How to Treat Myelodysplastic Syndromes: A Comprehensive Guide to Risk-Based Therapies
Myelodysplastic syndromes (MDS) are a group of diverse bone marrow disorders characterized by ineffective blood cell production and an increased risk of progressing to acute myeloid leukemia. Treatment strategies for MDS are primarily guided by the patient's risk category—classified as lower-risk or higher-risk—based on factors such as chromosomal abnormalities, blood cell counts, and blast percentage in the bone marrow.
Managing Lower-Risk MDS: Supportive Care and Symptom Control
Patients diagnosed with lower-risk MDS often experience chronic cytopenias, including anemia, neutropenia, and thrombocytopenia. The primary goal in this group is to improve quality of life, reduce symptoms, and prevent complications through supportive therapies.
Blood Cell Support and Growth Factors
Erythropoiesis-stimulating agents (ESAs), such as erythropoietin, are commonly used to stimulate red blood cell production and alleviate anemia. This can significantly reduce the need for frequent blood transfusions and improve energy levels and overall well-being. For patients with low white blood cell counts, granulocyte colony-stimulating factor (G-CSF) may be prescribed to boost neutrophil levels and decrease the risk of serious infections.
Transfusion Therapy and Iron Overload Management
When hemoglobin levels fall below 6 g/dL, regular red blood cell transfusions become necessary to manage severe anemia. Similarly, platelet transfusions are recommended when platelet counts drop under 20×10⁹/L to prevent spontaneous bleeding. However, long-term transfusion dependence can lead to iron overload, a condition where excess iron accumulates in vital organs like the liver, heart, and pancreas.
To mitigate this risk, chelation therapy should be initiated when serum ferritin levels exceed 1,000 μg/L. Medications such as deferasirox, deferoxamine, or deferiprone help remove excess iron and reduce the risk of organ damage, including cardiac dysfunction and liver fibrosis.
Treating Higher-Risk MDS: Moving Toward Disease Modification
In contrast, higher-risk MDS is associated with more aggressive disease progression and a greater likelihood of transformation into acute leukemia. Therefore, treatment focuses on altering the disease course and prolonging survival.
Hematopoietic Stem Cell Transplantation: The Only Potential Cure
Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative option for MDS. It involves replacing the patient's diseased bone marrow with healthy stem cells from a matched donor. This approach offers the best chance for long-term remission, with studies showing up to a 50% five-year survival rate in eligible recipients.
However, HSCT is typically reserved for younger, fitter patients—usually those under 60 years of age—who can tolerate the intense conditioning regimens and potential complications such as graft-versus-host disease (GVHD). Older adults or those with significant comorbidities are often not candidates due to higher transplant-related risks.
Alternative Treatments for Non-Transplant Candidates
For patients who are not eligible for stem cell transplantation, several lower-intensity therapeutic options are available. Hypomethylating agents like azacitidine and decitabine are frontline treatments that work by reversing abnormal DNA methylation patterns in cancer cells, helping restore normal gene function and slowing disease progression.
In addition, low-dose chemotherapy regimens may be used to control blood counts and reduce blast proliferation. These approaches aim to extend survival, delay leukemic transformation, and maintain functional independence for as long as possible.
Emerging therapies, including novel targeted drugs and immunomodulatory agents, are also being evaluated in clinical trials, offering hope for improved outcomes across all risk groups in the future.