Myelodysplastic syndrome (MDS) is a rare disease of the blood, only occurring in four out of every 1 million children. This rare disease keeps the body from properly producing blood cells and producing enough of them. MDS develops in the bone marrow, the soft, spongy center of the long bones that produces the three major blood cells. With this disease, the blood cells lose their ability to mature and function properly.
How Dana-Farber/Boston Children's approaches myelodysplastic syndrome
Dana-Farber/Boston Children's Cancer and Blood Disorders Center is a national pediatric hematology oncology referral center, with one of the nation's most experienced, multidisciplinary teams at diagnosing and treating pediatric MDS. Dana-Farber/Boston Children's is the only large pediatric center in the U.S. that has been awarded the MDS Centers of Excellence award by the MDS Foundation.
At Dana-Farber/Boston Children's Cancer and Blood Disorders Center, children with myelodysplastic syndrome are treated through our Myelodysplastic Syndrome Specialty Program. We offer specialized diagnostic and treatment options, including direct referral to our Pediatric Stem Cell Transplant Program, one of the nation's oldest and most experienced pediatric stem cell transplant programs.
In almost all instances, MDS in children can be cured only through a bone marrow transplant, also known as a hematopoietic stem cell transplant (HSCT). HSCT uses high doses of chemotherapy or radiation therapy to destroy all the cells in the bone marrow, healthy and diseased ones. Healthy cells from the bone marrow of another person — either a relative (usually a sibling) or an unrelated individual — are given through an infusion to the patient to restore the bone marrow that was previously destroyed by the chemotherapy and/or radiation therapy.
What is the prognosis for a child with MDS?
Your child's prognosis greatly depends on the specific diagnostic category of MDS, chromosomal abnormalities and the number of blasts in the blood and bone marrow and the availability of a suitable bone marrow transplantation donor. As with any serious medical condition, prognosis and long-term survival can vary greatly from child to child. Prompt medical attention and aggressive therapy are important for the best prognosis.
What is the latest research on MDS?
At the moment, very little is known about the initiating events that lead to MDS; therefore, limited specific therapies exist, and a hematopoietic stem cell transplant is currently the only treatment that can cure the disease. Dana-Farber/Boston Children's received grant funding from the National Institutes of Health (NIH) to establish the first nationwide Pediatric MDS and BMF Registry.
To learn more about participating in the registry, please contact our research nurse, Grace Yoon, at 888-5-pediMDS, or email us at firstname.lastname@example.org. For more information, visit our website at www.PediMDS.org.
For many children with rare or hard-to-treat conditions, clinical trials provide new options.
Learn more about myelodysplastic syndrome (MDS) on the Dana-Farber/Boston Children's website.
Myelodysplastic syndrome (MDS) is a rare disease of the blood. Most of the time it develops in older patients (over 60 years old), but it can occur at any age and affect children as well.
- MDS occurs when the bone marrow does not properly produce sufficient numbers of healthy red blood cells, white blood cells and platelets.
- MDS is very rare in children, and children get different types of MDS than adults.
- MDS may be hereditary or caused by another event or illness, but often there is no known cause.
- MDS used to be called smoldering leukemia or pre-leukemia, but only about one-third of cases of MDS actually progress to leukemia.
- In most instances, the only curative treatment for children with MDS is a bone marrow or stem cell transplant.
How Dana-Farber/Children's Hospital Cancer Center approaches MDS
Dana-Farber/Children's Hospital Cancer Center is a national pediatric hematology/oncology referral center, with one of the nation's most experienced, multidisciplinary team at diagnosis and treating pediatric MDS.
- We offer specialized diagnostic and treatment options, including stem cell transplantation.
- We offer direct referral to Dana-Farber/Children's Hospital Cancer Care's Pediatric Stem Cell Transplant Program, one of only eight institutions around the country investigating the use of umbilical cord transplantation for children with MDS.
- Boston Children's Hospital is establishing the first nationwide patient registry and tissue repository for Pediatric MDS and bone marrow failure disorders. This National Institute of Health (NIH)-funded project will help us better understand MDS and identify potential new treatments.
What is myelodysplastic syndrome?
