Myelodysplastic Syndrome (MDS)

Background of Myelodysplastic Syndrome (MDS)

Myelodysplastic syndrome (MDS), also referred to as myelodysplasia, is an umbrella term for several conditions in which the bone marrow does not function normally, causing shortages of one or more cell types in the blood. Bone marrow is the spongy tissue inside the bones of the body where red and white blood cells and platelets are made. In bone marrow of MDS patients, too few blood cells are made. The blood cells die prematurely in the marrow before being released into the blood. The impact of MDS can range from mild anemia to leukemia. About 30 percent of all MDS cases eventually turn into acute myelogenous leukemia.

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The incidence of MDS has not been well documented but it is estimated that there are about 10,000 to 15,000 new cases in the United States each year. More than half of all MDS patients are over age 70, and occurrence is rare in young people. MDS may develop following treatment with drugs or radiation therapy for other diseases. Most often, MDS develops without any known cause. Some MDS patients also have autoimmune disorders — diseases in which the immune system attacks itself — and, in fact, in a subgroup of MDS patients, the failure of the bone marrow appears to be caused by the patient's own immune system. MDS may also be caused by exposure to high levels of radiation.

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Hutchinson Center Myelodysplastic Syndrome Research

Overview of Hutchinson Center Myelodysplastic Syndrome Research

Hutchinson Center myelodysplastic syndrome (MDS) research includes clinical research to develop effective new treatments and fundamental studies to learn more about how MDS develops and progresses to leukemia, which will help scientists develop better strategies for diagnosing and treating these diseases.

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Pioneering new treatment advances for Myelodysplastic Syndrome:

• Presently, the only therapy with the potential to cure MDS is a blood stem-cell transplant. The transplant program at the Hutchinson Center and Seattle Cancer Care Alliance has some of the highest cure rates in the country for MDS patients. The best rates are in patients with early stage disease and in younger patients who are better able to tolerate the high-dose transplant regimens; however, more than half of all MDS patients are over 70 years old. Older individuals, as well as patients with certain other medical conditions, are often unable to withstand the intensive chemotherapy or irradiation used in this treatment. One alternative for these patients is a milder form of the traditional transplant, called a mini-transplant, that has been developed at the Hutchinson Center. Our researchers are currently leading multi-center clinical trials comparing traditional transplants with mini-transplants to determine the advantages and disadvantages of each method for MDS patients. They are also investigating drugs that may reduce the occurrence of graft-vs.-host disease (GHVD), an often serious complication of transplantation. They recently published results of a study that showed a drug called ATG significantly decreased chronic GVHD in patients who received blood stem-cell transplants. Findings from these studies are critical to helping doctors tailor treatment approaches to individual MDS patients and to laying the foundation for the next generation of therapies.



• MDS patients often experience low blood cell counts, which can lead to problems such as anemia, increased risk of infection and severe bleeding. To combat these problems, doctors use blood transfusions and an arsenal of drug therapies. Scientists have found that even if patients have low blood cell counts, there are still some normal marrow cells present, but those normal cells cannot function properly. Research from Drs. Joachim Deeg and Bart Scott suggests that the abnormal cells in MDS release proteins called cytokines that suppress the growth and function of normal blood cells. While the ultimate goal is to cure MDS, the findings indicate that if doctors can restore the normal function of patients' healthy blood cells by compensating for or dampening the effects of these cytokines, it may be possible to help patients live longer, more normal lives.



• Hutchinson Center researchers are also developing another novel treatment method that combines the intense disease-fighting power of traditional transplantation with the lower toxicity of the mini-transplant. Striking such a balance would make transplantation a viable option for a wider range of patients. To accomplish this, Center researchers are leading the development of a technique called targeted radiotherapy in which molecules called antibodies carry radiation specifically to cells in the bone marrow. The radio-labeled antibodies deliver more radiation to the cells involved in MDS, which destroys more of the disease while reducing exposure of healthy tissues and sparing the patient the toxic side effects associated with traditional conditioning regimens. Researchers led by the Center's Dr. John Pagel have begun treating MDS patients with this therapy followed by non-myeloablative transplants to determine the safe dose of the radioactive compound. Results so far have been promising, but investigators still need to conduct larger, randomized studies to learn more about the method and its effectiveness in treating MDS.

Fundamental insights into 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 the relationship between aging and MDS, Dr. Derek Stirewalt and his colleagues in the Center's Clinical Research Division are studying the basic changes that occur in our blood stem cells as we age. He is 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 and contribute 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.



• A group of investigators led by Drs. Anneclaire DeRoos and Scott Davis of the Center's Public Health Sciences Division have begun a population-based study to determine the actual incidence of MDS and how the disease develops. As the first study of its kind in the U.S., it is expected to provide new information on the causes, patterns and control of MDS in the general population. Those findings, in turn, should lead to a better understanding of environmental factors that contribute to the disease.

Improving diagnosis of Myelodysplastic Syndrome:

• The variable nature of MDS has made it difficult to develop a reliable system to classify the disease, which makes it challenging for doctors to predict prognosis and, therefore, counsel their patients about appropriate treatments. A new approach led by Dr. Joachim Deeg of the Clinical Research Division and his colleagues offers promise for refining MDS classification, which could ultimately improve patient care and outcomes. The researchers recently discovered that the increased expression of a gene called AF1q may correlate with an MDS patient's prognosis. Patients who have an early stage or a less aggressive form of MDS tend to have low levels of AFq1 expression while patients with more advanced disease have significantly higher levels. 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.

Articles Related to Myelodysplastic Syndrome and MDS Information

• Markers for measuring MDS — Gene AF1q may help researchers better understand, classify and treat collection of different disorders known as myelodysplastic syndrome
  
  
• Hope from an alternate strategy — Deeg trials show that when healing turns to cancerous cellular takeover, anti-inflammatory drugs may block fatal myelodysplastic syndrome
  
  
• Mini-transplants for those over 50: Success! — Storb/McSweeney study says outpatient treatment combination of low radiation, potent drugs works for older patients

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