In addition to the basic blood and bone marrow studies (morphology, blood count and immunophenotype) to be performed in any hematological disease by the hematology expert, cytogenetic studies (to detect specific chromosomal abnormalities) and molecular studies (to detect specific gene alterations) are essential to typify and classify the disease, since certain genetic or molecular alterations are accompanied by a greater or lesser risk of disease progression or greater or lesser sensitivity to chemotherapy treatment. The performance of a bone marrow biopsy can provide some relevant data, such as the presence or absence of myelofibrosis.
Diagnostic tests for myelodysplastic syndrome
Thus, the following tests and procedures can be used:
– Physical examination and history: examination of the body to check for general signs of health, check for signs of disease, including masses or anything that appears abnormal. A history of the patient’s past illnesses and treatments is also taken.
– Complete blood count (CBC) with differential: A procedure in which a blood sample is taken to check for the following:
o Number of red blood cells and platelets.
o Number and type of white blood cells
o The amount of hemoglobin (oxygen-carrying protein) in the red blood cells.
o Part of the sample made up of red blood cells.
– Complete blood count (CBC): blood is drawn by inserting a needle into a vein and drawing blood, flowing it into a tube. The sample obtained is analyzed for red blood cells, white blood cells and platelets. It is useful for testing, diagnosing and monitoring many conditions.
– Peripheral blood smear: A procedure in which a sample of blood is checked for changes in the number, type, shape, and size of white blood cells and for excessive iron in red blood cells.
– Cytogenetic analysis: A test in which cells in a sample of blood or bone marrow are viewed under a microscope to check for certain changes in the chromosomes.
– Blood chemistry studies: A blood sample is examined to measure the amounts of certain substances, such as vitamin B12 and folate, released into the blood by organs and tissues in the body. An abnormal (higher or lower than normal) amount of a substance may be a sign of disease.
– Bone marrow aspiration and biopsy – the removal of bone marrow, blood, and a small piece of bone by inserting a hollow needle into the hipbone or breastbone. A pathologist looks at the bone marrow, blood and bone under a microscope to check for abnormal cells.
In addition, the following tests may be performed on the tissue sample that is removed:
– Immunocytochemistry: a test in which antibodies are used to identify certain antigens in a sample of bone marrow. This type of study is used to tell the difference between myelodysplastic syndromes, leukemia and other conditions.
– Immunophenotyping: A process used to identify cells according to the types of antigens or markers present on the surface of the cell. This procedure is used to diagnose specific types of leukemia and other blood disorders by comparing cancer cells to normal cells of the immune system.
– Flow cytometry: A test in which the number of cells in a sample, the percentage of live cells, and certain cellular characteristics, such as size, shape, and the presence of tumor markers on the cell surface, are measured. Cells are stained with a light-sensitive dye, immersed in a liquid, and blasted with a laser or other type of light. Measurements are based on how the light-sensitive dye reacts to the light.
– FISH (fluorescence in situ hybridization): a technique used to look at genes or chromosomes in cells and tissues. Laboratory-produced DNA pieces containing a fluorescent dye are added to cells or tissues on a glass slide. When these pieces of DNA bind to specific genes or areas of chromosomes on the slide, they light up when viewed under a microscope with a special light.
Treatment and Prognosis of Myelodysplastic Syndrome
The prognosis (chance of recovery) and treatment options depend on:
– The number of blasts in the bone marrow.
– Whether one or more types of blood cells are affected.
– Whether the patient has signs or symptoms of anemia, bleeding, or infection.
– Whether the patient is at low risk for leukemia.
– Certain changes in the chromosomes.
– Whether the myelodysplastic syndrome occurred after chemotherapy or radiation therapy for cancer.
– The patient’s age and general health.
The treatment of myelodysplastic syndromes is very variable from one patient to another and will depend on the type of myelodysplastic syndrome and the intensity of the cytopenia, as well as the age and general condition of the patient. Cases with moderate cytopenias usually do not require any treatment and may remain stable for years. In these patients it is sufficient to perform periodic analytical controls to monitor their evolution.
The only curative treatment for MDS is allogeneic bone marrow transplantation (from a family donor, unrelated or umbilical cord blood), but the advanced age of many patients and the toxicity of the procedure limit its use in young patients with poor prognosis myelodysplastic syndrome, even if they have a compatible donor.
In patients who do not require a bone marrow transplant and who require treatment, some of the following measures, all of them without curative capacity, should be used:
– Blood or platelet transfusions. Most patients require periodic transfusions to maintain the level of red blood cells and platelets. Although they do not cure the disease, they may alleviate some symptoms and contribute to improve the general condition. To avoid the accumulation of iron in the organism produced by red blood cell transfusions, it is advisable to associate iron chelating agents that favor its elimination. This measure is particularly relevant in young patients who may be candidates for bone marrow transplantation. Platelet transfusions are usually indicated only when the patient has significant bleeding. Their prolonged prophylactic use carries the risk of developing refractoriness (rapid destruction of the administered platelets), limiting their effectiveness when they are necessary due to hemorrhage.
– Growth factors. These are substances synthesized in the laboratory and capable of stimulating the production of blood cells. The most commonly used are erythropoietin (EPO), which increases red blood cell production (in up to 50% of patients) and thus reduces anemia and transfusion requirements, and colony-stimulating factor (G-CSF), which increases granulocyte counts and thus reduces the risk of infections.
– Immunomodulators such as lenalinomide, which is highly effective in patients with 5q syndrome. In the rest of myelodysplastic syndromes there is an improvement of anemia in 45% of the cases and transfusion independence in 25%.
– Immunosuppressive agents such as antithymocyte globulin (ATG) and cyclosporine have occasionally been shown to be effective (30-40% of prolonged transfusion responses).
– Hypomethylating agents such as azacitidine, which achieves transfusion independence in 40-60% of patients, although these are usually transient responses. Because they are cytotoxic agents, they can produce the opposite effect to that desired and worsen cytopenias.
– Chemotherapy. When the number of blasts exceeds 10-20% in the bone marrow, the MDS is becoming an acute post-myelodysplastic leukemia and, as such, should be treated. After receiving high doses of chemotherapy 40-60% of patients achieve complete remission of the disease (apparent normal bone marrow observed microscopically with less than 5% blasts). However, this response is not usually long-lasting and the side effects of chemotherapy are often remarkable due to the advanced age of the patients. This is why chemotherapy is usually reserved for patients with a poor prognosis, who have a compatible donor for bone marrow transplantation, or for those who have progressed to acute leukemia.