Is Myelofibrosis A Cancer?
Myelofibrosis, also known as primary myelofibrosis or agnogenic myeloid metaplasia, is a rare clonal disorder in which the hematopoietic stem cells become cancerous. In addition, as the name implies, it is characterized by the formation of scar tissue in the bone marrow. It falls under the group of chronic myeloproliferative disorders along with polycythemia vera, essential thrombocytosis, chronic myelogenous leukemia, chronic neutrophilic leukemia and chronic eosinophilic leukemia. In about 10-15% cases, polycythemia vera and essential thrombocytosis may also progress to myelofibrosis, known as secondary myelofibrosis. It is mostly a cancer of the elderly with 65 years as the median age of diagnosis. Adult males are more commonly affected than females; however, when children are affected girls are more commonly affected.
Myeloid stem cell lineage is the most commonly affected cell line; however, fibroblasts and T cells may even be affected. The reason behind bone marrow fibrosis still remains unclear. The majority of the patients develop myelofibrosis due to mutations in Janus kinase 2 (JAK2), MPL and calreticulin (CALR) genes. However, in <5% patients, mutations in KRAS, NRAS, GATA2, PTPN11, TP53 and RUNX1 genes have been noted. Although, the etiology of primary myelofibrosis is still unclear, certain risk factors such as prior radiation and exposure to certain industrial solvents such as benzene and toluene have been known to increase the risk of the disease.(1)
Symptoms Of Myelofibrosis
The symptoms of myelofibrosis are associated with anemia, increased metabolism, splenomegaly, thrombocytopenia, extramedullary hematopoiesis, portal hypertension, changes in immune system and bone. In nearly, 25% patients, no symptoms are present and diagnosis is incidental in these patients. Others have symptoms of fatigue, weakness, shortness of breath, palpitations, pain/discomfort on upper left side of the stomach, diarrhea, feeling of early fullness, low grade fever, night sweats, weight loss, petechiae, melena, disseminated intravascular coagulation, hematuria, hemoptysis, ascites, seizures, respiratory distress, esophageal/gastric varices, hepatic encephalopathy, infections, and joint/bone pain. Splenomegaly and hepatomegaly are the two most common findings in myelofibrosis occurring in about 90% and 60-70% of the patients.(2)
Diagnosis Of Myelofibrosis
The diagnosis of myelofibrosis is determined based on CBC, which shows signs of anemia, thrombocytosis/thrombocytopenia, and leucopenia/leukocytosis. Imaging studies include skeletal radiographs to study the pattern of bony trabeculae, MRI is used bone marrow patterns, and splenomegaly and hepatomegaly can be assessed with ultrasonography and CT scans. Bone marrow biopsy is used for definitive diagnosis, while genetic testing can be done to rule out other differential diagnoses.
Management Of Myelofibrosis
There have been great advancements in the management of myelofibrosis. Asymptomatic patients or patients with mild symptoms are monitored. Intervention is provided for symptomatic patients. Ruxolitinib (Jakafi) is the only FDA approved drug for the management of myelofibrosis. There are other off label drugs to manage thrombocytosis, leukocytosis and organomegaly. These include hydroxyurea, cladribine, interferon, and busulfan. Other drugs include corticosteroids, thalidomide, lenalidomide, erythropoietin, and androgens (oxymetholone, danazol). Androgens and erythropoietin can be used to improve anemia.
Splenectomy is considered in patients requiring continuous RBC transfusions and progressing anemia despite treatment, portal hypertension, thrombocytopenia and symptomatic splenomegaly not managed with hydroxyurea. Radiation therapy is also used for the treatment of extramedullary hematopoiesis, bone pain or symptomatic splenomegaly. Splenic irradiation is only done in patients for whom surgery is contraindicated. Allogeneic stem cell transplantation is the only curative treatment for myelofibrosis resulting in complete remissions. However, the procedure itself carries high mortality and risk of complications.(3)
Prognosis Of Myelofibrosis
The prognosis of the patient depends whether the patient is low risk, intermediate risk or high risk. High risk patients have poor prognosis with median survival time of 13 months, intermediate risk patients have 26 months survival and low risk patients have 93 months survival time. Therefore, the median survival time is 3.5-5.5 years for myelofibrosis patients. The common causes of death include infections, bleeding, postsplenectomy mortality, and cardiac failure, transformation into acute leukemia (in about 20% patients), hepatic failure, renal failure and thrombosis.
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