About MDS and MPN
Childhood myelodysplastic syndromes
Myelodysplastic syndromes are a group of blood cancers 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 this group of blood cancers can vary in severity and the degree to which normal blood cell production is affected.
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. These blood cancers 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
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
MPNs, 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.
Causes of 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.
Symptoms of of childhood MDS and MPN
The types of symptoms that children with MDS and MPN experience depend on how severe their blood cancer 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
- weakness
- shortness of breath with minimal exercise
- looking pale.
Abnormal white cell function, often with low white cell counts, causes:
- recurring infections, especially chest infections
- fevers
- 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. 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.
Diagnosis of of childhood MDS and MPN
MDS and MPN are diagnosed by examining samples of your child’s blood and bone marrow.
Full blood count
The first step in the diagnosis is a simple blood test called a full blood count (FBC) or complete blood count (CBC). This involves a sample of blood from a vein in your child’s arm being sent to the laboratory for investigation. Most people with MDS have a low red cell and platelet count. A diagnosis needs to be confirmed by examining the cells in the bone marrow.
Bone marrow examination
If the results of the blood tests suggest MDS or MPN, a bone marrow biopsy may be required to help confirm the diagnosis. A bone marrow biopsy involves taking a sample of your child’s bone marrow (usually from the back of the hip bone) and sending it to the laboratory for examination under the microscope. The bone marrow biopsy may be done in the haematologist’s rooms, clinic or day procedure centre and is usually performed under a light anaesthetic or sedation given through a small drip in your child’s arm. The sample of bone marrow is examined in the laboratory to determine the number and type of cells present and the amount of haematopoiesis (blood-forming) activity taking place there.
Further testing
Once the diagnosis of MDS or MPN is made, blood and bone marrow cells are examined further using special laboratory tests. These include immunophenotyping and cytogenetic tests. These tests provide more information about the exact type of disease your child has, the likely course of the disease and the best way to treat it. Other tests may be conducted to provide information on your child’s general health and how their vital organs are functioning. These include a combination of further blood tests and imaging tests (like x-rays, scans and ECG). These results will provide a baseline of your child’s disease and general health which will be compared with later results to assess how well your child is progressing and responding to treatment.
Treatment of of childhood MDS and MPN
MDS treatment
Prognosis and treatment for children diagnosed with MDS is dependent on the specific type of MDS, the severity of the disease, whether the MDS is a primary or secondary and if there is an available stem cell donor. Some children with refractory cytopenia need only to be monitored with blood tests and may occasionally need blood transfusions to relieve symptoms, but their disease can remain stable for months or years.
Currently, an allogeneic (donor) stem cell transplant is the only long term curative option for MDS. The donor may be a matched sibling or an unrelated matched donor. This complex process replaces your child’s defective bone marrow, using high dose chemotherapy, then giving them a healthy donor’s stem cells.
A large proportion of children diagnosed with the MDS subtype of RC are cured after undergoing an allogeneic transplant. Fifty percent of children with RAEB and RAEB-T are also cured with a transplant.
For children with RC who are not eligible for an allogeneic transplant or are unable to find a matched donor, immunosuppressive therapy has shown some success, though further research is currently underway to examine this. This type of treatment can weaken a child’s general immune system and make them more susceptible to infections while undergoing the treatment.
Children diagnosed with a secondary type of MDS have less favourable outcomes compared to primary MDS, however allogeneic transplants have shown successful results in these children. Children with secondary MDS resulting from congenital diseases of the marrow may also be offered an allogeneic transplant as a treatment option.
Remember, however, that no two children are the same. In helping you to make the best treatment decision for your child, their doctor will consider all the information available including the details of your child’s particular situation.
MPN treatment
Incidence of MPN in children is very rare and therefore treatment is based on a child-by-child basis, examining their diagnosis, genes affected and previous medical history.
Potentially effective treatments include chemotherapy and an allogeneic (donor) transplant. Treatment with other medications may also result in a temporary improvement of the disease. Occasionally, some children may have a more indolent disease and with supportive care such as blood transfusions, they may survive for many years without any active treatment.
