Myelodysplastic Syndromes

What are myelodysplastic syndromes?

Myelodysplastic syndromes (MDS) in children are a group of rare disorders in which the bone marrow does not make enough healthy blood cells. Childhood MDS is a different disease than MDS in adults, which is more common and has different causes in most patients.

Bone marrow is the spongy material inside bones that makes blood stem cells. These stem cells are the “factories” that make mature blood cells found in the blood stream. Healthy bone marrow produces three kinds of blood cells:

• Red blood cells (erythrocytes), which carry oxygen to the organs
• White blood cells (leukocytes), which help protect against infections and fight them off when they occur. Granulocytes (neutrophils) fight off bacteria while lymphocytes (another type of white blood cell) kill viruses.
• Platelets (thrombocytes), which help blood clot and stop bleeding

In children with MDS, stem cells in the bone marrow are abnormal and have problems making new blood cells. Many of these defective blood cells die in the bone marrow or after entering the bloodstream. This can lead to dangerously low numbers of one or more type of blood cells.

What are the types of MDS in children?

The World Health Organization (WHO) categorizes MDS into two types: refractory cytopenia of childhood (RCC) and MDS with excess of blasts (MDS-EB). RCC and MDS-EB can be identified based on the number of blasts (cells that can become cancerous) in the bone marrow. In RCC these blasts are not elevated (less than 5%), while in MDS-EB the number of blasts is more than 5%.

Children with RCC can function without therapy, but their condition may get rapidly worse over time. This may lead to a blood transfusion or a bone marrow transplant. RCC can also progress to MDS-EB. Acute myeloid leukemia (AML) may also develop if the number of cancerous cells gets too high.

How common is MDS?

MDS is considered a rare disease in children. About 1 in a million children are diagnosed with MDS each year. Patients with MDS account for less than 5% of all pediatric cancers.

What are the symptoms of MDS?

It can be difficult to notice symptoms of MDS in the early stages of the disease. MDS is often found on blood tests due to low blood cell counts. While the symptoms of MDS can vary from person to person, some of the more noticeable symptoms can include:

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

What causes 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.

When MDS is caused by known factors, it's called secondary MDS. The inherited genetic conditions that can cause MDS are:

• Previous treatment with chemotherapy or radiation
• Previous aplastic anemia
• Inherited genetic mutations—MDS can be caused by gene changes that affect the whole body (germline). This can be inherited from parents or can develop before birth. Sometimes multiple individuals in one family can be affected, which is called familial MDS. The inherited genetic conditions that can cause MDS are:
  • Inherited Bone Marrow Failure syndromes—These syndromes can be present in one or several blood cell lines. 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 present at different ages and with different symptoms. In some patients, a low number of blood cells or low immune dysfunction 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

How is MDS treated?

The most effective treatment for most types of MDS is a bone marrow transplant, often referred to as an allogeneic stem cell transplant. This is a procedure in which a person receives healthy bone marrow from a donor, such as a sibling, unrelated donor from a donor bank or a parent. Learn more about this treatment at: Allogeneic Stem Cell/Bone Marrow Transplant.

Some patients with MDS and MDS-EB or patients who have developed AML may need chemotherapy.

• Chemotherapy (“chemo”) — is used to treat patients with MDS who are at high risk of their disease progressing to AML. Chemo uses powerful medicines to kill cancer cells or stop them from growing (dividing) and making more cancer cells.
  • Chemo may be injected into the bloodstream, so that it can travel throughout the body.
  • Some chemo may be given by mouth.
  • Combination therapy uses more than one type of chemo at a time.

Additionally, symptomatic treatment can ease symptoms without treating the cause of the disease. This can include:

• Red blood and platelet transfusions are used to improve symptoms of anemia and to prevent bleeding
• Antibiotics are used to prevent infections
• Hematopoietic growth factors may be used to help bone marrow make new blood cells

Many children with MDS or subtype refractory cytopenia however can remain stable for years and not need therapy. These children are generally closely followed by a specialized hematologist/oncologist doctor and require follow up bone marrow examinations and blood draw.

What are the survival rates 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 bone marrow transplantation donor

Some children with MDS can be cured with a bone marrow transplantation. Children with MDS who need transfusions and/or have developed blasts and are not able to undergo a transplant have a less favorable prognosis.

Why choose St. Jude for your child’s MDS treatment?

• St. Jude is the only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children.
• St. Jude has a team of renowned experts specializing in bone marrow failure and MDS who work with other specialists around the world.
• St. Jude has created more clinical trials for cancer than any other children’s hospital in the United States.
• The nurse-to-patient ratio at St. Jude is unmatched— averaging 1:3 in hematology and oncology, and 1:1 in the Intensive Care Unit.
• To improve outcomes and reduce side effects related to stem cell/bone marrow transplant, doctors in the St. Jude Transplant Program work closely with laboratory scientists to rapidly move discoveries from the lab to the clinic.
• Your child will have access to a close-knit team of specialists that includes: doctors, nurse practitioners and physician assistants who are experienced in treating this disease; doctors who specialize in hormones (endocrinologists), kidneys (nephrologists), genetic therapy, and diagnosis (pathologists); experts in diagnostic imaging and nuclear medicine; dietitians; speech therapists; rehabilitation specialists (physical therapists, occupational therapists); child life specialists; psychologists; and many others.
• The medical team works closely with laboratory researchers to better understand the disease causes and bring new treatments from the laboratory to the clinic.