MDS is a stem cell cancer. Stem cells are immature cells stored in the bone marrow that gradually develop to form the various types of blood cells, including red blood cells, platelets and white blood cells. In MDS, the stem cells do not mature properly. This means that there are large numbers of immature cells, called blasts, and abnormal or dysplastic cells in the blood. These immature, abnormal cells do not function effectively and crowd out the mature cells. There are several different types of MDS.
Myelo refers to blood cells. Dysplastic means that the blood cells are abnormal in shape and function. In MDS, these abnormalities can affect different kinds of blood cells and take different forms.
Approximately 10,000 people a year are diagnosed with some form of MDS. The average age of people diagnosed with MDS is 65 and at least 80% are over the age of 60. About one third of people with MDS develop a form of leukemia called acute myeloid leukemia..
Age is the most significant risk factor for MDS. It occurs most frequently in people over 60 and is rare in children and young people. People who have been treated for a previous cancer and received certain chemotherapy drugs and/or radiation therapy have an increased incidence of MDS, as do people with specific genetic syndromes, such as Down syndrome. Exposure to benzene and other toxic substances, especially with smoking can increase the incidence as well.
Many people with MDS do not have any symptoms of their disease, and it is diagnosed when they have a blood test for some other reason. When people do have symptoms, they are usually caused by having a low number of normal blood cells. This can result in paleness, fatigue, easy bruising, feeling weak, frequent infections and shortness of breath or dizziness.
MDS is known as an indolent disorder, meaning that it often evolves very slowly.
Other patients have a history of blood disorders known as cytopenias, or abnormally low numbers of one or more type of blood cell. They may have had infections or transfusions as a result of these problems. Cytopenias can also be caused by other conditions, or by medications that people take, so it is important to evaluate the reasons for these they happen and distinguish them from those other diseases or conditions.
MDS is usually diagnosed by using laboratory tests. These include a complete blood count which provides information on the numbers of each type of blood cell. Doctors also examine a sample of the blood under the microscope to look for abnormal and immature cells, blasts, which are characteristic of MDS. This is called a peripheral blood smear.
The blood cells will also be analyzed to determine if there are any specific genetic mutations or chromosomal abnormalities. This is called cytogenetics or molecular profiling and is an increasingly important part of diagnosing and treating cancers. Blood cells are stored in the bone marrow, the soft, spongy tissue inside of large bones, so it is important to obtain a bone marrow biopsy in diagnosing MDS. Patients with MDS often have large numbers of specific types of immature cells in their bone marrow, for example, the cells that are supposed to develop into platelets. Examining the bone marrow also allows the doctor to identify specific genetic abnormalities that are associated with MDS. This provides one way of distinguishing MDS from other blood disorders and categorizing the type of MDS involved. (Remember MDS is a group of diseases.)
MDS Subtypes: The terms used to describe the subtypes of MDS are very technical and describe specific features of the various blood cells. These terms are explained below. There are seven subtypes of MDS. Knowing the subtype is important to determining the best treatment an assessing the prognosis, as well as the probability that the disease will progress to AML.
Refractory anemia: People with this type have low numbers of red blood cells, anemia. Their white blood cell counts and platelet counts are normal. They have less than 5% blasts, immature cells in their bone marrow, and less than 1% blasts in their peripheral blood smear. This type of MDS usually does not turn into acute myelocytic leukemia. Refractory anemia with ringed sideroblasts: Sideroblasts are deposits of iron seen in red blood cells. If there is a large amount of iron, they are known as ringed sideroblasts. People with this type of MDS have greater than 15% ringed sideroblasts. Refractory cytopenia with multilineage dysplasia: People with this kind of MDS have less than 5% blasts in their bone marrow but have two or more cells lines that are abnormal, such as platelets and red blood cells.
Refractory anemia with excess blasts: People whose bone marrow has between 5-19% blasts have this type of MDS. This group is subdivided by how the number of blasts in the blood.
Refractory anemia with excess blasts in transformation: People with this type of MDS have 21-30% blasts in their bone marrow or 5% or more blasts in their blood. Some classification systems view this as a form of acute myelocytic leukemia.
MDS Unclassified: People who have low blood counts for one more type of blood cell but few or no blasts have unclassified MDS.
