Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) are a group of bone marrow disorders that cause ineffective production of red blood cells, white blood cells and platelets. MDS can progress to acute myeloid leukemia (AML).

MDS is rare, affecting about one person in 100,000 each year. It most commonly affects people older than 60 years, but it can occur at any age.

MDS occurs when the stem cells in your bone marrow grow abnormally and stop working properly. They no longer produce enough healthy blood cells for your body’s needs. The most common type of MDS is called refractory anemia with excess blasts (RAEB). This type accounts for more than 90% of all MDS cases.

Signs & Symptoms

The signs and symptoms of MDS vary between patients and may include:

Anemia — A lack of red blood cells or hemoglobin, the oxygen-carrying protein in red blood cells, causes anemia. You may feel tired, weak and short of breath because your body isn’t getting enough oxygen. Anemia also can cause pale skin, weakness, dizziness and irregular heartbeats (palpitations).

Leukopenia — Abnormally low white blood cell count (neutropenia) that makes you more susceptible to infections.

Thrombocytopenia — Abnormally low platelet count that makes you prone to bleeding.

Enlarged spleen — Your spleen is an organ located under your ribcage on the left side of your abdominal cavity near your stomach. If it becomes enlarged due to cancer or infection, you may experience pain when you breathe deeply or cough, as well as swelling in your abdomen that may feel hard to the touch.

Causes

The following are some potential causes of MDS:

Chemical exposure: Exposure to chemicals such as benzene or radiation can cause damage to the bone marrow and lead to MDS. Benzene is a chemical found in gasoline that can cause cancer in humans. It is also found in cigarette smoke, plastics, insecticides and other products used around the home or workplace.

Radiation exposure: Exposure to high doses of radiation can damage bone marrow cells, leading them to produce abnormal white blood cells or red blood cells. Certain tumors may also release chemicals that damage bone marrow cells directly; these tumors include Hodgkin lymphoma and non-Hodgkin lymphoma.

Infection: Infections such as HIV/AIDS can also cause bone marrow problems that lead to MDS.

How Many does have Myelodysplastic Syndromes?

The number of people with myelodysplastic syndromes (MDS) is not known. This is because MDS is not a common disease. In the United States, an estimated 10,000 people are diagnosed with MDS each year.

In the United States, an estimated 10,000 people are diagnosed with MDS each year.

Related Disorders to MDS

MDS is a blood disorder that can be caused by too much iron in the body. Iron overload occurs when you have too much iron in your body and it builds up in organs such as the liver, heart and spleen. The excess iron leads to organ damage. There are several types of MDS:

Refractory anemia with excess of blasts (RAEB) or refractory anemia with excess blasts 2 (RAEB2) – This type of MDS affects about 10 percent of people with MDS. It is a more severe form of the disease than other types and has a poorer prognosis because it doesn’t respond well to treatment.

Atypical chronic myeloid leukemia (aCML) – This MDS variant is more common than RAEB/RAEB2, affecting about 40 percent of people with MDS. It’s also associated with poor survival rates and often leads to acute myeloid leukemia (AML).

There are many disorders that are related to MDS. These include:

• Acute myelogenous leukemia (AML)
• Chronic myelogenous leukemia (CML)
• Hairy cell leukemia (HCL)
• Polycythemia vera (PV)

Diagnosis

The diagnosis of MDS is based on the clinical and laboratory findings, as well as a bone marrow biopsy. The features that help to distinguish MDS from other types of blood cancer include:

Bone marrow evaluation by a pathologist. The bone marrow biopsy is most helpful in evaluating the type and number of cells that make up the blood and bone marrow. This usually involves an aspiration procedure under local anesthesia. A pathologist looks at the sample under a microscope to identify abnormal cells and determine whether they are normal blood-forming cells that are simply not functioning well or true leukemia cells.

Blood cell counts (complete blood count). A complete blood count measures how many red blood cells, white blood cells and platelets are in your bloodstream at any given time and helps to assess your overall health status. Anemia (low red blood cell count) may be present due to low production or accelerated destruction of red blood cells by marrow replacement syndrome, or it may be present for other reasons unrelated to MDS. If there is no evidence of anemia, this may indicate that there is not enough bone marrow involvement for a diagnosis of MDS yet.

Standard Therapies for MDS

Standard therapies for MDS include intravenous (IV) chemotherapy and bone marrow transplantation.

The most common treatment is to give the patient a combination of drugs called anthracyclines and other agents to kill the abnormal cells. This treatment is usually given in cycles over a period of months. It can be given either as a single agent or in combination with other medications. The most common combination is with another medication called cytarabine, which also kills abnormal blood cells.

After each cycle, the patient’s blood counts are tested to see how much improvement is made. If there is no improvement or the disease gets worse, more cycles may be needed.

If patients continue to get worse after several cycles of chemotherapy, they may need a bone marrow transplant (BMT). BMT involves replacing diseased bone marrow with healthy bone marrow cells from another person (called an allogeneic donor).

MDS Clinical Trial

The clinical trial is recruiting patients who have been diagnosed with a myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). The purpose of the study is to compare two different doses of the drug, venetoclax, to determine which dose is most effective at reducing the risk of death from MDS or AML.

The treatment schedule for this study will be approximately 8 weeks in length. Patients may receive up to 3 cycles of treatment. Each cycle consists of 21 days of venetoclax followed by 7 days off treatment. During each cycle, venetoclax will be administered on days 1-21 and 28 of each treatment cycle.

Participants will be randomly assigned to receive either:

• Venetoclax at 150mg once daily for 21 days followed by 7 days off treatment (n=20) OR
• Venetoclax at 70mg once daily for 21 days followed by 7 days off treatment (n=20)