Myelodysplastic syndrome

Myelodysplastic syndrome: description

A myelodysplastic syndrome (MDS, myelodysplasia) involves a group of diseases affecting the bone marrow and thus the hematopoiesis affect. Normally, unripe bone marrow cells (blasts) in the bone marrow develop different types of blood cells that perform different tasks in the body. These include:

• Red blood cells (erythrocytes): oxygen transport
• White blood cells (leukocytes): part of the immune system
• Platelets (platelets): blood clotting

Myelodysplastic syndrome affects several of these cell lines. They are either less educated or limited in their function. It is different, which cell types and how strongly they are affected. When two of the three rows of cells are affected, one speaks of one Bizytopenieif all three are affected by one pancytopenia, That is also the reason why there is not “the” myelodysplastic syndrome. The term describes a group of different diseases, but in each of which the formation of blood is affected. In most cases, less functional cells of the affected cell type can be found (cytopenia). The bone marrow, however, is often interspersed with many immature cells (blasts), the precursor cell of the blood cells.

Myelodysplasia is most common in people around the age of 70 years. Every year, about four to five out of every 100,000 people contract MDS. Thus, the myelodysplastic syndrome belongs to the common malignant diseases of the blood. Among those over 70, 20 to 50 out of every 100,000 people get sick. A little more men (56 percent) than women (44 percent) develop a myelodysplastic syndrome. Life expectancy and disease progression are determined by various factors. Among other things, it is decisive how high the so-called blast proportion is, whether complex genetic changes are present and how severely the blood formation is impaired. A high blast content indicates a high disease activity and thus a less favorable prognosis. Likewise, age and previous illnesses play a role. Overall, the mean survival time of the MDS is about 30 months. However, in individual cases, large deviations from this statistical average are possible.

Myelodysplastic syndrome: symptoms

A myelodysplastic syndrome causes discomfort in about 80 percent of patients, which reduces the number of certain blood cells, while the remainder of the MDS is discovered by chance. Due to the disturbed formation of the different blood cells different consequences arise:

Anemia: Affects formation or function of red blood cells

Anemia is present in 70% of cases of MDS, making it the most common symptom of myelodysplasia. In MDS, the normal formation of red blood cells and hemoglobin is disturbed, causing anemia. Hemoglobin is the red dye in the red platelets that helps them transport gases. If there is too little, it can lead to signs of lack of oxygen. Patients feel chronically tired, less efficient and can concentrate less well. With little physical effort they are short of breath and feel a fast pulse (tachycardia). Often sufferers are noticeably pale and complain of dizziness on exertion. At the time of diagnosis, in about half of the patients the anemia is so pronounced that a blood transfusion is necessary.

Infections: impaired formation or function of white blood cells

A myelodysplastic syndrome leads to repeated infections in about 35 percent of the cases. In those affected, the number of white blood cells is reduced (leukopenia). If the cell count of the white blood cells is low, the immune system can no longer respond to pathogens sufficiently. MDS is therefore often associated with increased infections, sometimes accompanied by fever.

Bleeding tendency: formation or function of the platelets impaired

If the number of platelets is reduced (thrombocytopenia), faster bleeding may occur. The platelets normally cause blood clots when injured, stopping blood flow. About twenty percent of people who have a myelodysplastic syndrome, therefore, bleed easily. This is visible, for example, from small punctate bleeding under the skin, so-called petechiae.

Other symptoms

However, there are signs of disease that are not directly related to the diminished cell number of individual blood cells. In 20 to 50 percent of cases, for example, the spleen is enlarged (splenomegaly). Their function is, among other things, to sort out defective and obsolete red blood cells. If myelodysplasia causes an increase in non-functional red blood cells, the spleen also has to increase its performance. This becomes visible through an enlargement of the organ. Likewise, the liver can be enlarged (hepatomegaly) and trigger a dull feeling of pressure in the right upper abdomen. About one in ten patients with MDS gets lymphoma.

