What is Myelodysplastic Syndrome (MDS)?

Acute leukemia is the most aggressive type of blood cancer, but there are several other blood cancers that can develop into an acute leukemia. The most common cancer that can evolve into acute myelogenous leukemia (AML) is called myelodysplastic syndrome (MDS).

Dr. Jun Choi, a hematologist/oncologist at NYU Langone’s Perlmutter Cancer Center, explains MDS: “When there is a dysfunction in the bone marrow, there is a production of defective blood cells, and there is also a deep decrease in the production of blood cells. So the consequence of that is low blood cells in your bloodstream…MDS affects all types of blood cells and ultimately it is a considered a bone marrow failure disorder.”

What Is MDS?

MDS is a variety of bone marrow disorders that look similar: under a microscope, the bone marrow cells look like cancer, and genetically may have alterations that are known to cause MDS. Symptoms of MDS include frequent infections, fatigue or shortness of breath (anemia), or easy bleeding/bruising. These symptoms are the result of the bone marrow not being able to produce enough healthy, functional blood cells.

Because some patients with MDS will have their cancer evolve into AML, it is important for your doctor to monitor risk. There are several ways to do do this, but doctors will look at:

• A patient's blood counts
• The amount of cancer in the bone marrow
• The presence of certain genetic abnormalities on the cancer cells

“For the workup of MDS, you start with a regular blood check and you confirm that someone has low blood cells,” Dr. Choi explains. “And then when the suspicion for MDS is high, the ultimate gold standard diagnostic test is a bone marrow biopsy. And that is because the bone marrow is where all the blood cells are made. And we want to confirm that there is abnormal cells in the bone marrow.”

A bone marrow biopsy can confirm MDS. It can also provide other details on your cancer.

“The biopsy has to be reviewed by the pathologist to see if there is what’s called dysplasia in the blood cells. Dysplasia is abnormal-looking young blood cells that we also want to send the bone marrow sample to assess for any genetic changes,” Dr. Choi says. “And whether there is any abnormal changes in your chromosome, in the blood cells inside the bone marrow. And based on those, we can categorize the MDS into different categories, different types, and ultimately they can also help us guide the treatments and the prognosis as well.”

How is MDS Categorized?

Determining treatment will depend on several factors, as your doctor will assess blood counts, bone marrow, the number of immature cells in marrow, and how cells mature.

“You can think of MDS as a spectrum of diseases,” Dr. Lewis Silverman, director of the resource center for MDS at Mt. Sinai’s Tisch Cancer Institute, tells SurvivorNet. “On the one hand, there are patients who, when they present, are categorized as having very low-risk disease, and then it ranges up through middle categories to very high-risk disease. MDS patients can be categorized anywhere along that spectrum of disease.”

For low risk MDS, no treatment may be necessary, but many patients will need medications or blood transfusions to help improve their blood counts.  (A blood transfusion is a procedure in which donated blood or blood components are given to you through an intravenous line.)

For high risk MDS, more aggressive therapy is needed most commonly this will be a "hypomethylating agent" (HMA).  These medications work by disrupting unregulated cancer cell growth. A stem cell transplant can also be considered, which is potentially curative. Hematopoietic stem-cell transplantation (HSCT) is a medical procedure that consists of infusing healthy stem cells (from a matched related or unrelated donor) after a short course of chemotherapy or radiotherapy, or both.

While stem cell transplants can be potentially curative, they are not an option for all patients.

“The treatments that we have right now still are not curative except for stem cell transplants, and those are major undertakings, and not every individual is a great candidate for that,” Dr. Silverman says. “We do evaluate the patients for stem cell transplants and transplant those [eligible] patients.” Factors such as the patient’s age and overall health need to be considered when determining if a stem cell transplant should be done.

What Causes The Symptoms of MDS?

Symptoms of myelodysplastic syndrome (MDS) are generally related to the effect of the cancer on a person's circulating blood counts. The three major categories of blood cells that doctors look at are white blood cells (WBCs), red blood cells (RBCs) and platelets.