5Q Syndrome: People with this type of MDS have anemia, fewer than 5% blasts and a specific genetic abnormality on chromosome 5.
CMML: Chronic myelomonocytic leukemia: This type of leukemia is a mixture of MDS and leukemia. They have blasts which are characteristic of MDS but also have greatly increased numbers of monocytes, a type of white blood cell, which is more characteristic of leukemia.
The major goals of treating MDS are to manage any symptoms of the disease and to decrease the risk that it will progress to acute leukemia. Doctors use a system that assesses the prognosis of each patient in deciding on the best treatment.
This system looks a variety of factors including the percentage of blasts in the bone marrow, the types of blood cells that are affected, the types of genetic or chromosomal abnormalities found. They also take into account the age, the overall health of the patient and whether there is a history of red blood cell transfusions. They use these factors to assign a score that indicates the prognosis for overall survival and the risk that the MDS will progress to AML. This is known as risk stratification.
The risk categories are:
MDS is a chronic disease, one that people live with for years. Helping patients live normal, active lives is a very important part of the treatment for MDS. A large number of patients with MDS are older people who often have other diseases and conditions which can influence the treatment plan. Treatments can include:
Red blood cell transfusions: This is done to treat the anemia that is often a part of MDS, and is a very common component of managing symptoms and treating MDS. Patients who receive many red blood cell transfusions need to be monitored closely for an excessive build up or iron.
Growth Factors: These stimulate the growth of various blood cells. These tend to become less effective the longer they are used with MDS patients so they are often reserved for patients who have low white cell counts and frequent infections that do not respond well to antibiotics.
Low intensity chemotherapy: There are a number of chemotherapy drugs that work well in treating MDS. Some are more appropriate for patients with the lower risk subtypes while others are used for patients who are at high risk of developing acute myeloid leukemia. Many MDS patients receive what is known as low intensity therapy--lower doses of drugs and agents which cause minimal side effects-in combination with biological response modifiers.
Biological response modifiers: These are low intensity agents that work in different ways to stimulate the immune system or promote the growth of healthy blood cells.
High intensity therapy: The goal of high intensity therapy is to change the natural history of the disease--to prevent it from progressing. This is done by using high doses of chemotherapy in the initial treatment, known as induction therapy, and with stem cell transplants. This approach to treatment has the potential for long term, even permanent remissions, but also carries with it a much greater risk to the patient of serious side effects and even death. High intensity therapy and stem cell transplants should only be done in centers with the expertise and experience in treating MDS. Many high intensity protocols are clinical trials. Patients should discuss these options with their treatment teams.
Stem Cell Transplant: Stem cell transplant is the only potential cure for patients with MDS. This involves destroying the patient's diseased bone marrow with high dose chemotherapy and then replacing it with healthy cells from a donor. This is a high risk procedure and is usually only recommended for patients with under 60 years old and have a donor whose blood matches theirs.
AML: When MDS does progress to AML,(MDS-AML). it is often more resistant to standard treatment than AML that begins without a history of MDS (de novo AML). For this reason, it is treated with somewhat different treatment protocols than de novo AML. Patients with advanced MDS or MDS that has progressed to AML should be consider participating in a clinical trial.
Supportive Care: Blood diseases--and their treatment can cause a number of problems. Patients with MDS need good supportive care to address these issues, which can include anemia, infections and the accumulation of excessive iron in the system. Anemia, the result of too few healthy red blood cells, is a significant problem for MDS patients. Recognizing and treating the fatigue and other issues that are caused by anemia is an important part of the overall treatment plan for this disease.
Patients with MDS will need to be monitored very closely for the rest of their lives. This will include all the tests that were done to make the diagnosis. MDS is a complex group of diseases, so it is important that patients receive care in centers that have expertise and experience with treating all aspects of MDS.
MDS is not a one disease, but a group of diseases that happens when stem cells in the bone marrow do not mature normally. This can lead to low numbers of red cells, white cells and platelets which can cause a number of symptoms. MDS is considered to be a form of cancer but in some cases it can also progress to acute myelogenous leukemia. For most patients, it is a chronic disease, one that they live with for a number of years. Managing symptoms and keeping people active is an important goal of treatment. MDS is complicated and should be treated and followed in centers which have experience and expertise in managing all types of MDS. Cancer Bites.