What happens in the bone marrow
Due to mutations accumulated with age, the stem cell produces offspring with impaired maturation. The cells acquire an irregular shape and structure, which is called dysplasia, and most of them die directly in the bone marrow. This is why when there is an abundance of bone marrow, there are not enough cells in the blood. Some mutations affect genes responsible for reading and processing genetic information. In more severe variants, the proportion of immature blast cells increases, and it is this, together with chromosomal changes, that determines the risk of transition to acute leukemia.
- Mutations in the hematopoietic stem cell
- Improper cell maturation - dysplasia
- Cell death inside the bone marrow
- Rich bone marrow with poor blood
- The proportion of blasts determines the prognosis
- Possible progression to acute myeloid leukemia
Causes and risk factors
Most cases are considered primary and are associated with age-related changes in hematopoietic cells; the risk increases markedly after age sixty. Secondary syndrome develops years after chemotherapy and radiation therapy for another malignant disease, and is usually more severe. Additional factors include prolonged contact with benzene and other organic solvents, as well as smoking. Hereditary forms are rare and appear at a young age, often in combination with other developmental features.
- Age over 60 years
- Past chemotherapy
- Radiation therapy in the past
- Contact with benzene and solvents
- Smoking
- Rare hereditary forms in young people
Symptoms
Complaints depend on which cells are missing. Most often, anemia appears first: increasing weakness, fatigue, pallor, dizziness, shortness of breath and palpitations during normal exercise; in the elderly, increased frequency of angina attacks. The lack of neutrophils is manifested by prolonged bronchitis, pneumonia, and poorly healing wounds. Low platelets cause bruising, pinpoint rashes, bleeding gums and nosebleeds. Some patients have no complaints at all, and changes are found during a routine blood test, which allows observation to begin early.
- Weakness, fatigue, pallor
- Shortness of breath and palpitations on exertion
- Frequent and persistent infections
- Bruises and pinpoint rashes
- Bleeding gums and nose
- Absence of complaints in case of accidental discovery in the analysis
Diagnostics
First, more common causes of anemia are excluded: deficiency of iron, vitamin B12 and folic acid, hidden blood loss, kidney and thyroid diseases, chronic inflammation. If anemia persists and is not explained, a bone marrow examination is performed. In punctate and biopsy, signs of dysplasia, the proportion of blast cells and the presence of ring-shaped sideroblasts are assessed. A cytogenetic study is considered mandatory, and many centers also perform a molecular panel of mutations. The combination of blood parameters, the proportion of blasts and chromosomal changes allows us to classify the patient as a risk group.
- Complete blood count with smear and reticulocytes
- Ferritin, vitamin B12, folic acid
- Creatinine, TSH, inflammatory markers
- Bone marrow puncture and trepanobiopsy
- Cytogenetic study
- Molecular mutation panel
- Determination of the risk group using prognostic scales
Treatment and observation
Tactics depend on the risk group, age and concomitant diseases. When the risk is low, the goal is to maintain quality of life: erythropoiesis stimulants are used, for certain chromosomal variants, specific drugs are used, and red blood cells are transfused if necessary. Because frequent transfusions lead to iron overload, ferritin is monitored and iron-sparing medications are prescribed if necessary. At high risk, hypomethylating drugs are used, and young and healthy patients are offered donor bone marrow transplantation - the only method that provides a cure. Iron supplements without deficiency are contraindicated.
- Erythropoiesis stimulants at low risk
- Red blood cell transfusions according to indications
- Ferritin control and removal of excess iron
- Hypomethylating drugs at high risk
- Bone marrow transplantation in selected patients
- Early treatment of infections
- Do not take iron without a proven deficiency
