Myelodysplastic syndromes/ Chronic myeloproliferative neoplasms

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Dr. Blanca Xicoy. Clinical Hematology Unit; Catalan Institute of Oncology, Hospital Germans Trias i Pujol. Josep Carreras Leukaemia Research Institute.

What are myelodysplastic syndromes/myeloproliferative neoplasms and whom do they affect?

Chronic myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) are a group of diseases of the bone marrow (BM), the organ responsible for producing blood cells (red blood cells, white blood cells, platelets). Under normal circumstances these cells reproduce and mature in the bone marrow before then circulating in the blood. With MDS/MPN the bone marrow produces these cells abnormally, in terms of number, maturation and function, and these anomalies can be detected when the blood is analysed under the microscope.

In the case of MDS there is usually a decrease in the number of some blood cells with some morphological alterations (dysplasia) and in the case of MPN there is usually an increase (proliferation) of blood cells. MDS/MPN are a combination of these two kinds of alteration in varying degrees and some degree of dysplasia in the blood cells and in the bone marrow is always found. Proliferation manifests itself through an increase in the number of leukocytes (leukocytosis), platelets (thrombocytosis) and/or red blood cells (polycythemia); dysplastic alterations may be accompanied by macrocytic anemia (very large red blood cells), and a decrease in the number of white blood cells (leukopenia) and/or in the number of platelets (thrombocytopenia).

Similarly, the sick cells affected by MDS/MPN combine alterations of mechanisms implicated in both MDS and MPN; in the case of MDS there are DNA alterations that affect chromosomes, genes (mutations) and methylation (modifications of the DNA that may deactivate a gene's function) as well as other structures relating to DNA; in the case of MPN there are usually genetic alterations (mutations) such that the sick cell's "programme" (metabolism) functions at a faster rate than normal, being responsible for some of the patient's symptoms.

The causes of MDS/MPN are unknown, but in most cases they are diseases associated with aging, environmental exposure to toxic substances (through work or otherwise), or treatments such as radiotherapy and/or chemotherapy, amongst others.

Kinds of myelodysplastic syndromes/myeloproliferative neoplasms

The World Health Organisation (WHO) classifies the following subtypes of MDS/MPN:

1) Chronic myelomonocytic leukemia (CMML), the most frequent form in which an increase in the number of monocytes, a subtype of leucocyte, predominates;

2) Atypical chronic myeloid leukaemia (aCML), BCR/ABL1 negative (very rare);

3) Juvenile myelomonocytic leukaemia (during childhood);

4) Myelodysplastic/myeloproliferative neoplasm with ringed sideroblasts (abnormal distribution of iron in the red blood cell) and thrombocytosis;

5) Unclassifiable MDS/MPN (when the alterations observed in the blood and the bone marrow do not enable diagnosis as either an MDS or an MPN, nor one of the MDS/MPN as defined by the WHO).

Symptoms and diagnosis

If there is anemia on account of a decrease in the number of red blood cells, frequent symptoms include tiredness and weakness (when this is more significant there can also be dizziness, palpitations, perspiration, amongst others). In more serious cases there may be symptoms deriving from a decrease in the number of white blood cells and/or platelets leading to infections and/or hemorrhages respectively. When proliferative alterations predominate there is a risk of thrombosis because the increase in the number of red blood cells and/or platelets may lead to the blockage of the blood vessels, especially if the person smokes, has a high cholesterol level, or high blood pressure. Furthermore, given that the bone marrow works at a higher rate than normal, the liver and spleen may increase in size and contribute to this proliferation. Such an increase in size may cause discomforts such as swollen stomach, stomach ache, constipation, etc. There may also be symptoms, known as constitutional symptoms, such as fatigue, loss of appetite, weight loss and itchiness.

The following tests are required in order to diagnose MDS/MPN:

1) analysis of blood cells under the microscope in order to see the alterations and determine the number and shape of the cells;

2) bone marrow aspiration to determine whether the blood cell precursors are present in much larger numbers than normal and whether there are alterations in their shape or size; to see whether there is a variable percentage of abnormal immature cells (blasts) with possible chromosomal and genetic alterations and, lastly, to see whether there are ringed sideroblasts or not, and

3) a bone marrow biopsy to confirm the diagnosis, and to see whether there has been a considerable increase in the number of cells in the bone marrow, and to establish whether there is a light to moderate degree of fibrosis (a kind of 'net' or 'membrane' that impedes its normal functioning). The fact that the same patient may present both dysplastic and proliferative alterations can hinder the classification of the disease as defined by the categories established for MDS/MPN by the WHO, as well as making it difficult to distinguish clearly between MDS and MPN.


These diseases are characterised by different rates of evolution to leukaemia, and shortened life expectations. Unlike MDS and MPN, the prognosis is not so well defined, and for various reasons: 1) they are very rare diseases; 2) the difficulty in differentiating MDS and MPN, and classifying them; 3) there have been few specific studies into these diseases.

