What is myelodysplastic syndrome?
Myelodysplastic syndrome (MDS) is a rare disease of the blood, only occurring in four out of every 1 million children. While it develops in older patients (greater than 60 years old) most of the time, it can occur at any age. MDS develops in the bone marrow, the soft, spongy center of the long bones that produces the three major blood cells:
- white blood cells to fight infection
- red blood cells that carry oxygen
- platelets that help blood clot and stop bleeding
MDS occurs when the bone marrow does not properly produce sufficient numbers of healthy red blood cells, white blood cells and platelets. With this disease, the blood cells lose their ability to mature and function properly.
In normal bone marrow, the growth and development of blood cells are carefully controlled to produce the correct number of each type of blood cell to keep the body healthy.
All blood cells (white blood cells, red blood cells and platelets) originate in the bone marrow from a single type of cell, called a stem cell. Stem cells make up a very small portion of all the cells in the bone marrow. When more cells are needed, the bone marrow activates stem cells to rapidly produce more blood cells.
- In MDS, this process by which a stem cells matures into a red or white cell or a platelet is disturbed.
- Red and white blood cells may mature but not normally or in sufficient numbers.
- Sometimes, the number of immature blood cells, called blasts, increases and the number of mature cells goes down.
- As the disease progresses, these blasts continue to increase and invade the bone marrow, preventing them from working effectively.
MDS used to be called “smoldering leukemia” or “pre-leukemia,” but only about one-third of cases of MDS actually progress to childhood leukemia, a cancer of the blood and bone marrow.
What causes MDS?
There are two different major categories of myelodysplastic syndrome (MDS), divided up by cause:
- Primary MDS: The disease occurs with no known cause in previously healthy children.
- Secondary MDS: The disease is caused by another condition. This group includes MDS resulting from previous chemotherapy or radiation therapy for another cancer. MDS also can be caused by inherited bone marrow failure disorders, such as Fanconi anemia. In rare cases, MDS and leukemia can run in families, called familial MDS. We have recently identified genetic changes that lead to familial MDS.
Some pediatric patients with MDS have a chromosomal abnormality associated with the disease, most often involving chromosomes 7 and 8. However, these changes are not inherited from a parent. Instead, these abnormalities, which are thought to play a role in the development of MDS, arise on their own only within bone marrow cells and the blood cells they produce.
Sometimes, pediatric MDS can be associated with other rare conditions, such as inherited bone marrow failure disorders and other rare congenital disorders.
What are the different types of MDS?
Physicians have identified several sub-types of MDS, based on how blood and marrow cells appear under the microscope. The hallmark of MDS is dysplasia, which describes the abnormal and bizarre-looking cells under the microscope. The cells used to be normal, precursor cells that produce white blood cells, red cells or platelets. When MDS develops, these cells have an abnormal appearance. Pediatric MDS is largely classified by the fraction of blasts (immature white blood cells) found in the marrow and blood. Importantly, the subtypes that have been identified in children are somewhat different from the ones that physicians are using for adults and older people.
The types of pediatric MDS are:
- refractory cytopenia of childhood (RCC): less than 5 percent blasts in bone marrow. However, it can be normal to have a small number of blasts even in healthy bone marrow (up to 5 percent).
- refractory anemia with excess blasts (RAEB): 5 to 20 percent of blasts in the bone marrow
- RAEB in transformation (RAEB-t): 21 to 30 percent of blasts in the bone marrow
When the amount of blasts in a child’s bone marrow exceeds 30 percent, the condition is considered to be acute myelogenous leukemia (AML), which is a type of leukemia characterized by an increase in a particular type of white blood cell. AML that has developed after MDS is, in general, much harder to cure than de novo AML (regular AML that started anew, without any underlying MDS or other disease).
What are the symptoms of MDS?
Because MDS is a disease of the bone marrow, initial symptoms are often related to abnormal bone marrow function. The bone marrow is responsible for producing the body's red blood cells, white blood cells and platelets. The most common presenting symptom is bleeding related to low platelet counts. However, in many children, MDS is discovered accidentally when a child is having a routine blood test for other reasons.
While your child may experience symptoms differently, the most common symptoms of MDS include:
- Anemia: Anemia occurs when red blood cells are not produced properly or are produced in inadequate numbers, and the amount of oxygen-carrying protein hemoglobin is decreased. With anemia, the child may appear tired or pale and may breathe faster to compensate for the decreased ability to deliver oxygen to her body.
- Bleeding: In MDS, platelets, which help stop bleeding, often are reduced. Therefore, patients with MDS may experience bruising or abnormal bleeding (prolonged nose bleeds, bleeding from the gums).
- Infections: In many cases of MDS, the type of white blood cells that fight off bacterial infections (neutrophils) can be very low—a condition called neutropenia. Neutropenia may be the result of a failure of immature precursors in the bone marrow to mature, or an increase in blasts that crowds out normal cells in the bone marrow. In other cases of MDS, the white cell count can be unusually high. In either case, there are not enough normal healthy white blood cells present in the blood to fight infection. The child may have had repetitive infections or even serious infections with high fevers.
The symptoms of MDS may resemble other blood disorders or medical problems, some of which are very common and easy to treat, others of which could be more serious. The symptoms listed above are common presentations of the disease, but do not include all possible symptoms.
It is important to be evaluated by a physician to obtain an accurate diagnosis. Always consult your child's physician, if you have concerns.