Myelodysplastic syndromes

Myelodysplastic syndromes (MDSs) are a group of diseases where the bone marrow doesn’t make enough healthy mature blood cells. The immature blood cells, called blast cells (blasts), do not work properly. They build up in the bone marrow and the blood and crowd out healthy blood cells. As a result, there are fewer healthy red blood cells, white blood cells and platelets.

MDSs usually develop in older people. They develop more often in men than in women.

People with an MDS often have changes (mutations) in certain chromosomes within the MDS cells. Examples of chromosome changes that are found in MDS cells include:

• a deletion (loss) of the q-arm in one or more of chromosomes 5, 7 and 20
• complete deletion of chromosome 5 or 7
• an extra copy of chromosome 8

People with an MDS also often have mutations in certain genes within the MDS cells. Examples of gene mutations that are found in MDS cells include:

• SF3B1
• TP53

An MDS may be caused by certain genetic conditions, previous cancer treatment or coming into contact with certain chemicals at work.

An MDS will develop into acute myeloid leukemia (AML) about 30% of the time.

In the past, an MDS was classified as a disease that was not likely to develop into cancer and it was called pre-leukemia. Now that more is known about MDSs, they are considered to be a form of cancer.

An MDS may not cause any signs or symptoms in its early stages. Some people may have mild symptoms that slowly get worse over time. The symptoms that develop depend on the type of blood cell that is most affected. Many people with an MDS have a low red blood cell count (called anemia). A low white blood cell count (called neutropenia) or a low platelet count (called thrombocytopenia) or both can also mean you have an MDS. The most common symptoms of an MDS include:

• fever
• frequent infections
• easy bruising and bleeding
• fatigue
• shortness of breath

Many tests used to diagnose an MDS are used to diagnose leukemia, including a complete blood count and a bone marrow aspiration and biopsy with cytogenetic and special DNA testing (called next generation sequencing). Find out more about these tests for the diagnosis of leukemia.

The World Health Organization (WHO) identifies the different types of MDSs based on their cellular and clinical classifications.

Cellular classification is a way of identifying different types of MDSs based on:

• how the blood and bone marrow cells look under a microscope
• the degree of dysplasia in the blood and bone marrow cells
• chromosome changes in the blood and bone marrow cells
• how quickly the MDS is likely to develop into AML

Clinical classification is a way of identifying types of MDSs based on what doctors believe is the main factor in the disease’s development. If doctors can’t identify the main cause, it is called primary MDS. If doctors think a previous cancer treatment caused the disease, it is called secondary MDS or treatment-related MDS. Secondary MDS is more common than primary MDS.

Based on these classifications, doctors can identify the following types of MDSs.

Refractory cytopenia with unilineage dysplasia (RCUD) causes a low number of one type of blood cell. The counts for the other 2 types of blood cells are normal. The dysplasia is usually minimal.

Refractory anemia (RA) means there is a low number of red blood cells in the blood.

Refractory neutropenia (RN) means there is a low number of white blood cells in the blood.

Refractory thrombocytopenia (RT) means there is a low number of platelets in the blood.

RCUD rarely develops into AML.

Refractory anemia with ring sideroblasts (RARS) means there is a low number of red blood cells in the blood. The counts for white blood cells and platelets are normal. At least 15% of the red blood cells have too much iron (called ring sideroblasts).

About 1% to 2% of all cases of RARS develop into AML.

Refractory anemia with excess blasts (RAEB) means there is a low number of red blood cells in the blood and there may also be a low number of white blood cells or platelets. The blood cells look abnormal in the bone marrow.

RAEB is divided into 2 categories based on the percentage of blasts in the bone marrow.

RAEB-1 means 5% to 9% of the cells in the bone marrow are blasts. About 25% of RAEB-1 cases develop into AML.

RAEB-2 means 10% to 19% of the cells in the bone marrow are blasts. About 33% of RAEB-2 cases develop into AML.

Refractory cytopenia with multilineage dysplasia (RCMD) means that there are low numbers of at least 2 types of blood cells (red blood cells, white blood cells or platelets) in the blood. If red blood cells are affected and they have too much iron, it is called RCMD-RS.

Both RCMD and RCMD-RS may develop into AML.

Unclassifiable myelodysplastic syndrome (MDS-U) means there is a low number of one type of blood cell (red blood cells, white blood cells or platelets) in the blood. The percentage of blasts in the blood and bone marrow is normal.

