Myelodysplastic syndrome – Diagnostics – Overview of Information and Clinical Research

Diagnosing myelodysplastic syndrome involves a combination of blood tests and bone marrow examinations to understand what’s happening inside your body. Doctors look for specific changes in blood cells and bone marrow that show whether the cells are developing normally or not, helping them determine the right path forward for each person.

Introduction: Who Needs Testing and When to Seek Help

If you’ve been experiencing ongoing symptoms such as unusual tiredness, shortness of breath, frequent infections, or unexplained bruising or bleeding, your doctor may recommend testing for myelodysplastic syndrome (MDS). This group of conditions affects how your bone marrow produces blood cells, and catching it early can help guide important treatment decisions.^[1]

Most people with MDS are older adults, typically over age 65, though the condition can occur at any age. You should consider seeking medical evaluation if you notice persistent symptoms that don’t improve with time. These might include feeling weak even after resting, getting sick more often than usual, or noticing that small cuts bleed longer than they should.^[2]

People who have previously received chemotherapy or radiation therapy for other cancers may be at higher risk for developing MDS and should be particularly attentive to new symptoms. Similarly, those who have been exposed to certain chemicals like benzene, pesticides, or heavy metals such as mercury or lead may want to discuss screening with their healthcare provider.^[3]

⚠️ Important

Some people with MDS may not experience any symptoms at first, and the condition might be discovered during routine blood work for another reason. If blood tests show unusual results, your doctor will likely recommend further testing even if you feel fine.

Classic Diagnostic Methods for Identifying MDS

Diagnosing myelodysplastic syndrome requires several different types of tests to build a complete picture of what’s happening with your blood and bone marrow. The process typically starts with simpler tests and moves to more detailed examinations if needed.^[7]

Blood Tests

The first step in diagnosing MDS usually involves blood tests, particularly a complete blood count (CBC). This test measures the number of red blood cells, white blood cells, and platelets in your blood. When you have MDS, one or more of these blood cell types will typically be lower than normal. The test also examines the size, shape, and appearance of your blood cells to identify any abnormalities.^[7]

Doctors look for specific patterns in the blood test results. You might have anemia, which means too few red blood cells, causing you to feel tired and weak. You could have neutropenia, meaning too few white blood cells, which makes you more prone to infections. Or you might have thrombocytopenia, indicating too few platelets, which causes easy bruising and bleeding that’s hard to stop.^[4]

Blood tests can also reveal the presence of immature blood cells called blasts in your bloodstream. Normally, these cells should stay in the bone marrow until they mature. Finding them in the blood can be a sign of MDS and helps doctors understand how advanced the condition might be.^[8]

Bone Marrow Aspiration and Biopsy

To confirm a diagnosis of MDS, doctors need to examine your bone marrow directly. This involves two related procedures usually done at the same time: bone marrow aspiration and bone marrow biopsy. During a bone marrow aspiration, your doctor uses a thin needle to remove a small amount of liquid bone marrow, typically from the back of your hip bone. In the biopsy portion, a slightly larger needle removes a small piece of bone tissue along with the marrow inside it.^[7]

These samples are then sent to a laboratory where specialists examine them under a microscope. They look at how the cells appear and whether they’re developing normally. In MDS, many of the blood cells in the bone marrow have unusual shapes or appearances, a characteristic called dysplasia. The cells might look oddly formed or different from healthy cells, indicating they’re not maturing properly.^[10]

The bone marrow examination also reveals the percentage of blasts present. This is crucial information because the number of blasts helps determine the type of MDS you have and how likely it is to progress to acute myeloid leukemia (AML). If blasts make up 5% to 19% of the cells in your bone marrow, this indicates a more advanced form of MDS.^[6]

Specialized Laboratory Testing

Once your bone marrow and blood samples are collected, they undergo specialized tests to provide more detailed information. Cytogenetic testing examines the chromosomes within your blood and bone marrow cells. Chromosomes are the structures that contain your genetic information, and changes in them can affect how cells behave.^[7]

About half of people with MDS have detectable changes in their chromosomes. Common abnormalities include deletions (missing pieces) of chromosomes 5, 7, or 20, or having an extra copy of chromosome 8. One particular finding, called the 5q deletion, where part of chromosome 5 is missing, is associated with a specific type of MDS that often has a better outlook.^[4]

Doctors also use advanced genetic testing methods, such as next generation sequencing, to look for mutations in specific genes within the MDS cells. Common gene mutations found in MDS include changes in genes called SF3B1 and TP53. These genetic findings help doctors classify your MDS into a specific subtype and predict how the disease might behave over time.^[4]

Examining Cell Appearance

Laboratory specialists carefully examine how your blood and bone marrow cells look under the microscope. They check for several specific abnormalities. For example, they might find ring sideroblasts, which are immature red blood cells that have accumulated iron in a ring-like pattern around their center. These cells store iron instead of using it properly to make hemoglobin, the protein that carries oxygen in your blood.^[10]

Other abnormal features might include red blood cells that are larger than normal (macrocytic anemia), white blood cells that have too few or too many granules inside them, or platelets that are unusually shaped or sized. All these observations help doctors understand exactly what type of MDS you have.^[11]

