Myelodysplastic Syndrome (MDS)

Myelodysplastic syndrome develops when blood forming stem cells in the bone marrow change. These genetic changes disturb the normal maturation and function of blood cells. This leads to immature or poorly functioning blood cells. At the same time, normal blood formation becomes increasingly impaired. The cause of these changes cannot always be clearly identified. In general, doctors distinguish between primary and secondary myelodysplastic syndromes.

Primary myelodysplastic syndromes account for about 90% of all cases. In these cases, the disease develops without a clearly detectable external trigger. However, typical genetic or chromosomal changes in hematopoietic stem cells are often found. The risk rises with age. This is why MDS is mainly diagnosed in older adults.

Important causes and risk factors for primary MDS include:

• Older age
• Genetic mutations
• Epigenetic changes

Secondary myelodysplastic syndromes account for about 10% of cases. In these cases, an external trigger or previous bone marrow damage can often be identified. Forms that occur after chemotherapy or radiation therapy are especially well documented. Certain cytotoxic drugs and ionizing radiation can also damage DNA in stem cells over time. This can increase the risk of developing MDS.

Known causes and risk factors for secondary MDS include:

• Benzene or other organic solvents
• Radiation therapy or radioiodine therapy
• Ionizing or radioactive radiation
• Myeloproliferative neoplasms
• Paroxysmal nocturnal hemoglobinuria
• Previous cytostatic therapy
• Previous hematologic diseases

Certain hematologic stem cell diseases can also develop into MDS or acute myeloid leukemia over time. Therapy related forms are often linked to a more aggressive course. In many cases, however, the disease develops through an interplay of genetic changes, age related processes, and external influences. A detailed medical history, early imaging, and assessment of possible risk factors therefore play an important role in diagnosis.

The symptoms of MDS can vary widely. They mainly depend on which blood cells in the bone marrow are affected. Some people have hardly any symptoms for a long time. Others develop symptoms early because they lack enough functioning blood cells. In many cases, MDS remains asymptomatic at first. It is therefore often discovered by chance during a blood test.

The symptoms mainly result from cytopenias. This means a reduced number of red blood cells, white blood cells, or platelets. Anemia is especially common. In many cases, several blood cell lines are affected at the same time. Alongside anemia, there may also be a shortage of white blood cells or platelets. This is called bicytopenia or pancytopenia.

Typical symptoms of anemia include:

• Tiredness and exhaustion
• Feeling weak
• Physical weakness
• Paleness
• Problems concentrating
• Rapid heartbeat
• Shortness of breath, especially during physical activity

If the white blood cells are mainly reduced, this is called leukocytopenia. It can weaken the immune system. Many people then develop a higher susceptibility to infections. They may also notice that infections are more severe or last longer than usual.

Typical signs of leukocytopenia include:

• Increased susceptibility to infections
• Recurrent infections
• Fever of unclear cause
• Delayed or slower recovery from infections

Thrombocytopenia means a shortage of platelets. In this case, primary blood clotting is impaired. This can lead to bleeding or bruising more easily.

Typical symptoms of thrombocytopenia include:

• Petechiae
• Bleeding gums
• Nosebleeds
• Tendency to bruise
• Longer bleeding time, even after small injuries

In some cases, the liver or spleen may also become enlarged. Autoimmune accompanying diseases are described more rarely. These include inflammatory joint symptoms or arthritis.

The symptoms often begin slowly and are usually nonspecific at first. For this reason, myelodysplastic syndrome is often diagnosed at a later stage. Warning signs such as ongoing tiredness, recurrent infections, unexplained bleeding, or abnormal blood counts should always be checked by a doctor.

The diagnosis of myelodysplastic syndrome is usually based on several steps. These include a clinical examination, blood tests, and a histologic assessment of the bone marrow. MDS often begins slowly. Early symptoms are often nonspecific. It is therefore often found because blood values are abnormal. Changes in red blood cells, white blood cells, or platelets can point to disturbed blood formation.

Diagnosis usually begins with a detailed medical history and a physical examination. The doctor pays close attention to symptoms such as tiredness, susceptibility to infections, or bleeding tendencies. Risk factors are also assessed. These include previous chemotherapy, radiation therapy, or workplace exposure to toxic substances.

Blood testing is also important. Typical findings include cytopenias. This means a reduced number of cells in one or more blood cell lines. Anemia is also often found during a blood test. The blood cells are also examined under a microscope. In MDS, characteristic maturation defects and changes in cell appearance can often be detected.

To confirm the diagnosis, doctors usually perform a bone marrow puncture. The bone marrow is then examined cytologically, histopathologically, and genetically. This helps assess how severely blood formation is impaired. It also shows whether typical changes in hematopoietic stem cells are present. The typical maturation defects and the blast count in the bone marrow are especially important for distinguishing MDS from other forms of leukemia. In classic MDS, the blast count is below 20%. Genetic mutations or chromosomal changes can also be examined. They are important for diagnosis, prognosis, and treatment planning.

Another important part of diagnosis is excluding other causes of abnormal blood values. These include vitamin B12 deficiency and folate deficiency. Both can disturb blood formation and change the blood count. Their findings can resemble those seen in myelodysplastic syndrome. Iron deficiency, chronic infections, autoimmune diseases, and other hematologic neoplasms must also be considered as differential diagnoses.

Treatment for myelodysplastic syndrome mainly depends on the individual risk profile. Age, other illnesses, and general health also play an important role. The course and aggressiveness of MDS can vary. For this reason, doctors usually plan treatment based on special risk classifications. In general, they distinguish between lower risk and higher risk MDS.

In lower risk MDS, the first goals are to improve blood formation and control symptoms. If there are no symptoms, or only minor changes in the blood count, doctors may first consider a watch and wait approach. This means that the disease is monitored closely without starting intensive treatment right away. If cytopenia causes symptoms, supportive treatment may be used. This can include blood transfusions, growth factors to support blood formation, or measures to prevent infections. Depending on the MDS subtype, specific medication may also be used.

In higher risk MDS, there is a much higher risk that the disease will progress or develop into acute myeloid leukemia. In these cases, therapies such as hypomethylating agents or more intensive treatment strategies are used more often. The only potentially curative treatment for myelodysplastic syndrome is currently allogeneic stem cell transplantation. In this treatment, the diseased blood forming system is replaced with healthy donor stem cells. Because of the risk of complications, transplantation is usually considered mainly for fitter and younger patients.

Alongside conventional medical treatment, complementary medicine and holistic medicine may be used as supportive approaches. These can include acupuncture, methods from traditional Chinese medicine, hyperthermia, phytotherapy, and nutrition based concepts. The aim is to support quality of life and ease distressing symptoms caused by the disease or its treatment. These symptoms can include fatigue, chronic exhaustion, pain, sleep disorders, or loss of appetite.

With hyperthermia, controlled heat may influence circulation and metabolic processes. It is also discussed in relation to the sensitivity of tumor cells to certain therapies. The role of antioxidant substances, nutrition based concepts, and phytotherapeutic approaches is also discussed. These may include plant based compounds with antioxidant or inflammation modulating properties. They may help reduce oxidative stress and thereby reduce cell damage.

Life expectancy in MDS can vary greatly. It mainly depends on the subtype, genetic changes, blast count, and response to treatment. Lower risk forms may remain stable for years. Higher risk forms often have a more aggressive course and a higher risk of AML transformation. Molecular genetic diagnostics and modern therapies have improved the prognosis of many MDS forms in recent years.

The information listed contains relevant topics and serves to improve understanding.