MDS-U is not common. Doctors make a diagnosis of MDS-U when the cells in the blood and bone marrow don’t fit any other type of MDS. The number of any type of blood cell in the blood may be lower than normal, but less than 10% of that type of blood cell looks abnormal in the bone marrow. The cells in the bone marrow have at least one chromosome abnormality that is seen only in an MDS or in leukemia.

In myelodysplastic syndrome associated with an isolated del[5q] chromosome abnormality, the number of red blood cells in the blood is low, the white blood cell count is normal and the platelet count is higher than normal. There is also a specific change in chromosome 5.

This type of MDS rarely develops into AML.

A prognosis is the doctor's best estimate of how a disease will affect someone and how it will respond to treatment. Prognosis for an MDS depends on many factors. Only a doctor familiar with your medical history, the type and other features of the MDS, the treatments chosen and the response to treatment can put all of this information together to arrive at a prognosis.

Doctors use prognostic scoring systems for MDSs. Different factors are given a value and then a score. The total score is used to assign the MDS a risk category. A higher score suggests a greater chance that an MDS will develop into AML and have a less favourable prognosis.

To get a prognosis, the doctor will look at certain aspects of the MDS or a characteristic of the person (such as their age). These aspects are called prognostic factors.

The doctor will also look at predictive factors, which influence how the MDS will respond to a certain treatment.

Prognostic and predictive factors are often discussed together. They both play a part in deciding on a prognosis and a treatment plan. The following are prognostic and predictive factors for an MDS.

RCUD and RARS are the least likely to develop into AML. They have a more favourable prognosis than other types of MDSs.

Myelodysplastic syndrome associated with an isolated del[5q] chromosome abnormality rarely develops into AML and has a more favourable prognosis than other types of MDSs.

A high percentage of blasts in the bone marrow means a less favourable prognosis.

Low numbers of more than one type of blood cell (red blood cells, white blood cells or platelets) is a sign of a less favourable prognosis.

Changes to chromosome 7 usually mean a less favourable prognosis.

Simple changes mean that there are less than 3 changes to chromosomes. Simple changes are linked with a more favourable prognosis.

Complex changes mean that there are 3 or more changes to chromosomes. Complex changes are linked with a less favourable prognosis.

An SF3B1 mutation in the MDS cells, which is often seen in RARS, is linked with a more favourable prognosis.

A TP53 mutation in the MDS cells is linked with a less favourable prognosis.

The goal of treatment for an MDS is to relieve symptoms, slow or stop the MDS from developing into AML and improve quality of life.

Your healthcare team will work with you to create a treatment plan, which may include treating the symptoms or complications from the MDS (called supportive therapy), like low blood cell counts, or treating the disease itself.

Supportive therapy may include:

• transfusions
• growth factors
• drug therapy

Treatments that treat the MDS itself include:

• chemotherapy
• a stem cell transplant

These treatments may use different drugs. For more information on certain drugs, go to sources of drug information.

If you have low red blood cell counts (called anemia), you may be given blood transfusions. Having blood transfusions can cause a buildup of extra iron, which is treated with medicines such as deferoxamine (Desferal) and deferasirox (Exjade, Jadenu).

If you have bleeding problems due to low platelet counts, you may be given platelet transfusions.

Growth factors are substances that regulate the growth, division and survival of cells. Not having enough healthy blood cells causes most of the symptoms of an MDS. Growth factors help return blood cell counts to normal.

Epoetin alfa (Eprex) helps improve the production of red blood cells.

Drugs that may be used to treat or prevent problems caused by low blood counts include:

• antibiotics
• lenalidomide (Revlimid)
• luspatercept (Reblozyl)
• eltrombopag (Revolade)
• anti-thymocyte globulin

Anti-thymocyte globulin and cyclosporin may be used in a rare subtype of MDS where the bone marrow has very few blood cells.

Chemotherapy uses drugs that are cytotoxic to destroy cancer cells. Cytotoxic means the drugs are poisonous to all cells in your body. These drugs destroy cancer cells, but they can also harm healthy cells. Chemotherapy may also be used to treat the symptoms of an MDS and to help slow or prevent the MDS from developing into AML.

The most common chemotherapy drugs used to treat an MDS are:

• azacitidine
• decitabine (Demylocan)
• decitabine and cedazuridine combination therapy (Inqovi)

The chemotherapy drugs used as induction treatments for AML may sometimes be offered as well.

A stem cell transplant may be a treatment option for younger people who are in relatively good health.

Follow-up for an MDS is often shared among the cancer specialists (oncologists) or blood specialists (hematologists) and your family doctor. Your healthcare team will work with you to decide on follow-up care to meet your needs.

Don’t wait until your next scheduled appointment to report any new symptoms and symptoms that don’t go away.