Myelodysplasia in Cats

What is myelodysplasia?

Myelodysplasia syndrome (MDS) is a group of blood diseases arising from dysfunction from the hematopoietic stem cells which start to produce abnormal immature myeloid cells.

The disease causes cytopenias (cytopenia is the medical term for a reduction in any of the three types of blood cells) in the peripheral blood and dysplastic changes in the bone marrow cells.

For cats with myelodysplasia, the myeloid cells start to produce abnormal immature blasts, which are unable to mature and develop as normal blood cells should, or, if specialised blood cells are made, they die shortly before or after leaving the bone marrow.

The myeloid cells produce three types of blood cells:

• Red blood cells (erythrocytes) – These cells transport oxygen around the body. Anemia is a reduced number of red blood cells.
• White blood cells (leukocytes) – Responsible for fighting infection. Leukopenia is a reduced number of white blood cells.
• Platelets (thrombocytes) – Not cells but cell fragments, platelets are a part of the blood clotting process, forming a plug to stop bleeding. Thrombocytopenia is a reduced number of platelets.

Myelo=marrow (myeloid cells), dys=abnormal, plasia=appearance.

Causes

Below is a very basic description of the development of blood cells, which is known as hematopoiesis.

Normal blood cell production

Multipotential hematopoietic stem cell (hemocytoblast) > Immature myeloid cells > Immature specialised cells (red, white, megakaryocyte, the latter will form platelets) > Specialised cells mature (red, white or platelets) and are released into the bloodstream.

Myelodysplasia (abnormal) cell production

Hematopoietic stem cell > Abnormal immature myeloid cells can crowd out normal stem cells as they are often no longer able to move onto the next step and differentiate into red, white blood cells and platelets, or they do become immature specialised cells but are abnormal > Specialised cells (red, white cells or platelets) aren’t produced, or are produced but are abnormal and die shortly before or after being released into the bloodstream

Usually, the percentage of myeloid cells in the bone marrow is between 2-3%, cats with myelodysplasia often (but not always) have a much higher number of abnormal immature myeloid cells. Once that number goes over 20%, the disease has progressed to acute myeloid leukemia (AML). That is why myelodysplasia is sometimes referred to as preleukemia.

Myelodysplasia can involve one cell line, for example, red blood cell only, or multiple cell lines. Erythrocytes (red blood cells) are the most common cell involved.

Refractory cytopenia with unilineage dysplasia (RCUD) means that your cat has low numbers of one type of blood cell. For example:

1. Refractory thrombocytopenia means he has low blood platelets but normal red and white blood cells.
2. Refractory anemia means he has low red blood cells but normal white blood cells and platelets.
3. Refractory leukopenia means he has low white blood cells but normal red blood cells and platelets.

Refractory cytopenia with multilineage dysplasia (RCMD) means that more than one type of blood cell is affected.

There are no age or gender predilections with this myelodysplasia, Persians, and Birmans appear to be slightly over-represented. Cats with feline immunodeficiency disease and feline leukemia are at a higher risk of developing myelodysplasia. It may be primary or secondary.

• Primary myelodysplasia arises from mutations in the stem cells.

• Secondary myelodysplasia is due to myeloid leukemia, copper deficiency, exposure to toxins such as lead, nutritional deficiency or certain drugs such as chemotherapy or radiotherapy and the feline leukemia virus.

Symptoms

Symptoms depend on the affected cell line(s), but may include:

Anemia (red blood cells)

• Pale mucous membranes
• Lethargy
• Rapid breathing
• Rapid heart rate
• Weakness

Leukopenia (white blood cells)

• Fever
• Fatigue
• Mouth sores
• Recurrent infections

Thrombocytopenia (platelets)

• Increased bleeding such as nosebleed or gums
• Black tarry stools due to internal bleeding

Other symptoms

• Weight loss
• Loss of appetite
• Fever

If more than one cell line is affected, your cat will experience a combination of the above symptoms.

Diagnosis

Your veterinarian will perform a complete physical examination of your cat and obtain a medical history from you including any drug therapies your cat has received.

Diagnostic workup:

Baseline tests: Biochemical profile, complete blood count, and urinalysis. These can help to show how your cat’s organs are functioning if an infection is present and give a count of the types of blood cells, which will reveal anemia, leukopenia, thrombocytopenia or a combination. There may also be abnormally formed cells in the blood. These will give your veterinarian a preliminary diagnosis.

As there are many causes of anemia, leukopenia, and thrombocytopenia, he will need to perform some additional tests to narrow down the cause.

Bone marrow biopsy: Your cat will be anesthetised, and a needle will be inserted into the bone of the pelvis or the femur and into the centre where the bone marrow is. The sample will go to a laboratory for evaluation. The normal percentage of myeloid cells within the bone marrow is around 2-3%, a cat with myelodysplasia may have a much higher percentage of myeloid cells although it is possible for the myeloid cell numbers to be normal or even reduced.

Blood smears: To examine the morphology (shape and structure) of the circulating blood cells.

The veterinarian may also recommend a feline leukemia virus and feline immunodeficiency virus test as a large number of cats with myelodysplasia are infected with these viruses.

Treatment

Treatment depends on the type of myelodysplasia and the severity of the condition.

• Whole blood or platelet transfusions to maintain blood cell and platelet counts. Platelets don’t live for long so transfusions of platelets will need to be more frequent than whole blood. Cats who receive whole blood are at increased risk of iron overload.
• Broad-spectrum antibiotics if needed.
• Hematopoietic growth factors are proteins that can stimulate cell differentiation and production. Erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF) and granulocyte-monocyte colony-stimulating factor (GM-CSF).
• Immunosuppressive drugs can be prescribed if it is the cat’s immune system slows down the production of blood cells.
• Low dose chemotherapy is administered orally, or via injection. These drugs can help the cells of the bone marrow develop normally by killing rapidly dividing (abnormal) cells, and help prevent the disease from progressing to acute myeloid leukemia (AML).

There only cure for myelodysplasia is a bone marrow transplant. This is used in some human cases; usually when the patient is young; however, it is only experimental in cats. The procedure involves high doses of chemotherapy to destroy the patient’s own dysfunctional bone marrow cells, followed by a bone marrow transplant from a healthy cat. The procedure is highly intensive and not without risks.

Possible outcomes

There are three possible outcomes in cats who have myelodysplasia;

• the cat will go on to develop acute myeloid leukemia
• the cat lives with a chronic disease
• the cat dies