Primary myelofibrosis, also known as idiopathic myelofibrosis and agnogenic myeloid metaplasia, is a malignant disease, one of the chronic myeloproliferative neoplasms, along with polycythemia vera and essential thrombocythemia, amongst others (see table 1).

Table 1.- Chronic myeloproliferative neoplasms

— Chronic myeloid leukaemia BCR-ABL positive — Primary myelofibrosis — Essential thrombocythemia — Polycythemia vera — Chronic eosinophilic leukaemia — Chronic neutrophilic leukaemia — Unclassified myeloproliferative neoplasms

In these diseases the stem cells in the bone marrow, responsible for producing all the blood cells, have acquired a genetic defect which makes them produce one of the myeloid lineage blood cells in an uncontrolled manner. This genetic alteration is not hereditary (it is not transmitted from parents to their offspring), although some families have a predisposition to develop myeloproliferative neoplasms.

Primary myelofibrosis is characterised by the presence of a fibrous tissue in the bone marrow, and by the migration of bone marrow stem cells to the blood, where they colonise organs from a distance (mainly the spleen and the liver).

It is a disease that occurs very infrequently, with an incidence of 5-7 cases per million, per year. It affects predominantly patients of advanced age, the average age for diagnosis being 65. It is more frequently found in men and, very occasionally, is diagnosed in infancy.

A proportion of patients with polycythemia vera and essential thrombocythemia will, over the course of time, develop symptoms of bone marrow fibrosis indistinguishable from that in primary myelofibrosis. 

In a third of cases the disease shows no symptoms and is therefore detected by chance during a routine blood test. When there are clinical manifestations, they tend to be: constitutional symptoms (30%)(loss of appetite, weight loss, heavy night sweats, fever), anemic syndrome (25%)(fatigue, shortness of breath with physical effort, edema of the legs), abdominal pain related to the enlargement of the spleen (called splenomegaly) (20%)(bloated sensation after eating, pain to the left of the abdomen), or, less frequently, arterial or venous thrombosis (7%), bleeding, recurrent infections, generalised itchiness (pruritus), bone pain and gout attack (due to hyperuricemia).

For diagnosis it is essential to perform a bone marrow analysis and biopsy. Cytogenetic and molecular studies are also required, being important for diagnosis, and also in order to estimate the course of the disease. In this respect, two thirds of patients have a mutation in the JAK2 (50-60%), CALR (20-30%) or MPL (5-10%) genes that is present in the blood cells and which constitutes a marker for the disease. 

Myelofibrosis is a very heterogeneous disease at the clinical level and it requires individualised treatment that is adjusted to risk. Some people can live for years without showing any symptoms, while others may suffer from an aggressive disease from the beginning, or one which worsens progressively. In both cases patients need to be monitored regularly at a centre with experience of dealing with myelofibrosis.

The first decision to be made with regard to how to respond to a patient with myelofibrosis is whether to treat the patient, or not. If the patient is asymptomatic and does not present analytic data that suppose a potential risk, it is feasible to wait and to carry out regular tests with a view to starting treatment when the need to do so arises. Otherwise, it must be determined whether the patient is a candidate for an allogenic transplant of hematopoietic progenitors (from a family member on non-related donor), bearing in mind the patient's age, general state of health, and perceived chances of survival in accordance with standardised prognosis indices.

An allogenic transplant is, at the present time, the only treatment that offers the possibility of a cure for myelofibrosis. However, given that it carries a high risk of mortality and morbidity, this procedure is reserved for young patients, in an otherwise generally good state of health, but who have been diagnosed with a myelofibrosis with a poor prognosis.

In practice, most patients are not candidates for a transplant and their treatment is directed at controlling the symptoms. There are a number of therapeutic strategies for doing this which, in general, are aimed at improving the anemia, or controlling the hyperproliferative manifestations of the disease (constitutional symptoms and painful splenitis). In this regard, the most outstanding advance over recent years has been the introduction of ruxolitinib, a drug that is very effective for controlling the hyperproliferative manifestations of the disease and pruritus (itching), something that generally leads to a considerable improvement in the patient's quality of life.

When these symptoms are not very severe, hydroxyurea may be administered, given its ease of use and good tolerance levels. Erythropoietic agents (erythropoietin, darbepoetin) and danazol are especially efficacious for improving anemia, while in refractory cases treatment may also benefit from the use of immunomodulatory drugs (thalidomide, lenalidomide) or low levels of corticoids. Splenectomy (the surgical removal of the spleen) has practically been abandoned given its high rates of mortality and morbidity, although it may be indicated in very specific cases. Available therapeutic options have a transitory effectiveness and the inclusion of patients in clinical trials with new drugs must be considered.

The survival of patients with myelofibrosis varies considerably depending on the presence or otherwise of unfavourable prognostic factors (advanced age, intense anemia, constitutional symptoms, leucocytosis, thrombocytopenia, circulating blast count and high-risk cytogenetic or molecular alterations).

The main causes of death are progressive clinical deterioration deriving from the myelofibrosis itself, transformation to leukaemia (20%, 10 years after diagnosis), heart failure, infections and thrombotic and hemorrhagic complications.

For more quality information about primary myelofibrosis you can consult the following websites:

 

• Myelofibrosis. Leukemia and Lymphoma Society

• Myelofibrosis treatment. Leukemia and Lymphona Society
  
  
• Chronic myeloproliferative neoplasms treatment. National Cáncer Institute

• Bone marrow transplant guide. Fundación Josep Carreras

There are other resources and links (in Spanish) of interest that may be of use to essential thrombocythemia patients:

 

• Recomendaciones generales sobre la alimentación durante el tratamiento del cáncer. ICO