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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 -
Pediatric Blood & Cancer Dec 2005Shwachman-Diamond syndrome (SDS) is an inherited marrow failure disorder with varying cytopenia, pancreatic dysfunction, and metaphyseal dysostosis. SDS is also... (Review)
Review
Shwachman-Diamond syndrome (SDS) is an inherited marrow failure disorder with varying cytopenia, pancreatic dysfunction, and metaphyseal dysostosis. SDS is also characterized by a risk of myelodysplasia and leukemia in up to one third of the patients. Over the last 5 years, major advances have been made in understanding the bone marrow phenotype. The gene associated with the disease, SBDS, has recently been identified. Herein we provide an update on the clinical features, the hematopoietic defects, and the genetics of the disease as they are currently understood. We also review the diagnostic and therapeutic approaches to the hematological complications in the syndrome.
Topics: Bone Marrow Diseases; Child; Child, Preschool; Dysostoses; Exocrine Pancreatic Insufficiency; Female; Hematopoiesis; Humans; Male; Proteins; Syndrome
PubMed: 16047374
DOI: 10.1002/pbc.20478 -
[Rinsho Ketsueki] the Japanese Journal... 2021Inherited bone marrow failure syndromes (IBMFS) are a heterogeneous group of genetic disorders characterized by bone marrow failure, congenital anomalies, and increased... (Review)
Review
Inherited bone marrow failure syndromes (IBMFS) are a heterogeneous group of genetic disorders characterized by bone marrow failure, congenital anomalies, and increased risk of malignant disease. Next generation sequencing methods have greatly facilitated the discovery of genetic etiology in IBMFS. Recently, de novo mutations activating TP53 were detected in patients with BMFS, mimicking Diamond-Blackfan anemia (DBA), using whole exome sequencing, and these patients were recognized as having a novel disorder. This discovery provides important insights into the previously postulated connection between p53 activation and IBMFS. Furthermore, a novel IBMFS, aldehyde degradation deficiency syndrome, was found in patients with aplastic anemia resembling Fanconi anemia (FA). This disorder is caused by combined inactivating mutations in ADH5 and ALDH2 coding formaldehyde-detoxifying enzymes. In this review, we highlight recent studies on DBA, FA, and their related diseases in Japan.
Topics: Aldehyde Dehydrogenase, Mitochondrial; Anemia, Aplastic; Anemia, Diamond-Blackfan; Bone Marrow Diseases; Bone Marrow Failure Disorders; Congenital Bone Marrow Failure Syndromes; Hemoglobinuria, Paroxysmal; Humans
PubMed: 34732617
DOI: 10.11406/rinketsu.62.1455 -
Seminars in Hematology Apr 2002Shwachman-Diamond syndrome (SDS), described just under 40 years ago, is a rare, autosomal-recessive disorder usually manifest in infancy and characterized by exocrine... (Review)
Review
Shwachman-Diamond syndrome (SDS), described just under 40 years ago, is a rare, autosomal-recessive disorder usually manifest in infancy and characterized by exocrine pancreatic insufficiency, short stature, and bone marrow dysfunction. Additional clinical features include metaphyseal dysostosis, epiphyseal dysplasia, immune dysfunction, liver disease, growth failure, renal tubular defects, insulin-dependent diabetes mellitus, and psychomotor retardation. Hematological manifestations other than neutropenia include anemia, raised fetal hemoglobin (HbF) levels, thrombocytopenia, impaired neutrophil chemotaxis, and aplastic anemia; as with other constitutional bone marrow failure syndromes, there is a predilection to malignant myeloid transformation. No unifying pathogenetic mechanism(s) has yet been shown to be responsible for SDS, although new insights into the molecular, genetic, and cellular basis of this rare disease have recently been described.
Topics: Bone Marrow Diseases; Exocrine Pancreatic Insufficiency; Growth Disorders; Humans; Stem Cell Transplantation; Syndrome
PubMed: 11957191
DOI: 10.1053/shem.2002.31915 -
Experimental and Clinical... Nov 2016Liver transplant may complicated by various hematologic conditions, resulting in indication for bone marrow biopsy. Immunosuppressive therapies, specific infections, and...
