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Hematology. American Society of... Dec 2016Pure red cell aplasia (PRCA) is a syndrome defined by a normocytic normochromic anemia with severe reticulocytopenia and marked reduction or absence of erythroid... (Review)
Review
Pure red cell aplasia (PRCA) is a syndrome defined by a normocytic normochromic anemia with severe reticulocytopenia and marked reduction or absence of erythroid precursors from the bone marrow. Diamond-Blackfan anemia is a congenital form of PRCA. Acquired PRCA may be either a primary disorder or secondary to some other disorder or agent. Primary acquired PRCA is an autoimmune disorder that is frequently antibody-mediated. Myelodysplastic syndromes may also present with the morphologic appearance of PRCA. Secondary acquired PRCA may be associated with collagen vascular/autoimmune disorders such as systemic lupus erythematosus; lymphoproliferative disorders such as chronic lymphocytic leukemia or large granular lymphocyte leukemia; infections, particularly B19 parvovirus; thymoma and other solid tumors; or a variety of other disorders, drugs, or toxic agents. The therapeutic approach to PRCA typically involves immunosuppression, but specific pathogenic subtypes are associated with specific therapeutic approaches. Cyclosporine A, with or without concurrent corticosteroids, appears to be the single most effective immunosuppressive agent.
Topics: Adrenal Cortex Hormones; Anemia, Diamond-Blackfan; Autoimmune Diseases; Cyclosporine; Humans; Immunosuppressive Agents; Leukemia, Large Granular Lymphocytic; Leukemia, Lymphocytic, Chronic, B-Cell; Myelodysplastic Syndromes; Parvoviridae Infections; Parvovirus B19, Human; Thymoma; Vasculitis
PubMed: 27913462
DOI: 10.1182/asheducation-2016.1.51 -
Blood Oct 2020
Topics: Aged, 80 and over; Anemia, Sideroblastic; Arteriosclerosis; Biopsy; Blood Transfusion; Blood Vessels; Bone Marrow; Deferasirox; Female; Humans; Iron; Iron Overload; Metals, Heavy; Myelodysplastic-Myeloproliferative Diseases; Thrombocytosis; Transfusion Reaction; Treatment Failure
PubMed: 33091139
DOI: 10.1182/blood.2020007779 -
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 -
Journal of Clinical and Experimental... 2018Bone marrow failure (BMF) is a rare but life-threatening disorder that usually manifests as (pan)cytopenia. BMF can be caused by a variety of diseases, but inherited BMF... (Review)
Review
Bone marrow failure (BMF) is a rare but life-threatening disorder that usually manifests as (pan)cytopenia. BMF can be caused by a variety of diseases, but inherited BMF (IBMF) syndromes are a clinically important cause, especially in children. IBMF syndromes are a heterogeneous group of genetic disorders characterized by BMF, physical abnormalities, and predisposition to malignancy. An accurate diagnosis is critical, as disease-specific management, surveillance, and genetic counselling are required for each patient. The major differential diagnoses of IBMF syndromes are acquired aplastic anemia (AA) and refractory cytopenia of childhood (RCC). These diseases have overlapping features, such as BM hypocellularity and/or dysplastic changes, which make the differential diagnosis challenging. RCC has been defined as a histomorphologically distinct entity. Therefore, understanding the BM histopathology of these diseases is essential for the differential diagnosis. However, the BM histopathological features have not been characterized in detail, as descriptions of BM histopathology are very limited due to the rarity of the diseases. This review provides a detailed description of the BM histopathology in cases of RCC, AA, and the four most common IBMF syndromes: Fanconi anemia (FA), dysketatosis congenita (DC), Diamond-Blackfan anemia (DBA), and Shwachman-Diamond syndrome (SDS). An overview, including the clinical features and diagnosis, is also provided.
Topics: Adolescent; Anemia, Aplastic; Bone Marrow Diseases; Bone Marrow Failure Disorders; Child; Child, Preschool; Diagnosis, Differential; Female; Hemoglobinuria, Paroxysmal; Histological Techniques; Humans; Infant; Male
PubMed: 29998978
DOI: 10.3960/jslrt.18018 -
Hematology/oncology Clinics of North... Aug 2018Dyskeratosis congenita (DC) is a rare, inherited bone marrow failure (BMF) syndrome characterized by variable manifestations and ages of onset, and predisposition to... (Review)
Review
Dyskeratosis congenita (DC) is a rare, inherited bone marrow failure (BMF) syndrome characterized by variable manifestations and ages of onset, and predisposition to cancer. DC is one of a spectrum of diseases caused by mutations in genes regulating telomere maintenance, collectively referred to as telomere biology disorders (TBDs). Hematologic disease is common in children with DC/TBD. Timely diagnosis of underlying TBD in patients with BMF affects treatment and has been facilitated by increased awareness and availability of diagnostic tests in recent years. This article summarizes the pathophysiology, evaluation, and management of hematopoietic failure in patients with DC and other TBDs.
