Myelodysplastic syndromes: A practical approach to diagnosis and treatment

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ABSTRACTThe myelodysplastic syndromes (MDS) are clonal bone marrow disorders that lead to underproduction of normal blood cells. The consequent cytopenias result in infections and bleeding complications. MDS transform to acute myeloid leukemia in one-third of patients. The number of diagnoses has exploded in the past decade as a result of increased recognition and understanding of the disease and the aging of the population. New therapies can extend life. MDS are now considered the most common form of leukemia, and in some cases deserve immediate intervention. This review describes common presentations of MDS, optimal diagnostic approaches, and therapies for lower-and higher-risk disease.


  • Multilineage cytopenia almost always suggests abnormal bone marrow function and can be the reason for referral to a hematologist-oncologist.
  • Factors that make MDS more difficult to manage and that worsen the prognosis are older age at diagnosis and comorbidities such as coronary artery disease, chronic obstructive pulmonary disease, and chronic kidney disease.
  • Patients with lower-risk disease can continue followup with their primary care provider once the treatment goals and plans are established.



Myelodysplastic syndromes (MDS) are a heterogeneous group of disorders of blood cell production in the bone marrow that can transform into acute myeloid leukemia (AML).1,2 They are diagnosed most often in the elderly.

Primary care physicians and geriatricians tend to be the first to identify the problem, as they recognize that cytopenias are not simply a normal consequence of aging.

MDS are considered to be cancers, akin to chronic leukemia or acute leukemia, with epidemiologic data tracked by national cancer registries and the US Centers for Disease Control and Prevention, under the auspices of the Surveillance, Epidemiology, and End Results (SEER) program.3

In this article, we briefly review the classification of MDS, current epidemiologic data, key diagnostic features, and current management options.


In many patients, MDS are asymptomatic and appear as an abnormality on a routine complete blood cell count (CBC) or as part of a workup for anemia. Symptoms develop as the bone marrow’s ability to produce normal-functioning blood cells is more and more compromised. The range of symptoms depends on the bone marrow cell type affected.

Patients with MDS typically have some degree of anemia, often detected incidentally on a routine CBC, or they have symptoms stemming from anemia or thrombocytopenia, or have recurrent infections.

Subtypes of MDS have different pathologic and clinical presentations and different prognoses. They are often categorized as lower-risk or higher-risk, depending on the likelihood of transforming to AML. Patients with lower-risk MDS survive a median of 3 to 7 years. Higher-risk types are pathobiologically similar to AML in older adults, and patients either develop AML or die of complications of MDS, on average within 1.5 years.

Several classification schemes and prognostic models guide the selection of the most appropriate therapy.

Older age and comorbidities such as coronary artery disease, chronic obstructive pulmonary disease, and chronic kidney disease make MDS more difficult to manage and worsen the prognosis.4


Only since 2001, when MDS became reportable to SEER,3,5 has the epidemiology of MDS been reported in the United States.

MDS are currently diagnosed in an estimated 3.4 per 100,000 US citizens yearly.

The incidence rate increased from 3.28 per 100,000 per year in 2001 to 3.56 per 100,000 in 2004.5 The increase has been attributed to enhanced awareness of the disease and to the aging of the population, with the number of people age 65 or older in the United States expected to double from the year 2000 to 2030. Another factor is that effective therapies are now available, possibly making hematologists and oncologists more likely to pursue the diagnosis.

These numbers translate to 10,000 to 15,000 new cases annually, and given the life expectancy of patients affected by this disease (and the life-extending treatments for it), an estimated 30,000 to 60,000 Americans living with MDS.6,7

Even though MDS can occur at any age, most patients are older. The median age at diagnosis is 71 years,3,5,8 and 72% of patients are age 70 or older.3 The prevalence increases with age, to a rate of 36 per 100,000 in those age 80 and older.9 However, in areas of East Asia, it occurs at ages almost 2 decades younger than in the rest of the world.5

MDS are more common in men than in women and in whites than in blacks. Smoking appears to increase the risk, but alcohol consumption does not.10

About 10% of cases of MDS are secondary, most often due to radiation treatment or chemotherapy (particularly with alkylating agents and topoisomerase inhibitors) for cancer. The time from treatment of a primary malignancy (most often prostate, breast, bladder, lung, or non-Hodgkin lymphoma) to the development of MDS is about 5 years.5 A small number of cases are due to occupational exposure to radiation or benzene or other organic solvents, as might occur in the rubber industry (see below). Secondary MDS have a worse prognosis than primary (de novo) MDS.


The cause of de novo MDS is not known. Genetic and environmental factors probably both play a role. The lower median age at diagnosis in Eastern countries such as Japan than in the United States suggests that environmental factors11 such as smoking, ionizing radiation, and benzene exposure play a role.12,13 Some epidemiologic evidence suggests a higher incidence of MDS after exposure to solvents, hair dyes, and pesticides.13

Congenital conditions such as Down syndrome, Fanconi anemia, and Bloom syndrome are associated with MDS. Those affected usually present at an earlier age,13 suggesting a “multiple-hit” mechanism of cancer development with genetic and environmental factors. MDS rarely run in families.


Symptoms of MDS are often vague and nonspecific, and the diagnosis is often made during a workup for anemia, thrombocytopenia, or neutropenia discovered on a CBC. If present, signs and symptoms depend on the blood and bone marrow cell types that are affected.

When erythrocytes are affected (the most common situation), patients present with signs of anemia, including pallor, pale conjunctiva, tachycardia, hypotension, fatigue, headache, and exercise intolerance, or with signs and symptoms of a worsening underlying condition such as angina pectoris, heart failure, or emphysema.

When platelets or neutrophils are affected. Fewer than 20% of patients present with symptoms of isolated thrombocytopenia such as minor bleeding (eg, mucosal bleeding, petechiae, easy bruising, epistaxis) or major bleeding (eg, gastrointestinal bleeding, intracranial hemorrhage) or of isolated neutropenia (eg, fatigue, frequent bacterial infections of different organs systems).

Splenomegaly and lymphadenopathy are uncommon in MDS and, if detected, should raise suspicion of a myeloproliferative or lymphoproliferative neoplasm.

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