Myelofibrosis is a myeloproliferative neoplasm that results in bone marrow fibrosis along with deficiency in myeloid blood cell production and extramedullary hematopoiesis resulting in constitutional symptoms. It is classified as primary or secondary. The exact etiology for primary disease is unknown, but environmental factors such as prior radiation exposure and chemicals (benzene, toluene) have been implicated. Whereas, secondary myelofibrosis occurs subsequent to polycythemia vera and essential thrombocythemia. It is a relatively rare condition, affecting about 0.1-3 individuals per 100,000 individuals across the world. It is an elderly disease that is diagnosed in the people of the age of 50-60 years.
What Happens If Myelofibrosis Goes Untreated?
Since, myelofibrosis is a heterogeneous disease; the prognosis is also quite varied. Some individuals with advanced disease may succumb to the disease early in life while others with mild form of the disease may continue to live for years. Since, the disease is a progressive form of myeloproliferative neoplasm, without treatment the patient has poor prognosis. The treatment is aimed at reducing the symptoms and preventing the progression of the disease, so if it is left untreated the disease may progress and lead to progressive signs and symptoms along with complications and early death. (1)
Myelofibrosis is an asymptomatic disease in as much as 21% of all cases at the time of diagnosis. Therefore, blood tests play an important role in early and accidental detection of the disease, which often shows signs of anemia, leucocytosis/leucocytopenia, thrombocytosis/thrombocytopenia, splenomegaly and hepatomegaly. When myelofibrosis is left untreated, fatigue is exasperating and greatly reduces the patient’s quality of life.
Other constitutional symptoms associated with the disease are also exaggerated, which have an impact on the prognosis of the patient, thereby reducing it significantly. Constitutional symptoms encompass pruritus, night sweats, fever and weight loss.
Splenomegaly is characteristic of myelofibrosis, probably due to extramedullary hematopoiesis. It seen in more than 80% of patients at the time of diagnosis presenting symptoms of early satiety (feeling of fullness), abdominal discomfort, and left upper quadrant pain. If left untreated splenomegaly may worsen due to continued sequestration of immature myeloid cells by spleen. This may lead to worsening of abdominal swelling and pain and may even cause splenic infarct. Splenomegaly may also lead to portal hypertension, which is also complicated by hepatomegaly that is also a common presenting sign of myelofibrosis. Portal hypertension subsequent to hepatomegaly as well as excessively enlarged spleen is a life threatening complication. It may lead to ascites, esophageal varices and gastric varices, which when rupture may lead to profuse bleeding. Other complications include splanchnic vein thrombosis and Budd Chiari syndrome. (1)
Extramedullary hematopoiesis may also lead to complications associated with other organs including, central nervous system causing intracranial hypertension and ensuing symptoms of headache, dizziness, papilledema, altered mental state, gait instability, paralysis, coma and even death; pleura leading to symptoms of hemothorax and pleural effusions; gastrointestinal tract complicating already present symptoms with intestinal lumen obstruction, bile duct obstruction, cholecystitis; kidney leading to kidney failure. It may also lead to arthritis and skin manifestations leading to neutrophilic dermatosis.
The symptoms of anemia and thrombocytopenia along with leucopenia/leucocytosis are worsened with progression of bone marrow fibrosis, if left unmanaged. Worsening anemia leads to debilitating fatigue and weakness and may even affect cardiovascular system, brain and lungs leading to cardiac failure, stroke and worsening of worsening of pre-existing pulmonary diseases.
Thrombocytopenia may worsen with increased risk and severity of hemorrhage that may even lead to hemorrhage inside the organs and disseminated intravascular coagulation. DIC is a life threatening condition especially if it is accompanied by portal hypertension. The chances of infections also increase due to leucopenia/neutropenia.
In addition, there is an increased possibility of bone marrow failure and transformation to acute myeloid leukemia, which is further associated with worse prognosis. (1)
Myelofibrosis, in itself is associated with increased morbidity and mortality. So when it is left untreated the survival is further reduced and chances of death increases.
Therefore, it is important to seek treatment for this life threatening neoplasm.