Myelodysplastic syndrome: causes and risk factors

In healthy people, the so-called stem cells of the blood in the bone marrow undergo different maturation and division stages. At the end of these processes, red blood cells, white blood cells and platelets are formed. In patients with MDS, the bone marrow stem cells are degenerate and normal blood formation (hematopoiesis) is disturbed. The pathologically altered stem cells produce massless dysfunctional cells. These die quickly or are sorted out in the spleen. Of the three cell lines of the blood (red blood cells, white blood cells, platelets), one, two or all three may be degenerate. When all three cell lines are degenerate, it is called pancytopenia. In some patients who have a myelodysplastic syndrome, the immature stem cells proliferate over time, massively and uncontrollably. The MDS then goes into acute leukemia. That’s why they call a myelodysplastic syndrome too Pre-leukemia.

The reasons for this degeneration of blood formation in more than 90 percent of cases are not clear (primary myelodysplastic syndrome). In ten percent of those affected, however, more or less certain triggers can be found (secondary myelodysplastic syndrome). In most cases, chromosomal changes in the genetic material are evident in this case. The more chromosome changes are present, the more serious the disease is. The triggers include:

• Previous chemotherapy with cytotoxins (cytotoxic drugs)
• Irradiation (for example for the treatment of cancer or nuclear accidents)
• Radioiodine therapy (for hyperthyroidism or thyroid cancer)
• Benzene and other solvents

Myelodysplastic syndrome: examinations and diagnosis

The right person to contact if you suspect a myelodysplastic syndrome is a specialist in internal medicine, who specializes in diseases of the blood or cancer (Hematologist, haematooncologist). At the doctor’s appointment, the doctor first inquires about your current complaints and any previous illnesses (Anamnese). The physician might ask you the following questions if you suspect a myelodysplastic syndrome:

• Are you feeling tired and beaten lately or are you experiencing a performance drop?
• Are you out of breath, even with little physical effort?
• Do you have palpitations or dizziness more often?
• Are you suffering from more infections lately?
• Are you prone to punctate skin bleeding (petechiae) and increased nosebleeds?
• Have you been irradiated in the past or have you received chemotherapy?

After the anamnesis follows the physical examination, In particular, the doctor checks whether the liver or the spleen are enlarged and whether lymph nodes are swollen. Since a myelodysplastic syndrome is primarily a blood disorder, a blood test is essential. Among other things, it serves to clarify possible other causes of the symptoms. In addition to the blood, the bone marrow is also examined in suspected myelodysplastic syndrome.

Myelodysplastic syndrome: blood test

The first indication of a myelodysplastic syndrome is the blood test. The sample tested typically contains fewer blood cells than a healthy human. The different cell types can be affected in different combinations or alone. Mostly the red blood cells are diminished (anemia). However, unlike iron deficiency anemia, the iron content in these cells is not altered or even increased. In addition, white blood cells and platelets may be reduced (leukopenia and thrombocytopenia). Sometimes, however, the white blood cells are also elevated.

A myelodysplastic syndrome can affect the size and hemoglobin content of the blood cells in addition to an altered cell count. The red blood cells may be enlarged (macrocytic) or downsized (microcytic), have an altered shape, and have a decreased (hypochromic) or increased hemoglobin (hyperchromic) content. Based on the blood count, it is assessed whether more immature blood progenitor cells occur. This is also an indication of a disturbed blood formation. In order to clarify other possible causes of the symptoms, the iron storage value ferritin and the cell decay parameter LDH are also determined in the blood. Vitamin B12, folic acid and erythropoietin are involved in the formation of blood and are therefore often also controlled.

