A person who feels tired or weak, is paler than usual and noticing shortness of breath might have anemia, caused by an iron deficiency due to a shortage of red blood cells. But, though it is not all that common, sometimes the anemia itself is a sign of a different condition, called myelodysplastic syndrome. This is a type of cancer that affects the blood stem cells and often prevents the body from producing enough red blood cells.

Every year, about 10,000 Americans are diagnosed with a myelodysplastic syndrome. Most often this condition arises in people over the age of 50 and it becomes more common with advancing age. This type of cancer is uncommon among children and young adults.

Myelodysplastic syndromes are actually a group of cancers that occur when the blood-producing cells in the bone marrow begin to function abnormally, producing too few healthy, mature blood cells. Often, this condition leads to anemia, a shortage of red blood cells, but some people with myelodysplastic syndromes experience a shortage of white blood cells or platelets.

Normally, blood-producing cells within the bone marrow create blood stem cells that eventually mature into healthy red blood cells, white blood cells and platelets. During the maturation process, blood stem cells first become immature blood cells known as “blasts.” In healthy people, these blasts transform into mature blood cells. When people have a myelodysplastic syndrome, their blasts don’t mature properly; the blasts may die off sooner than expected, or the body may destroy them because the blasts are abnormal. Over time, a person with a myelodysplastic syndrome ends up with a lower blood count than is healthy.

Genetic mutations, chromosomal abnormalities and external environmental factors may lead to the development of myelodysplastic syndromes. For a minority of people, the cancer may eventually progress to acute myeloid leukemia (AML).

Several factors are known to cause myelodysplastic syndromes. About half of them are due to chromosomal abnormalities. Some cases are caused by genetic mutations, which may or may not be inherited. Still others are related to chemical exposures that have altered an individual’s DNA, leading to illness. Some chemical exposures may have happened at work. Other times, someone may have been exposed to chemotherapeutic agents during prior cancer treatment, which is known to increase risk of myelodysplastic syndromes.

It’s not uncommon for a myelodysplastic syndrome to be diagnosed when someone is sent for routine blood work, before they notice any symptoms. Other times, people may experience:

• Fatigue
• Shortness of breath
• Fever
• Frequent infections
• Bruising easily
• Frequent nosebleeds
• Bleeding gums
• Weight loss
• Loss of appetite
• Anemia
• Weakness
• Dizziness
• Pale skin
• Bone pain

Increasing age is an important risk factor for myelodysplastic syndromes. People are at greater risk from ages 60, 70 and beyond.

Other factors which may increase the risk of myelodysplastic syndromes include:

• Being male
• Having had previous chemotherapy treatments
• Having had previous radiation therapy treatments
• History of smoking
• Family history of myelodysplastic syndromes
• Long-term exposure to insecticide
• Exposure to benzene in the workplace
• Exposure to chemicals while working in the rubber or petroleum industries
• Fanconi anemia
• Shwachman-Diamond syndrome
• Diamond Blackfan anemia
• Familial platelet disorder with a propensity to myeloid malignancy
• Severe congenital neutropenia
• Dyskeratosis congenita
• Thrombocytopenia
• Familial aplastic anemia

A medical history, a physical exam and diagnostic tests are all important in diagnosing a myelodysplastic syndrome.

As part of the medical history, a doctor will ask about previous treatment for cancer, if the individual smokes or if they have known exposure to certain chemicals. Doctors will also want to know if there’s a family history of myelodysplastic syndromes or other inherited disorders. Doctors should also ask whether there have been episodes of bleeding, such as a history of nosebleeds, bruising, or bleeding gums. They’ll also be looking for signs of bruising and exceptionally pale skin.

Doctors may order blood tests to check for the presence of a myelodysplastic syndrome. A complete blood count (CBC) can show whether or not there are normal levels of white blood cells, red blood cells and platelets. Another test—a blood smear test—involves smearing a small blood sample on a slide and then examining it under a microscope to look for cell abnormalities and to see whether the correct proportions of blood cells are present. Other blood tests can check the levels of iron and vitamin B12 in the blood, to see if they are normal or not.

