Myelodysplastic syndromes
Myelodysplastic syndromes (MDS) are a group of disorders characterized by ineffective production of blood cells due to abnormalities in the bone marrow. In MDS, the bone marrow produces an overabundance of abnormal stem cell clones, which leads to a decrease in normal red blood cells, white blood cells, and platelets. There are seven subtypes of MDS, categorized as either primary or secondary, with primary forms accounting for approximately 80% of cases. The risk of developing MDS is higher in males, individuals over 60, and those with certain genetic predispositions or environmental exposures, such as radiation and specific chemicals. Symptoms may not appear in the early stages but can progress to fatigue, frequent infections, and easy bruising as the disease advances. Diagnosis involves a thorough medical history, physical examination, blood tests, and possibly a bone marrow biopsy. Treatment varies based on individual circumstances and may include blood transfusions, growth factors, chemotherapy, and potentially stem cell or bone marrow transplants. Preventative measures focus on lifestyle changes to reduce exposure to harmful substances and maintain overall health.
Myelodysplastic syndromes
ALSO KNOWN AS: MDS; myelodysplasia; preleukemia; smoldering leukemia; subacute leukemia
DEFINITION Myelodysplastic syndromes (MDS) are a group of diseases that involve dysfunction of the bone marrow. Bone marrow is the tissue found within the bones; its task is to create mature blood cells from stem cells. In all forms of MDS, this normal process of cell creation is disrupted by the overproduction of clones of a single stem cell. This leads to a decrease in production of normal red blood cells, white blood cells, and platelets.
There are seven subtypes of MDS, which is also classified as primary or secondary MDS. About 80 percent of cases are primary. Some forms are more serious than others; all of them are serious enough to require a physician’s care. About one-third of people with MDS develop acute myeloid leukemia (AML), according to the American Cancer Society. Leukemia is a cancer of the white blood cells and their parent cells. Many blood disease experts consider MDS to be a type of cancer.
Risk Factors
Individuals who have family members with MDS or Fanconi anemia (a rare type of anemia) have a higher risk for developing myelodysplastic syndromes. Males, individuals who are sixty years of age or older, and individuals who have Down syndrome are also at risk. Additional risk factors include exposure to large amounts of radiation; exposure to certain chemicals, such as benzene; exposure to pesticides; radiation therapy and/or chemotherapy treatment for cancer; and smoking. According to 2022 statistics from the National Cancer Institute, about 10,000 people in the United States were diagnosed with MDS annually.
Etiology and Genetics
Myelodysplastic syndromes are heterogeneous disorders with contributing factors that can be both genetic and environmental. The more common adult-onset forms are sometimes correlated with mutations in either the TP53 gene (at position 17p13.1), but in many cases no genetic determinants can be identified. One study suggests that mutations in the RUNX1 gene, located on the long arm of chromosome 21 at position 21q22.3, are often associated with myelodysplastic syndromes that are likely to develop into acute myeloid leukemia. Cytogenetic abnormalities (deletions, translocations, or missing chromosomes) are often noted in bone marrow cells, but these are always somatic mutations and are not heritable. In particular, deletions of part or all of chromosome 7 are frequently observed, as well as deletions of part of the long arm of chromosome 5. A involving the NUP98 gene (at position 11p15) and the HOXD13 gene (at position 2q31-q32) has been reported in several patients, and an effective preclinical system has been developed in mice to study this gene fusion.
The juvenile forms of myelodysplastic syndromes are rare, and the molecular and genetic mechanisms responsible for the early onset of the disease are not well understood. Mutations in the TP53 gene are not generally observed, and cytogenetic abnormalities of blood stem cells appear to be more widespread. One study suggests that as many as 30 percent of children with the juvenile form of the disease will have a deletion of part or all of chromosome 7.
Symptoms
Typically, there are no symptoms in the early stages of MDS. Later-stage symptoms may vary from person to person, depending on how serious the disease is. Later-stage symptoms may include signs of anemia due to underproduction of red blood cells; these signs may include fatigue, shortness of breath, pale skin, feeling weak and tired, and congestive heart failure (in severe cases).
Neutropenia occurs when there are inadequate levels of white blood cells. White blood cells fight infection. Signs of this condition include fever, cough, and frequent, unusual, or especially serious infections.
Thrombocytopenia occurs when there are inadequate levels of platelets in the blood. Platelets stop bleeding by clotting the blood. Signs of thrombocytopenia include bruising easily and bleeding easily, especially from the nose and gums.
Screening and Diagnosis
The doctor will ask about a patient’s symptoms and medical history and will perform a physical exam. The symptoms for MDS can indicate many other conditions. Doctors have to rule out other conditions before diagnosing MDS.
Tests may include a blood test to check a patient’s red and white blood cell counts and platelet counts and to check how the blood cells look. A bone marrow biopsy—the removal of a sample of bone marrow for testing—can also check for MDS. The doctor may also order additional tests to rule out other conditions.
Treatment and Therapy
Treatment for MDS depends on the patient’s age, other medical conditions, and the seriousness of the disease. Treatment also depends on how far along the disease has progressed to AML. Often, treatment includes relieving the symptoms of MDS.
Patients should talk with their doctors about the best plans for them. Patients may be referred to a hematologist and an oncologist. A hematologist specializes in blood diseases; an oncologist specializes in cancer.
Treatment options include blood transfusions for patients with low red blood cell, white blood cell, or platelet counts. A blood transfusion involves receiving blood products (red cells, white cells, platelets, clotting factors, plasma, or whole blood) through a vein. The blood components may come from an unrelated donor or from a related donor, or may have been banked in advance by the recipient.
Patients with a low white blood cell count may receive antibiotics to fight infection. Another treatment option is the use of growth factors, which can help the bone marrow produce blood cells. Erythropoietin (EPO) is a growth factor that helps the bone marrow produce red blood cells; granulocyte colony-stimulating factors (G-CSF) and granulocyte macrophage colony-stimulating factors (GM-CSF) are growth factors that help the bone marrow produce white blood cells.
Chemotherapy is the use of drugs to kill cancer cells. Chemotherapy may be given in many forms, including pill, injection, or via a catheter. The drugs enter the bloodstream and travel through the body, killing mostly cancer cells. Some healthy cells are also killed. Many patients receive immunotherapy after chemotherapy. A type of immunotherapy to treat MDS is antithymocyte globulin, or ATGAM. Researchers are working to develop other forms of immunotherapy as well, notably in the area of monoclonal antibodies.
A stem cell transplant is another treatment option. Many doctors will perform a stem cell transplant only on a patient who is age fifty or younger. A stem cell transplant is a procedure in which healthy stem cells from a donor’s blood are injected into a recipient’s vein.
Another possible treatment is a bone marrow transplant. Many doctors will perform a bone marrow transplant only on a patient who is age fifty or younger. A bone marrow transplant is a procedure in which healthy stem cells from a donor’s bone marrow are injected into a recipient’s vein.
Prevention and Outcomes
To help reduce their chances of getting MDS, individuals should avoid exposure to hazardous chemicals, such as benzene. They should not smoke; if they smoke, they should quit. Individuals should also reduce their risks for developing cancer by eating a balanced, healthy diet; staying active; maintaining a healthy weight; and avoiding environmental and occupational risks.
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