Topics: Anemia, Aplastic; Bone Marrow Diseases; Bone Marrow Failure Disorders; Child; Child, Preschool; Dyskeratosis Congenita; Genetic Predisposition to Disease; Hemoglobinuria, Paroxysmal; Humans; Mutation; Neoplasms; Telomere; Telomere Homeostasis
PubMed: 30047419
DOI: 10.1016/j.hoc.2018.04.003 -
Seminars in Fetal & Neonatal Medicine Feb 2016The inherited bone marrow failure syndromes (IBMFS) are a rare yet clinically important cause of neonatal hematological and non-hematological manifestations. Many of... (Review)
Review
The inherited bone marrow failure syndromes (IBMFS) are a rare yet clinically important cause of neonatal hematological and non-hematological manifestations. Many of these syndromes, such as Fanconi anemia, dyskeratosis congenita and Diamond-Blackfan anemia, confer risks of multiple medical complications later in life, including an increased risk of cancer. Some IBMFS may present with cytopenias in the neonatal period whereas others may present only with congenital physical abnormalities and progress to pancytopenia later in life. A thorough family history and detailed physical examination are integral to the work-up of any neonate in whom there is a high index of suspicion for an IBMFS. Correct detection and diagnosis of these disorders is important for appropriate long-term medical surveillance and counseling not only for the patient but also for appropriate genetic counselling of their families regarding recurrence risks in future children and generations.
Topics: Anemia, Aplastic; Anemia, Diamond-Blackfan; Bone Marrow Diseases; Bone Marrow Failure Disorders; Congenital Bone Marrow Failure Syndromes; Dyskeratosis Congenita; Exocrine Pancreatic Insufficiency; Fanconi Anemia; Hemoglobinuria, Paroxysmal; Humans; Infant, Newborn; Lipomatosis; Neutropenia; Radius; Shwachman-Diamond Syndrome; Thrombocytopenia; Upper Extremity Deformities, Congenital
PubMed: 26724991
DOI: 10.1016/j.siny.2015.12.003 -
Pediatric Research Dec 2022Shwachman Diamond syndrome (SDS) is an inherited bone marrow failure syndrome (IBMFS) associated with pancreatic insufficiency, neutropenia, and skeletal dysplasia.... (Review)
Review
BACKGROUND AND OBJECTIVES
Shwachman Diamond syndrome (SDS) is an inherited bone marrow failure syndrome (IBMFS) associated with pancreatic insufficiency, neutropenia, and skeletal dysplasia. Biallelic pathogenic variants (PV) in SBDS account for >90% of SDS. We hypothesized that the SDS phenotype varies based on genotype and conducted a genotype-phenotype correlation study to better understand these complexities.
METHODS
We reviewed records of all patients with SDS or SDS-like syndromes in the National Cancer Institute's (NCI) IBMFS study. Additional published SDS cohorts were reviewed and compared with the NCI cohort.
RESULTS
PVs in SBDS were present in 32/47 (68.1%) participants. Biallelic inheritance of SBDS c.258 + 2T > C and c.183_184TA > CT was the most common genotype in our study (25/32, 78.1%) and published cohorts. Most patients had the SDS hallmark features of neutropenia (45/45, 100%), pancreatic insufficiency (41/43, 95.3%), and/or bony abnormalities (29/36, 80.6%). Developmental delay was common (20/34, 58.8%). Increased risk of hematologic malignancies at young ages and the rarity of solid malignancies was observed in both the NCI cohort and published studies.
CONCLUSIONS
SDS is a complex childhood illness with a narrow genotypic spectrum. Patients may first present to primary care, gastroenterology, orthopedic, and/or hematology clinics. Coordinated multidisciplinary care is important for diagnosis and patient management.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT00027274.
IMPACT
The clinical and genetic spectrum of Shwachman Diamond Syndrome was comprehensively evaluated, and the findings illustrate the importance of a multidisciplinary approach for these complex patients. Our work reveals: 1. a narrow genotypic spectrum in SDS; 2. a low risk of solid tumors in patients with SDS; 3. patients with SDS have clinical manifestations in multiple organ systems.
