Myelofibrosis is a clonal disorder characterized by neoplastic transformation of hematopoietic stem cells along with bone marrow fibrosis. Myelofibrosis can further be divided into primary with no known etiology and secondary, which are subsequent to polycythemia vera and essential thrombocythemia. In about 60% of patients, there is JAK mutation in patients of myelofibrosis. Prior exposure to radiation and chemicals such as benzene and toluene has been associated with increased risk of myelofibrosis development. Myelofibrosis is a malignancy of the elderly individuals with a median age of diagnosis being 65 years. It has a slight male predilection.
How Serious Is Myelofibrosis?
The only probable cure for patients with myelofibrosis is allogeneic stem cell transplantation; however, only about 3% patients fall in the eligibility criteria. In addition, it is associated with high mortality rates, thereby reducing life expectancy further. No drug, except ruxolitinib has the ability to modify the disease course; however, ruxolitinib is associated with side effects of anemia and myelosuppression, therefore it has to be used with caution. Thus, with reduced quality of life with myelofibrosis and lack of effective treatment, it is considered a serious disease with considerable complications related to both disease and treatment. (1)
Clinical Manifestations Of Myelofibrosis
Approximately 21% of patients with myelofibrosis are asymptomatic and the patients are diagnosed by discrepancy in blood count showing signs of anemia, leucocytosis/leucocytopenia, thrombocytosis/thrombocytopenia, splenomegaly and hepatomegaly. Surveys have showed that more than 80% patients have at least one disease associated symptom at the time of initial diagnosis. Fatigue is commonly present in patients with myelofibrosis at the time of diagnosis, which is often chronic and associated with reduction in the quality of life.
Other disease related constitutional symptoms are also quite common. These include fever, itching, diaphoresis, and weight loss. These symptoms are considered to be subsequent to disproportionate cytokines production and which drastically reduce the quality of life of people, in addition to reduced life expectancy. Splenomegaly and hepatomegaly are two other characteristic features of myelofibrosis, considered to be due to extramedullary hematopoiesis. Splenomegaly is noted in about 80% of people at the time of diagnosis. It can cause symptoms of upper left quadrant pain, abdominal discomfort and feeling of early fullness. Splenic infarct may be noted as a complication of splenomegaly.
Hepatomegaly is seen in about 39-65% of patients at the time of diagnosis of myelofibrosis. The most common complication associated with it is portal hypertension, which itself can become life threatening. Symptoms of portal hypertension may include ascites along with variceal bleeding that may lead to severe hemorrhage. Apart from hepatosplenomegaly, extramedullary hematopoiesis is associated with other complications when other organs are affected. When central nervous system is affected, it may cause intracranial hypertension leading to symptoms of headache, papilledema, delirium, altered consciousness, gait instability, paralysis, coma and even death. It may even lead to hemothorax and pleural effusions when pleura is affected.
The symptoms of anemia include weakness, fatigue, increased heart rate, palpitations, shortness of breath, and can even lead to stroke and cardiac failure in patients with pre-existing cardiovascular disease. Lung problems can also be exacerbated in patients with pre-existing lung diseases.
Thrombocytopenia is associated with increased risk of bleeding and on occasions can lead to disseminated intravascular coagulation. DIC is considered a life threatening complication of thrombocytopenia, more so if it is accompanied by portal hypertension. Thrombosis can also be found in patients with thrombocytosis and has been associated with increased mortality. Myelofibrosis is also associated with increased risk of infections and decreased immunity, mainly attributed to leukopenia. Few patients transform into acute myeloid leukemia.
Myelofibrosis is associated with increased morbidity and mortality. Since, it is a disease of the elderly, other systemic diseases such as diabetes, hypertension, obesity, atherosclerosis or pulmonary complications can further impact the survival of patients and lead to poor outcomes. Although, low risk patients have a longer life expectancy, intermediate risk patients have a survival rate of about 5 years, which is reduced to 2 years in high risk patients. (2)
- Mughal TI, Vaddi K, Sarlis NJ, Verstovsek S. Myelofibrosis-associated complications: pathogenesis, clinical manifestations, and effects on outcomes. Int J Gen Med. 2014;7:89–101. Published 2014 Jan 29.