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Pathobiology : Journal of... 2019This review highlights the main changes in the revised 2016 WHO Classification of Myeloid Neoplasms (published in 2017) that impact the diagnosis and management of... (Review)
Review
This review highlights the main changes in the revised 2016 WHO Classification of Myeloid Neoplasms (published in 2017) that impact the diagnosis and management of patients with myelodysplastic syndrome (MDS). The revision was based on data accumulated since the 2008 WHO classification of MDS, much of which relates to new molecular genetic information about these neoplasms. The new information has led to some reorganization of the MDS disease categories, including a broadening of the subset of cases classified as MDS with ring sideroblasts, many of which have mutations in the spliceosome gene SF3B1. Other revisions have refined the definitions of some disease categories to improve disease risk stratification. The revised categories in the new classification ensure that MDS patients receive risk-adapted therapies based on the most recently available data.
Topics: Algorithms; Cytogenetics; Humans; Mutation; Myelodysplastic Syndromes; Myeloproliferative Disorders; Phosphoproteins; RNA Splicing Factors; World Health Organization
PubMed: 30041243
DOI: 10.1159/000489702 -
Pathobiology : Journal of... 2019The diagnosis and classification of myelodysplastic syndromes (MDS) are based on cytomorphology and cytogenetics (WHO classification). Prognosis is best defined by the... (Review)
Review
The diagnosis and classification of myelodysplastic syndromes (MDS) are based on cytomorphology and cytogenetics (WHO classification). Prognosis is best defined by the Revised International Prognostic Scoring System (IPSS-R). In recent years, an increasing number of molecular aberrations have been discovered. They are already included in the classification (e.g., SF3B1) and, more importantly, have emerged as valuable markers for better classification, particularly for defining risk groups. Mutations in genes such as SF3B1 and IDH1/2 have already had an impact on targeted treatment approaches in MDS.
Topics: Biomarkers; Humans; Isocitrate Dehydrogenase; Mutation; Myelodysplastic Syndromes; Pathology, Molecular; Phosphoproteins; Prognosis; RNA Splicing Factors
PubMed: 29791902
DOI: 10.1159/000488712 -
International Journal of Molecular... Sep 2021Myelodysplastic syndrome (MDS) is a heterogeneous, clonal hematological disorder characterized by ineffective hematopoiesis, cytopenia, morphologic dysplasia, and... (Review)
Review
Myelodysplastic syndrome (MDS) is a heterogeneous, clonal hematological disorder characterized by ineffective hematopoiesis, cytopenia, morphologic dysplasia, and predisposition to acute myeloid leukemia (AML). Stem cell genomic instability, microenvironmental aberrations, and somatic mutations contribute to leukemic transformation. The hypomethylating agents (HMAs), azacitidine and decitabine are the standard of care for patients with higher-risk MDS. Although these agents induce responses in up to 40-60% of patients, primary or secondary drug resistance is relatively common. To improve the treatment outcome, combinational therapies comprising HMA with targeted therapy or immunotherapy are being evaluated and are under continuous development. This review provides a comprehensive update of the molecular pathogenesis and immune-dysregulations involved in MDS, mechanisms of resistance to HMA, and strategies to overcome HMA resistance.
Topics: Antineoplastic Agents; Combined Modality Therapy; DNA Methylation; Humans; Immunotherapy; Molecular Targeted Therapy; Myelodysplastic Syndromes; Treatment Outcome
PubMed: 34638574
DOI: 10.3390/ijms221910232 -
Annals of Hematology Nov 2018Autoimmune disorders (ADs) are encountered in 10 to 20% of patients with myelodysplastic syndromes (MDS). Available data suggest that ADs concern more often younger... (Review)
Review
Autoimmune disorders (ADs) are encountered in 10 to 20% of patients with myelodysplastic syndromes (MDS). Available data suggest that ADs concern more often younger patients with higher risk IPSS. MDS subtypes associated with ADs are mainly MDS with single lineage dysplasia (MDS-SLD) and MDS with excess blasts (MDS-EB). Various types of ADs have been described in association with MDS, ranging from limited clinical manifestations to systemic diseases affecting multiple organs. Defined clinical entities as vasculitis, connective tissue diseases, inflammatory arthritis, and neutrophilic diseases are frequently reported; however, unclassified or isolated organ impairment can be seen. In general, ADs do not seem to confer worse survival, although certain ADs may be associated with adverse outcomes (i.e., vasculitis) or progression of MDS (Sweet syndrome). While steroids and immunosuppressive treatment (IST) remain the backbone of first-line treatment, increasing evidence suggests that MDS-specific therapy as hypomethylating agents, based on their immunomodulatory effect, may be effective in treating these complications and for sparing steroids.
