Myelodysplastic Syndromes (MDS) are a group of bone marrow disorders where the body fails to produce enough healthy, mature blood cells. Often described as a form of blood cancer, MDS is a condition stemming from a defect in the hematopoietic stem cells within the bone marrow. This defect leads to the production of abnormal or “dysplastic” blood cells that either die prematurely or do not function correctly.
The Core Problem: Defective Blood Cell Production
Myelodysplastic Syndromes originate as a clonal disorder of the hematopoietic stem cells, which are the precursors to all mature blood cells. The bone marrow acts as the body’s blood cell factory, but in MDS, this factory becomes dysfunctional due to genetic changes acquired in these stem cells over time. This cellular defect results in a process known as ineffective hematopoiesis, where the bone marrow is often cellularly rich but fails to release sufficient numbers of healthy cells into the bloodstream.
The abnormal development of blood cells is referred to as dysplasia, which can affect the red cell, white cell, and platelet lines. These abnormal cells often undergo programmed cell death, or apoptosis, while still inside the bone marrow, contributing to the low counts seen in the circulation. This results in cytopenia, characterized by low counts of one or more mature blood cell types in the circulation.
MDS is considered a heterogeneous group of disorders, meaning its severity and course vary widely among patients. In some cases, the disease is classified as a pre-leukemia because it carries a risk of progression to an aggressive blood cancer called Acute Myeloid Leukemia (AML). Progression to AML is marked by a significant increase in immature cells, or blasts, which eventually crowd out the remaining healthy blood-forming cells in the marrow.
Recognizing the Symptoms and Confirming Diagnosis
A low red blood cell count causes anemia, which manifests as chronic fatigue, weakness, paleness, and shortness of breath. Similarly, a reduction in functional white blood cells, particularly neutrophils, compromises the immune system, leading to recurrent or severe infections.
A low platelet count, known as thrombocytopenia, impairs the body’s ability to clot blood effectively. This deficiency can result in easy bruising, frequent nosebleeds, or the appearance of small red spots under the skin called petechiae. MDS is sometimes discovered incidentally during a routine medical examination when a complete blood count (CBC) reveals abnormal levels of one or more cell lines.
Diagnosis requires a bone marrow aspiration and biopsy. This procedure allows pathologists to examine the cells for signs of dysplasia, count the percentage of blasts, and rule out other conditions that might cause low blood counts. Cytogenetic testing is also performed on the bone marrow sample to look for specific chromosomal abnormalities, as these genetic changes help classify the disease and predict its potential behavior.
Known Causes and Risk Factors
The development of MDS is usually considered primary or “de novo.” The likelihood of developing MDS increases significantly with age, with most diagnoses occurring in people over the age of 65. This association is partly due to age-related changes and mutations that accumulate in the blood-forming stem cells over a lifetime.
MDS is classified as secondary or treatment-related when it results from previous exposure to cancer therapies. Prior treatment with certain chemotherapy drugs, such as alkylating agents, or high-dose radiation therapy, can damage the bone marrow stem cells and increase the risk of developing MDS later. Exposure to environmental toxins, such as long-term contact with the chemical benzene, has also been linked to a higher risk of the disease.
Managing Myelodysplastic Syndromes
Treatment goals focus on alleviating symptoms, improving quality of life, and slowing the progression of the disease. For low-risk patients with minimal symptoms, a strategy of watchful waiting, involving regular monitoring of blood counts, may be the initial approach.
Supportive care includes red blood cell transfusions to treat severe anemia and platelet transfusions for bleeding issues. Growth factors, such as erythropoiesis-stimulating agents, may also be used to encourage the bone marrow to produce more red blood cells.
For patients with higher-risk disease or those who require frequent transfusions, disease-modifying drug therapies are often employed. These include hypomethylating agents like azacitidine and decitabine, which work by altering gene expression in the faulty stem cells to improve blood cell production. The only potentially curative treatment option for MDS is an allogeneic hematopoietic stem cell transplant, where the patient’s diseased bone marrow is replaced with healthy donor stem cells. This procedure is generally reserved for younger, healthier patients due to the intensity of the treatment.