Myelodysplastic syndrome (MDS) is a rare disease of the blood. Most of the time it develops in older patients (over 60 years old), but it can occur at any age and affect children as well. 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 the normal bone marrow growth and development of blood cells is carefully controlled to produce the correct number of each type of blood cell to keep the body healthy. All blood cells (while blood cells, red blood cells and platelets) are made from the start in the bone marrow from a single type of a cell called a stem cell. Stem cells make up a very small portion of all the cells in the bone marrow. The stem cells are stored in the bone marrow until a specific type of cell is needed, for example a red cell. When more red cells are needed the bone marrow activates the stem cells in reserve to rapidly produce more red cells. At that time the stem cell matures and develops more and more into a red cell.
- In MDS this process of maturation from a stem cell into a mature cell is disturbed.
- Red and white blood cells may mature, but not normally or in insufficient numbers.
- Sometimes the number of immature blood cells, called blasts, increases.
- As the disease progresses these blasts continue to increase and invade the bone marrow, making it impossible to work effectively.
MDS used to be called smoldering leukemia or pre-leukemia, but only about one-third of cases of MDS actually progress to leukemia. Leukemia is a cancer of the blood and bone marrow. As you read further below, you will find general information about MDS.
What causes MDS?
MDS occurs in 4 out of one million children.
- Most of the time MDS develops in previously healthy children, with no identifiable cause.
- In some patients, MDS occurs secondary to some other event or illness. We call this secondary MDS. It can occur in patients who have had chemotherapy or radiation therapy for another illness or malignancy.
- Other patients have rare underlying conditions of their bone marrow called inheritedbone marrow failure disorders.
Many patients with MDS have a chromosomal abnormality associated with the disease; however, these changes are not inherited from someone in the family. Instead, these abnormalities are changes in the chromosomes that only exist in the diseased blood and bone marrow cells.
- The most common abnormalities occur in chromosomes 5 and 7 and 8.
- These acquired chromosomal alterations are thought to play a role in the development of the disease.
- Certain congenital chromosomal disorders, including Down syndrome, are also associated with an increased risk for the development of childhood MDS and leukemia.
What are the different types of MDS?
Physicians have identified several types of MDS, based on how blood and marrow cells appear under the microscope. However, they are largely classified by the fraction of blasts (immature blood cells) found in the marrow and blood. The subtypes that have been identified in children are somewhat different then the ones physicians have identified for adults and older people.
The types of MDS in children are:
- Refractory cytopenia (RC) - less than 5 percent blasts in bone marrow
- Refractory anemia with excess blasts (RAEB) - 5-20% of blasts in the bone marrow
- RAEB in transformation (RAEB-t) - 21-30% of blasts in the bone marrow
When MDS predominantly affects white blood cells, the immature forms of white blood cells (blasts) increase in number and the number of mature white blood cells typically decrease.
- It is normal to have a small number of blasts even in a healthy bone marrow (up to 5%).
- However, in MDS patients with number often increases over 5%, which is then called Refractory Anemia with Excess Blasts (RAEB).
- If the blasts become especially numerous and the disease gains more and more the appearance of acute myeloid leukemia (AML), the disease is called Refractory Anemia with Excess Blasts in transformation (RAEB-t).
- AML 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?
The most common symptoms of MDS are:
- Anemia -- Anemia occurs when red blood cells are not produced properly or in inadequate numbers the amount of the oxygen carrying protein hemoglobin is decreased. With anemia, the child may appear tired, pale, and may breathe faster to compensate for the decrease in the ability to deliver oxygen to the body.
- Infections -- In many cases of MDS the type of white blood cells that fight off bacterial infections (neutrophils) can be very low. This condition is 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 both cases 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.
- Bleeding -- In MDS platelets, which help stop bleeding, are often reduced. Therefore patients with MDS may experience bruising or abnormal bleeding (prolonged nose bleeds, bleeding from the gums).
It is important to understand that the symptoms of MDS may resemble other blood disorders or medical problems, some of them which are very common and simple, others which could be more serious. The symptoms listed above are common presentations of the disease, but do not include all possible symptoms. Children may experience symptoms differently.
How is Myelodysplastic Syndrome diagnosed?
In addition to a complete medical history and physical examination, myelodysplastic syndrome (MDS) can only be diagnosed accurately by a full evaluation of the blood and bone marrow.