Determining MDS Type

Based on all the test results, doctors classify MDS into different types. The classification system considers how many types of blood cells are affected, the percentage of blasts present, what the cells look like under the microscope, and what chromosome or gene changes are present. Some types of MDS rarely progress to leukemia, while others are more likely to do so. Some affect only one type of blood cell, while others affect multiple types.^[2]

The most common MDS subtypes include MDS with single lineage dysplasia (affecting one type of blood cell), MDS with multilineage dysplasia (affecting two or more types), MDS with ring sideroblasts, MDS with excess blasts (which has a higher risk of becoming leukemia), and MDS associated with the isolated 5q deletion. Each type has different characteristics and requires different monitoring or treatment approaches.^[10]

Diagnostics for Clinical Trial Qualification

When considering participation in clinical trials for MDS, specific diagnostic criteria must be met. Clinical trials test new treatments or approaches to managing MDS, and researchers need to ensure that participants have confirmed diagnoses and that their condition fits the study requirements.^[11]

To qualify for most MDS clinical trials, you must have a confirmed diagnosis based on bone marrow examination and blood tests that show the characteristic features of MDS. Trials typically require documentation of your MDS subtype according to the World Health Organization classification system. This classification is based on the comprehensive testing described earlier, including blood counts, bone marrow appearance, blast percentage, and genetic findings.^[4]

Many clinical trials use a system called the International Prognostic Scoring System (IPSS) or its updated version (R-IPSS) to determine eligibility. These systems assign scores based on several factors: the percentage of blasts in your bone marrow, the types of chromosome abnormalities present, and the severity of your blood cell deficiencies. Based on the total score, patients are categorized into risk groups such as low, intermediate, or high risk.^[3]

Some trials specifically recruit patients with lower-risk MDS who don’t yet need intensive treatment, while others focus on higher-risk patients or those whose disease has not responded to standard treatments. The trial may require repeated blood tests and bone marrow examinations to monitor how your disease changes over time and how you respond to the experimental treatment.^[11]

⚠️ Important

Clinical trial qualification often requires that you have not received certain previous treatments, or that you have specific genetic mutations or chromosome changes. Your healthcare team can help determine which trials might be appropriate for your specific situation based on your diagnostic results.

Before enrolling in a clinical trial, you’ll typically undergo baseline testing to establish your starting point. This includes comprehensive blood work, bone marrow examination, and possibly additional tests to assess your overall health and organ function. These baseline measurements allow researchers to track changes and evaluate whether the experimental treatment is working.^[11]

Throughout the trial, you’ll have regular monitoring visits with repeated blood tests and periodic bone marrow examinations. The frequency of these tests depends on the trial protocol and the treatment being studied. This close monitoring helps ensure your safety and provides valuable data about how the treatment affects MDS at the cellular level.^[8]

Some clinical trials may also collect additional samples for research purposes, such as extra blood or bone marrow for genetic analysis or to study how MDS cells respond to treatment in the laboratory. These samples help researchers understand more about MDS and develop better treatments in the future.^[11]

Prognosis and Survival Rate

Prognosis

The outlook for people with myelodysplastic syndrome varies widely and depends on several important factors. One key factor is the type of MDS you have, determined by the characteristics seen in your blood and bone marrow tests. People with certain chromosome changes tend to have different outcomes. For instance, those with the 5q deletion often have a more favorable prognosis compared to those with changes affecting chromosome 7.^[3]

The percentage of blast cells in your bone marrow is another crucial factor. Higher blast counts generally indicate more advanced disease and a greater chance that MDS might progress to acute myeloid leukemia. About 30% of people with MDS will eventually develop AML, though this varies significantly depending on the MDS subtype. Some types rarely progress to leukemia, while others, particularly those with excess blasts, carry a higher risk of transformation.^[4]

The severity of your blood cell deficiencies also affects prognosis. Having low counts in multiple types of blood cells (red cells, white cells, and platelets) generally indicates a more serious condition than having just one type affected. Many patients face complications from these low blood counts, such as severe infections, bleeding problems, or profound anemia, before the disease progresses to leukemia.^[11]

Your age and overall health status play important roles as well. MDS primarily affects older adults, with a median age at diagnosis of around 70 years. Younger patients often have better outcomes, partly because they may be able to tolerate more intensive treatments. The disease course is variable, and not all patients require immediate treatment. Some people with lower-risk MDS live for many years with minimal or no treatment, while others with higher-risk disease need more aggressive interventions.^[3]

Survival Rate

The average survival time following an MDS diagnosis is approximately 2.5 years, but this number doesn’t tell the whole story. Survival varies dramatically based on individual factors, and some people live much longer.^[5]

Doctors use scoring systems like the International Prognostic Scoring System (IPSS) to help predict outcomes. These systems divide patients into different risk categories based on blast percentage, chromosome abnormalities, and blood count deficiencies. Patients in lower-risk categories may have survival times measured in many years, while those in higher-risk groups may face shorter timelines.^[3]

It’s important to understand that these are statistical averages based on groups of people, and individual outcomes can differ significantly. Some people respond very well to treatment and live longer than expected, while others may face more challenges. Your healthcare team can provide more personalized information based on your specific test results, MDS type, and overall health condition.^[11]