NORD gratefully acknowledges John Barrett, MD, NIH National Heart, Lung, and Blood Institute, for assistance in the preparation of this report.
Myelodysplastic syndromes (MDS) are a rare group of blood disorders that occur as a result of disordered development of blood cells within the bone marrow. The three main types of blood elements (i.e., red blood cells, white blood cells and platelets) are affected. Red blood cells deliver oxygen to the body and remove carbon dioxide, white blood cells help fight infections, and platelets assist in clotting to stop blood loss. In MDS dysfunctional blood cells fail to develop normally and enter the bloodstream. As a result, individuals with MDS have abnormally low blood cell levels (low blood counts). General symptoms associated with MDS include fatigue, dizziness, weakness, bruising and bleeding, frequent infections, and headaches. In some cases, MDS may progress to life-threatening failure of the bone marrow or develop into an acute leukemia. The exact cause of MDS is unknown. There are no clear risk factors but genetics and the environment may play a part. Myelodysplastic syndromes were first noted in the medical literature in 1930s where they were described as pre-leukemic conditions. Myelodysplastic syndromes were not regarded as separate, distinct disorders until 1976. In the past, these disorders have also been known by a variety of names including refractory anemia, oligoblastic anemia, myelodysplastic anemia, pre-leukemia, and smoldering leukemia.
The symptoms of MDS occur because the bone marrow fails to produce enough functioning blood cells. The specific symptoms and progression of the disorder vary greatly from case to case. Some individuals may have mild symptoms that remain stable for many years; others may rapidly develop serious symptoms that can progress to life-threatening complications.
The bone marrow, occupies the spongy center of large bones of the body. Blood cells, produced in the red marrow, are released into the bloodstream to travel throughout the body performing their specific functions. In individuals with MDS, the bone marrow develops immature or defective versions of red cells white cells and platelets some of which are are destroyed within the bone marrow. In the process, healthy marrow cells are progressively eliminated. The consequence is a lack of healthy blood cells in the bloodstream and a reduced supply of MDS blood cells, causing symptoms associated with MDS.
The most common symptom in individuals with MDS is anemia due to low levels of circulating red blood cells. Anemia causes tiredness, increased need for sleep, weakness, lightheadedness, dizziness, irritability, palpitations, headaches, and pale skin color. Low levels of white blood cells (neutropenia) increase the risk of contracting bacterial and fungal infections. Low levels of platelets (thrombocytopenia) makes the individual more susceptible to excessive bruising following minimal injury and spontaneous bleeding from the gums and nose. Women may develop increased menstrual blood loss. Bleeding may also occur in the digestive tube causing blood loss in the stools. Sometimes the bleeding occurs as a scattered red rash chiefly on the limbs–so-called petechial hemorrhages.
MDS has a tendency to get worse with time as the normal bone marrow function dwindles. The pace of progression varies. In some individuals the condition worsens within a few months of diagnosis, while others have relatively little problem for several decades. In about 50 percent of cases, MDS deteriorates into a form of cancer known as acute myeloid leukemia (AML). The transition to leukemia is accompanied by worsening marrow function and the accumulation, first in the marrow and subsequently in the blood, of undeveloped immature cells called blasts which have no useful function and suppress any remaining marrow cell production. As a consequence, the complications from anemia, bleeding, and infection become life-threatening. Because some cases of MDS may progress into leukemia, myelodysplastic syndromes have also been known as pre-leukemia and smoldering leukemia. Patients who do not progress to leukemia may experience a gradual fall-off in marrow function leading to worsening anemia bleeding and infection which despite transfusions of red cells and platelets and antibiotics to treat infection can ultimately be fatal.
MDS is sub-classified according to the type and number of blasts in the bone marrow. A group of French, American and British hematologists created the so-called FAB classification. This classification describes five MDS subtypes: refractory anemia; refractory anemia with sideroblasts; refractory anemia with excess blasts; refractory anemia with excess blasts in transformation; and chronic myelomonocytic leukemia. The first two types are the most common forms of myelodysplastic syndromes and are also the most stable.
The World Health Organization (WHO) released its own classification system for MDS that modifies the FAB classification system. The new system has not been universally accepted because of several controversial issues. For more information on the WHO system, contact the World Health Organization listed in the Resources section below.
When the cause of MDS is unknown it is called idiopathic MDS. A so-called secondary MDS can develop after chemotherapy and radiation treatment for cancer or autoimmune diseases It is possible that some chemicals (pesticides and benzene), cigarette smoking, and possibly viral infections can predispose to MDS. However, these links are circumstantial and in the majority of individuals developing MDS no obvious connection with environmental hazards can be found. MDS sometimes runs in families, suggesting a genetic link with the disease, but apart from an association with a rare congenital form of anemia (Fanconi aplastic anemia), no definite MDS provoking gene has been found.
