Introduction
The myelodsyplastic syndromes, commonly referred to as ‘MDS ’, are a diverse group of bone marrow disorders characterized by abnormal blood cell growth. MDS may be considered cancerous because these disorders are clonal, meaning that all cells arise from a common parental cell.
Unlike other blood cancers, MDS is not typically characterized by a complete failure to produce functional blood cells. While MDS may behave differently depending on the subtype, all cases of MDS have dysplasia and ineffective hematopoiesis. Dysplasia occurs when cells have an abnormal appearance when examined under a microscope due to disrupted maturation of blood cells. Ineffective hematopoiesis results when the bone marrow fails to produce sufficient numbers of mature white blood cells (WBCs), red blood cells (RBC), and platelets.
While the course of MDS varies based on subtype and the individual, MDS can develop into a more aggressive type of blood cancer called acute myeloid leukemia (AML). Both MDS and AML are characterized by a reduced number of mature cell types in the peripheral blood known as cytopenia. A hematologist, a physician who specializes in blood disorders, treats both conditions.
Cause
The etiology of MDS is unknown and remains an active area of research. However, it is known that MDS results when there are changes in the DNA of a gene, known as a mutation, in a hematopoietic stem cell. Hematopoietic stem cells live in the bone marrow, never lose the ability to divide, and give rise to mature blood cells.
It is thought that MDS arises from a genetic transformation event of a hematopoietic stem cell by a series of acquired genetic mutations. As described earlier, MDS is clonal in nature, meaning that all the affected blood cells ultimately arise from the same transformed stem cell.
There are a number of known risk factors associated with MDS with the most important factor being advanced age. The median age at diagnosis in the United States is 70 years, with men more frequently affected than women. Environmental factors such as exposure to benzene, prior chemotherapy, or radiation therapy are also associated with increased risk for developing MDS. In most patients with MDS, the only risk factor is age.
Symptoms and signs
Signs and symptoms of MDS are driven by abnormal levels of certain blood cells. Anemia is the most common presenting symptom and is caused by a low RBC count. Patients with anemia typically experience fatigue, shortness of breath, and weakness. Anemia can be asymptomatic and is only discovered as part of blood work done for another reason.
Another feature of MDS is a low platelet count, also known as thrombocytopenia. The function of platelets is to stop bleeding. The platelets in the blood are already abnormal in MDS due to ineffective hematopoiesis as discussed above; therefore, MDS may be detected because of bleeding resulting from thrombocytopenia and/or dysfunctional platelets. Thrombocytopenia can be asymptomatic and discovered only as part of blood work done for another reason.
WBCs can be low in MDS. When WBC counts are low, it is referred to as leukopenia. Leukopenia occurs less frequently than anemia or thrombocytopenia. However, patients with MDS always present with neutropenia, a deficiency of a specific type of WBC that serves as the primary defense against bacterial and certain fungal infections.
Because of ineffective hematopoiesis, neutropenia, and leukopenia, patients with MDS are prone to recurrent or atypical infections even when the WBC count is normal. As with anemia or thrombocytopenia, leukopenia can be asymptomatic and only come to attention when blood work is done for another reason.
Most common MDS symptoms:
| •. | Fatigue | ||||
| •. | Shortness of breath | ||||
| •. | Weakness | ||||
| •. | Unusual bruising | ||||
| •. | Excessive bleeding | ||||
Tests
The most important tests for diagnosing MDS include a complete blood count (CBC), a peripheral blood smear, and a bone marrow biopsy. A CBC quantifies the amount of WBCs, platelets, and RBCs in the blood. If the history, physical, and the peripheral blood smear are suggestive of MDS, a bone marrow biopsy is performed.
To perform a bone marrow biopsy, a physician inserts a special hollow needle into a patient's pelvic bone while the patient lays on his/her stomach. The hollow needle is used to pull or suck out a sample of bone marrow, called the aspirate. The needle is then used to remove a small piece of bone, the biopsy. A bone marrow biopsy is required for a diagnosis of MDS.
The bone marrow biopsy in MDS typically reveals an increased number of cells with an abnormal appearance. An increased number of cells in the marrow, accompanied by a decreased number of cells in the peripheral blood are indicators of ineffective hematopoiesis. Genetic analysis may also be conducted on a bone marrow sample in order to detect changes to chromosomes and genetic mutations. Specific chromosomal changes and genetic mutations may provide prognostic and treatment information. Analysis of chromosomes may provide more information on how aggressive the subtype of MDS will be.
Treatment options
Given the heterogeneity of MDS, treatments are typically tailored to the individual patient based on the perceived risk and subtype. Other factors that may be considered during treatment include patient age, functional status, comorbid conditions, genetic and chromosome analysis, the risk of MDS progressing to AML, and patient preference.
As previously discussed, some cases of MDS follow a more benign and indolent course. In these situations, MDS should only be treated when symptoms can be attributed to MDS or when cytopenias are severe.
When treatment for MDS is indicated, there are a number of options including transfusions of blood products, growth factors (medicines that stimulate hematopoiesis), chemotherapy, clinical trials, medications, or transplantation.
MDS is generally not a curable condition; the only curative therapy is allogeneic stem cell transplantation. In allogeneic transplantation, hematopoietic stem cells from another individual are infused into the patient. The goal is for the transplanted stem cells to undergo normal hematopoiesis and also clear the remaining MDS cells. However, not all patients with MDS should be treated with a transplant as the risks may outweigh the benefits.
Additional resources
Myelodsyplastic Syndromes Foundation – http://www.mds-foundation.org