Topics: Age Factors; Autoimmune Diseases; Disease-Free Survival; Humans; Immunosuppression Therapy; Myelodysplastic Syndromes; Risk Factors; Survival Rate
PubMed: 30091023
DOI: 10.1007/s00277-018-3472-9 -
Annals of Laboratory Medicine May 2022Myelodysplastic syndrome (MDS) is a diverse hematological malignancy with a wide spectrum of presentations and implications. Treatment strategies for patients with MDS... (Review)
Review
Myelodysplastic syndrome (MDS) is a diverse hematological malignancy with a wide spectrum of presentations and implications. Treatment strategies for patients with MDS heavily rely on prognostic scoring systems, such as the revised international prognostic scoring system (IPSS-R). Bone marrow fibrosis (BMF) has been identified as an independent risk factor for poor survival in patients with MDS, irrespective of the IPSS-R risk category. However, BMF is not widely included in scoring systems and is not always considered by clinicians when making treatment decisions for patients. In this review, we discuss the available literature about the presentation and prognosis of patients with MDS and concurrent BMF. The prognostic impact of BMF should be factored in when deciding on transplant candidacy, especially for intermediate-risk patients.
Topics: Humans; Myelodysplastic Syndromes; Primary Myelofibrosis; Prognosis; Risk Factors
PubMed: 34907099
DOI: 10.3343/alm.2022.42.3.299 -
British Journal of Haematology Jun 2020The prognosis in Myelodysplastic syndromes (MDS), although recently refined by molecular studies, remains largely based on conventional prognostic scores [International... (Review)
Review
The prognosis in Myelodysplastic syndromes (MDS), although recently refined by molecular studies, remains largely based on conventional prognostic scores [International Prognostic Scoring System (IPSS), revised IPSS], classifying patients into "lower risk" MDS (LR-MDS) and "higher risk" MDS (HR-MDS). In LR-MDS, treatment mainly aims at improving cytopenias, principally anaemia, while in HR-MDS it aims at delaying disease progression and prolonging survival. In LR-MDS without deletion 5q, anaemia is generally treated first by erythropoietic stimulating factors, while second line treatments are currently not approved [lenalidomide, hypomethylating agents (HMA), luspatercept] or rarely indicated (antithymocyte globulin). Lenalidomide has major efficacy in LR-MDS with deletion 5q. Allogeneic stem cell transplantation (allo-SCT) is sometimes considered in LR-MDS, and iron chelation can be considered when multiple red blood cell transfusions are required. Allo-SCT is the only potentially curative treatment for HR-MDS; however, it is rarely applicable. It is generally preceded by intensive chemotherapy (IC) or HMA in patients with excess of marrow blasts (especially if >10%). In other patients, HMA can improve survival. The role of new drugs, including venetoclax or, in case of specific mutations, IDH1 or IDH2 inhibitors, is investigated. IC is mainly indicated as a bridge to allo-SCT, in the absence of unfavourable karyotype.
Topics: Activin Receptors, Type II; Adult; Antilymphocyte Serum; Bridged Bicyclo Compounds, Heterocyclic; Erythrocyte Transfusion; Female; Humans; Immunoglobulin Fc Fragments; Lenalidomide; Male; Mutation; Myelodysplastic Syndromes; Recombinant Fusion Proteins; Sulfonamides
PubMed: 31568568
DOI: 10.1111/bjh.16206 -
Hematology. American Society of... Dec 2020Myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) overlap syndromes are uniquely classified neoplasms occurring in both children and adults. This category... (Review)
Review
Myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) overlap syndromes are uniquely classified neoplasms occurring in both children and adults. This category consists of 5 neoplastic subtypes: chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), BCR-ABL1-negative atypical chronic myeloid leukemia (aCML), MDS/MPN-ring sideroblasts and thrombocytosis (MDS/MPN-RS-T), and MDS/MPN-unclassifiable (U). Cytogenetic abnormalities and somatic copy number variations are uncommon; however, >90% patients harbor gene mutations. Although no single gene mutation is specific to a disease subtype, certain mutational signatures in the context of appropriate clinical and morphological features can be used to establish a diagnosis. In CMML, mutated coexpression of TET2 and SRSF2 results in clonal hematopoiesis skewed toward monocytosis, and the ensuing acquisition of driver mutations including ASXL1, NRAS, and CBL results in overt disease. MDS/MPN-RS-T demonstrates features of SF3B1-mutant MDS with ring sideroblasts (MDS-RS), with the development of thrombocytosis secondary to the acquisition of signaling mutations, most commonly JAK2V617F. JMML, the only pediatric entity, is a bona fide RASopathy, with germline and somatic mutations occurring in the oncogenic RAS pathway giving rise to disease. BCR-ABL1-negative aCML is characterized by dysplastic neutrophilia and is enriched in SETBP1 and ETNK1 mutations, whereas MDS/MPN-U is the least defined and lacks a characteristic mutational signature. Molecular profiling also provides prognostic information, with truncating ASXL1 mutations being universally detrimental and germline CBL mutations in JMML showing spontaneous regression. Sequencing information in certain cases can help identify potential targeted therapies (IDH1, IDH2, and splicing mutations) and should be a mainstay in the diagnosis and management of these neoplasms.
