Myelodysplastic syndromes
What is it?
Myelodysplastic syndromes (also called myelodysplasia, MDS) are blood diseases caused by an abnormality of the stem cells present within the bone marrow. In myelodysplastic syndromes, one of the myeloid stem cells in the bone marrow undergoes DNA changes, which damage it. The damaged stem cell multiplies, producing cells with an abnormal structure (dysplastic), which cannot complete their maturation to become blood cells, or at least cannot survive for long. This causes a depletion of the blood, which is left without red blood cells, white blood cells and / or platelets. Abnormal cells in MDS patients often contain genetic mutations that can affect large pieces of DNA called chromosomes (missing or damaged chromosomes 5, 7, or 20, presence of an extra chromosome 8) or smaller pieces of DNA called genes (SF3B1, TET2, SRSF2, ASXL1 or TP53).
The causes of myelodysplastic syndromes are not yet known, although the chances of developing this pathology increase with age and with exposure to toxic external agents. Myelodysplastic syndromes are a group of very dissimilar diseases in terms of clinical and biological behavior and therefore need to be classified to identify patients with similar characteristics and prognosis. In addition, the classifications are constantly updated based on the latest knowledge. The classification currently in force is that of the World Health Organization (WHO) revised in 2016. It is based on the number of immature cells (blasts) present in the bone marrow, on the evaluation of dysplasia (i.e. inadequate maturation) in the bone marrow, and on the presence of peculiar cytogenetic anomalies.
The prognostic systems (able to predict the course of the disease) most used in myelodysplastic syndromes are the WPSS (WHO classification based Prognostic Scoring System), the IPSS (International Prognostic Scoring System) and the IPSS-R (International Prognostic Scoring System Revised). These systems allow patients to be classified into different risk groups with significantly different life expectancy and risk of progression to acute myeloid leukemia (AML).
Causes and risk factors
Every year in Europe, myelodysplastic syndrome is diagnosed in 1 person in 12,500 inhabitants. But basically, the disease affects elderly people: over 70 years old, about 1 person per 3000 inhabitants gets sick annually, and at the age of 60 years it appears very rarely.
Which are the symptoms?
These are diseases whose onset may not be immediately apparent. Usually, a doctor is consulted after a state of anemia is detected, which may be asymptomatic for some time, depending on the rate of spread of the disease and the body's ability to adapt to a decrease in hemoglobin. In addition to the state of anemia, severe neutropenia and thrombocytopenia may also be evident at the diagnosis, presenting with skin hemorrhagic manifestations (petechiae, ecchymosis or hematomas).
Before a diagnosis of myelodysplastic syndrome can be confirmed, it must be ensured that the anemia and cytopenia are not due to other causes. Once secondary causes have been excluded, bone marrow evaluation is carried out, which allows to define exactly which myelodysplastic syndrome the patient is suffering from.
How is it diagnosed?
The following tests are necessary for a complete diagnosis:
- the blood count allows to quantify the various types of cells present in the blood;
- the dosage of erythropietin (EPO) helps to choose the most effective treatment for anemia
- microscopic observation of blood cells and bone marrow allows to identify cells with structural alterations (dysplastic), immature cells (blasts) and ring sideroblasts;
- the immunophenotype allows to characterize the proteins present in the pathological cells;
- the cytogenetic analysis of chromosomes is used to identify the chromosomal alterations present in the pathological cells, which decisively influence the evolution of the disease;
- DNA analyzes make it possible to establish whether all pathological cells derive from a single damaged stem cell (clonality);
- the histological examination can allow to exclude causes of cytopenia other than MDS (bone marrow aplasias, lymphoproliferative disorders, etc.) and provides information on the distribution and percentage of the blast portion, in addition to cellularity (hypoplastic forms) and medullary fibrosis.
How is it treated?
Before starting treatment, patients with myelodysplastic syndromes undergo a follow-up period, especially if they are elderly or in poor health, or if there are doubts about the diagnosis. In any case, treatment is started only when symptoms appear due to anemia or a lack of white blood cells and platelets. The choice of therapy depends on the characteristics of the patient (age, health status) and the disease (IPSS and WPSS rating systems). Based on these estimates, treatment modalities can range from periodic patient follow-up to maintenance therapy alone, hypomethylating drugs, to intensive chemotherapy and donor stem cell transplantation. There are also numerous clinical trials of MDS that allow the patient to access treatments that would otherwise not be possible.
Where do we treat it?
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