Myelodysplastic syndromes (MDS) are a heterogeneous collection of hematopoietic disorders that are thought to be clonal and are characterized by low blood counts and a tendency to progress to acute myeloid leukemia (AML). The incidence rate of MDS for 2001 to 2003 was 3.3/100,000, and the overall 3-year survival for MDS was 45%. The incidence increases with age, and the median age of diagnosis is 70 to 75 years. Patients with MDS may be asymptomatic or may present with complaints related to cytopenias. The majority of patients have macrocytic anemia at presentation.
Diagnosis and Prognosis
The differential diagnosis of MDS includes other causes of macrocytic anemia such as vitamin B12 and folate deficiencies, alcohol consumption, and thyroid disorders. Initial laboratory workup includes blood counts, serum ferritin levels, total iron-binding capacity, serum iron, reticulocyte counts, vitamin B12 levels, red blood cell (RBC) folate levels, and thyroid-stimulating hormone levels. Persistent unexplained cytopenias warrant additional investigation with bone marrow aspiration and biopsy including cytogenetic testing and iron staining.
The diagnosis of MDS is based on the presence of dysplasia within single or multiple lineages (Table 1). The World Health Organization (WHO) criteria distinguish between MDS and AML on the basis of a myeloblast percentage of ≥ 20%, thus eliminating the previous French-American-British (FAB) diagnosis of refractory anemia with excess blasts in transformation (RAEB-T). Other important differences include the incorporation of multilineage dysplasia, which has been shown to impart an inferior prognosis, and the incorporation of isolated deletion of chromosome 5q, which is associated with improved survival. The WHO classification has proved helpful for prognosis and in selection of therapy. Despite advancements with the WHO classification, there is often limited concordance among pathologists in diagnosing lesser degrees of dysplasia, and the diagnosis may be delayed for months following initial presentation.
The International Prognostic Scoring System (IPSS) was developed on the basis of 816 patients with primary MDS. Investigators found that myeloblast percentage, cytogenetic status, and number of low blood counts offer prognostic information (Table 2). The IPSS divided patients into four risk groups (low, intermediate [int]-1, int-2, and high) and reliably discriminated between these groups in survival and AML progression (Figure 1). The limitations of the IPSS are that it is only applicable using data from the time of diagnosis and that it is not applicable to patients with secondary MDS.
Recent data have shown that transfusion burden is associated with inferior survival in MDS patients. On the basis of this finding, a new prognostic system—the WHO Classification-Based Prognostic Scoring System (WPSS)—incorporated the WHO classification, transfusion dependence, and IPSS cytogenetic status (Table 3). Patients with secondary MDS were also excluded from the WPSS. The advantage of the WPSS is that it provides a real-time assessment of prognosis (Figure 2). Whether the WPSS offers an advantage over IPSS classifications with regard to prognosis at time of diagnosis is not yet known.
A recently validated flow cytometric scoring system (FCSS) may add information regarding prognosis, particularly in patients who are otherwise thought to be at low risk. Flow cytometry may be helpful with both diagnosis and prognosis.
Treatment of MDS
As described above, the term MDS incorporates a broad and heterogeneous group of disorders. Not surprisingly, it is difficult to recommend a routine method of determining the appropriate course of action in all patients. Therefore, appropriate therapeutic choices are influenced by factors such as patient preference, performance status, cost, cytogenetic status, tempo of blood count decline, and patient age.
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