OBJECTIVES
Liver transplant may complicated by various hematologic conditions, resulting in indication for bone marrow biopsy. Immunosuppressive therapies, specific infections, and secondary neoplasms affect bone marrow. In the present study, we evaluated the histologic spectrum of bone marrow findings in liver allograft recipients.
MATERIALS AND METHODS
Of 338 patients who received liver transplants and were followed at the Başkent University, Faculty of Medicine, 44 patients underwent bone marrow biopsy. The medical and pathologic information about these patients were evaluated, including age at liver transplant, age at bone marrow biopsy, sex, primary disease, bone marrow histology, and indication for bone marrow biopsy.
RESULTS
Of 44 patients who required bone marrow sampling, 30 were male (68.2%), and 14 were female (31.8%). Fifteen patients (34.1%) were in pediatric age group at the time of transplant. The most common cause of liver insufficiency leading to liver transplant was viral hepatitis in 11 patients (25%), followed by cryptogenic cirrhosis in 10 patients (22.8%). The source of the graft liver was a living donor in 40 patients (90.9%). The average age at transplant was 28.8 years, and the mean age at bone marrow sampling was 29.9 years. Nineteen patients (43.2%) required bone marrow sampling within the first year after transplant. The most common histologic findings were hypocellular, and normocellular bone marrow, observed in 18 patients (40.9%) each. Six patients (13.6%) had bone marrow biopsies for staging of posttransplant lymphoproliferative disorder. Only 1 patient of the 6 with this disease (16.7%) had malignant infiltration of the bone marrow, which was a case of Burkitt lymphoma developed as posttransplant lymphoproliferative disorder, and this was the only malignant infiltration in this patient group (2.3%). Neither specific infections nor granulomatous inflammation was detected.
CONCLUSIONS
Bone marrow morphology has a major role in the follow-up of liver transplant patients, who may present with peripheral blood cytopenias. The present study represents the first systematic evaluation of bone marrow findings in liver allograft recipients.
Topics: Adult; Allografts; Anemia; Biopsy; Bone Marrow; Bone Marrow Diseases; Bone Marrow Examination; Burkitt Lymphoma; Female; Hospitals, University; Humans; Leukopenia; Liver Transplantation; Male; Pancytopenia; Retrospective Studies; Time Factors; Treatment Outcome; Turkey
PubMed: 27805526
DOI: No ID Found -
Seminars in Hematology Jul 2006Shwachman-Diamond syndrome (SDS) is an autosomal recessive marrow failure syndrome associated with exocrine pancreatic insufficiency and leukemia predisposition. Bone... (Review)
Review
Shwachman-Diamond syndrome (SDS) is an autosomal recessive marrow failure syndrome associated with exocrine pancreatic insufficiency and leukemia predisposition. Bone marrow failure typically manifests with neutropenia, but anemia, thrombocytopenia, or aplastic anemia may also develop. Additional organ systems, such as liver or bone, may also be affected. Clonal cytogenetic abnormalities, particularly those involving chromosome 7 such as monosomy 7 or isochromosome 7, may develop. Mutations in the SBDS gene are found in approximately 90% of patients meeting clinical diagnostic criteria. SBDS is a highly conserved gene of unknown function. Studies of the yeast orthologue YLR022c and structurally related proteins suggest a role in RNA metabolism. In human cells, the SBDS protein localizes to both the cytoplasm and the nucleus, and shuttles in and out of the nucleolus in a cell cycle-dependent manner. A discussion of diagnostic workup, medical management, and treatment is presented.
