Myelodysplastic syndromes (MDS) are disorders where the bone marrow fails to produce enough healthy, mature blood cells due to mutations in hematopoietic stem cells. Hypoplastic myelodysplastic syndrome (hMDS) is a specific subtype, accounting for about 10-15% of all MDS cases. Its defining characteristic is a “hypoplastic” or hypocellular bone marrow, which contains significantly fewer cells than is normal for a person’s age.
This lack of cells contrasts with more common forms of MDS where the marrow is often hypercellular, or packed with cells. In those cases, the problem is that the abundant cells are dysfunctional and fail to mature properly. In hMDS, the sparsely populated marrow leads directly to a shortage of red blood cells, white blood cells, and platelets in the bloodstream, which shapes its clinical features.
Symptoms and Diagnosis
The symptoms of hypoplastic MDS are a direct consequence of low blood cell counts, a condition known as cytopenia. A lack of red blood cells leads to anemia, causing persistent fatigue, weakness, shortness of breath, and pale skin. A deficiency in white blood cells, specifically neutrophils (neutropenia), compromises the body’s ability to fight infections, resulting in more frequent illnesses. A low platelet count (thrombocytopenia) impairs blood clotting, leading to easy bruising, petechiae, nosebleeds, and prolonged bleeding from minor cuts.
The diagnostic process often begins when a routine complete blood count (CBC) reveals persistently low levels of one or more blood cell types. These findings prompt a more thorough investigation, with the definitive procedure being a bone marrow aspiration and biopsy. This test involves taking a small sample of liquid marrow and a solid core of marrow tissue from the back of the hip bone.
A pathologist examines the marrow sample to confirm it is hypoplastic, with cellularity often below 25-30%. The pathologist also looks for dysplasia, which is the abnormal development and maturation of the remaining blood-forming cells. The presence of more than 10% dysplastic cells in any major blood cell lineage helps confirm the hMDS diagnosis.
Distinguishing Hypoplastic MDS from Similar Conditions
A significant challenge in diagnosing hMDS is its similarity to another bone marrow failure disorder, aplastic anemia (AA). Both conditions are characterized by a hypocellular bone marrow and resulting cytopenias, which cause nearly identical symptoms. The primary distinguishing feature between hMDS and AA lies in the morphology of the bone marrow cells.
In hMDS, there is clear evidence of dysplasia, meaning the few cells being produced are abnormal in size, shape, or appearance. In contrast, classic aplastic anemia is defined by a hypocellular marrow where the few remaining hematopoietic cells are morphologically normal. This can be compared to a factory that is nearly empty but whose few workers produce faulty goods (hMDS), versus a factory where the few workers still make products correctly (AA).
The presence of significant dysgranulopoiesis (abnormal white blood cells) or dysmegakaryopoiesis (abnormal platelet precursors) strongly favors a diagnosis of hMDS. Genetic testing for specific mutations can further aid in making a precise diagnosis, as certain markers are more common in MDS than in AA.
Treatment Approaches
Treatment for hypoplastic MDS is tailored to the individual, considering their age, overall health, and symptom severity. Because hMDS shares features with aplastic anemia, immunosuppressive therapy (IST) is often a primary treatment. This approach uses drugs such as anti-thymocyte globulin (ATG) and cyclosporine to dampen the immune system’s attack on hematopoietic stem cells, which can allow the bone marrow to recover and produce more cells.
Supportive care is used to manage the day-to-day effects of the disease. Patients with severe anemia frequently receive red blood cell transfusions to alleviate fatigue and improve oxygen delivery. Those with dangerously low platelet counts may receive platelet transfusions to prevent or control bleeding. Growth factors, such as erythropoiesis-stimulating agents (ESAs), may also be used to encourage the bone marrow to produce more of its own red blood cells.
The only potentially curative treatment for hMDS is an allogeneic stem cell transplant. This procedure involves replacing the patient’s diseased bone marrow with healthy hematopoietic stem cells from a matched donor. The goal is to establish a new, healthy blood-forming system. Due to significant risks, such as graft-versus-host disease, this option is generally reserved for younger, medically fit patients who have a suitable donor.
Prognosis and Disease Management
The long-term outlook for individuals with hMDS is variable and depends on factors like age, overall health, the severity of cytopenias, and specific genetic mutations. To help predict the disease course, hematologists use risk stratification tools like the International Prognostic Scoring System (IPSS-R). These systems assign points based on factors like bone marrow blast percentage and chromosomal analysis to categorize patients into different risk groups.
Hypoplastic MDS is a chronic condition that requires ongoing management and monitoring. Regular follow-up appointments with a hematologist are standard to track blood counts and watch for signs of disease progression. Patients who receive frequent red blood cell transfusions may develop iron overload, which may require treatment with iron chelation therapy to remove it.
Management focuses on maintaining quality of life by controlling symptoms, reducing the risk of infection and bleeding, and delaying or preventing the potential transformation to acute myeloid leukemia (AML). This is achieved through a combination of supportive care, periodic treatments, and careful monitoring.