Myeloproliferative syndromes types, symptoms, causes, treatments

The myeloproliferative syndromes They are a group of chronic diseases that have serious consequences on the health and life in general of the people who suffer from it. These types of syndromes, currently called myeloproliferative neoplasms, include all conditions in which at least one type of blood cell, produced in the bone marrow, develops and proliferates uncontrollably.

The main difference of these syndromes compared to myelodysplastic syndromes is that, in myeloproliferative syndromes, the bone marrow makes cells in an uncontrolled way, while in myelodysplastic syndromes there is a deficit in the manufacture of cells.

To understand the subject well, it is necessary to know how blood cells develop from bone marrow stem cells, explained in the article on myelodysplastic syndromes.

Article index

• 1 Causes
  • 1.1 Genetic factors
  • 1.2 Environmental factors
  • 1.3 Risk factors
• 2 Types of myeloproliferative syndromes
  • 2.1 Polycythemia vera
  • 2.2 Essential thrombocythemia
  • 2.3 Primary myelofibrosis
  • 2.4 Chronic myeloid leukemia
• 3 Symptoms
  • 3.1 -Polycythemia vera
  • 3.2 -Essential thrombocythemia
  • 3.3 -Primary myelofibrosis
  • 3.4 -Chronic myeloid leukemia
• 4 Treatment
  • 4.1 Polycythemia vera
  • 4.2 Essential thrombocythemia
  • 4.3 Primary myelofibrosis
  • 4.4 Chronic myeloid leukemia
• 5 References

Causes

Myeloproliferative syndromes occur because the bone marrow creates cells in an uncontrolled way, but why this occurs is not entirely clear. As in most syndromes, there are two types of factors that seem to be related to the onset of the syndrome:

Genetic factors

In some patients, a chromosome, called the Philadelphia chromosome, has been found to be shorter than normal. So it seems that there is a genetic component that increases the predisposition to suffer from this disease.

Environmental factors

genetic factors alone are not explanatory of these syndromes since there are people in whom the Philadelphia chromosome shortening has not been found and, however, present one of the syndromes.

Some studies suggest that environmental factors such as continued exposure to radiation, chemicals, or heavy metals increase the likelihood of suffering from this type of disease (as it occurs in other cancers).

Risk factor's

Other factors, such as the age or gender of the patient, can increase the risk of developing a myeloproliferative syndrome. These risk factors are described in the following table:

Types of myeloproliferative syndromes

The current classification of myeloproliferative syndromes includes:

Polycythemia vera

This syndrome is characterized by the fact that the bone marrow produces too many blood cells, especially red blood cells, which thicken the blood. It is related to the JAK2 gene, which appears mutated in 95% of cases (Ehrlich, 2016).

Essential thrombocythemia

This condition occurs when the bone marrow produces too many platelets, causing the blood to clot and form thrombi that obstruct the blood vessels, which can cause both cerebral and myocardial infarctions..

Primary myelofibrosis

This disease, also called myelosclerosis, occurs when the bone marrow produces too much collagen and fibrous tissue, which decreases its ability to create blood cells..

Chronic myeloid leukemia

This syndrome, also called marrow cancer, is characterized by the uncontrolled production of granulocytes, a type of white blood cell, which end up invading the bone marrow and other organs, preventing their proper functioning..

Symptoms

In most cases, symptoms are not noticeable early in the disease, so people often realize they have the syndrome on routine tests. Except for primary myelofibrosis, in which the spleen normally enlarges, resulting in abdominal pain.

Each syndrome has a different clinical picture with characteristic symptoms, although some symptoms are present in various conditions.

-Polycythemia vera

The clinical manifestation includes the following symptoms:

Nonspecific symptoms (occur in 50% of cases)

• Asthenia (physical weakness or fatigue).
• Night sweats.
• Weightloss.
• Gout crisis.
• Epigastric discomfort.
• Generalized itching (itching).
• Difficulty breathing.

Thrombotic phenomena (occur in 50% of cases)

• Cerebrovascular accidents.
• Angina pectoris.
• Heart attacks.
• Intermittent claudication (muscle pain) of the lower extremities.
• Thrombosis in abdominal veins.
• Peripheral vascular insufficiency (with redness and pain in the fingers and soles of the feet that worsens with exposure to heat).

Bleeding (occurs in 15-30% of cases)

• Epistaxis (bleeding from the nostrils).
• Gingivorrhagia (bleeding gums).
• Digestive bleeding.

Neurological manifestations (occur in 60% of cases)

• Headaches.
• Tingling in the hands and feet.
• Feeling dizzy.
• Visual disturbances.

-Essential thrombocythemia

The clinical manifestation includes the following symptoms:

Microcirculation disorders (occur in 40% of cases)

• Redness and pain in the fingers and toes.
• Distal ganglia.
• Transient cerebrovascular accidents.
• Ischemias.
• Syncope.
• Instability
• Visual disturbances.