Myelodysplastic syndromes affect males slightly more often than females. The disorder occurs in any age group, but is far more common in older adults, occurring most often in individuals over 60 years of age. According to one estimate, 22 to 45 per 100,000 people over the age of 70 years have MDS. Approximately 20,000 new cases are diagnosed each year in the United States. The number of new cases diagnosed each year is increasing, possibly due to better recognition of the disorder combined with an increasing proportion of elderly adults in the general population. Determining the exact frequency of MDS in the general population is difficult because of the lack of a standard classification system or specific diagnostic criteria.
A diagnosis of myelodysplastic syndrome is made based upon a thorough clinical evaluation, a detailed patient history, and a variety of specialized tests including complete blood counts, examination of the blood smear (often more than one is needed), and bone marrow aspiration and biopsy. A complete blood count measures the number of red and white blood cells and platelets in the body. The blood smear and the small sample of bone marrow removed via a needle (the aspirate) is examined under a microscope for the characteristic features of MDS.
Treatment varies, depending upon the individual's age, general health, and type of myelodysplastic syndrome. The first aim of treatment is supportive care – giving red cell transfusions to correct anemia, platelet transfusions to treat or prevent serious bleeding, and antibiotics to treat or prevent infections.
A consequence of multiple red cell transfusions of red cells is the accumulation of iron derived from red cell hemoglobin being broken down in the body. Too much build-up of iron can lead to numerous complications which can be avoided by treatment with drugs that bind the iron and eliminate it from the body. In 2005, the drug desferasirox (Exjade) given in tablet form was approved by the FDA for marketing for the treatment of some MDS individuals who have been transfused for many years and have dangerous build-up of iron in the body. For information on this drug, contact Novartis Pharmaceuticals Corporation. http://www.us.novartis.com/
Further treatment aims, where possible, to correct the bone marrow failure. The marrow failure in some patients responds to immunosuppressive treatment with an agent called antithymocyte globulin (ATG). This can sometimes restore the blood count to normal sometimes indefinitely and can be repeated if relapses occur. The same treatment is used with success to treat aplastic anemia. Younger female patients with the refractory anemia MDS subtype respond best to ATG.
Growth factors are substances normally found in the body that control production of blood cells. They include granulocyte-colony stimulating factor (filgrastim G-CSF [Leukine]) and erythropoietin (Procrit or Epogen). These growth factors stimulate the production of red cells and white cells (but not platelets) in MDS. Given by daily to weekly injection, according to blood count severity, these marrow stimulators can be very helpful in some patients.
Replacement of the MDS bone marrow with that of a healthy donor is the only curative treatment for MDS. Patients who are relatively fit even into their 70s, may be suitable for a bone marrow stem cell transplant from a healthy related donor or an unrelated volunteer. Although SCT can cure MDS this success is offset by the mortality from the transplant. SCT is therefore only performed in selected patients and in specialized centers. Many centers throughout the United States perform marrow stem cell transplants for MDS. For more information, contact the International Bone Marrow Transplant Registry (IBMTR) in Milwaukee (see Resources section).
In the bone marrow immature cells known as stem cells and myeloblast. develop through cell divisions into the mature healthy cells that populate the bloodstream, a process known as differentiation. In MDS the marrow cells fail to differentiate normally. Differentiating agents (including interferons, synthetic derivatives of vitamin A [retinoids], vitamin D compounds, 5-azacytidine, thalidomide, and decitabine) may correct the problem and improve blood cell production in MDS. Clinical studies are being conducted to study the effectiveness of these agents, either alone or in conjunction with one another. The most promising of these agents 5-azacytidine (Vidaza) was approved In 2004 by the FDA for treatment of MDS. This drug can retard progression of MDS and prolong survival but it causes a temporary drop in blood counts during the treatment period requiring dose adjustments, Vidaza, distributed by Celgene, is the first approved drug therapy for MDS. For information, Contact Celgene Corporation Website: www.celgene.com
In 2005, the U.S. Food and Drug Administration (FDA) approved the drug lenalidomide (Revlimid) for the treatment of patients with a subtype of myelodysplastic syndrome. The subtype is MDS patients with deletion 5q cytogenetic abnormality. Revlimid is structurally similar to thalidomide a drug known to cause severe birth defects. Additional studies are ongoing in animals to address whether there is a risk that Revlimid will also cause birth defects when taken during pregnancy. While these studies are underway, Revlimid is being marketed under a risk management plan called RevAssist, designed to prevent fetal exposure. Under RevAssist, only pharmacists and prescribers registered with the program will prescribe and dispense Revlimid. Revlimid is distributed by Celgene Corporation. For information, contact: Celgene Corporation Website: www.celgene.com
Many studies are currently being conducted to develop better treatments for MDS. Information on current clinical trials is posted on the Internet at www.clinicaltrials.org. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.
For information about clinical trials being conducted at the National Institutes of Health (NIH) Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder.
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