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The Journal of Bone and Joint Surgery.... Jan 2022Bone marrow edema (BME) is a nonspecific but relevant finding, usually indicating the presence of an underlying pathology. (Review)
Review
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Bone marrow edema (BME) is a nonspecific but relevant finding, usually indicating the presence of an underlying pathology.
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The gold standard technique for detecting BME is magnetic resonance imaging (MRI), as it allows for a correct diagnosis to be made, which is extremely important given the heterogeneity of BME-related diseases.
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Depending on the severity of painful symptomatology and the MRI evidence, different treatment strategies can be followed: physical modalities, pharmacological options, and surgical therapy.
Topics: Bone Marrow Diseases; Diagnosis, Differential; Edema; Humans; Magnetic Resonance Imaging
PubMed: 34780382
DOI: 10.2106/JBJS.21.00300 -
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 Aug 2022Inherited bone marrow (BM) failure syndromes are a diverse group of disorders characterized by BM failure, usually in association with ≥1 extrahematopoietic...
Inherited bone marrow (BM) failure syndromes are a diverse group of disorders characterized by BM failure, usually in association with ≥1 extrahematopoietic abnormalities. BM failure, which can involve ≥1 cell lineages, often presents in the pediatric age group. Furthermore, some children initially labeled as having idiopathic aplastic anemia or myelodysplasia represent cryptic cases of inherited BM failure. Significant advances in the genetics of these syndromes have been made, identifying more than 100 disease genes, giving insights into normal hematopoiesis and how it is disrupted in patients with BM failure. They have also provided important information on fundamental biological pathways, including DNA repair: Fanconi anemia (FA) genes; telomere maintenance: dyskeratosis congenita (DC) genes; and ribosome biogenesis: Shwachman-Diamond syndrome and Diamond-Blackfan anemia genes. In addition, because these disorders are usually associated with extrahematopoietic abnormalities and increased risk of cancer, they have provided insights into human development and cancer. In the clinic, genetic tests stemming from the recent advances facilitate diagnosis, especially when clinical features are insufficient to accurately classify a disorder. Hematopoietic stem cell transplantation using fludarabine-based protocols has significantly improved outcomes, particularly in patients with FA or DC. Management of some other complications, such as cancer, remains a challenge. Recent studies have suggested the possibility of new and potentially more efficacious therapies, including a renewed focus on hematopoietic gene therapy and drugs [transforming growth factor-β inhibitors for FA and PAPD5, a human poly(A) polymerase, inhibitors for DC] that target disease-specific defects.
Topics: Anemia, Aplastic; Bone Marrow Diseases; Bone Marrow Failure Disorders; Child; Dyskeratosis Congenita; Humans; Neoplasms; Pancytopenia
PubMed: 35605178
DOI: 10.1182/blood.2020006481 -
Best Practice & Research. Clinical... Jun 2021
Topics: Anemia, Aplastic; Bone Marrow Diseases; Bone Marrow Failure Disorders; Humans; Syndrome
PubMed: 34404531
DOI: 10.1016/j.beha.2021.101288 -
The Veterinary Clinics of North... Jan 2017Important steps in bone marrow aspirate evaluation include determining if bone marrow evaluation is indicated; using appropriate aspirate collection, smear preparation,... (Review)
Review
Important steps in bone marrow aspirate evaluation include determining if bone marrow evaluation is indicated; using appropriate aspirate collection, smear preparation, and staining techniques; and performing a systematic approach for the cytologic evaluation. The cytologic evaluation of bone marrow requires knowledge of the morphology of bone marrow cell types, the proportion of these cell types normally present, and the ability to evaluate overall cellularity of bone marrow. Accurate interpretation of bone marrow cytologic findings depends on evaluation of a current complete blood cell count. These components are the pillars of getting the most useful information in the diagnosis of hematologic disorders.
Topics: Animals; Biopsy, Needle; Bone Marrow Diseases; Bone Marrow Examination; Cytological Techniques; Specimen Handling
PubMed: 27720279
DOI: 10.1016/j.cvsm.2016.07.003 -
Annals of Hematology Apr 2023ERCC excision repair 6 like 2 (ERCC6L2) gene encodes for different helicase-like protein members of the Snf2 family involved in transcription-coupled nucleotide excision... (Review)
Review
ERCC excision repair 6 like 2 (ERCC6L2) gene encodes for different helicase-like protein members of the Snf2 family involved in transcription-coupled nucleotide excision repair and in cell proliferation. Germline homozygous mutations in children and adults predispose to a peculiar bone marrow failure phenotype characterized by mild hematological alterations with a high risk of developing acute myeloid leukemia. The outcome for patients with leukemia progression is dismal while patients undergoing hematopoietic stem cell transplantation in the early stage have better outcomes. The ERCC6L2-related hematological disease presents a high penetrance, posing important questions regarding the treatment strategies and possible preemptive approaches. This review describes the biological function of ERCC6L2 and the clinical manifestations of the associated disease, trying to focus on the unsolved clinical questions.
