Myeloproliferative neoplasms
What is it?
Myeloproliferative neoplasms (MPNs), formerly called myeloproliferative diseases, are a group of bone marrow disorders characterized by abnormal and neoplastic proliferation of myeloid lineage cells, precursors of white blood cells that reside in the bone marrow. If these cells start multiplying uncontrollably, they invade the bone marrow and hinder the production of healthy blood cells; sometimes this also happens in the liver and spleen. Each myeloproliferative neoplasm is identified according to its predominant marrow and blood characteristics.
Myeloproliferative neoplasms are differentiated by the presence or absence of the Philadelphia chromosome (abnormality of chromosomes 9 and 22).
Philadelphia-positive myeloproliferative neoplasms include:
- chronic myeloid leukemia (CML): this condition is also known as Philadelphia-positive myeloproliferative neoplasm, as it is characterized in almost all cases by the Philadelphia chromosome. It is characterized by the excessive proliferation of granulocytes. The white blood cells of these patients are numerically excessive and often unable to defend against infection.
Philadelphia-negative myeloproliferative neoplasms include:
- polycythemia rubra vera (also known as Osler-Vaquez disease or Di-Guglielmo's disease, PV): uncontrolled proliferation affects mainly red hyglobules, manifests with excessive increase in hematocrit and hemoglobin values resulting in increased risk of developing vascular events (mainly thrombotic);
- essential thrombocythemia (ET): uncontrolled proliferation mainly involves platelets resulting in an increased risk of developing vascular events (mainly thrombotic);
- primary myelofibrosis (MF): defect in the production of white blood cells and platelets with the appearance of areas of bone marrow fibrosis, frequently associated with volumetric increase of the spleen.
There are also rare forms of Philadelphia-negative myeloproliferative neoplasms called hypereosinophilic syndromes and chronic neutrophilic leukemia characterized by excessive production of eosinophils or neutrophils, respectively. Systemic mastocytosis (SM) is also part of the MPN category. Each of these conditions has the potential to develop into acute leukemia, but the risk rates vary greatly depending on the type and characteristics of the underlying disease.
Causes and risk factors
The causes of myeloproliferative neoplasms are not known, and risk factors to avoid have not been identified. However, they may increase the likelihood of developing the disease:
- advanced age;
- exposure to radiation;
- exposure to petrochemicals such as benzene and toluene.
Which are the symptoms?
MPNs often lack early symptoms, which can make diagnosis difficult. The symptoms are rather vague and heterogeneous and are not indicative of pathology. In some cases, patients are completely asymptomatic. Symptoms may include:
- progressive asthenia (fatigue);
- dyspnea (feeling of shortness of breath);
- fever and recurrent infections;
- major weight loss in a short period of time;
- profuse night sweats;
- abdominal pain; difficulty during digestion; feeling of early postprandial stuffiness if the spleen is enlarged;
- bleeding in cases of reduced platelet counts;
- systemic itching (in PV cases typically occurs on contact with water, aquagenic);
- drowsiness;
- headache;
- vascular manifestations: skin redness associated with pain (predominantly facial in PV); superficial or deep venous thrombosis also in atypical sites (abdominal and cerebral); arterial thrombosis (myocardial infarction and cerebral stroke).
How is it diagnosed?
If a myeloproliferative neoplasm is suspected, a medical examination and interview will be conducted. In-depth blood and instrumental tests will then be prescribed:
- blood tests: blood tests include CBC, peripheral blood smear with optical leukocyte formula count, body iron status and vitamins used by the marrow (vitamin B12, vitamin B6, folic acid), erythropoietin assay. In particular, molecular analysis of some specific mutations (BCR-ABL, Jak2 V617F, Jak2 exon 12, MPL, CALR, c-KIT) known to be related to the various types of myeloproliferative neoplasia is needed;
- myeloaspirate and bone marrow biopsy: using a long needle attached to a syringe, the doctor aspirates a small amount of bone marrow and a fragment of bone to examine under a microscope to determine and quantify cancerous cells. This examination is essential for diagnosis and also provides genetic and molecular information about the type of the myeloproliferative neoplasm;
- instrumental examinations such as ultrasound of the abdomen aimed at assessing the size of the liver and spleen. MRI or CT scans of certain body districts may be proposed in case the specialist wants to rule out thrombotic phenomena.
Suggested exams
How is it treated?
The treatment of myeloproliferative neoplasia depends on the type of disease and is discussed and proposed by specialists based on a comprehensive evaluation that takes into account several factors, including the type and biology of the disease, age, and general health condition of the patient. Treatment is mainly given in a dedicated outpatient clinic, only in special cases in day hospital and/or inpatient ward. International guidelines are followed and officially recognized standard drugs are used, e.g., tyrosine kinase inhibitors (TKIs) for CML, oncocarbide, interferon (IFN), JAK2 inhibitors in Philadelphia negative MPNs. Appropriate molecular response monitoring according to the recognized standard is performed, and patients diagnosed with CML who meet the criteria required by the guidelines are offered discontinuation of therapy. In selected cases, protocols with new drugs are proposed if potentially beneficial to the patient. In cases of no response to standard therapy and/or clonal evolution of disease, intensive treatment programs are considered, which may include bone marrow transplantation.
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