Myelofibrosis is a clonal, myeloid stem cell neoplastic disorder that is grouped under Philadelphia chromosome negative myeloproliferative neoplasms along with polycythemia vera and essential thrombocytosis. It is an uncommon disorder that leads to bone marrow fibrosis. It is either classified as primary or secondary. The cause of primary myelofibrosis (PMF) is still unknown; however, prior radiation and chemical (benzene, toluene) exposure have been implicated as possible risk factors. Secondary myelofibrosis occurs due to polycythemia vera and essential thrombocytosis. It is mostly caused by mutation in JAK2 (Janus kinase-2), along with MPL (myeloproliferative leukemia virus oncogene) and CALR (calreticulin) gene mutation. It is mostly seen in elderly people over 50 years of age and has slight male predilection.
Common signs include anemia, leucopenia/leucocytosis, thrombocytopenia/thrombocythemia, splenomegaly, hepatomegaly and constitutional symptoms of the disease along with their complications. These may lead to symptoms of fatigue, weakness, fever, night sweats, itching, weight loss, tachycardia, palpitations, dyspnea, easy bruising/bleeding, infections, abdominal pain, and early satiety. Complications may include splenic infarct, portal hypertension, stroke, cardiac failure (in patients with pre-existing cardiac condition), disseminated intravascular coagulation, and transformation to acute myeloid leukemia. (2)
What Is The Life Expectancy Of A Person With Primary Myelofibrosis?
Since, primary myelofibrosis is a progressive myeloproliferative neoplasm; the life expectancy of a person with it is generally poorer to disease free individual of the same age. Primary myelofibrosis patients also have reduced life expectancy in comparison to other myeloproliferative neoplasms such as polycythemia vera and essential thrombocytosis. This was supported by a Swedish study in a population of 9384 patients diagnosed with Ph negative MPNs from 1973-2008. Although, survival rate improved significantly over time, the improvement diminished after 2000 and was only seen in patients with polycythemia vera and essential thrombocythemia.
Another European study on primary myelofibrosis patients between two time frames, including 1980-1995 (number of participants 434) and 1996-2007 (number of participants 368) showed significant improvement in the median survival between the two time frames, viz., 4.6 vs. 6.5 years. However, increase in life expectancy was observed only in patients categorized as low risk. No improvement in life expectancy was observed in intermediate risk and high risk patients.
The introduction and FDA approval of JAK 1 and 2 inhibitor, ruxolitinib for intermediate and high risk primary myelofibrosis patients has proved a beneficial treatment option for these patients. It has shown promise in modifying the disease course and increasing life expectancy in these patients. This has been justified by randomized clinical trials and meta-analysis in the United States and Europe.
IPSS (International Prognostic Scoring System) and DIPSS (Dynamic IPSS) are the two most popular prognostic systems among various scoring systems. IPSS is used at the time of diagnosis and DIPSS can be used at any time of the course of the disease. IPSS used five clinical variables, namely, age >65 years, hemoglobin <10 g/dl, leucocytes >25 x 109/l, circulating blasts ≥1% and constitutional symptoms. Based on these variables, prognosis is made as low, intermediate-1, intermediate-2 and high with a survival of 135, 95, 48 and 27 months, respectively. DIPSS scoring system assigned 2 points to anemia (IPSS assigned 1 point each to all the variables) and therefore, median survival now was 14.2, 4 and 1.5 years for low (0 score), intermediate-1, intermediate-2 and high risk patients. DIPPS is useful in predicting progression to blast phase and outcome for allogeneic stem cell transplantation in primary myelofibrosis patients.
Later unfavorable karyotype, red blood cell transfusion dependency and thrombocytopenia (<100 x 109/l) were noted to impact the outcome of primary myelofibrosis, so they were added to DIPPS prognostic scoring system and modified to DIPPS-plus. This scoring system summed the survival rate at 180, 80, 35 and 16 months, respectively for low, intermediate-1, intermediate-2 and high risk patients.
Patients have an increased risk of transformation to myeloid leukemia depending on circulating blasts and platelets ≤50 x 109/l and can be classified into low, intermediate and high risk patients. These patients have a risk of transformation of 3%, 10% and 35%, respectively. (1)
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