Myelodysplastic Syndrome (MDS)

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Myelodysplastic Syndrome: Fast Facts

• Myelodysplastic syndrome, or myelodysplasia, is an umbrella term for several diseases in which the bone marrow does not function normally. Bone marrow is the spongy tissue inside the bones where blood cells are produced.
• In MDS patients, the production of blood cells is ineffective, in part because blood cells die prematurely in the bone marrow.
• MDS may progress slowly, over years, or rapidly, over a few months. Patients develop anemia, bruising, bleeding or infections.
• About one-third of MDS patients will develop acute myeloid leukemia. MDS is more common than AML, with about 9,700 new cases per year in the United States.

Read more about myelodysplastic-syndrome symptoms and treatment options at the Seattle Cancer Care Alliance. »

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Myelodysplastic Syndrome: Some of Our Key Research

Hutchinson Center research on myelodysplastic syndrome includes clinical trials to develop effective new treatments and more basic studies to understand how MDS develops and progresses to acute myeloid leukemia. New information from these investigations will help scientists to develop better strategies for diagnosing and treating MDS.

So far, the only therapy that has been shown convincingly to have the potential for curing MDS is transplantation of hematopoietic, or blood-forming, stem cells. Transplant physicians at the Hutchinson Center and its partner, the Seattle Cancer Care Alliance, have reported some of the highest cure rates for patients with MDS, with follow-up now extending to more than 25 years. Clinical trials include numerous transplant and non-transplant protocols.

Making MDS treatments less toxic
The average MDS patient is 70 to 75 years when diagnosed, but older patients tend not to tolerate conventional blood stem-cell transplants as well as younger patients. Treatment options for the remaining older patients are primarily non-transplant clinical trials. The continuing development of increasingly less-toxic conditioning regimens, however, is allowing physicians to offer transplantation to a growing number of older patients.

One such alternative is a milder form of the traditional transplant, called the non-myeloablative stem-cell transplant, which was developed in the late 1990s by Dr. Rainer Storb and colleagues. This less toxic regimen is sometimes referred to as a "mini" transplant because of the reduced intensity of the conditioning regimen that the patient receives before the transplantation. This regimen does not wipe out bone marrow and involves minimal doses of radiation. That means the side effects are generally milder, and the procedure typically can be performed without a hospital stay.

Retrospective studies have indicated that mini-transplants can yield similar results to the traditional and more toxic bone-marrow transplants. Studies are underway to compare these regimens in patients with MDS. Dr. Bart Scott and colleagues are conducting research that compares conditioning regimens given prior to stem-cell transplantation.

Learn more about reduced-intensity transplants. »

Pioneering new treatments for MDS

• Our researchers, led by Dr. John Pagel, were the first to use a novel combination of therapies to successfully treat a group of older advanced acute myeloid leukemia and high-risk myelodysplastic syndrome patients who previously had no other curative treatment options. The treatment regimen employed low-intensity chemotherapy, targeted radiation delivered by an antibody, and a stem cell transplant. Learn more. »



• Our researchers have developed methods that combine low-intensity conditioning regimens affecting the entire body with treatment directed only at the MDS cells. Striking this balance would make transplantation a more effective option for a wider range of patients.
  
  Our researchers are using a technique called targeted radiotherapy, in which molecules called antibodies carry radiation specifically to cells in the bone marrow. These radio-labeled antibodies deliver a more powerful dose of radiation to the cells involved in MDS, destroying more of the disease while sparing most of the healthy tissues. This process reduces the toxic side effects associated with traditional conditioning regimens.
  
  Dr. John Pagel and colleagues have begun treating MDS patients with this therapy, followed by a low-intensity regimen, to determine the safe dose of the radioactive compound involved. So far, results have been promising, and investigators are conducting larger studies to learn more about the method and its effectiveness.
  
  
• Dr. Joachim Deeg and colleagues are investigating the use of a new drug called treosulfan. This chemotherapy agent has some similarities to busulfan, which has been in use for several decades, but appears to be less toxic and may lead to improved survival.
  