To confirm presence of a myelodysplastic syndrome, a bone marrow biopsy is done. During this diagnostic test, doctors examine a a thin sliver of bone, plus bone marrow, to look for abnormal cells. After numbing a spot on the hipbone, a sample is taken using a hollow needle. The cells from this biopsy are then examined under a microscope to look for signs of cancer, including genetic mutations and chromosome abnormalities.

While a low blood count or the presence of other symptoms indicate treatment should start immediately, in other cases people diagnosed with a myelodysplastic syndrome won’t need immediate treatment.

When needed, treatments include:

• Blood transfusions. Because people with myelodysplastic syndromes have low blood counts, they may need blood transfusions periodically. If blood counts remain low, repeated transfusions may be required.
• Chelation therapy. If a patient has multiple blood transfusions, iron levels may rise to an unhealthy high level, which may negatively affect the liver or heart. Oral or intravenous chelating agents help to remove excessive levels of iron from the body. They may help people with a myelodysplastic syndrome to live longer.
• Chemotherapy. Treatment for myelodysplastic syndromes may include chemotherapy drugs such as azacitidine, decitabine or decitabine combined with cedazuridine. These medications may kill rapidly dividing cells, and they may encourage immature blood cells to mature. This therapy may reduce the need for blood transfusions. Doctors may occasionally prescribe the chemotherapy drug cytarabine in combination with other medications, but this is uncommon today, since the newer medications azacitidine and decitabine, with or without cedazuridine, tend to be more effective.
• Growth factors. When blood counts are low, growth factors that encourage the bone marrow to produce more blood cells may help individuals with a myelodysplastic syndrome to avoid blood transfusions. Doctors may prescribe the growth factor erythropoietin or epoetin, a synthetic version, to raise red blood cell counts. They may prescribe filgrastim or sargramostim to increase white blood cell counts. The drugs romiplostim and eltrombopag may help to increase low platelet levels.
• Stem cell transplant. People with myelodysplastic syndromes may benefit from stem cell transplants, although the procedure is not recommended or appropriate for all. Though some myelodysplastic syndromes can be cured with a stem cell transplant, the treatment is not universally effective. Stem cells from a healthy donor can be given by infusion after a patient has undergone chemotherapy and/or radiation to destroy malfunctioning blood-producing cells in the bone marrow. The goal of this treatment is that receipt of donor stem cells should trigger a patient to produce normal, healthy blood cells. Because stem cell transplants are associated with risks and complications, the procedure is typically only offered to patients with high-risk disease. Also, it may not be an option for individuals who aren’t healthy enough to undergo the procedure.

People who are diagnosed with myelodysplastic syndromes may have different outcomes, depending upon their specific diagnosis. Some patients can expect to live for 9 years after diagnosis, while others may survive only for 1 or 2 years.

Some people with myelodysplastic syndromes may experience life-threatening hemorrhages.

About one-third of people who have myelodysplastic syndromes develop acute myeloid leukemia (AML), which requires further treatment.

“Being a patient at Yale means getting more than the ‘standard of care,’” says Smilow Cancer Hospital hematologist Rory Shallis, MD. “When someone is either diagnosed with or has a concern for MDS [myelodysplastic syndromes], they are seen by an MDS specialist who performs a thorough evaluation in conjunction with other members of our collective team comprised not only of physicians, but also advanced practice providers, nurses, social workers, nutritionists, and clinical trial staff, among others who also span across other specialties from Palliative Care to Bone Marrow Transplant.”

Every patient is evaluated for a clinical trial, which is personalized to the disease and patient specifics and has the potential to offer access to cutting-edge agents that may be game-changers in the near future, he adds.

“Although Yale rests between two major metropolitan centers with cancer centers with whom we collaborate and have many of the same clinical trials, resources, and patient outcomes, our family-like atmosphere sets us apart,” he says. “When combined with our excellent tools to help patients along their journey with MDS, Yale is definitely a special place to seek and receive care.”