Myelodysplastic Syndrome (MDS)

ByAshkan Emadi, MD, PhD, West Virginia University School of Medicine, Robert C. Byrd Health Sciences Center;
Jennie York Law, MD, University of Maryland, School of Medicine
Reviewed/Revised Oct 2023
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The myelodysplastic syndrome (MDS) is group of clonal hematopoietic stem cell disorders typified by peripheral cytopenia, dysplastic hematopoietic progenitors, a hypercellular or hypocellular bone marrow, and a high risk of conversion to acute myeloid leukemia

The number of people diagnosed with myelodysplastic syndromes (MDS) in the United States each year is not known. Some estimates put this number at about 10,000, while other estimates have been much higher. MDS is most commonly diagnosed in people in their 70s.

Pathophysiology of MDS

Myelodysplastic syndromes are a group of clonal hematopoietic stem cell disorders unified by the presence of distinct mutations of hematopoietic stem cells, most frequently in genes involved in RNA splicing. Myelodysplastic syndromes are characterized by ineffective and dysplastic hematopoiesis and include the following:

  • Refractory anemia: Anemia with reticulocytopenia; normal or hypercellular marrow with erythroid hyperplasia, and dyserythropoiesis; blasts 5% of nucleated marrow cells

  • Refractory anemia with ringed sideroblasts: Same as refractory anemia with reticulocytopenia, except that ringed sideroblasts are > 15% of nucleated marrow cells

  • Refractory cytopenia with multilineage dysplasia: Cytopenia not restricted to red cells; prominent dysplasia of white cell precursors and megakaryocytes

  • Refractory cytopenia with multilineage dysplasia and ringed sideroblasts: With ringed sideroblasts that are > 15% of nucleated marrow cells

  • Refractory anemia with excess blasts (RAEB): Cytopenia of 2 cell lines with morphologic abnormalities of hematopoietic cells; hypercellular marrow with dyserythropoiesis and dysgranulopoiesis; blasts 5 to 9% (RAEB-I) or 10 to 19% (RAEB-II) of nucleated marrow cells

  • Myelodysplastic syndrome, unclassified: MDS that does not fall into any defined category

  • MDS with isolated del(5q): Typically severe anemia and thrombocytosis, with deletion of the long arm of chromosome 5

  • Chronic myelomonocytic leukemia (CMML) and juvenile myelomonocytic leukemia (JMML): Mixed myelodysplastic/myeloproliferative neoplasms; absolute monocytosis (> 1000/mcL [> [> 1 x 10 9/L]) in blood; significant increase in marrow monocyte precursors

  • Chronic neutrophilic leukemia: Characterized by neutrophilia and absence of the Philadelphia chromosome and the BCR-ABL1 fusion gene

The bone marrow can be hypocellular or hypercellular. The ineffective hematopoiesis causes anemia (most common), neutropenia, thrombocytopenia, or a combination of these, even to the point of marrow aplasia. Patients with significant, refractory, or chronic anemia eventually develop iron overload due to transfusions and/or increased iron absorption from the gut.

The disordered cell production is also associated with morphologic cellular abnormalities in bone marrow and blood. Extramedullary hematopoiesis may occur, leading to hepatomegaly and splenomegaly. Myelofibrosis may develop during the course of MDS. Classification is by blood and bone marrow findings and also by karyotype and mutation. The MDS clone tends to progress to acute myeloid leukemia.

Symptoms and Signs of MDS

Symptoms of myelodysplastic syndrome tend to reflect the most affected cell line and may include pallor, weakness, and fatigue (anemia); fever and infections (neutropenia); and increased bruising, petechiae, epistaxis, and mucosal bleeding (thrombocytopenia). Splenomegaly and hepatomegaly are not uncommon.

Diagnosis of MDS

  • Complete blood count (CBC)

  • Peripheral smear

  • Bone marrow examination

Myelodysplastic syndrome is suspected in patients (especially older patients) with refractory anemia, leukopenia, or thrombocytopenia. Cytopenias secondary to autoimmune disorders, vitamin B12 deficiencies, folate deficiencies, idiopathic aplastic anemia, paroxysmal noctural hemoglobinuria, , zinc toxicity, or drug effects must be ruled out.

