Myelodysplastic Syndromes (MDS)

Myelodysplastic syndromes, also known as myelodysplastic neoplasms (MDS), are a group of myeloid cancers that arise from blood-forming stem cells.

Normally, stem cells in the bone marrow mature into red blood cells, white blood cells, and platelets. In MDS, abnormal stem cells do not develop normally, leading to ineffective blood cell production and low levels of one or more types of blood cells.

As a result, patients may develop anemia, an increased risk of infection, or problems with bruising and bleeding.

MDS is not a single disease. Its biological features and clinical course can vary considerably. Some patients have lower-risk disease that remains stable for years, while others have higher-risk disease that may progress more quickly and can develop into acute myeloid leukemia (AML).

MDS develops through chromosomal, genetic, and other molecular changes in blood-forming stem cells. These changes interfere with normal blood cell development and allow abnormal cell clones to gradually build up in the bone marrow.

In many patients, no specific cause can be identified. Factors that may be associated with MDS include:

• Previous treatment with certain types of chemotherapy or radiation therapy

• Significant or long-term exposure to harmful chemicals such as benzene

• Older age

• In a small number of patients, inherited genetic conditions that increase the risk of myeloid cancers

Myeloid cancers that develop after certain chemotherapy or radiation treatments are evaluated in the context of the previous treatment and the biological features of the disease.

Having a risk factor does not mean that someone will develop MDS, and many people diagnosed with MDS have no identifiable cause.

MDS may cause no noticeable symptoms in its early stages. Some people are diagnosed after routine blood tests show low blood cell counts.

Symptoms depend largely on which types of blood cells are affected and how low the counts become.

Low Red Blood Cell Counts

Anemia is one of the most common features of MDS and may cause: Ongoing fatigue or weakness, Pale skin, Shortness of breath, Heart palpitations, Dizziness.

Low White Blood Cell Counts

A low level of infection-fighting neutrophils may lead to: An increased risk of infection, Recurrent infections, Fever or other signs of infection.

Low Platelet Counts

A low platelet count may cause: Easy bruising, Nosebleeds or bleeding gums, Tiny red or purple spots under the skin, Prolonged bleeding from cuts or injuries.

Low blood cell counts alone are not enough to diagnose MDS. Anemia, low white blood cell counts, and low platelet counts can also be caused by infections, nutritional deficiencies, medications, immune disorders, and other blood conditions.

Diagnosis of MDS usually involves a combination of blood tests, bone marrow evaluation, chromosomal testing, and molecular genetic testing.

These tests help confirm the diagnosis, determine the type and risk of MDS, and guide treatment decisions.

Blood Tests

A complete blood count (CBC) measures red blood cells, white blood cells, platelets, hemoglobin, and other blood cell parameters.

A peripheral blood smear allows blood cells to be examined for abnormalities in size, shape, and maturity and can show whether abnormal or immature cells are present.

Additional tests may be performed to rule out vitamin B12 or folate deficiency and other conditions that can cause low blood cell counts.

Bone Marrow Tests

Bone marrow aspiration and biopsy are important tests for diagnosing MDS.

Bone marrow fluid and tissue are usually collected from the pelvic bone and examined to evaluate the number, appearance, and maturity of blood-forming cells, including the percentage of blast cells.

These findings help confirm and classify MDS and assess the risk of disease progression.

Cytogenetic Testing

Abnormal blood-forming cells in MDS may have changes in the number or structure of chromosomes.

Karyotyping, FISH, and related tests can identify chromosomal abnormalities that may be important for diagnosis, risk assessment, and treatment decisions, such as deletion of part of chromosome 5 [del(5q)].

Genetic and Molecular Testing

Genetic and molecular testing has become increasingly important for classifying MDS, assessing risk, and selecting treatment.

MDS may involve changes in genes such as SF3B1 and TP53. Some genetic abnormalities are now incorporated into modern disease classification and may influence risk assessment and treatment decisions.

Risk Assessment

Unlike many cancers that are described mainly as “early” or “advanced,” MDS is often evaluated using risk categories.

