When the bone marrow does not produce enough blood cells
Myelodysplastic syndromes (MDS) are a group of conditions in which the bone marrow does not properly produce enough blood cells. Normally the bone marrow produces three major types of blood cells:
- red blood cells (carry oxygen)
- white blood cells (help fight infection)
- platelets (help stop bleeding)
MDS occurs when the bone marrow cells do not mature into healthy blood cells. Normal blood cells are made in an orderly process from immature “stem cells” in the bone marrow (the spongy, red tissue that fills large bones). In MDS, damaged bone marrow stem cells give rise to clones (multiple copies) of abnormal blood cells that cause low blood cell counts. The cells in the blood and bone marrow look dysplastic (abnormal). As the abnormal blood cells in MDS are clonal, it is considered a type of slowly growing cancer of bone marrow cells.
MDS becomes more common with advancing age. The average age of diagnosis is 68 years and tends to occur more frequently in males. MDS is one of the most common causes of low blood counts among the elderly and patients with pre-existing bone marrow injury, such as from prior chemotherapy for other cancers. There are approximately 10,000 cases diagnosed annually in the United States. Risk for development of MDS has been linked to the following: smoking, benzene, organic chemicals, heavy metals, herbicides, pesticides, fertilizers, and petroleum and diesel containing substances. However, in most cases, the cause of MDS is unknown. It is likely related to the gradual accumulation of mutations in bone marrow stem cells associated with aging. In general, it is not an inherited malignancy that can be passed down to future generations; although there are rare inherited genetic syndromes associated with MDS.
Some people have no symptoms when they are diagnosed with MDS. Others may have symptoms related to low blood cell counts. Anemia (low red cell count) is the most common cause of symptoms in patients with MDS. Red blood cells carry oxygen to tissues, and as a result, patients with anemia may be pale, tired, short of breath, dizzy, or have chest pain. Patients with low platelet counts may experience bleeding, such as spontaneous bruising, as platelets help blood to clot normally. Patients with low white bloods cells, especially neutrophils, a specific type of white blood cell that helps fight infections, may be more likely to have recurrent infections. Other symptoms may include fever and weight loss.
The diagnosis of MDS requires laboratory testing, which includes a complete blood count (CBC), which shows the number of red blood cells, white blood cells, and platelets. Other tools for diagnosis include a review of a blood smear preparation under the microscope, to look at the blood cells and evaluate their characteristics (number, size, shape, maturity) and whether they look normal or abnormal (dysplastic). Final diagnosis of MDS involves examination of the bone marrow itself, which produces the blood cells of the body. A small sample of bone marrow, usually from the hip/pelvic bone, is taken and examined under the microscope for abnormal appearing cells and for increased numbers of immature cells. It is also tested for abnormal chromosomes/certain genes of the bone marrow stem cells. Based on the review of the bone marrow biopsy by a pathologist (physician who diagnoses disease based on examining tissue specimens), a diagnosis of MDS can be made.
MDS is a form of bone marrow/blood cancer with varying degrees of severity, need for treatment and life expectancy. MDS is categorized into different groups by The World Health Organization (WHO) based on blood cell counts, the percentage of immature bone marrow blast cells, and chromosome (genetic) abnormalities of the bone marrow stem cells. These categories have prognostic significance. Some patients with MDS live for years with little or no treatment. For other patients, MDS may evolve into acute myeloid leukemia (AML), and life expectancy without successful treatment is only one to two years.
The clinical severity of MDS can be classified using the revised International Prognostic Scoring System (IPSS-R). The IPSS-R score is based on the percentage of immature blasts in the bone marrow, the number and types of blood cell lines that are low, and types of chromosomes of the bone marrow cells. Based on these criteria, there are five risk groups: very low, low, intermediate, high, and very high.
Treatment recommendations are based on a patients’ risk group as discussed above. A person with low risk MDS may live for many years before needing treatment, while a patient with high risk MDS usually needs more immediate treatment.
Several treatments can prolong survival, improve quality of life, control symptoms, and prevent complications. Treatment choices are determined by the person’s age, performance status (level of function in normal everyday tasks), and disease characteristics (IPSS-R score). Currently, the only way to cure MDS is with a bone marrow transplantation.
Supportive therapy involves blood transfusions for anemia when symptoms develop. If the transfusions are needed at least every 1-2 months a trial of vitamins or other medications may be added. Platelet transfusions can also be given when the platelet count falls below 10,000 or if there is bleeding or an upcoming surgery is required. Antibiotics can be given for treatment of bacterial infections. Vaccinations, such as the yearly influenza vaccine and pneumococcal vaccines are given to prevent infections. Sometimes hematopoietic growth factors can be given in an attempt to increase a patient’s red blood cell counts (Epoetin, EPO, Procrit, darbepoetin) and/or white blood cell counts (G-CSF, granulocyte colony-stimulating factor).
Low intensity chemotherapy can be used as well. These treatments are less likely to produce serious side effects and usually do not require hospital admission. People with lower risk MDS are generally treated with low intensity therapy or supportive care alone. Examples of low intensity chemotherapy include azacitidine, decitabine, and lenalidomide. Lenalidomide is particularly effective for patients with anemia and lower risk MDS with abnormalities of chromosome 5 (called “5q minus syndrome").
High intensity therapies include combination chemotherapy with multiple drugs (similar to that used for acute leukemia) and hematopoietic stem cell transplantation. Allogeneic (from another person) stem cell transplantation is the only hope for cure in a small subset of patients. However, these treatments have a higher chance of side effects and frequently require hospitalization. For some patients with high risk MDS, such as those less than 70 years old and otherwise healthy, the increased chance of effectiveness may outweigh the increased risk of these treatments. Transplant is not suggested for people with lower risk MDS. Although there is a significant chance of cure (approximately 60%), transplant-related death and relapse rate at five years are also high (approximately 40%).
There is great interest in clinical trials for MDS because none of the current treatment approaches is completely satisfactory. Ask your doctor for more information.
Learn more about MDS Clinical Trials
How the IHTC can help you
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- The Washington Manual, Subspecialty Consult Series: Hematology and Oncology Subspecialty Consult; Lippincott, Williams, & Wilkins, 2004.
- Bethesda, Handbook of Clinical Hematology; Rodgers, Griffin, Young, Neal, 2005.
- Disorders of Hemostasis & Thrombosis, Second Edition; Goodnight, Scott, Jr., Hathaway, William, 2001.
- The Myelodysplastic Syndromes: A Review for Patients, Families, Friends, and Healthcare Professionals; Bennett, M.D., University of Rochester Cancer Center, http://www.mds-foundation.org
- Patient education: Myelodysplastic syndromes (MDS) in adults (Beyond the Basics). https://www.uptodate.com/contents/myelodysplastic-syndromes-mds-the-basics?search=MDS&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1. UpToDate, 2018.