The diagnosis is suggested by the finding of peripheral blood and bone marrow morphologic abnormalities in 10 to 20% of cells of a particular lineage but is established by demonstrating specific cytogenetic abnormalities and somatic mutations. Bone marrow hypoplasia can occur.

Anemia is the most common feature, associated usually with macrocytosis and anisocytosis. With automatic cell counters, these changes are indicated by an increased mean corpuscular volume and red blood cell distribution width.

Some degree of thrombocytopenia is usual; on peripheral smear, platelets vary in size, and some appear hypogranular. Patients with refractory sideroblastic anemia may have thrombocytosis in combination with the JAK2 V617F mutation.

The white blood cell count may be normal, increased, or decreased. Neutrophil cytoplasmic granularity is decreased, with anisocytosis and variable numbers of granules or sometimes no granules. Eosinophils also may have abnormal granularity. Pseudo Pelger-Huët cells (hyposegmented neutrophils) may be seen.

Monocytosis is characteristic of the chronic and juvenile myelomonocytic leukemia subgroups, and immature myeloid cells may occur in the less well differentiated subgroups. The cytogenetic pattern is usually abnormal, with one or more clonal cytogenetic abnormalities often involving chromosomes 5 or 7.

Treatment of MDS

  • Symptom amelioration and supportive care

  • Chemotherapy

  • Stem cell transplantation

In general, treatment is reserved for symptomatic patients.

Symptomatic patients usually require chronic blood and platelet transfusions. These patients subsequently often develop secondary iron overload. Patients with lower-risk myelodysplastic syndrome and serum ferritin level > 1,000 ng/mL (> 1,000 mcg/L) may benefit from iron chelation.

Drugs used to treat MDS include

is also a pyrimidine nucleoside analog. It induces remission in as many as 43% of patients with MDS. It is indicated for treatment of patients with MDS of all subtypes.

is an immunomodulator that is effective in reducing red blood cell transfusion requirements in patients with MDS with deletion 5q syndrome.

Allogeneic hematopoietic stem cell transplantation is the only curative treatment for MDS. Allogeneic hematopoietic stem cell transplantation is indicated in younger, medically fit patients generally in intermediate-2 and high risk groups.

Prognosis for MDS

The prognosis of myelodysplastic syndrome depends greatly on classification and on any associated disorders. Patients with the deletion 5q syndrome, refractory anemia, or refractory anemia with ringed sideroblasts are less likely to progress to the more aggressive forms.

The Revised International Prognostic Scoring System (IPSS-R) in MDS predicts the outcome of patients with MDS. The IPSS-R considers the following risk factors:

  • Cytogenetics: Worst prognosis associated with high-risk or multiple abnormalities

  • Percentage of bone marrow blasts: Worst prognosis associated with increasing numbers of (particularly >10%) blasts

  • Degree of cytopenia: Worst prognosis associated with hemoglobin < 8 g/dL (< 80 g/L), platelet count < 50,000/mcL (< 50 × 109/L) and absolute neutrophil count (ANC) < 800/mcL (0.8 × 109/L)

Outcome is worse with an increasing number of risk factors. Patients in the highest risk group have a median overall survival of 0.8 year. Patients in the lowest risk group have a median overall survival of about 8 years.

Key Points

  • Myelodysplastic syndrome is a disorder of hematopoietic cell production involving clonal proliferation of an abnormal hematopoietic stem cell.

  • Patients usually present with a deficiency of red cells (most common), white cells, and/or platelets.

  • Transformation to acute myeloid leukemia is common.

  • Stem cell transplantation is the only curative treatment and is the treatment of choice in younger, medically fit patients.

More Information

The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.

  1. MDS Foundation: Additional resources for healthcare professionals: Provides information on diagnosis and treatment and resources for clinical trials, centers for excellence, and professional learning resources

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