Healthcare teams consider factors such as the percentage of blasts in the bone marrow, the severity of low blood cell counts, chromosomal abnormalities, and gene mutations to estimate the risk of disease progression and transformation to AML.

Risk assessment systems include the IPSS-R and the newer IPSS-M, which incorporates additional molecular genetic information.

Risk level plays an important role in treatment planning. In general, treatment for lower-risk MDS focuses on improving blood cell counts, reducing transfusion needs, and maintaining quality of life, while treatment for higher-risk MDS focuses more on controlling the abnormal cell clone, delaying disease progression, and evaluating whether allogeneic stem cell transplantation may be appropriate.

Treatment for MDS depends on disease risk, low blood cell counts, symptoms, chromosomal and genetic abnormalities, age, overall health, and individual treatment goals.

Treatment can vary considerably. Some people with lower-risk MDS may initially be monitored or receive supportive care, while others need treatment for anemia or other low blood cell counts. Patients with higher-risk disease may need more intensive disease-directed therapy and evaluation for allogeneic stem cell transplantation.

Active Monitoring

Some patients with lower-risk MDS who have no significant symptoms and relatively stable blood cell counts may not need immediate disease-directed treatment.

Regular blood tests and clinical evaluations are used to monitor the disease. Treatment can be started if blood counts worsen, significant symptoms develop, or the risk profile changes.

Supportive Care

Supportive care is an important part of MDS management and focuses on reducing symptoms and complications caused by low blood cell counts.

Depending on the individual situation, supportive care may include:

• Red blood cell transfusions for symptomatic anemia

• Platelet transfusions for selected patients with severe thrombocytopenia or significant bleeding risk

• Prevention and treatment of infections in patients with severe neutropenia or active infection

Some patients who receive frequent red blood cell transfusions over a long period may develop iron overload and may need additional evaluation or treatment.

Treatments for Anemia

For some patients with lower-risk MDS in whom anemia is the main concern, treatment may be selected based on factors such as serum erythropoietin levels, transfusion needs, and disease characteristics.

Erythropoiesis-stimulating agents (ESAs) can help some patients increase red blood cell production, improve anemia, and reduce the need for transfusions.

Other treatments for anemia are also available for selected types of MDS, depending on disease characteristics, previous treatment, and eligibility.

Treatment Based on Specific Disease Features

As MDS classification becomes more precise, treatment can sometimes be selected according to specific genetic or disease features.

For example, lenalidomide may be considered for selected patients with lower-risk MDS and del(5q).

Other therapies may also be available for patients with particular molecular or clinical features. For this reason, chromosomal and molecular testing may directly influence treatment decisions as well as diagnosis.

Hypomethylating Agents

Hypomethylating agents such as azacitidine and decitabine are important disease-directed treatments for MDS.

They are commonly used for some patients with higher-risk MDS and may also be used in other situations where disease-directed treatment is needed.

The goals may include controlling the abnormal blood-forming cell clone, improving blood counts, and delaying disease progression. Treatment decisions depend on disease risk, age, overall health, and whether stem cell transplantation is planned.

Immunosuppressive Therapy

Immunosuppressive therapy may be considered for a small group of patients with particular clinical and bone marrow characteristics.

This approach is not appropriate for everyone with MDS and is selected based on factors such as age, bone marrow features, disease risk, and other clinical characteristics.

Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important treatment with curative potential for MDS.

However, transplantation is not appropriate for every patient. For some patients with higher-risk disease or other indications for transplantation, the healthcare team considers age, overall health, disease risk, donor availability, previous treatments, and transplant-related risks to determine whether and when transplantation is appropriate.

Reduced-intensity conditioning may make transplantation possible for some older adults or patients who are not candidates for traditional high-intensity conditioning.

Clinical Trials

Treatment for MDS continues to evolve. Clinical trials are studying new targeted therapies, treatment combinations, and approaches for different molecular subtypes of MDS.

Patients with either lower-risk or higher-risk MDS can discuss available clinical trials with their healthcare team based on disease characteristics and previous treatments.