Topics: Humans; Bone Marrow Diseases; Bone Marrow Failure Disorders; Pancytopenia; DNA Repair; Leukemia, Myeloid, Acute; Clonal Evolution; Hematopoietic Stem Cell Transplantation; DNA Helicases
PubMed: 36790458
DOI: 10.1007/s00277-023-05128-2 -
Hematology/oncology Clinics of North... Aug 2016Bone marrow is the essential for function of hematopoiesis, which is vital for the normal functioning of the body. Bone marrow disorders or dysfunctions may be evaluated... (Review)
Review
Bone marrow is the essential for function of hematopoiesis, which is vital for the normal functioning of the body. Bone marrow disorders or dysfunctions may be evaluated by blood workup, peripheral smears, marrow biopsy, plain radiographs, computed tomography (CT), MRI and nuclear medicine scan. It is important to distinguish normal spinal marrow from pathology to avoid missing a pathology or misinterpreting normal changes, either of which may result in further testing and increased health care costs. This article focuses on the diffuse bone marrow pathologies, because the majority of the bone marrow pathologies related to hematologic disorders are diffuse.
Topics: Bone Marrow Diseases; Humans; Magnetic Resonance Imaging; Tomography, X-Ray Computed
PubMed: 27444005
DOI: 10.1016/j.hoc.2016.03.012 -
The Veterinary Clinics of North... Jan 2023The traditional role of cytologic and histologic evaluation of bone marrow remains important in understanding diseases and conditions that affect this tissue. It is only... (Review)
Review
The traditional role of cytologic and histologic evaluation of bone marrow remains important in understanding diseases and conditions that affect this tissue. It is only through correlation of historical and clinical findings with hematologic, bone marrow, and other ancillary data that an accurate diagnosis can be made. Thus, the clinician is an essential link in helping establish a correct diagnosis. This article is a primer for understanding key features of bone marrow evaluation and provides practical tips for developing the best practices for optimal patient care.
Topics: Animals; Bone Marrow; Bone Marrow Examination; Bone Marrow Diseases
PubMed: 36270840
DOI: 10.1016/j.cvsm.2022.08.002 -
Blood Mar 2023Shwachman-Diamond syndrome (SDS) is an inherited multisystem ribosomopathy characterized by exocrine pancreatic deficiency, bone marrow failure, and predisposition to... (Review)
Review
Shwachman-Diamond syndrome (SDS) is an inherited multisystem ribosomopathy characterized by exocrine pancreatic deficiency, bone marrow failure, and predisposition to myeloid malignancies. The pathobiology of SDS results from impaired ribosomal maturation due to the deficiency of SBDS and the inability to evict the antiassociation factor eIF6 from the 60S ribosomal subunit. Clinical outcomes for patients with SDS who develop myeloid malignancies are extremely poor because of high treatment-related toxicities and a high rate of refractory disease/relapse even after allogeneic hematopoietic stem cell transplant (HSCT). Registry data indicate that outcomes are improved for patients with SDS who undergo routine bone marrow surveillance and receive an HSCT before developing an overt malignancy. However, the optimal approach to hematologic surveillance and the timing of HSCT for patients with SDS is not clearly established. Recent studies have elucidated distinct patterns of somatic blood mutations in patients with SDS that either alleviate the ribosome defect via somatic rescue (heterozygous EIF6 inactivation) or disrupt cellular checkpoints, resulting in increased leukemogenic potential (heterozygous TP53 inactivation). Genomic analysis revealed that most myeloid malignancies in patients with SDS have biallelic loss-of-function TP53 mutations. Single-cell DNA sequencing of SDS bone marrow samples can detect premalignant biallelic TP53-mutated clones before clinical diagnosis, suggesting that molecular surveillance may enhance the detection of incipient myeloid malignancies when HSCT may be most effective. Here, we review the clinical, genetic, and biologic features of SDS. In addition, we present evidence supporting the hematologic surveillance for patients with SDS that incorporates clinical, pathologic, and molecular data to risk stratify patients and prioritize transplant evaluation for patients with SDS with high-risk features.
Topics: Humans; Shwachman-Diamond Syndrome; Bone Marrow Diseases; Exocrine Pancreatic Insufficiency; Lipomatosis; Neoplasm Recurrence, Local; Myeloproliferative Disorders; Disease Susceptibility
PubMed: 36542827
DOI: 10.1182/blood.2022017739 -
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