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Best Practice & Research. Clinical... Dec 2023The bone marrow failure syndromes (BMFS) are a diverse group of acquired and inherited diseases which may manifest in cytopenias, haematological malignancy and/or... (Review)
Review
The bone marrow failure syndromes (BMFS) are a diverse group of acquired and inherited diseases which may manifest in cytopenias, haematological malignancy and/or syndromic multisystem disease. Patients with BMFS frequently experience poor outcomes, and improved treatment strategies are needed. Collation of clinical characteristics and patient outcomes in a national disease-specific registry represents a powerful tool to identify areas of need and support clinical and research collaboration. Novel treatment strategies such as gene therapy, particularly in rare diseases, will depend on the ability to identify eligible patients alongside the molecular genetic features of their disease that may be amenable to novel therapy. The Australian Aplastic Anaemia and other Bone Marrow Failure Syndromes Registry (AAR) aims to improve outcomes for all paediatric and adult patients with BMFS in Australia by describing the demographics, treatments (including supportive care) and outcomes, and serving as a resource for research and practice improvement.
Topics: Adult; Humans; Child; Anemia, Aplastic; Bone Marrow Diseases; Australia; Bone Marrow Failure Disorders; Syndrome; Registries
PubMed: 38092475
DOI: 10.1016/j.beha.2023.101516 -
British Journal of Haematology Feb 2021
Topics: Anemia, Aplastic; Benzoates; Child; Humans; Hydrazines; Immunosuppression Therapy; Pyrazoles
PubMed: 33400262
DOI: 10.1111/bjh.17233 -
Haematology and Blood Transfusion 1978
Review
Topics: Anemia, Aplastic; Animals; Blood Platelets; Bone Marrow; Cell Membrane; Chloramphenicol; Drug Hypersensitivity; Female; Haptens; Humans; Immunoglobulins; Male
PubMed: 367892
DOI: 10.1007/978-3-642-66945-3_13 -
Bailliere's Clinical Haematology Jan 1989No single pathophysiological phenomenon--neither the intrinsic defect of haemopoiesis nor any of the described immune effects--explains aplastic anaemia. Since the... (Review)
Review
No single pathophysiological phenomenon--neither the intrinsic defect of haemopoiesis nor any of the described immune effects--explains aplastic anaemia. Since the intrinsic defect is compatible with near normal haemopoietic function, as seen in autologous bone marrow reconstitution, it cannot be the cause of severe pancytopenia. On the other hand, immune mechanisms cannot be the primary cause of the disease, otherwise haemopoietic function would recover to complete normality after immunosuppressive therapy. From these observations we deduce that the intrinsic defect, a premalignant haemopoietic disorder, can either be clinically quiescent by virtue of repair mechanisms, or induce auto-reactivity of the immune system against the abnormal haemopoietic tissue, drugs, chemicals and viruses acting as non-specific triggers or amplifiers. In this sense, aplastic anaemia could be interpreted as an attempt to 'self-cure' from a variant type of preleukaemia. This means that the original concept of aplastic anaemia being a hypoplastic variant of leukaemia may be true. The fact that aplastic anaemia can present either as acute severe bone marrow failure, as chronic mild pancytopenia or as a myelodysplasia-like syndrome does not imply that the underlying pathophysiological mechanisms are basically different. Variations of the clinical course and the response to immunosuppressive treatment could be explained by variations in the balance between the primary defect and the secondary immune reaction; the co-involvement of accessory cells in the primary disease; the relative time course of the two components and the efficiency of repair mechanisms. From repeated in vitro studies in a large group of aplastic anaemia patients at various stages of disease this concept can be applied to the majority of cases, including chloramphenicol- and virus-induced aplastic anaemia. In a small proportion of patients with pancytopenia occurring after exposure to certain drugs other than chloramphenicol, aplastic anaemia is rapidly and completely reversible after withdrawal of the drug. These patients probably have truly benign aplastic anaemia and thus differ from the majority of patients who are left with a permanently fragile bone marrow once they have acquired aplastic anaemia.