Topics: Bone Marrow Diseases; Exocrine Pancreatic Insufficiency; Humans; Leukemia; Proteins; Syndrome
PubMed: 16822460
DOI: 10.1053/j.seminhematol.2006.04.006 -
Archives of Pathology & Laboratory... Apr 2008Examination of the bone marrow poses several unique challenges to the pathologist: it is a semisolid organ without helpful gross correlation, it exists in a dynamic... (Review)
Review
Examination of the bone marrow poses several unique challenges to the pathologist: it is a semisolid organ without helpful gross correlation, it exists in a dynamic state with the peripheral blood and other organs of the lymphohemopoietic system, and the diagnosis of diseases affecting bone marrow often depends heavily on ancillary special studies. The bone marrow examination ideally encompasses review of the bone marrow biopsy histology (with or without additional nondecalcified clot preparation material), bone marrow aspirate smear cytology, and the peripheral blood smear; optimal procurement and processing of these samples is critical in ensuring that a maximal level of diagnostic information can be extracted. The pathologist must be aware of the clinical context of the bone marrow and the results of ancillary tests, whether these are ordered by the pathologist or the clinician. A combination of excellent diagnostic samples, appropriate ancillary tests, and knowledge of the clinical context provides the best background to distinguish between the common reactive and neoplastic processes that involve the bone marrow and to avoid diagnostic pitfalls in making these distinctions.
Topics: Biopsy; Bone Marrow; Bone Marrow Diseases; Bone Marrow Examination; Bone Marrow Neoplasms; Diagnosis, Differential; Humans; Pathology
PubMed: 18384210
DOI: 10.5858/2008-132-587-RVNBMP -
American Journal of Clinical Pathology Jan 2013New-onset pancytopenia can be caused by a wide variety of etiologies, leading to a diagnostic dilemma. These etiologies range from congenital bone marrow failure to... (Review)
Review
New-onset pancytopenia can be caused by a wide variety of etiologies, leading to a diagnostic dilemma. These etiologies range from congenital bone marrow failure to marrow space-occupying lesions, infection, and peripheral destruction, to name a few. Bone marrow examination, in addition to a detailed clinical history, is often required for an accurate diagnosis. The purpose of this review is to provide a brief overview of many of the causes of new-onset pancytopenia in adults and children, with emphasis on bone marrow findings and recommendations of additional testing and clinical evaluation when needed, with the overall aim of aiding the pathologist's role as a consultant to the patient's treating physician.
Topics: Adult; Anemia, Aplastic; Autoimmune Diseases; Bone Marrow Cells; Bone Marrow Diseases; Bone Marrow Examination; Bone Marrow Failure Disorders; Child; Chromosome Aberrations; Diagnosis, Differential; Female; Hemoglobinuria, Paroxysmal; Humans; Infant; Male; Middle Aged; Pancytopenia; Referral and Consultation
PubMed: 23270895
DOI: 10.1309/AJCP50AEEYGREWUZ -
Seminars in Hematology Jan 2022Fanconi anemia, telomeropathies and ribosomopathies are members of the inherited bone marrow failure syndromes, rare genetic disorders that lead to failure of... (Review)
Review
Fanconi anemia, telomeropathies and ribosomopathies are members of the inherited bone marrow failure syndromes, rare genetic disorders that lead to failure of hematopoiesis, developmental abnormalities, and cancer predisposition. While each disorder is caused by different genetic defects in seemingly disparate processes of DNA repair, telomere maintenance, or ribosome biogenesis, they appear to lead to a common pathway characterized by premature senescence of hematopoietic stem cells. Here we review the experimental data on senescence and inflammation underlying marrow failure and malignant transformation. We conclude with a critical assessment of current and future therapies targeting these pathways in inherited bone marrow failure syndromes patients.
Topics: Anemia, Aplastic; Bone Marrow Diseases; Cellular Senescence; Congenital Bone Marrow Failure Syndromes; Fanconi Anemia; Humans
PubMed: 35491056
DOI: 10.1053/j.seminhematol.2022.01.003 -
American Journal of Hematology Feb 2021
Topics: Aged; Bone Marrow Diseases; Erdheim-Chester Disease; Humans; Male
PubMed: 33398894
DOI: 10.1002/ajh.25948