Myelodysplastic Syndromes in Older Adults
Myelodysplastic syndromes (MDS) are among the most common hematological malignancies in Western countries, with a median age at diagnosis of 74. They are a stem cell disorder characterized by cellular dysplasia, cytopenias, and an increased risk of transformation to acute myeloid leukemia. Disease trajectory is commonly determined by the international and world prognostic scoring systems (International Prognostic Scoring System and the World Health Organization [WHO] classification–based prognostic scoring system) and the WHO classification. Some patients have an indolent disease course, while others experience a rapid deterioration and short overall survival. For many years, the mainstay of therapy was supportive care with blood transfusions and hematopoietic growth factors. Fortunately, novel effective agents including lenalidomide, hypomethylating agents, and oral iron chelators have emerged over the past 5–10 years that improve transfusion dependence and may alter the natural history of the disease. These new therapeutic options offer new hope for individuals with MDS and bolster the role for the investigation of unexplained cytopenias in the older patient.
Key words: myelodysplastic syndrome, erythropoietin, anemia, red blood cell transfusions, stem cell disorder.
Introduction: What Are the Myelodysplastic Syndromes?
The myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal hematopoietic disorders characterized by ineffective hematopoiesis, cellular dysplasia, peripheral cytopenias, and an increased risk of transformation to acute myeloid leukemia.1 The majority of people with MDS present with anemia, which is usually macrocytic in nature. However, other presentations may include unexplained neutropenia, thrombocytopenia, or infections.2 The cytopenias may be chronic in nature and detected incidentally on routine blood work, or patients may be symptomatic with fatigue, dyspnea, angina, and increased bruising and bleeding.
Who Gets Myelodysplastic Syndromes and How Common Are They?
Older adults are primarily affected by MDS, with a median age at diagnosis of 74 years.3 The incidence of MDS increases substantially with age and is more common among males than females (Figure 1).4 Most clinicians agree that the reported incidence figures represent a gross underestimation of the true disease burden since many older adults with unexplained anemia are never referred to hematologists for diagnostic evaluation. Using the prevalence of unexplained anemia in older adults, the prevalence of MDS in the U.S. has been estimated to be as high as 63 in 100,000.5 Based on our analysis of bone marrow examinations for unexplained cytopenias at Sunnybrook Health Sciences Centre, we speculate that MDS prevalence may be as high as 10,629 cases in Canada or 246 in 100,000 Canadians >65 years.6 Myelodysplastic syndromes develop de novo 90% of the time but may develop after mutagenic chemotherapy or radiotherapy (often with complex or poor-risk cytogenetics) in 10% of cases.
How Are Myelodysplastic Syndromes Diagnosed and Classified?
A bone marrow aspirate and biopsy are necessary to make a definitive diagnosis of MDS. The marrow is usually hypercellular or normocellular despite the patient being cytopenic. This paradox is explained by ineffective hematopoiesis and increased apoptosis in the bone marrow, resulting in decreased mobilization of myeloid cells to the peripheral blood. Hypocellular MDS may be found in a minority of cases and may be confused with aplastic anemia. Bone marrow samples must show dysplastic changes in at least 10% of the cells in one or more lineages (neutrophil and/or erythroid precursors and/or megakaryocytes).7 It is important to determine whether bone marrow dysplasia is primary (due to a clonal disorder) or secondary. Secondary