Q&A: Focus on myelodysplastic syndromes

A growing incidence of myelodysplastic syndromes (MDS), mostly in older adults, has sent researchers and clinicians scrambling for answers to the biology and treatment of this group of serious blood disorders.
    
Below, Guillermo Garcia-Manero, M.D., answers questions about MDS. 

What is MDS?
It's a very complex group of hematological disorders characterized by progressive peripheral blood cytopenias, conditions in which there's a lower than normal number of blood cells. There's an eventual need for transfusion and a tendency for it to transform into acute myelogenous leukemia (AML).

A fraction of patients have a "smoldering" course that resembles more the clinical history of other bone marrow failure syndromes, whereas other patients' symptoms are more like those of AML. We're starting to understand the molecular basis of the disease; recent data indicates that different mutations occur in a small subset of patients. This adds significant complexity to the known karyotypic -- chromosomal characteristics -- of these patients' disease.

What are the symptoms of MDS?
There are no specific symptoms. Most patients are diagnosed incidentally when having a routine blood analysis. In early cases, symptoms may include anything from fatigue and decreased physical resistance to evidence of bleeding or even transformation to leukemia (fever, infections, weight loss) in more advanced cases.

How is it diagnosed?
Initially, a complete blood count will point towards the diagnosis. This should be confirmed by a bone marrow aspiration and biopsy. The diagnosis is still morphological -- made by studying the form or shape of the organisms. There are no molecular markers for the disease diagnosis. Cytogenetic (chromosomal) analysis is needed for prognosis and may also help when morphological diagnosis is ambiguous.

Are some people at higher risk for this disease? If so, who?
Yes, older males have a significantly higher tendency to develop this disease. There's also a clear association between prior exposures to chemicals and MDS. Patients treated with chemotherapy or radiation therapy are also at risk for MDS. In this setting, we refer to these cases as "therapy-related." Overall prognosis is poor for this subset. There are also some associations between smoking and MDS.

What are the main treatments for MDS?
It depends on the risk level of the patient. Usually patients are divided into a lower-risk group and a higher-risk one. Options for lower-risk patients include observation, growth factor support and lenalidomide or hypomethylating agents (which help the bone marrow function more normally). For those at high risk, patients can be treated with hypomethylating agents, intensive chemotherapy or allogeneic stem cell transplantation (from a related or matched donor). Recently, a Phase III study has shown improvement in survival with a hypomethylating agent compared to other interventions. In my opinion, all MDS patients should be treated in a clinical trial.

What factors might affect a patient's prognosis and/or treatment options?
Age, comorbidities (the presence of more than one disorder or health condition, such as diabetes or heart problems) and presence of cytogenetic (chromosomal) alterations are fundamental when assessing patients with MDS. I think over the next few months we're going to start seeing results of some large molecular studies performed at several centers, including MD Anderson. The clinical data together with the models mentioned earlier allow us to personalize therapy for patients with MDS.

What research is being conducted at MD Anderson in regard to this disease?
This is an important area of research at MD Anderson. Our leukemia clinic is probably the largest referral center for patients with MDS in the United States, maybe worldwide. We have clinical trials for nearly every possible clinical situation a patient with MDS might experience.

We also have a program in allogeneic (from a related or matched donor) stem cell transplantation with our colleagues in the Department of Stem Cell Transplantation and Cellular Therapy. At the basic and translational level, we have active programs in the study of epigenetic alterations of this disease -- something that affects a cell without directly affecting its DNA -- and drug development. Also, we have active collaborations with other centers performing large-scale genetic analyses. My laboratory is now focused on the analysis of innate immune responses in patients with MDS.