Side effects of childhood MDS and MPN treatment
All treatments can cause side effects. The type and severity however will vary between individuals, depending on the type of treatment used and how an individual responds to it. In general, more intensive treatment is associated with more severe side effects. It is important to report any symptoms to the doctor or nurse. In most cases they can be treated and are reversible. Information about the specific side effects of your child’s treatment should be discussed with your treating doctor.
When to contact your doctor or hospital
As a general rule, while your child is having treatment you will need to contact their doctor or hospital immediately if they have any of the following:
- a temperature of 38oC or over (even if it returns to normal) and/or an episode of uncontrolled shivering (a rigor)
- bleeding or bruising, for example blood in their urine, faeces, sputum, bleeding gums or a persistent nose bleed
- nausea or vomiting that prevents them from eating or drinking or taking their normal medications
- severe diarrhoea, stomach cramps or constipation
- coughing or shortness of breath
- a new rash, reddening of the skin, itching
- a persistent headache
- a new pain or soreness anywhere
- if they cut or otherwise injure themselves
- if you notice pain, swelling, redness or pus anywhere on their body.
What are the side effects of childhood MDS and MPN treatment?
Chemotherapy side effects
Chemotherapy kills cells that multiply quickly, such as MDS or MPN cells. It also causes damage to fast-growing normal cells, including hair cells and cells that make up the tissues in the mouth, gut and bone marrow. The side effects of chemotherapy occur as a result of this damage. These include:
Effects on the bone marrow
Chemotherapy affects the bone marrow’s ability to produce adequate numbers of blood cells. As a result, the blood count (the number of white cells, platelets and red cells circulating in your child’s blood) will generally fall within a week of treatment. The length of time it takes for the bone marrow and blood counts to recover mainly depends on the type of chemotherapy given.
When the platelet count is very low (thrombocytopenic) your child can bruise and bleed more easily. During this time it is helpful to avoid sharp objects in their mouth such as chop bones or potato chips as these can cut their gums. Using a soft toothbrush also helps to protect their gums. In many cases a transfusion of platelets is given to reduce the risk of bleeding until their platelet count recovers.
If the red blood cell count and haemoglobin levels drop your child will probably become anaemic. When a child is anaemic they feel more tired and lethargic than usual. If their haemoglobin level is very low, the doctor may prescribe a blood transfusion.
Risk of infection
The point at which the white blood cell count is at its lowest is called the nadir. This is usually expected 10 to 14 days after having chemotherapy. During this time your child will be at a higher risk of developing an infection. At this stage they will also be neutropenic, which means that their neutrophil count is low.
Neutrophils are important white blood cells that help us to fight infection. While their white blood cell count is low you should take sensible precautions to help prevent infection. These include avoiding crowds, avoiding close contact with people with contagious infections (for example colds, flu, chicken pox), and ensuring your child is only eating food that has been properly prepared and cooked.
If your child does develop an infection they may experience a fever, which may or may not be accompanied by an episode of shivering where they shake uncontrollably. Infections while they are neutropenic can be quite serious and need to be treated with antibiotics as soon as possible.
Nausea and vomiting
Nausea and vomiting are often associated with chemotherapy and some forms of radiotherapy. These days however, thanks to significant improvements in anti-sickness (anti-emetic) drugs, nausea and vomiting are generally very well-controlled. Your child will be given anti-sickness drugs before and for a few days after their chemotherapy treatment. Be sure to tell the nurses and doctors if the anti-emetics are not working for your child.
Some people find that eating smaller meals more frequently during the day, rather than a few large meals, helps to reduce nausea and vomiting. Many find that eating cool or cold food is more palatable, for example jelly or custard. Drinking ginger ale or soda water and eating dry toast may also help if your child is feeling sick.
Changes in taste and smell
Both chemotherapy and radiation therapy can cause changes to the sense of taste and smell. This is usually temporary but in some cases it lasts up to several months. There are lots of reasons why children may not feel like eating much during treatment, especially while they are having treatment or are in hospital. Allowing your child to eat when they are hungry, which often means snacking in between meal times, and offering them nutritious snacks and drinks throughout the day can be helpful.
