Myelodysplastic syndromes

What are they?

Red blood cells, the different kinds of leukocytes, and platelets all originate in the bone marrow, from immature cells called blasts that differentiate until the various cell types are created. Within these initial cells two large types differentiate: lymphoblasts, the precursors of lymphocytes, and myeloblasts, from which red blood cells, platelets and the rest of leukocytes develop.

When, due to different causes, an alteration of the myeloid germ cells occurs in their most primitive state, before differentiating into the precursors of red blood cells, non-lymphocyte leukocytes and platelets, all the cells derived from these altered blasts cannot carry perform its normal function, be it oxygen transport, defense or coagulation. The precursors of mature cells undergo alterations in their shape that in turn alter their function, that is, they suffer what is called a spinal dysplasia. For this reason, the diseases that are included under these characteristics are called myelodysplastic syndromes.

How they are produced

In almost all cases, there is no clear trigger that gives rise to the different myelodysplastic syndromes. However, in approximately 10% of cases it has been seen that they may be related to other diseases or factors, such as:

• cytostatic drugs
• radiation
• AIDS
• chronic inflammatory diseases
• lead exposure

Most myelodysplastic syndromes occur in advanced ages and in many cases there is an increase in iron uptake by blood cells forming in the bone marrow, which is why abnormal erythroblasts are formed.

The different types of myelodysplastic syndromes are:

• Simple refractory anemia, in which there is an alteration in the synthesis of the heme group, a constituent part of hemoglobin in red blood cells and which is formed by an iron core that has the ability to reversibly bind oxygen.
• Refractory anemia with ring sideroblasts, erythroblasts that accumulate an excess of iron that is arranged around the nucleus in the form of a ring. It is the most benign myelodysplastic syndrome.
• Refractory anemia with excess blasts, which is determined when the altered precursor cells in the bone marrow are between 5% and 20% of the total.
• Refractory anemia with excess of blasts in transformation, when the blasts represent between 20% and 30% of the total.
• Chronic myelomonocytic leukemia, in which there is a proliferation of the immature forms of both myelocytes and monocytes.

The first two have a survival of about 2-5 years from diagnosis. The other three tend to have a survival of less than one and a half years, especially refractory anemia with excess transforming blasts.

A high percentage of patients with myelodysplastic syndrome develop acute leukemia, which generally has a worse prognosis than those that occur in previously healthy patients.

Symptoms

These are generally silent diseases, that is, they do not develop overt symptoms. In general, they are elderly people who have anemia that does not respond to the usual treatments (hence the name of refractory anemia). Patients usually present symptoms typical of an anemic syndrome as a consequence of poor oxygenation of the tissues, namely:

• Paleness of skin and mucous
• asthenia
• dyspnoea
• palpitations
• headache
• lack of concentration
• irritability
• insomnia
• decreased libido

Likewise, since myelodysplastic syndromes affect all blood cell lines, patients may also present with recurrent infections derived from a decrease in leukocytes in the blood, as well as coagulation disorders due to a decrease in platelets.

Diagnosis

A myelodysplastic syndrome should be suspected in any elderly patient with symptoms compatible with anemic syndrome that does not respond to usual treatment and is accompanied by recurrent infections or bleeding disorders.

In the blood analysis, anemia can be seen that can be with red cells of normal or increased size, with increased reticulocytes or not in peripheral blood and morphological alterations. In the same way, there is usually a decrease in the number of both leukocytes and platelets and alterations in the shape of both types of cells.

It is also common to find an increase in iron levels in the blood, as well as in transferrin saturation, that is, in the ability of the iron transporter protein (transferrin) to bind to it.

The bone marrow puncture may present a normal, decreased, or high number of cells. Its study will make it possible to assess and quantify the existence of blasts and the presence of ring sideroblasts, a fact that may help in the classification of myelodysplastic syndrome and thus determine the prognosis of the patient.

Treatment

The ideal treatment for patients with myelodysplastic syndromes is bone marrow transplantation. The problem lies in the fact that the majority of patients with these syndromes are elderly and therefore are not candidates for bone marrow transplantation.

There are comfort treatments aimed at alleviating the possible complications of these diseases, such as the accumulation of iron in the blood, recurrent infections or possible bleeding episodes.

There are no specific measures to prevent myelodysplastic syndromes. At most, it is recommended to see a specialist as soon as possible in all patients with symptoms compatible with these diseases, such as anemia that does not respond adequately to the usual treatments.