White Blood Cells

WBCs are involved in many immune-related processes, but the primary goal of WBCs is to fight infections.

• Because patients with MDS have fewer healthy blood stem cells to mature into healthy WBCs, patients may be at high risk for bacterial, fungal, or viral infections.
• Your doctor will look at a specific type of WBC called a neutrophil.
• If your neutrophils are lower than 500 cells per microliter ("neutropenia"), you may need preventative (prophylactic) antimicrobial medications to lower your risk for developing an infection. This fortunately does not happen very often.

Red Blood Cells

RBCs are involved in carrying oxygen to the organs of the body.

• If your RBCs are low ("anemia"), then you may feel more tired than usual; sometimes, it may even cause you to be short of breath or dizzy especially when you stand up from sitting.
• It can be difficult to tell whether these symptoms are due to MDS or due to other illnesses, since fatigue, shortness of breath, and dizziness can be caused by many other things.
• Typically, MDS will cause some degree of anemia and you may require some blood transfusions to help you feel better.
• Doctors will commonly look at the hemoglobin count and decide to give you a transfusion if your hemoglobin is less than 7-8 grams per deciliter; however, every cancer center and situation is different.

Platelets

Platelets are cell fragments that are important for helping blood to clot.

• Even though the normal range of platelets are around 150-450,000 per microliter of blood, symptoms of easy bleeding and bruising don't usually arise until platelets are below 50,000, and even often below 10-20,000 ("thrombocytopenia").
• Your platelets can be quite low without needing a platelet transfusion. Again, every cancer center and situation is different, but platelets are commonly transfused when they drop below 10-20,000.
• If you have frequent nosebleeds, painful bruising when lightly bumping into objects or during lab draws, or gum bleeding with light teeth brushing, talk to your doctor to see how he/she can best help you.

Remember that although neutropenia, anemia, and thrombocytopenia can cause the above symptoms, the cancer itself can also cause symptoms, which include:

• Loss of appetite
• Low energy
• Unexplained weight loss
• Drenching night sweats

These may be less common with MDS compared with other blood cancers but can happen. Conversely, many patients with MDS may have few or no symptoms at all.

“A lot of time, people can have no symptoms and MDS can be suspected when there’s low blood cells in a routine blood check by your primary care physician,” Dr. Choi says. “So a lot of people don’t know that they are carrying MDS, and they incidentally find abnormal blood cells.”

If you have MDS, we recommend asking your doctor about what symptoms to expect from your MDS based on your blood counts. Therefore, if you experience a new and unexpected symptom, this may require more urgent investigation by a doctor.

How Is MDS Treated?

MDS is treated based on symptoms and the risk for it to evolve into AML. Doctors gather information about circulating blood counts, bone marrow findings, and the presence of genetic mutations to determine risk.

For lower-risk MDS:

• Many people may only need to monitor blood counts every few months without needing specific treatment.
• Some people may be started on medications to stimulate RBC or platelet production.
• Some people may need a blood transfusion every few months.
• Specific types of MDS may benefit from lenalidomide (Revlimid), luspatercept (Reblozyl), or immunosuppressing medications.

For higher-risk MDS:

• Treatment usually starts with a class of drugs known as hypomethylating agents (HMAs). HMAs include intravenous or oral forms of azacitidine (Vidayza, Onureg) or decitabine (Dacogen, Inqovi).
• Other treatments are possible depending on the presence of certain mutations or if the disease is more aggressive.
• Some patients may require more frequent transfusions, from every few weeks to even several times a week.
• Some patients may be eligible for a bone marrow transplant.
• Many patients should consider enrolling in a clinical trial if available.

Because the diagnosis, prognosis, and treatment plans offered depend on appropriate testing, it is important to talk to your doctor about whether molecular testing on your bone marrow biopsy has been conducted. This may also provide opportunities for clinical trials in the future. Additionally, we recommend asking your doctor if referring for a bone marrow transplant is right for you. Although MDS generally affects older adults, there is no “age limit” for doctors to consider a potentially curative transplant, as long as you are otherwise healthy.

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