MDS

Often unrecognized and underdiagnosed, myelodysplastic syndromes (MDS) are a rare group of cancers in which the bone marrow fails to produce sufficient healthy blood cells. Although patients with lower-risk MDS can live for >5 years, those with high-risk disease that evolves into acute myeloid leukemia is associated with significantly lower overall survival. At the NCCN 2019 Annual Congress: Hematologic Malignancies, Dr. Rafael Bejar summarized current standard treatment options for patients with MDS and discussed the importance of genetic testing to identify mutations that may impact treatment...

Myelodysplastic syndromes (MDS) include a group of clonal myeloid neoplasms characterized by cytopenias due to ineffective hematopoiesis, abnormal blood and marrow cell morphology, and a risk of clonal evolution and progression to acute myeloid leukemia (AML). Because outcomes for patients with MDS are heterogeneous, individual risk stratification using tools such as the revised International Prognostic Scoring System (IPSS-R) is important in managing patients-including selecting candidates for allogeneic hematopoietic stem cell transplantation (ASCT), the only potentially curative therapy for MDS...

Myelodysplastic syndromes (MDS) are a heterogeneous group of hemopathies that exhibit physical manifestations with clinical consequences of bone marrow failure and inherent risk of progression to acute myeloid leukemia. Iron overload (IO) is common in MDS due to chronic transfusion support and disease-related alterations in iron metabolism. IO has been conclusively associated with inferior outcomes among MDS patients. Despite lack of randomized trials showing a survival impact of iron chelation therapy (ICT), ICT is recommended by experts and guidelines for select MDS patients with IO and is often used...

BACKGROUND: Thrombocytopenia is a life-threatening complication in patients with advanced myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). In this study (ASPIRE), we aimed to assess eltrombopag, an oral thrombopoietin receptor agonist, for thrombocytopenia (grade 4) treatment in adult patients with advanced MDS or AML. METHODS: ASPIRE consisted of an open-label, double-blind phase for 8 weeks and a randomised, double-blind phase (parts 1 and 2, reported here) for 12 weeks, and an open-label extension (part 3)...

Lower risk myelodysplastic syndromes (MDS), defined as MDS with a Revised International Prognostic Scoring System score ≤3.5 points, will remain a challenging entity in 2018. Supportive care continues to be the linchpin of treatment, although the options to reduce transfusion needs are broadening. To achieve red blood cell transfusion independence in non-del(5q) patients, erythropoiesis-stimulating agents remain a mainstay of therapy as long as endogenous erythropoietin levels are <500 U/L (and preferably <200 U/L)...

Several haematological malignancies, including multiple myeloma (MM) and acute myeloid leukaemia (AML), have well-defined precursor states that precede the development of overt cancer. MM is almost always preceded by monoclonal gammopathy of undetermined significance (MGUS), and at least a quarter of all patients with myelodysplastic syndromes (MDS) have disease that evolves into AML. In turn, MDS are frequently anteceded by clonal haematopoiesis of indeterminate potential (CHIP). The acquisition of additional genetic and epigenetic alterations over time clearly influences the increasingly unstable and aggressive behaviour of neoplastic haematopoietic clones; however, perturbations in the bone-marrow microenvironment are increasingly recognized to have key roles in initiating and supporting oncogenesis...

DISEASE OVERVIEW: The myelodysplastic syndromes (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML). MDS occurs more frequently in older males and in individuals with prior exposure to cytotoxic therapy. DIAGNOSIS: Diagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy. Information obtained from additional studies such as karyotype, flow cytometry or molecular genetics is usually complementary and may help refine diagnosis...

A 27-gene panel was used for next-generation sequencing (NGS) in 179 patients (median age 73 years) with primary myelodysplastic syndromes (MDS); risk distribution according to the revised International Prognostic Scoring System (IPSS-R) was 11% very high, 18% high, 17% intermediate, 38% low and 16% very low. At least one mutation/variant was detected in 147 (82%) patients; 23% harbored three or more mutations/variants. The most frequent mutations/variants included ASXL1 (30%), TET2 (25%), SF3B1 (20%), U2AF1 (16%), SRSF2 (16%), TP53 (13%), RUNX1 (11%), and DNMT3A (10%)...

Hypoplastic myelodysplastic syndrome (hMDS) is a distinct entity with bone marrow (BM) hypocellularity and the risk of death from BM failure (BMF). To elucidate the characteristics of hMDS, the data of 129 patients diagnosed between April 2003 and March 2012 were collected from 20 institutions and the central review team of the National Research Group on Idiopathic Bone Marrow Failure Syndromes, and compared with 115 non-hMDS patients. More RA and fewer CMMoL and RAEB-t in French-American-British (FAB) and more RCUD and MDS-U and fewer RCMD in World Health Organization (WHO) classifications were found in hMDS than non-hMDS with significant differences...

This corrects the article DOI: 10.1038/leu.2016.303.

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BACKGROUND: Genetic mutations drive the pathogenesis of the myelodysplastic syndrome (MDS) and are closely associated with clinical phenotype. Therefore, genetic mutations may predict clinical outcomes after allogeneic hematopoietic stem-cell transplantation. METHODS: We performed targeted mutational analysis on samples obtained before transplantation from 1514 patients with MDS who were enrolled in the Center for International Blood and Marrow Transplant Research Repository between 2005 and 2014...

An increasingly complete compendium of recurrently mutated genes in myelodysplastic syndromes (MDS) has been defined, and the application of massively parallel sequencing to identify mutations in clinical practice now promises to improve the care of patients with this disease. More than 25 recurrent MDS-associated somatic mutations have been identified, involving biologic pathways as diverse as chromatin remodeling and pre-mRNA splicing. Several of these mutations have been shown to have prognostic implications that are independent of existing risk stratification systems based on clinical and pathologic parameters...

Myelodysplastic syndrome (MDS) is clonal disorder characterized by ineffective hematopoiesis and a tendency to evolve into acute myeloid leukemia (AML). Genetic studies have enabled the identification of a set of recurrently mutated genes central to the pathogenesis of MDS, which can be organized into a limited number of cellular processes, including RNA splicing, epigenetic and traditional transcriptional regulation, and signal transduction. The sequential accumulation of mutations drives disease evolution from asymptomatic clonal hematopoiesis to frank MDS, and, ultimately, to secondary AML...