Myelodysplastic Syndromes (MDSs)

How to Cite This Chapter: Khalaf D, Crowther M, Dwilewicz-Trojaczek J. Myelodysplastic Syndromes (MDSs). McMaster Textbook of Internal Medicine. Kraków: Medycyna Praktyczna. Accessed May 21, 2024.
Last Updated: February 9, 2022
Last Reviewed: February 9, 2022
Chapter Information

Definition, Etiology, Pathogenesis Top

Myelodysplastic syndromes (MDSs) are clonal hematologic disorders characterized by peripheral blood cytopenia, dysplasia of ≥1 hematopoietic lineage, ineffective hematopoiesis, and risk of transformation to acute myeloid leukemia. It could be preceded by acquisition of somatic mutations that drive clonal expansion in the absence of abnormal counts or dysplasia, referred to as clonal hematopoiesis of indeterminate potential (CHIP), which are precursor states for hematologic neoplasms but are usually benign and do not progress. This can be analogous to monoclonal gammopathy of undetermined significance (MGUS) and monoclonal B-cell lymphocytosis.

Risk factors include exposure to chemicals (eg, benzene, toluene) and heavy metals; tobacco smoke; ionizing radiation; chemotherapy/cytotoxic agents; and radiation therapy. The median age of onset is between 60 and 75 years of age with an incidence of ~2/100,000 population per year.

Clinical Features And Natural HistoryTop

Patients may present with signs and symptoms due to low counts, symptomatic anemia, recurrent infections in neutropenia, or bruises and ecchymosis in cases with thrombocytopenia. It could be detected on routine blood tests in asymptomatic individuals.


Diagnostic Tests

1. Complete blood count (CBC): Pancytopenia is common. Macrocytic or normocytic anemia with increased red cell distribution width (RDW); leukopenia with neutropenia (~50% of cases); and severe thrombocytopenia (~25% of cases). Thrombocytosis possible in patients with abnormalities of 5q–. Circulating blasts may be seen. Blood smears may show dysmorphic or bilobed neutrophils, polychromasia, poikilocytosis, anisocytosis, and severe thrombocytopenia. Inappropriately low reticulocyte counts are common due to poor bone marrow reserve.

2. Bone marrow examination reveals features of hypercellular marrow for age. In 10% of cases MDS may be hypoplastic with decreased cellularity. Unilineage or multilineage dysplasia, dyserythropoiesis with appearance of ring sideroblasts (iron laden mitochondria visible as perinuclear granules with Prussian iron stain), dysplastic granulocytes, and increased monocytes can be seen. Classification based on appearance of myeloblasts or Auer rods is known as MDS with excessive blasts type 1 (MDS-EB-1) (5%-9%) or type 2 (MDS-EB-2) (10%-19%).

3. Cytogenetic testing: Normal cytogenetic findings or common abnormalities such as loss of the Y chromosome do not exclude the diagnosis of MDS. Fluorescence in situ hybridization (FISH) may be used for selected specific mutations, such as del(5q), which is seen in elderly female patients. Other abnormal karyotypes including del(7) or del(17p) are diagnostic for MDS in the absence of cytopenias or dysplasia.

4. Molecular studies: NPM1 or wild-type, FLT3-ITD/TKD; BCR-ABL1 to exclude chronic myelogenous leukemia; JAK2 V617F to exclude myeloproliferative neoplasm (MPN). The next generation sequencing panel is now used to detect epigenetic driver mutations or splicing mutations that are associated with poor risk and progression to acute myeloid leukemia (AML) or TP53 mutation, which is known for resistance to conventional chemotherapy.

5. Other laboratory studies: Any of elevated serum iron, serum ferritin, fetal hemoglobin (HbF), and endogenous erythropoietin levels may be seen (lower erythropoietin levels are predictors of better response to erythropoietin-stimulating agents [ESAs]).

Differential Diagnosis

Megaloblastic anemia, aplastic anemias, nutritional causes of leukopenia with neutropenia, immune thrombocytopenia, acute leukemia, myelofibrosis, or metastatic disease involving bone marrow. In patients with cytopenia and no documented features of MDS or with dysplasia not accompanied by cytopenia, the diagnosis of idiopathic dysplasia of undetermined significance or idiopathic cytopenia of uncertain significance, respectively, is made. These conditions may progress to MDS.


Treatment, conducted in specialized centers, depends on performance status and age of the patient as well as on the risk category according to the International Prognostic Scoring System (IPSS) (this takes into consideration the proportion of blasts in bone marrow, karyotype, and number of lineages affected by cytopenia) or newer prognostic systems (World Health Organization [WHO]-adapted Prognostic Scoring System [WPSS]:; or revised IPSS [IPSS-R]:

1. ESAs are used in patients with low-risk to intermediate-risk IPSS score. In transfusion-dependent anemia and failure of ESA treatment in lower-risk MDS, luspatercept is used.

2. Combined immunosuppressive treatment (antithymocyte immunoglobulin, cyclosporine [INN ciclosporin] in patients with hypoplastic MDS).

3. Lenalidomide is used in patients with del(5q).

4. Hypomethylating agents (azacitidine, decitabine) are effective in disease control, prevent progression to AML, and result in transfusion independence and improved quality of life.

5. Intensive induction chemotherapy (using the same agents as in AML) and/or allogeneic hematopoietic stem cell transplant (HSCT) (the only curative treatment) are reserved for younger symptomatic patients with excellent physiologic reserve and low comorbidity index scores.

6. Supportive treatment is the mainstay of therapy:

1) Packed red blood cell (PRBC) transfusions (using leukocyte-depleted preparations).

2) ESAs in patients with low to intermediate-1 risk with hemoglobin <10 g/dL, endogenous erythropoietin <500 mIU/mL, and/or requiring transfusion of <2 units of PRBCs per month.

3) Management of febrile neutropenia (see Febrile Neutropenia). The use of granulocyte colony-stimulating factor (G-CSF) is controversial, as it may lead to progression to AML.

4) Platelet transfusions are used in case of bleeding due to thrombocytopenia.

5) Iron-chelating agents (deferoxamine or deferasirox) can be considered in selected younger patients with low-risk disease and predicted long-term survival.

Prognosis Top

Intermediate-2 or high-risk disease based on IPSS or IPSS-R scores are associated with risk of progression to AML and early mortality within 5 to 12 months. Poor risk or complex cytogenetic abnormalities, in addition to mutations in TP53, EZH2, ETV6, RUNX1, and ASXL1, are associated with poor overall survival.

In patients undergoing allogeneic HSCT, 3-year to 5-year disease-free survival rates are 30% to 50%. Overall prognosis without intensive treatment is determined by the risk score at presentation and frequency and type of complications.

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