To diagnose MDS the following test might be preformed:
- Complete blood count (CBC) - a measurement of size, number, and maturity of different blood cells in blood, which tells us if the bone marrow is working properly. If the results are abnormal a bone marrow test might be indicated.
- Additional blood tests - may include blood chemistries, evaluation of liver and kidney functions, and genetic studies.
- Bone marrow aspiration and biopsy -- A bone marrow sample is usually taken from the back of the hipbone. A sample is removed by inserting a needle into the hipbone and sucking out some of the liquid part of the marrow with a syringe (a bone marrow aspirate). In addition a small piece of the spongy bone containing intact marrow may be obtained (a bone marrow biopsy). The procedure is usually done under local anesthesia and some sedation to limit pain or discomfort. Both, the aspirate and the biopsy will be examined by an expert pathologist (a pediatric hematopathologist) under the microscope. In most cases doctors will perform additional special tests on the bone marrow such as chromosomal analysis (see below).
- Chromosomal analysis -- This test is also called cytogenetic testing. It evaluates all of our chromosomes, which carry our genetic information, to detect any abnormalities. The test usually takes about one week. Cytogenetic studies often help to confirm the diagnosis of MDS and can help distinguish it from certain forms of leukemia. This is important to help physicians tailor treatment to the specific disease.
MDS is often more difficult to diagnose than other disorders of the bone marrow and takes an expertise physician and pathologist to make the correct diagnosis. This is particularly true for children. Therefore the diagnostic process may take time and occasionally repeated blood and bone marrow tests are needed to make the diagnosis with certainty.
What are the treatments for MDS?
Treatment usually begins with supportive care, which intends to control and treat the consequences of the disease, but not to eradicate it.
- Children may receive a transfusion of red cells and platelets to improve symptoms of anemia and to prevent bleeding.
- Because patients with MDS are at higher risk of developing infections, immediate evaluation by a health care provider for any fevers is critical.
- Treatment with antibiotics is often necessary and important, when a child has a fever.
Chemotherapy is usually used for the treatment of cancers, including leukemia. However, chemotherapy is not typically useful for the treatment of MDS.
In almost all instances, MDS in children can only be cured through a bone marrow transplant also known as a hematopoietic stem cell transplant (HSCT).
- HSCT uses high doses of chemotherapy or radiation therapy to destroy all the cells in the bone marrow, healthy and diseased ones.
- Healthy cells from the bone marrow of another person are given through an infusion to the patient to restore the bone marrow that was previously destroyed by the chemo- and/or radiation therapy.
- The use of stem cells from another individual whose tissue is the same as, or almost the same as, the patient's is called allogeneic transplantation.
- The donor cells may come from a relative, usually a sibling, or an unrelated individual.
Continuous follow-up care to determine response to treatment, detect recurrent disease, and manage late effects of treatment is critical. Frequent examinations by a specialist and laboratory test (including repeat bone marrow examinations) are most important for a successful management of disease.
What is the prognosis for a child with MDS?
Prognosis greatly depends on:
- The specific diagnostic category of MDS, chromosomal abnormalities, and the number of blasts in the blood and bone marrow.
- Whether the MDS is a primary disorder or secondary to another disease.
- The availability of a suitable bone marrow transplantation donor.
As with any serious medical condition, prognosis and long-term survival can vary greatly from child to child. Prompt medical attention and aggressive therapy are important for the best prognosis. Continuous follow-up care is essential for the child diagnosed with MDS. Side effects of chemotherapy, as well as second malignancies, can occur in survivors of MDS. New methods are continually being discovered to improve treatment and to decrease side effects of the treatment for the disease.
What is the latest research on MDS?
At the moment, very little is known about the initiating events that lead to MDS, therefore limited specific therapies exist and a hematopoietic stem cell transplantation is currently the only curative option to treat the disease.
Dana-Farber/Children's Hospital Cancer Care's Pediatric Stem Cell Transplant Program is one of only eight institutions around the country investigating the use of umbilical cord transplantation for children with MDS.
Recently, Boston Children's Hospital received grant funding from the National Institute of Health (NIH) to establish the first nationwide patient registry and tissue repository for Pediatric MDS and bone marrow failure disorders.