Topics: Aged; Chromosome Aberrations; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Genomics; Humans; Male; Mutation; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Prognosis
PubMed: 33275756
DOI: 10.1182/hematology.2020000130 -
Genes Jul 2021Myelodysplastic syndromes (MDS) are a clonal disease arising from hematopoietic stem cells, that are characterized by ineffective hematopoiesis (leading to peripheral... (Review)
Review
Myelodysplastic syndromes (MDS) are a clonal disease arising from hematopoietic stem cells, that are characterized by ineffective hematopoiesis (leading to peripheral blood cytopenia) and by an increased risk of evolution into acute myeloid leukemia. MDS are driven by a complex combination of genetic mutations that results in heterogeneous clinical phenotype and outcome. Genetic studies have enabled the identification of a set of recurrently mutated genes which are central to the pathogenesis of MDS and can be organized into a limited number of cellular pathways, including RNA splicing (, , , genes), DNA methylation (, , ), transcription regulation (), signal transduction (, ), DNA repair (), chromatin modification (, ), and cohesin complex (). Few genes are consistently mutated in >10% of patients, whereas a long tail of 40-50 genes are mutated in <5% of cases. At diagnosis, the majority of MDS patients have 2-4 driver mutations and hundreds of background mutations. Reliable genotype/phenotype relationships were described in MDS: mutations are associated with the presence of ring sideroblasts and more recent studies indicate that other splicing mutations (, ) may identify distinct disease categories with specific hematological features. Moreover, gene mutations have been shown to influence the probability of survival and risk of disease progression and mutational status may add significant information to currently available prognostic tools. For instance, mutations are predictors of favourable prognosis, while driver mutations of other genes (such as , , , ) are associated with a reduced probability of survival and increased risk of disease progression. In this article, we review the most recent advances in our understanding of the genetic basis of myelodysplastic syndromes and discuss its clinical relevance.
Topics: Genetic Predisposition to Disease; Humans; Mutation; Myelodysplastic Syndromes; Prognosis
PubMed: 34440317
DOI: 10.3390/genes12081144 -
Archives of Pathology & Laboratory... Apr 2024Myelodysplasia cutis is an emerging concept in cutaneous neoplasia. Many of these cases were previously included under the umbrella of histiocytoid Sweet syndrome.... (Review)
Review
CONTEXT.—
Myelodysplasia cutis is an emerging concept in cutaneous neoplasia. Many of these cases were previously included under the umbrella of histiocytoid Sweet syndrome. However, with the advent of next-generation sequencing, cutaneous involvement by myelodysplastic syndrome is being increasingly recognized.
OBJECTIVE.—
To review histiocytoid Sweet syndrome and myelodysplasia cutis and discuss our current understanding of these entities. Additionally, to discuss how next-generation sequencing can be applied in the evaluation of cutaneous infiltrates of immature histiocytoid cells.
DATA SOURCES.—
The English-language literature from 2005 to 2023 on the topic of histiocytoid Sweet syndrome and myelodysplasia cutis was reviewed.
CONCLUSIONS.—
Biopsy specimens showing infiltrates of histiocytoid, immature myeloid cells may represent cutaneous involvement by myelodysplastic syndrome. Close clinical correlation is recommended in these cases. Recent studies suggest that next-generation sequencing is useful in separating myelodysplasia cutis from true histiocytoid Sweet syndrome. This distinction has important implications for patients.
Topics: Humans; Myelodysplastic Syndromes; Skin; Skin Neoplasms; Sweet Syndrome
PubMed: 37787422
DOI: 10.5858/arpa.2023-0132-RA -
Transplantation and Cellular Therapy Feb 2023The sole curative therapy for myelodysplastic syndrome (MDS) is allogeneic hematopoietic cell transplantation (HCT). Here this therapeutic modality is reviewed and... (Review)
Review
Hematopoietic Cell Transplantation in the Management of Myelodysplastic Syndrome: An Evidence-Based Review from the American Society for Transplantation and Cellular Therapy Committee on Practice Guidelines.
The sole curative therapy for myelodysplastic syndrome (MDS) is allogeneic hematopoietic cell transplantation (HCT). Here this therapeutic modality is reviewed and critically evaluated in the context of the evidence. Specific criteria were used for searching the published literature and for grading the quality and strength of the evidence and the strength of the recommendations. A panel of MDS experts comprising transplantation and nontransplantation physicians developed consensus treatment recommendations. This review summarizes the standard MDS indications for HCT and addresses areas of controversy. Recent prospective trials have confirmed that allogeneic HCT confers survival benefits in patients with advanced or high-risk MDS compared with nontransplantation approaches, and the use of HCT is increasing in older patients with good performance status. However, patients with high-risk cytogenetic or molecular mutations remain at high risk for relapse. It is unknown whether administration of novel therapies before or after transplantation may decrease the risk of disease relapse in selected populations. Ongoing and future studies will investigate revised approaches to disease risk stratification, patient selection, and post-transplantation approaches to optimize allogeneic HCT outcomes for patients with MDS.
Topics: Humans; United States; Aged; Transplantation Conditioning; Hematopoietic Stem Cell Transplantation; Myelodysplastic Syndromes; Transplantation, Homologous; Recurrence
PubMed: 36436780
DOI: 10.1016/j.jtct.2022.11.014