Myelodysplastic Syndromes

What are myelodysplastic syndromes?

Myelodysplastic syndromes (MDS) are a group of rare disorders in which the bone marrow does not make enough healthy blood cells. Bone marrow is the spongy material inside bones that makes blood stem cells. These stem cells make mature blood cells found in the blood stream.

Healthy bone marrow makes 3 kinds of blood cells:

• Red blood cells, which carry oxygen to the body
• White blood cells, which help protect against infections
• Platelets, which help blood clot and stop bleeding

In MDS, stem cells in the bone marrow are damaged and can’t make enough healthy blood cells. The new blood cells are abnormal and do not work properly. The blood cells may die in the bone marrow or after entering the bloodstream. This can lead to dangerously low numbers of one or more types of blood cells.

MDS is very rare in children. About 4 in 1 million children are diagnosed with MDS each year. MDS in adults is more common and usually has different causes than MDS in children.

Complications of MDS include serious infections, bleeding, and feeling tired or having pale skin. MDS also increases the risk of developing acute myeloid leukemia (AML), a cancer of the blood and bone marrow.

Symptoms of MDS

Signs and symptoms of MDS can be hard to notice in the early stages of the disease. MDS symptoms are often related to low blood cell counts. The symptoms can vary from person to person but may include:

• Anemia
  • Feeling tired, weak, or dizzy
  • Shortness of breath
  • Pale skin
• Bleeding and easy bruising due to low platelets (thrombocytopenia)
• Frequent infections due to low blood cells (neutropenia)
• Fever
• Weight loss

Causes of MDS

For many children with MDS, the cause is unknown. When MDS is caused by unknown factors, it is called primary MDS. Having an overactive immune system might play a role in some patients.

Secondary MDS is caused by known factors. Factors that can cause MDS include previous treatment with chemotherapy or radiation, previous aplastic anemia, and inherited gene changes (mutations).

Genetic conditions that cause MDS

MDS can be caused by gene changes that affect the whole body (germline mutation). This can be inherited from parents or can develop before birth. Sometimes multiple people in one family can be affected, which is called familial MDS. Types of genetic conditions that cause MDS include bone marrow failure syndromes and MDS predisposition syndromes.

• Inherited bone marrow failure syndromes: These syndromes can affect one or more blood cell types. They include:
  • Fanconi anemia
  • Congenital neutropenia
  • Shwachman-Diamond syndrome
  • Dyskeratosis congenita
  • Diamond-Blackfan anemia
  • Thrombocytopenia syndromes such as CAMT, MECOM or GATA1
• MDS predisposition syndromes: These diseases can occur at different ages and with different symptoms. In some patients, a low number of blood cells or immune system problems may happen first. It is possible for MDS to develop without prior problems. The most common MDS predisposition syndromes are:
  • GATA2 deficiency
  • SAMD9 and SAMD9L syndromes (also referred to as MIRAGE and Ataxia-Pancytopenia syndromes)
  • Familial platelet disorder with predisposition to acute myelogenous leukemia (FPD/AML) due to RUNX1 mutations
  • ETV6-/ and ANKRD26-related thrombocytopenia with predisposition to hematopoietic malignancy
  • DDX41 and CEBPA genetic predisposition to MDS/AML

Diagnosis of MDS

MDS is diagnosed based on your child’s medical history, physical exam, and lab tests. Your doctor may ask you about any changes in bleeding or bruising, recent illnesses, or medicines your child is taking.

Lab tests for MDS may include:

• Bone marrow aspiration and biopsy to look at the number and size of cells found in a bone marrow sample
• Complete blood count (CBC) to measure the number of cells found in the blood
• Genetic testing to check for inherited disorders or gene changes

Types of MDS in children

There are 2 main types of pediatric MDS:

1. Refractory cytopenia of childhood (RCC)
2. MDS with excess blasts (MDS-EB)

RCC and MDS-EB can be identified based on the number of blasts (immature blood cells) in the bone marrow. In healthy people blasts, make up less than 5% of the cells in bone marrow. The higher the blasts, the more severe the MDS.

In RCC, the number of blasts is not high (less than 5%).

In MDS-EB, the number of blasts is high (more than 5%).

Children with RCC may not need therapy. But their condition may get worse over time. RCC can also progress to MDS-EB. Acute myeloid leukemia (AML) can develop if the number of blast cells gets too high.

Treatment of MDS 

Many children with less severe forms of MDS can remain stable for years without treatment. It is important to have close monitoring by a pediatric hematologist/oncologist, a doctor who specializes in blood disorders and cancers.

Treatments for MDS include:

• Stem cell (bone marrow) transplant is the most effective treatment for most types of MDS. An allogeneic transplant replaces a patient’s damaged stem cells with healthy ones from a donor.
• Red blood cell and platelet transfusions are used to give blood products through a vein by IV. Transfusions can improve symptoms of anemia and prevent bleeding.
• Antibiotics are medicines used to prevent infections.
• Hematopoietic growth factors are medicines that can help bone marrow make new blood cells.
• Chemotherapy (“chemo”) uses powerful medicines to kill cancer cells or stop them from growing (dividing) and making more cancer cells. Some patients with more severe MDS or patients who have developed AML may need chemotherapy.

Prognosis for MDS

The prognosis and long-term survival of children with MDS varies greatly by:

• The specific features of the disease
• Whether the patient has primary or secondary MDS
• The availability of a donor for stem cell transplant

Patients with MDS can have serious complications, such as severe infections, bleeding, heart problems, or AML. Some children with MDS can be cured with a bone marrow transplant. Children who need transfusions or have developed blasts have a less favorable prognosis.

Living with MDS

If your child has been diagnosed with MDS, there may be certain lifestyle changes that can help manage the condition and prevent problems. Here are some possible ways to help manage MDS:

Keep all medical appointments: Your child may need regular lab tests and monitoring. Be sure to keep all appointments and seek medical care if your child’s condition changes.

Take steps to prevent infection: Wash hands often, keep patient areas clean, and stay away from people who are sick.

Don’t give your child any medicine without talking to your doctor: Some medicines can increase the risk of bleeding or interact with other medicines your child is taking. Talk to your care team before giving your child any medicine or supplement.

Alert others of your child’s condition: Be sure that others know about your child’s medical condition and know what to do if an accident or injury occurs. Tell all health care providers about your child’s diagnosis and any medicines they take. This is especially important before any medical or dental procedures.

Know what activities to avoid: If your child has fewer red blood cells, they may get tired more easily or get out of breath. Be sure your child does not overdo physical activity. When platelet counts are low, your child is at higher risk of bleeding. Your child should avoid contact sports, rough play, and activities that could involve falls or injury to the head or stomach.

When to call your care team

Call your health care provider if your child:

• Looks pale, has trouble breathing, or is more tired than usual
• Has skin or eyes that look yellow
• Has a fever higher than 101°F (38.3°C) by mouth or 100°F (37.8°C) under the arm
• Has other symptoms of illness or infection
• Bleeds easily or for too long after an injury

Questions to ask your care team

• What is the underlying cause of my child's MDS?
• What follow-up appointments and monitoring will my child need?
• What treatment options are available for my child?
• Are there any clinical trials or research studies for pediatric MDS that my child may be eligible to participate in?
• What lab test values do I need to know and what lab results do I need to watch closely?
• How will my child's condition affect their daily life, such as school attendance, sports, and other activities?
• What signs or symptoms should we watch out for that may indicate a worsening of my child's condition?

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