system leading to autoreactive T-cell destruction of hematopoietic stem and progenitor cells in a genetically susceptible host. The authors review the literature and propose that the major driver of acquired aplastic anemia is a combination of hematopoietic stem and progenitor cells intrinsic defects and an inappropriately activated immune response in the setting of a viral infection. Alterations in bone marrow microenvironment may also contribute to the disease process.
Topics: Anemia, Aplastic; Hematopoietic Stem Cells; Humans; Stem Cell Niche; Virus Diseases
PubMed: 30047412
DOI: 10.1016/j.hoc.2018.03.001 -
British Journal of Haematology Jan 2016
Topics: Aged; Anemia, Aplastic; Benzoates; Blood Component Transfusion; Female; Hematopoietic Stem Cell Transplantation; Hemoglobinuria, Paroxysmal; Humans; Hydrazines; Immunosuppressive Agents; Opportunistic Infections; Pregnancy; Pregnancy Complications, Hematologic; Pyrazoles; Severity of Illness Index
PubMed: 26568159
DOI: 10.1111/bjh.13853 -
Current Opinion in Hematology May 2008Most acquired aplastic anemia is the result of immune-mediated destruction of hematopoietic stem cells causing pancytopenia and an empty bone marrow, which can be... (Review)
Review
PURPOSE OF REVIEW
Most acquired aplastic anemia is the result of immune-mediated destruction of hematopoietic stem cells causing pancytopenia and an empty bone marrow, which can be successfully treated with either immunosuppressive therapy or hematopoietic stem-cell transplantation.
RECENT FINDINGS
In aplastic anemia, oligoclonally expanded cytotoxic T cells induce apoptosis of hematopoietic progenitors. T-bet, a transcription factor that binds to the interferon-gamma promoter region, is upregulated in aplastic anemia T cells. Regulatory T cells are significantly reduced in patients' peripheral blood and in an aplastic anemia murine model, infusion of regulatory T cells ameliorates disease progression. In a minority of cases, loss-of-function mutations in telomerase complex genes may underlie disease development. Long-term survival, once strongly linked to response to immunosuppressive therapy, can now be achieved even among nonresponders due to significant advances in supportive care and better salvage treatments.
SUMMARY
Evidence has accumulated in the recent years further corroborating an immune-mediated process underlying aplastic anemia pathogenesis. Hematopoietic stem-cell transplantation from a matched sibling donor is preferred for children and young adults with severe aplastic anemia, and immunosuppressive therapy is employed when hematopoietic stem-cell transplantation is not feasible due to age, lack of a histocompatible sibling, co-morbidities, or by patient choice.
Topics: Anemia, Aplastic; Antilymphocyte Serum; Hematopoiesis; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents
PubMed: 18391779
DOI: 10.1097/MOH.0b013e3282fa7470 -
Annals of Internal Medicine Apr 2002In aplastic anemia, hematopoiesis fails: Blood cell counts are extremely low, and the bone marrow appears empty. The pathophysiology of aplastic anemia is now believed... (Review)
Review
In aplastic anemia, hematopoiesis fails: Blood cell counts are extremely low, and the bone marrow appears empty. The pathophysiology of aplastic anemia is now believed to be immune-mediated, with active destruction of blood-forming cells by lymphocytes. The aberrant immune response may be triggered by environmental exposures, such as to chemicals and drugs or viral infections and, perhaps, endogenous antigens generated by genetically altered bone marrow cells. In patients with post-hepatitis aplastic anemia, antibodies to the known hepatitis viruses are absent; the unknown infectious agent may be more common in developing countries, where aplastic anemia occurs more frequently than it does in the West. The syndrome paroxysmal nocturnal hemoglobinuria (PNH) is intimately related to aplastic anemia because many patients with bone marrow failure have an increased population of abnormal cells. In PNH, an entire class of proteins is not displayed on the cell surface because of an acquired X-chromosome gene mutation. The PNH cells may have a selective advantage in resisting immune attack. In contrast, the disease myelodysplasia can be confused with aplasia and can also evolve from aplastic anemia. The occurrence of cytogenetic abnormalities in patients years after presentation implies that genomic instability is a feature of this immune-mediated disease. Aplastic anemia can be effectively treated by stem-cell transplantation or immunosuppressive therapy. Transplantation is curative but is best used for younger patients who have histocompatible sibling donors. Antithymocyte globulin and cyclosporine restore hematopoiesis in approximately two thirds of patients. However, recovery of blood cell count is often incomplete, recurrent pancytopenia requires retreatment, and some patients develop late complications (especially myelodysplasia).
Topics: Anemia, Aplastic; Animals; Diagnosis, Differential; Hematologic Diseases; Hematopoiesis; Hematopoietic Stem Cell Transplantation; Hemoglobinuria; Humans; Immunosuppressive Agents; Lymphocytes; Neural Tube Defects
PubMed: 11926789
DOI: 10.7326/0003-4819-136-7-200204020-00011 -
Advances in Clinical and Experimental... May 2022Anemia is a common finding among patients with liver diseases. Patients who suffer from anemia are at a higher risk of liver function decompensation and hospitalization.... (Review)
Review
Anemia is a common finding among patients with liver diseases. Patients who suffer from anemia are at a higher risk of liver function decompensation and hospitalization. It affects significantly their quality of life and contributes to mortality. Anemia is present in 70% of patients with liver cirrhosis and with varying incidence accompanies other liver disorders. As the etiology of anemia in liver diseases is multifactorial, various cases represent different clinical entities. Anemia accompanying hepatic disorders can be broadly divided into several types, such as anemia associated with blood loss, as well as aplastic, hemolytic and micronutrient deficiency anemia. However, it is sometimes difficult to delineate between those types in the clinical practice, as several pathophysiological causes can be present in one patient. It is reported that the most common cause of anemia in liver disease is blood loss and iron deficiency. Still, the incidence of unclear cases reaching over 50% suggests that other types of anemia can be underdiagnosed. This review comprehensively describes less frequent types of anemia associated with liver disease, namely hemolytic and aplastic anemia (AA). Hemolytic anemia can complicate autoimmune liver diseases or be a manifestation of membranopathy of red blood cells, dependent on severe hepatic function impairment or alcoholic liver disease. Aplastic anemia is best known as a sequela of viral hepatitis, but some degree of bone marrow inhibition can complicate virtually all advanced liver diseases.
Topics: Anemia, Aplastic; Bone Marrow; Humans; Iron Deficiencies; Liver Diseases; Quality of Life
PubMed: 35275448
DOI: 10.17219/acem/145984