Topics: Anemia, Aplastic; Antibodies; Hematopoiesis; Hematopoietic Stem Cells; Humans; Lymphokines; T-Lymphocytes
PubMed: 2645963
DOI: 10.1016/s0950-3536(89)80006-x -
British Journal of Haematology Oct 1979
Review
Topics: Androgens; Anemia, Aplastic; Antilymphocyte Serum; Bone Marrow Transplantation; Colony-Forming Units Assay; Humans; T-Lymphocytes; Transplantation, Homologous
PubMed: 389276
DOI: 10.1111/j.1365-2141.1979.tb03738.x -
Revista Do Hospital Das Clinicas 1989Aplastic anemia is a condition characterized by bone marrow hipoplasia and pancytopenia. Various etiologic agents are related to the acquired form of this disease but in... (Review)
Review
Aplastic anemia is a condition characterized by bone marrow hipoplasia and pancytopenia. Various etiologic agents are related to the acquired form of this disease but in many cases the causative agents remain obscure. Severe aplastic anemia has been treated by immunosuppression and allogeneic marrow transplantation.
Topics: Anemia, Aplastic; Bone Marrow Transplantation; Humans; Immunosuppression Therapy
PubMed: 2696069
DOI: No ID Found -
Lancet (London, England) Nov 1976
Topics: Anemia, Aplastic; Animals; Cell Count; Cell Differentiation; Cell Division; Hematopoietic Stem Cells; Humans; Mice
PubMed: 63002
DOI: No ID Found -
International Journal of Hematology Aug 2016Aplastic anaemia (AA) is frequently associated with other disorders of clonal haemopoiesis such as paroxysmal nocturnal haemoglobinuria (PNH), myelodysplastic syndrome... (Review)
Review
Aplastic anaemia (AA) is frequently associated with other disorders of clonal haemopoiesis such as paroxysmal nocturnal haemoglobinuria (PNH), myelodysplastic syndrome (MDS) and T-large granular lymphocytosis. Certain clones may escape the immune attack within the bone marrow environment and proliferate and attain a survival advantage over normal haemopoietic stem cells, such as trisomy 8, loss of heterozygosity of short arm of chromosome 6 and del13q clones. Recently acquired somatic mutations (SM), excluding PNH clones, have been reported in around 20-25 % of patients with AA, which predispose to a higher risk of later malignant transformation to MDS/acute myeloid leukaemia. Furthermore, certain SM, such as ASXL1 and DNMT3A are associated with poor survival following immunosuppressive therapy, whereas PIGA, BCOR/BCORL1 predict for good response and survival. Further detailed and serial analysis of the immune signature in AA is needed to understand the pathogenetic basis for the presence of clones with SM in a significant proportion of patients.
Topics: Anemia, Aplastic; Clone Cells; Humans; Mutagenesis
PubMed: 27084249
DOI: 10.1007/s12185-016-1972-8 -
The Journal of the Association of... Mar 2015
Topics: Anemia, Aplastic; Disease Management; Drug-Related Side Effects and Adverse Reactions; Hematopoiesis; Hematopoietic Stem Cells; Humans; Virus Diseases
PubMed: 26529859
DOI: No ID Found -
British Journal of Haematology Sep 2018This review examines the evidence that bone marrow failure (BMF) in aplastic anaemia (AA) is due to loss of haematopoietic stem cells (HSCs), which, in turn, is caused... (Review)
Review
This review examines the evidence that bone marrow failure (BMF) in aplastic anaemia (AA) is due to loss of haematopoietic stem cells (HSCs), which, in turn, is caused by deranged immunity and inflammation. We also consider how the course of the disease and the response to immuno-suppressive therapy are influenced by the nature and specificity of the pathogenic process. A somatic mutation of the PIGA gene underlies the clonal disease paroxysmal nocturnal haemoglobinuria (PNH): there is direct evidence that the expansion of the PIGA mutant clone results from Darwinian selection exerted by a glycosyl-phosphatidyl-inositol -specific auto-immune attack. Thus, PNH patients are a unique subset of patients with AA, in whom haematopoiesis recovers through this escape mechanism. A similar process, although less effective, may operate when the auto-immune attack is against a human leucocyte antigen (HLA) molecule and an HLA mutation has produced a clone missing that molecule. We then discuss the significance of other mutant clones that are frequently found in AA, presumably due to a combination of genetic drift and selection. These clones are not causative of AA, but they emerge in AA and they may be pre-leukaemic: unlike a PIGA mutant clone, in general they are unable to effectively reconstitute haematopoiesis.
Topics: Anemia, Aplastic; Animals; Bone Marrow; Hematopoiesis; Hematopoietic Stem Cells; Hemoglobinuria, Paroxysmal; Humans; Membrane Proteins; Mutation
PubMed: 29974931
DOI: 10.1111/bjh.15443