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Key Clinical Updates in Myelodysplastic Syndromes

A novel agent, luspatercept, has been developed to target signaling via the SMAD2–SMAD3 pathway which is constitutively increased in the bone marrow cells of patients with MDS and ineffective erythropoiesis.

In a randomized study, luspatercept induced transfusion independence in 38% of lower-risk MDS patients who did not respond to growth factor therapy compared to 13% in the placebo arm.


  • Cytopenias with a hypercellular bone marrow.

  • Morphologic abnormalities in one or more hematopoietic cell lines.


The MDS are a group of acquired clonal disorders of the hematopoietic stem cell. They are characterized by the constellation of cytopenias, a usually hypercellular marrow, morphologic dysplasia, and genetic abnormalities. The disorders are usually idiopathic but may be caused by prior exposure to cytotoxic chemotherapy, radiation or both. In addition to cytogenetics, sequencing can detect genetic mutations in 80–90% of MDS patients. Importantly, acquired clonal mutations identical to those seen in MDS can occur in the hematopoietic cells of ~10% of apparently healthy older individuals, defining the disorder of clonal hematopoiesis of indeterminate potential (CHIP).

Myelodysplasia encompasses several heterogeneous syndromes. A key distinction is whether there is an increase in bone marrow blasts (greater than 5% of marrow elements). The category of MDS with excess blasts represents a more aggressive form of the disease, often leading to AML. Those without excess blasts are characterized by the degree of dysplasia, eg, MDS with single lineage dysplasia and MDS with multilineage dysplasia. The morphologic finding of ringed sideroblasts is used to define a subcategory of the lower-risk MDS syndromes. Patients with isolated 5q loss, which is characterized by the cytogenetic finding of loss of part of the long arm of chromosome 5, comprise an important subgroup of patients with a different natural history. Lastly, a proliferative syndrome including sustained peripheral blood monocytosis more than 1000/mcL (1.0 × 109/L) is termed chronic myelomonocytic leukemia (CMML), a disorder that shares features of myelodysplastic and myeloproliferative disorders. An International Prognostic Scoring System (IPSS) classifies patients by risk status based on the percentage of bone marrow blasts, cytogenetics, and severity of cytopenias. The IPSS is associated with the rate of progression to AML and with overall survival, which can range from a median of 6 years for the low-risk group to 5 months for the high-risk patients.


A. Symptoms and Signs

Patients are usually over age 60 years. Many patients are asymptomatic when the diagnosis is made because of the finding of abnormal blood counts. Fatigue, infection, or bleeding related to bone marrow failure are usually the presenting symptoms and signs. The course may be indolent, and the disease may present as a wasting illness with fever, weight loss, and general debility. On examination, splenomegaly may be present in combination with pallor, bleeding, and various signs ...

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