Parotitis
Associated with radiotherapy, parotitis is an inflammation of the saliva-producing glands in the mouth, which can occur if these glands are within the treatment field used. These include the parotid or submandibular glands, which are situated at the top of the jaw line, in front of the ears. Parotitis causes dryness of the mouth and jaw pain, which usually settles down within a few days, once the inflammation subsides.
Mucositis
Mucositis, or inflammation of the lining of the mouth, throat or gut is a common and uncomfortable side effect of chemotherapy and some forms of radiotherapy. It usually starts about a week after the treatment has finished and goes away once their blood count recovers, usually a couple of weeks later. During this time the mouth and throat could get quite sore. Soluble pain medication and other topical drugs (ones that can be applied to the sore area) can help. Always check your child’s temperature before giving them pain medication as this drug can “mask” signs of infection (a raised temperature).
If the pain becomes more severe, stronger pain killers might be needed. It is important to keep your child’s mouth as clean as possible while they are having treatment to help prevent infection. Avoid commercial mouthwashes as these are often too strong or they may contain alcohol, which will hurt their mouth.
Bowel changes
Chemotherapy can cause some damage to the lining of the bowel wall. This can lead to cramping, wind, abdominal swelling and diarrhoea. Be sure to tell the nurses and doctors if your child experiences any of these symptoms. If they develop diarrhoea, a specimen will be required to ensure that the diarrhoea is not the result of an infection.
After this they will be given some medication to help stop the diarrhoea and/or the discomfort. It is also important to tell the nurse or doctor if they are constipated or feeling any discomfort or tenderness around their anus while they are trying to move their bowels. They may need a gentle laxative to help soften their bowel motion.
Hair loss
Hair loss is unfortunately a very common side effect of chemotherapy and some forms of radiotherapy. It is, however, usually only temporary. The hair starts to fall out within a couple of weeks of treatment and tends to grow back three to six months later. Avoiding the use of heat or chemicals and only using a soft hairbrush and a mild baby shampoo can help reduce the itchiness and scalp tenderness that can occur while your child is losing their hair.
Your child will need to avoid direct sunlight on their exposed head (get them to wear a hat) because chemotherapy (and radiotherapy) makes their skin even more vulnerable to the damaging effects of the sun (i.e. sunburn and skin cancers). Remember that without hair their head can get quite cold so a beanie might be useful. Hair can also be lost from their eyebrows, eyelashes, arms and legs. Many young children are not worried by losing their hair and are happy to wear hats, scarves or bandanas. Older children and teenagers are often more concerned about the effects of hair loss and other changes to their appearance. They are often encouraged to get a wig; while they may never wear it, having the wig may give them the confidence to participate in everyday activities, particularly those involving friends.
Fatigue
Most children experience some degree of tiredness in the days and weeks following chemotherapy and radiotherapy. Having plenty of rest and a little light exercise each day may help to make your child feel better during this time. It is important for them to rest when they are tired.
Fertility
Most children who are treated for MDS or MPN will grow up and be able to have, normal, healthy babies. For others, treatment may cause a reduction in their fertility and their ability to have children in the future. This may depend on the age of the child when they were treated and the type of treatment they received.
In boys, sperm production may be impaired for a while following chemotherapy but it is important to realise that production of new sperm may become normal again in the future.
In girls chemotherapy and radiotherapy can cause varying degrees of damage to the normal functioning of the ovaries. This will depend on the age of the child and the dose of radiotherapy or chemotherapy given. In some cases this leads to menopause earlier than expected. The onset of puberty can also be affected and some children may require hormonal supplements to ensure normal sexual development.
Body image, sexuality and sexual activity
Hair loss, skin changes and fatigue can all interfere with how your child feels about and sees themselves. If you have older children who are sexually active, it is usually recommended that they do not become pregnant as some of the treatments given might harm the developing baby; therefore a suitable form of contraception should be used.
Caring for someone with childhood MDS and MPN
We have a range of information and resources that may help when you are caring for someone with childhood MDS and MPN.