  
• A hallmark of MDS is low blood cell counts, which can lead to anemia, increased risk of infection, and bruising. Interestingly, however, scientists have found that even if patients have low blood cell counts, there are still normal marrow cells present in the marrow, but they do not function properly.
  
  Research from Drs. Joachim Deeg, Bart Scott and colleagues has suggested that the abnormal cells in MDS release proteins called cytokines, which suppress the growth and function of normal blood cells and, in fact, may cause them to die. These findings have resulted in treatment strategies that block those proteins and modify the patient's immune system, thereby leading to improved or even normal blood cell counts. Some patients who received this treatment have gone for as many as five years without needing additional therapy.
  
  

Investigating the origins of myelodysplastic syndrome

• Scientists have observed that some of the changes associated with aging may also be involved in the development of MDS. To better understand this relationship, Dr. Derek Stirewalt and his colleagues are studying the changes that normally occur in our blood stem cells as we age. They are searching for naturally occurring events or processes, such as the cells' ability to repair damage to their DNA or changes in the expression of certain genes, that may become distorted or broken, contributing to the development of MDS. Hutchinson Center researchers are also examining how environmental exposures may, over time, promote damage to blood stem cells that can increase the risk for developing MDS.
  
  
• Research led by Dr. Beverly Torok-Storb and colleagues focuses on interactions among cells that control the development of blood cells in the bone-marrow microenvironment. Her team has observed, for example, that in MDS patients, abnormal macrophages – a type of white blood cell that serves as a factory for important proteins – appear to make inappropriate proteins that can change the function of the marrow environment in key ways. Torok-Storb and colleagues are working to confirm a cause-and-effect relationship between the macrophages' activity and changes in the microenvironment that compromise orderly blood-cell production and maturation. Learn more. »

Calculating more-accurate MDS incidence rates
Drs. Anneclaire De Roos, Joachim Deeg and Scott Davis are working to determine the actual incidence rate of MDS through a population-based study that draws from a health maintenance organization's records. Calculating accurate incidence rates is important for estimating how many people will need medications and other treatments for MDS. As the first study of its kind, its goal is not only to estimate the number of cases but also to identify patient characteristics, such as blood cell counts, that help to predict who develops MDS. Those findings will lead to better ways of accurately identifying MDS cases in health care databases, which may lead to further research on risk factors for the disease. Learn more. »

Improving diagnosis of myelodysplastic syndrome
The variable nature of MDS has made it difficult to develop a reliable system to classify the disease, which poses a challenge for doctors aiming to predict its course and advise their patients about appropriate treatments. A new approach led by Dr. Joachim Deeg, Bart Scott, Derek Stirewalt and colleagues offers promise for refining MDS classification, which could ultimately improve patient care and outcomes.

The researchers have carried out genetic analyses to identify genes that are abnormally expressed in patients with MDS and may be related to the disease's course for a given patient with MDS. They have also carried out studies using flow cytometric analysis – in essence, a computer method that identifies abnormalities in cell structure and the expression of antigens on the cell surface. They recently showed that some patterns are associated with a higher probability and others with a lower probability of being cured of MDS through transplantation.

Investigators are also studying molecules involved in the process of programmed cell death, which malfunctions in MDS patients. One such molecule, known as FLIP, leads to the premature death of marrow cells, which contributes to bone marrow failure, a sign of MDS progression. Learn more. »

Find out more about our MDS investigators:
Scott Davis » Joachim Deeg » Anneclaire De Roos » Eli Estey » Matthew Fero » Michael Linenberger »	Keith Loeb » John Pagel » Brenda Sandmaier » Bart Scott » Derek Stirewalt » Beverly Torok-Storb »

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Myelodysplastic Syndrome: More Resources

• Every advance in cancer treatment in recent years has come out of clinical trials that test innovative medical approaches on patients.Find out more about clinical trials on myelodysplastic syndrome. »

• The Hutchinson Center also conducts ongoing studies that depend on participation of healthy volunteers. Learn more about getting involved in research studies. » 

• In need of medical attention for myelodysplastic syndrome? Visit the Seattle Cancer Care Alliance to get help. »

• The Hutchinson Center is on a mission to eliminate cancer and related diseases as causes of human suffering and death, and you can help. Make a gift today. »

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