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Question: Dr. Chiragbhai, thank you for explaining in last part about Essential Thrombocytosis – differential diagnosis of high platelet count, importance of testing for CML even with only high platelet count, good prognosis, simple treatment with hydroxyurea and aspirin, or no treatment in many cases, risk of bleeding not just thrombosis, and other interesting facts.
Ans: Yes. ET is an interesting diagnosis, with many misconceptions re which patients to treat and how much to treat. Now let us talk about PMF – primary myelofibrosis – another interesting disorder, but probably worst prognosis among the MPNs, with some important new therapies.
Que: How do you diagnose this disease?
Ans: Most patients with PMF present with fatigue due to anemia, abdominal pain or early satiety due to large spleen, and other nonspecific symptoms. Large splenomegaly is common but not essential for diagnosis. Small spleen may also be seen. Peripheral smear in typical cases shows leucoerythroblastic picture i.e. left shift of myeloid series, normoblasts; and presence of tear drop cells. Bone marrow trephine biopsy is mandatory for diagnosis, which shows fibrosis, by reticulin stain. Aspirate is frequently not possible due to fibrosis. JAK 2 mutation is positive in 50% cases. It is important to rule out CML, MDS etc as marrow fibrosis can be seen in other MPNs and various diseases apart from PMF. Even infections like tuberculosis can cause bone marrow fibrosis.
Extramedullary hematopoiesis is an interesting complication of this disease. As bone marrow function reduces to fibrosis, other body parts may start producing blood. Hence islands of bone marrow like soft tissue form in various areas, resulting in complications like spinal cord compression, GI bleeding, hemorrhagic pleural effusion, seizures etc.
Bleeding and thrombosis both are important complications of this disease. Bleeding is due to platelet count and quality, subclinical DIC seen in many cases, portal hypertension with varices, peptic ulcer, acquired factor V deficiency. A hypermetabolic state may be seen with weight loss, night sweats, low grade fever, high uric acid, gout, kidney stones.
Median survival is about 3-5 years.
Que: How do you treat PMF? Is splenectomy helpful?
Ans: In the past, treatment has been mainly supportive. Blood transfusions, androgens, hydroxyurea and aspirin have been the common medicines used.
More recently, thalidomide and prednisone combination has been used with reasonable improvement overall. Interferon, busulfan etc have been used with some results.
Splenectomy is avoided as far as possible, as there is significant mortality with this procedure in PMF patients. Main complications are serious bleeding due to platelet dysfunction or low platelet count and subclinical DIC, infections, thrombosis. Patients may develop marked hepatomegaly, and there is significantly increased risk of transformation to AML. In patients with painful splenomegaly unresponsive to medical measures, radiotherapy to spleen is also an option.
Most recently, a JAK1/JAK2 inhibitor drug Ruxolitinib has been approved. It reduces spleen size in 25-40% patients, and is generally well tolerated oral agent. Everolimus, an mTOR inhibitor has also been shown, in small studies, to reduce spleen size and other effects of PMF.
ONLY CURATIVE OPTION however is Allogeneic Stem Cell Transplant, with cure rates of about 30% to 70% in some modern series. It is a preferred option in younger patients below 40 years, especially if there is a sibling match. There is some controversy regarding timing of transplant. Some prefer to transplant in early stages when patients are otherwise well without complications and outcome is better overall. Some like to wait till higher stages to delay an aggressive treatment like transplant as far as possible. Patients should be given adequate information to make an informed decision in this regard. Younger the patient and higher the stage, transplant is a better option.
Dr. Chirag A. Shah; M.D. Oncology/Hematology (USA), 079 26754001. Diplomate American Board of Oncology and Hematology. Ahmedabad. Shyam Hem-Onc Clinic. 402 Galaxy, Near Shivranjani, Opp Jhansi ki Rani BRTS, Ahmedabad.