Childhood MDS and MPN
Childhood myelodysplastic syndromes
Myelodysplastic syndromes are a group of diseases which all affect, to a greater or lesser extent, the production of normal blood cells in the bone marrow. MDS occurs as a result of a mutation (or change) in one or more of the genes that control blood cell development. In MDS, abnormal bone marrow stem cells (called blast cells) produce increased numbers of immature blood cells. These cells do not grow properly and often die prematurely. This results in lower numbers of mature red blood cells, white blood cells and platelets being produced.
The blood cells that do survive are often of poor quality, are abnormal in shape (dysplastic) and unable to function properly. This means that children with MDS often have a very active bone marrow but a low number of circulating blood cells.
Without enough red blood cells, white blood cells and platelets your child can become fatigued, more susceptible to infections, and to bleeding and bruising more easily. There are different types of MDS and the disease can vary in its severity and the degree to which normal blood cell production is affected.
MDS is sometimes described as a “clonal blood stem cell disorder”. Mutations in dividing cells occur all the time and cells have clever ways of stopping these abnormalities persisting and causing problems within the body. The longer we live, however, the more chance we have of acquiring mutations that manage to escape these safeguards. That is why MDS, like most leukaemias and other cancers, becomes more common as we get older. This naturally occurring or spontaneously-arising MDS is referred to as primary MDS. The subtypes of childhood MDS are based on the World Health Organisations (WHO) classification in adults.
What are the most common types of childhood MDS?
Refractory cytopenia (RC)
Accounts for 50% of MDS diagnoses in children. Treatment for RC may involve a “watch and wait” approach, whereby the child’s blood counts are monitored and the child is given blood transfusions as required. The disease may remain stable for months to years before intensive treatment is required.
Refractory anaemia with excessive blasts (RAEB)
Requires treatment soon after diagnosis.
Refractory anaemia with excessive blasts – transformation (RAEB-T)
Similar to RAEB, RAEB-T requires immediate treatment. RAEB-T has a high incidence of transforming into childhood AML. This type of AML is often more difficult to treat than a child who is diagnosed with AML without the history of MDS.
Secondary MDS develops in children with predisposing factors or mutations that make them more susceptible to an MDS mutation of their stem cells. A child treated with radiotherapy or chemotherapy for a previous cancer diagnosis is at higher risk of developing MDS. This type of secondary MDS accounts for 7-18% of all childhood MDS diagnoses. A history of congenital disorders or a history of MDS diagnosis in an immediate family member also places a child at a higher risk of developing MDS than the general population.
Childhood myeloproliferative neoplasms
Myeloproliferative neoplasms (MPN) are a group of disorders in which the bone marrow stem cells also grow and reproduce abnormally. In MPN abnormal stem cells produce excess numbers of one or more types of blood cells (red cells, white cells and/or platelets). These abnormal cells cannot function properly and can cause serious health problems unless properly treated and controlled.
MPNs are chronic diseases that in most cases remain stable for many years and progress gradually over time. They are usually described according to the type of blood cell that is most affected. MPNs are closely related diseases, so it’s not uncommon for people to have features of more than one MPN when they are first diagnosed, or during the course of their illness. In some cases, one disorder may transform over time to another, or to a type of leukaemia called acute myeloid leukaemia.
The World Health Organisation have classified childhood MPN as follows:
- chronic nyelomonocytic leukaemia (CMML)
- atypical chronic myeloid leukaemia
- juvenile myelomonocytic leukaemia (JMML)
- MDS/MPN, unclassifiable
How common are MDS and MPN in children?
MDS diagnoses in children account for only 5% of all blood cancer diagnoses in this age group, while MPN is extremely rare in children.
Who gets childhood MDS and MPN?
MDS can occur at any age, including very occasionally in children. The different types of MPN are more common in adults and do occur in children, although they are rare.
What are the causes of childhood MDS and MPN?
Why defects arise in the bone marrow causing MDS in a particular child at a particular time is difficult to understand. Any process which damages genes and leads to mutations may have a role in the development of MDS. There are also some recognised factors which may put some children at a higher risk of developing secondary MDS, like:
- congenital disorders – Fanconi anaemia, Severe congenital neutropenia or Shwachman-Diamond Syndrome
- an immediate family member having been diagnosed with MDS
- a history of radiotherapy of chemotherapy treatments for a previous cancer diagnosis.
The exact cause of MPN remains unknown but there are likely to be a number of factors involved. A mutation of a particular gene (a segment of DNA that makes proteins) known as Janus kinase 2 (JAK 2) is found in a large proportion of people with myeloproliferative neoplasms.
The exact meaning of this mutation remains unclear but it appears to play a role in the overproduction of blood cells seen in these disorders. The discovery of a mutation in the JAK2 gene is important because it is likely to have a significant impact on the way myeloproliferative neoplasms are diagnosed and treated in the future.
What are the symptoms of childhood MDS and MPN?
The types of symptoms that children with MDS and MPN experience depend on how severe their disease is and the type of blood cell which is most affected.
The most common symptoms are caused by a lack of red cells, or anaemia:
- persistent tiredness and fatigue
- shortness of breath with minimal exercise
- looking pale.
Abnormal white cell function, often with low white cell counts, causes:
- recurring infections, especially chest infections
- sore mouth due to mouth ulcers.
Abnormal platelet function, often with low platelet counts, causes:
- easy bruising
- purpura – a rash of small red dots, seen often on the lower limbs initially, due to small superficial capillary bleeds that are known as petechiae
- tendency to bleed from the nose and gums.
Many children with MDS and MPN have a combination of these symptoms. This is because the production of all of the blood cell types may be affected by the disease. Some of these symptoms may also be seen in other illnesses, including viral infections. It is important to see your doctor if your child has any symptoms that do not go away so that they can be examined and treated properly.