Thrombosis (occurs in 25% of cases)

Bleeding (occurs in 5% of cases).

-Primary myelofibrosis

The clinical manifestation includes the following symptoms:

Constitutional (occur in 30% of cases)

• Lack of appetite.
• Weightloss.
• Night sweats.
• Fever.

Derivatives of anemia (occur in 25% of cases)

• Asthenia (physical weakness or fatigue).
• Dyspnea on exertion (feeling short of breath).
• Edema in the lower extremities (swelling caused by fluid retention).

Splenomegaly (occurs in 20% of cases)

• Spleen swelling with abdominal pain.

Other less frequent causes (occur in 7% of cases)

• Arterial and venous thromboses.
• Hyperuricemia (increased uric acid in the blood), which can trigger gout.
• Generalized itching (itching).

-Chronic myeloid leukemia

Most of the symptoms are constitutional:

• Asthenia (physical weakness or fatigue).
• Loss of appetite and weight.
• Fever and night sweats.
• Trouble breathing.

Although patients can also suffer other symptoms such as infections, weakness and broken bones, heart attacks, gastrointestinal bleeding and an enlarged spleen (splenomegaly).

Treatment

Currently there is no treatment available that can cure myeloproliferative syndromes, but there are treatments to alleviate the symptoms and prevent possible future complications that the patient may suffer..

The treatment used depends on the type of proliferative syndrome, although there are some indications (such as nutritional changes) that are generic for all myeloproliferative syndromes.

Polycythemia vera

The treatments used to alleviate the symptoms of polycythemia vera are intended to reduce the number of red blood cells, for this, medications and other therapies are used, such as phlebotomy.

Phlebotomy is performed to evacuate a certain amount of blood, through a small incision, to lower the levels of red blood cells and reduce the likelihood of patients having a heart attack or other cardiovascular disease.

This is a first-line treatment, that is, the first treatment that the patient receives once they have been diagnosed. This is so because it has been shown to be the only treatment that increases the life expectancy of people suffering from polycythemia vera..

Medication treatment includes:

• Myelosuppressive therapy with hydroxyurea (trade names: Droxia or Hydrea) or anagrelide (trade name: Agrylin). These drugs reduce the number of red blood cells.
• Low doses of aspirin, to reduce fever and redness and burning of the skin.
• Antihistamines, to reduce itching.
• Allopurinol, to reduce the symptoms of gout.

In some cases it is also necessary to apply other therapies, such as blood transfusions if the patient has anemia or surgery to remove the spleen if it has increased in size..

Essential thrombocythemia

Essential thrombocythemia is primarily managed mediation, including:

• Myelosuppressive therapy with hydroxyurea (trade names: Droxia or Hydrea) or anagrelide (trade name: Agrylin), to reduce red blood cell levels.
• Low doses of aspirin, to reduce headaches and redness and burning of the skin.
• Aminocaproic acid, to reduce bleeding (usually used before surgery, to prevent bleeding).

Primary myelofibrosis

Primary myelofibrosis is basically treated with medication, although in severe cases other treatments such as surgeries, transplants and blood transfusions may be necessary..

Medication treatment includes:

• Myelosuppressive therapy with hydroxyurea (trade names: Droxia or Hydrea), to reduce the number of white blood cells and platelets, improve the symptoms of anemia and prevent some complications such as an enlarged spleen.
• Thalidomide and lenalidomide, to treat anemia.

In some cases the spleen noticeably increases in size and it is necessary to perform surgery to remove it.

If the person has severe anemia, they will need blood transfusions, in addition to continuing with the medication..

In the most severe cases, it is necessary to perform a bone marrow transplant, which replaces the damaged or destroyed cells with healthy ones.

Chronic myeloid leukemia

The number of treatments available for chronic myeloid leukemia has increased dramatically and mainly includes drug therapies and transplants..

Medication treatment includes:

• Targeted therapy for cancer, with drugs such as dasatinib (brand name: Sprycel), imatinib (brand name: Gleevec), and nilotinib (brand name: Tasigna). These drugs affect certain proteins in cancer cells that prevent them from multiplying uncontrollably.
• Interferon, to help the patient's immune system fight cancer cells. This treatment is only used if a bone marrow transplant cannot be performed..
• Chemotherapy, drugs such as cyclophosamide and cytarabine are given to kill cancer cells. It is usually done just before the patient receives a bone marrow transplant..

In addition to medical therapy, there are other treatments that can significantly improve the conditions and life expectancy of patients, such as a bone marrow or lymphocyte transplant..

References

1. Ehrlich, S. D. (February 2, 2016). Myeloproliferative disorders. Obtained from the University of Maryland Medical Center: 
2. Josep Carreras Foundation. (s.f.). Chronic myeloproliferative syndromes. Retrieved on June 17, 2016, from Fundación Josep Carreras
3. Gerds, Aaron T. (April 2016). Myeloproliferative Neoplasms. Obtained from Cleveland Clinic