Topics: Humans; Shwachman-Diamond Syndrome; Bone Marrow Diseases; Congenital Bone Marrow Failure Syndromes; Lipomatosis; Exocrine Pancreatic Insufficiency; Neutropenia; Genotype
PubMed: 35322185
DOI: 10.1038/s41390-022-02009-8 -
Hematology. American Society of... Dec 2017Despite significant progress in transplantation by the addition of alternative hematopoietic stem cell sources, many patients with inherited bone marrow failure... (Review)
Review
Despite significant progress in transplantation by the addition of alternative hematopoietic stem cell sources, many patients with inherited bone marrow failure syndromes are still not eligible for a transplant. In addition, the availability of sequencing panels has significantly improved diagnosis by identifying cryptic inherited cases. Androgens are the main nontransplant therapy for bone marrow failure in dyskeratosis congenita and Fanconi anemia, reaching responses in up to 80% of cases. Danazol and oxymetholone are more commonly used, but virilization and liver toxicity are major adverse events. Diamond-Blackfan anemia is commonly treated with corticosteroids, but most patients eventually become refractory to this treatment and toxicity is limiting. Growth factors still have a role in inherited cases, especially granulocyte colony-stimulating factor in congenital neutropenias. Novel therapies are warranted and thrombopoietin receptor agonists, leucine, quercetin, and novel gene therapy approaches may benefit inherited cases in the future.
Topics: Androgens; Bone Marrow Diseases; Chemical and Drug Induced Liver Injury; Danazol; Female; Genetic Diseases, Inborn; Genetic Therapy; Humans; Leucine; Oxymetholone; Quercetin; Stem Cell Transplantation; Syndrome; Virilism
PubMed: 29222242
DOI: 10.1182/asheducation-2017.1.96 -
The Journal of Veterinary Medical... Jun 2020Non-neoplastic bone marrow disorders such as non-regenerative immune-mediated anemia, pure red cell aplasia, and myelodysplastic syndrome are major causes of...
Non-neoplastic bone marrow disorders such as non-regenerative immune-mediated anemia, pure red cell aplasia, and myelodysplastic syndrome are major causes of non-regenerative anemia in dogs. However, there has been no study on the clinical and clinicopathological features of canine non-neoplastic bone marrow disorders in Japan. Hence, we first investigated the breed disposition of non-neoplastic bone marrow disorders that induce anemia as a retrospective study and found that Miniature Dachshund (MD) was a predisposed breed. Based on this finding, we investigated the clinical and clinicopathological features of non-neoplastic bone marrow disorders in MDs as a preliminary retrospective study, and we compared them between immunosuppressive treatment-responsive and -resistant MDs. We found that treatment-resistant MDs showed thrombocytosis and increased frequencies of dysplastic features in the peripheral blood. These results indicate that bone marrow disorders in treatment-resistant MDs might manifest distinct features compared with those in treatment-sensitive MDs, and sensitivity to immunosuppressive treatments could be predicted based on thrombocytosis and dysplastic features in the peripheral blood. Further studies that examine aberrations in the genome are needed to elucidate the pathophysiology of bone marrow disorders in MDs.
Topics: Anemia, Hemolytic; Animals; Bone Marrow Diseases; Dog Diseases; Dogs; Female; Genetic Predisposition to Disease; Glucocorticoids; Immunosuppressive Agents; Japan; Male; Prednisolone; Retrospective Studies; Species Specificity; Treatment Outcome
PubMed: 32307340
DOI: 10.1292/jvms.19-0439 -
British Journal of Haematology May 2017Acquired aplastic anaemia (AA) is an immune-mediated bone marrow failure disorder inextricably linked to clonal haematopoiesis. The majority of AA patients have somatic... (Review)
Review
Acquired aplastic anaemia (AA) is an immune-mediated bone marrow failure disorder inextricably linked to clonal haematopoiesis. The majority of AA patients have somatic mutations and/or structural chromosomal abnormalities detected as early as at diagnosis. In contrast to other conditions linked to clonal haematopoiesis, the clonal signature of AA reflects its immune pathophysiology. The most common alterations are clonal expansions of cells lacking glycophosphotidylinositol-anchored proteins, loss of human leucocyte antigen alleles, and mutations in BCOR/BCORL1, ASXL1 and DNMT3A. Here, we present the current knowledge of clonal haematopoiesis in AA as it relates to aging, inherited bone marrow failure, and the grey-zone overlap of AA and myelodysplastic syndrome (MDS). We conclude by discussing the significance of clonal haematopoiesis both for improved diagnosis of AA, as well as for a more precise, personalized approach to prognostication of outcomes and therapy choices.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia, Aplastic; Bone Marrow Diseases; Bone Marrow Failure Disorders; Child; Child, Preschool; Clone Cells; Diagnosis, Differential; Female; Genetic Markers; Hematopoiesis; Hemoglobinuria, Paroxysmal; Humans; Immune Evasion; Infant; Intercellular Signaling Peptides and Proteins; Male; Middle Aged; Mutation; Myelodysplastic Syndromes; Prognosis; Recurrence; Young Adult
PubMed: 28107566
DOI: 10.1111/bjh.14510