The prognosis for CMML (the most frequent and best studied MDS/MPN) takes into account:

1) the intensity of decrease in the number of red blood cells and/or the need for a red blood cell transfusion;

2) the intensity of increase in the number leukocytes in the blood and of the blasts in the bone marrow;

3) the chromosomal alterations of the sick cells; and

4) the mutations presented by these cells (but this can not be determined for all patients, and their impact on the prognosis is still subject to final definition).

With this information in hand it is possible to quantify the degree of the disease by means of the CMML specific prognostic scoring system - CPSS, in which each parameter has a score, depending on its gravity, enabling an approximate prediction to be made regarding the risk of developing a leukaemia, within what time period, and the patient's chances of survival. The least aggressive cases of CMML may imply a life expectancy of 6 years while, with more aggressive forms, life expectancy may be for just one year. Therefore, treatment must aim to prevent the disease from becoming more aggressive and, if the patient is young, a bone marrow transplant may be proposed in an attempt to cure the disease.

There are still no specific prognostic indices for the other subtypes of MDS/MPN and it is not possible to predict how the disease will progress.


There are few effective treatments for aggressive forms of MDS/MPN and there is no established treatment protocol. On the other hand, there are specific treatment response criteria for these diseases. Generally speaking, the predominant characteristics presented by the patient are borne in mind (dysplasia or proliferative) and a treatment similar to that for MDS is administered for the former, and similar to that for MPN for the latter. If the disease is less aggressive it is enough to attempt to control the patient's symptoms. If the disease is more aggressive, and especially for younger patients, a bone marrow transplant may be proposed, which is the only treatment that presents the possibility for a cure, although it may cause serious complications resulting from infections and/or rejection of the transplanted bone marrow


Aggressive MDS/MPN (including high-risk CMML as defined by the CPSS):

Bone marrow transplant

bone marrow transplant (from a family member or a non-related person) is the only treatment that offers a cure, but can generally only be performed for younger patients.


Less aggressive MDS/MPN (including high-risk CMML as defined by the CPSS):

a) Predominance of dysplastic alterations (similar focus to that for MDS)


To treat anemia and the fatigue this causes, and the consequent deterioration in the patient's quality of life, and if the hemoglobin is less than 8g/dL, red blood cell transfusions are recommended. Transfusions are not without risk of the transmission of infectious diseases, and the accumulation of iron (this metal accumulates in the liver and heart especially).

Elimination of accumulated iron resulting from transfusions

In the case of an excess of iron resulting from a transfusion, the oral administration of Deferasirox, an iron chelator, is recommended, to eliminate the excess iron.


The subcutaneous administration of erythropoietin can improve the anemia and obviate the need for a transfusion. As is the case MDS, this treatment is administered if the erythropoietin in the blood is less than 500 U/L.

Hypomethylating agents

Treatment with drugs (azacytidine administered subcutaneously, and decitabine administered intravenously), may be considered to decrease DNA methylation (hypomethylation) because it has been observed that some patients respond to treatment. Azacytidine may be administered to AMML patients with dysplastic alterations (to administer it for the other kinds of MDS/MPN, or to administer decitabine, special permission is required).

These hypomethylating agents are tolerated better than chemotherapy (used less and less on account of its side effects). After approximately 6 courses of treatment (6 months) they can improve the anemia, thereby avoiding the need for the patient to receive transfusions, and any decrease in the number of white blood cells and/or platelets, thereby avoiding infections and/or hemorrhages. Treatment is continued until it ceases to work.

b) Predominance of proliferative alterations (similar focus to that for MPN)

In cases where there is a predominance of leukocytosis, thrombocytosis and/or polycythemia, as in the case of MPN, hydroxyurea is administered orally to prevent the bone marrow from producing these cells in excess. This drug can also control the swelling of the spleen, to some extent. If the patient is a smoker or has high levels of cholesterol or high blood pressure, aspirin may also be administered on account of the increased risk of thrombosis.

What does the future hold?

CMML apart, there is a need for prognostic indices for MDS/MPN to help predict patients' progress over the years, both in terms of life expectancy and the probability of developing a leukaemia.

With regard to treatment: 1) for patients with a predomination of proliferative alterations (such as enlarged spleen or constitutional symptoms), research is being conducted with drugs that attack the mutations that accelerate the cell metabolism such as ruxolitinib, administered to patients suffering from myelofibrosis, a subtype of MPN); and 2) research is being conducted into combinations of hypomethylating drugs with others that attack the mutations that accelerate the cell metabolism of patients who present both dysplastic and proliferative alterations.

Links of interest concerning medical issues relating to myelodysplastic syndromes

For more quality information about myelodysplastic syndromes, you can consult the following websites:


Links of interest about other general issues that may be of interest for patients with myelodysplastic syndromes

There are other resources and links of interest that may be of use to myelodysplastic syndrome patients:

There are other resources and links of interest that may be of use to adult acute myeloid leukaemia patients:


Help and support

On our website you will also find the testimonies of people who are suffering, or who have suffered, from this disease. We would also like to invite you to follow us on our main social networks (FacebookTwitter e Instagram) where we often share patients' accounts of overcoming the disease.

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Webpage updated 12/01/2023 13:27:05