Myelodysplastic syndromes (MDS) refer to a group of hematopoietic disorders characterized by ineffective hematopoiesis and increased risk of transformation to acute myelogenous leukemia (AML). Median age of patients with MDS is 70 to 75 years and it is likely that environmental factors play an important role in the pathogenesis of this disease. MDS is classified according to WHO criteria and a number of prognostic scores can be used to calculate survival and risk of transformation. Cytogenetic alterations, more frequently involving chromosomes 5 and 7, are common in MDS and help in the prediction of prognosis. Over the last decade we have witnessed significant improvements in supportive care and therapeutic modalities for patients with MDS. These include growth factors, immune modulatory agents, such as lenalidomide, and hypomethylating agents including 5-azacitidine and decitabine. In this chapter, we summarize our knowledge of MDS and the treatment approach we use at MD Anderson Cancer Center.
Every year approximately 250 to 300 patients are referred to our center with a diagnosis of MDS. Although percentages vary from month to month, nearly 30% of patients referred to us with a diagnosis of MDS receive a different diagnosis in our center. In most instances, the final diagnosis is that of AML but other benign and malignant conditions are often observed. Therefore, it is critical to confirm the morphological diagnosis of the patient referred and it is usually important to repeat a bone marrow aspiration and biopsy at the time of initial reevaluation of the patient.
Once the diagnosis is confirmed, the next more important step is to calculate the "risk" of the patient. Most clinicians and investigators use the IPSS (1) score to perform such analysis but newer potentially more precise models have been developed (2–4). In general, patients with low or intermediate-1 risk by the IPSS or those with less than 10% blasts in the bone marrow are considered as having "lower" risk disease whereas those with excess blasts or intermediate-2 or high-risk disease are considered as having "higher" risk disease.
Patients with lower risk disease can be candidates for a wide range of interventions, depending on their specific characteristics and transfusion needs. Patients with minimal cytopenias, transfusion independent, low percentage of blasts in the bone marrow and diploid cytogenetics are more frequently observed as their 4-year survival is close to 80% (3). At the end of the spectrum, older patients with significant cytopenias and transfusion needs can have very poor prognosis particularly if their cytogenetics are abnormal (3). The median survival of these patients is less than 12 months. Despite the fact that probably around 60 to 70% of patients with MDS are in this category, there are very few interventions known to alter the natural history of these patients. Transfusion and growth factor support are usually started on these patients. Interventions such as lenalidomide have significant activity in improving red cell counts in ...