Myelodysplastic syndrome: bone marrow puncture

If a conspicuous blood test suspects a myelodysplastic syndrome, a bone marrow biopsy can confirm the suspected diagnosis. Even in the bone marrow, immature precursors (blasts) of normal blood formation are increasingly found in MDS. The patient is usually given a sedative or light sleep drug in this study. In children, a general anesthetic is usually performed. Then, first an area in the iliac crest or sternum is disinfected and covered with sterile towels. So that the patient does not develop any pain during the biopsy, a local anesthetic is injected under the skin. The doctor can then use a needle to remove cells and tissue from the bone marrow. Subsequently, cells and tissues are examined in the laboratory. Important for the subsequent therapy of the myelodysplastic syndrome is the proof of whether and how the genome of the bone marrow cells is altered. This succeeds with a chromosome or gene analysis.

Myelodysplastic syndrome: treatment

A myelodysplastic syndrome is diagnosed and classified according to the appearance and condition of the bone marrow and blood cells under the microscope. Depending on the microscopic changes in the hematopoietic cells, the World Health Organization (WHO) distinguishes two types of myelodysplasia, each requiring different therapeutic measures: the high-risk MDS and the low-risk MDS. Criteria for this classification include the type and proportion of altered cells in blood and bone marrow. The treatment of MDS takes place in specialized departments of a hospital or especially recommended, a university hospital.

Myelodysplastic Syndrome: Treatment of Low Risk MDS

Low-risk MDS uses a “supportive therapy”, which is a supportive treatment for the disease. One tries to replace the loss of function without being able to heal the disease. Myelodysplastic syndrome may require the following supportive measures:

• Transfusion of red and white blood cells or platelets
• Drugs that bind iron in the blood (iron chelators). This is necessary because repeated blood transfusions will otherwise cause iron overload on the body.
• Early antibiotic treatment with every unclear infection
• Pneumococcal vaccine and annual flu vaccine
• Waiver of non-steroidal painkillers or cortisone

Myelodysplastic syndrome: growth factors

A myelodysplastic syndrome leads to a lower cell concentration of certain cell types in the blood. In order for the body to form more new cells of this type of cell, the blood formation can be stimulated by certain drugs. In order to produce more red blood cells, the hormone erythropoietin (also known as EPO in sports sports doping) or valproic acid can be administered. For the other cell lines, there are also stimulators, which stimulates the formation of new cells.

Myelodysplastic syndrome: immunomodulators

Myelodysplastic syndrome also affects the cells of the immune system. In certain cases, medications that suppress or modulate the immune system can help. In the long term, patients must receive fewer blood transfusions. In addition, this therapy can cause the number of platelets in the blood to rise again.

Myelodysplastic syndrome: treatment of high-risk MDS

There are several options for treating the high-risk group myelodysplastic syndrome, including altering DNA metabolism (such as azacytidine or decitabine), intensive chemotherapy, or “allogeneic stem cell transplantation.” Stem cell transplantation is the only treatment option that may allow the disease to be cured. All cells in the patient’s bone marrow are destroyed by radiation and chemotherapy. Since a person without blood formation can not live, donor stem cells must be implanted by another person. These divide and start the blood formation again. However, it is not always easy to find a donor that is genetically similar enough to be considered a donor.

In principle, the possibility of a stem cell transplantation should be checked in all patients with a high-risk MDS, before, for example, interfering with the DNA metabolism. If a stem cell transplant is not possible, the other methods of treatment are used.

Myelodysplastic syndrome: disease course and prognosis

Overall, the prognosis of an MDS is rather poor. Particularly unfavorable factors are a high proportion of blasts in the blood, complex chromosomal changes, high cell disintegration in the blood test, older age, pre-existing conditions and a reduced general condition.

Depending on the risk group, the diagnosis of “myelodysplastic syndrome” is life expectancy and disease progression. Patients at high risk survive on average five months. However, high-risk MDS sometimes has the potential for stem cell therapy and potentially a chance of recovery. If a low-risk type of disease is present, life expectancy may increase to an average of 68 months. Over 60 percent die from infections, bleeding or sudden acute myeloid leukemia (AML). These complications are immediate consequences of the disease Myelodysplastic syndrome.