Fatal and nonfatal thrombosis was associated with age more than 60 years and JAK2 positivity in a multivariable analysis of 707 patients followed from 1973 to 2008. Bone marrow examination including cytogenetic testing may exclude other causes of myelophthisis, such as CML, myelodysplastic syndrome, metastatic cancer, lymphomas, and plasma cell disorders. In acute myelofibrosis, patients present with pancytopenia but no splenomegaly or peripheral blood myelophthisis. Peripheral blood or marrow monocytosis is suggestive for myelodysplasia in this setting.
There is no staging system for this disease.
Prognostic factors include:[9,10,11,12,13]
- Age 65 years or older.
- Anemia (hemoglobin <10 g/dL).
- Constitutional symptoms: fever, night sweats, or weight loss.
- Leukocytosis (WBC >25 � 109 /L).
- Circulating blasts of at least 1%.
Patients without any of these adverse features, excluding age, have a median survival of more than 10 years, while the presence of any two of these adverse features lowers the median survival to less than 3 years. An international prognostic scoring system has been proposed by the Working Group for Myelofibrosis Research and Treatment.
Karyotype abnormalities can also affect prognosis. In a retrospective series of 200 patients, 13q and 20q deletions and trisomy 9 correlated with improved survival and no leukemia transformation in comparison to the trisomy 8 or a complex karyotype.
The profound anemia that develops in this disease usually requires red blood cell transfusion. Red blood cell survival is markedly decreased in some patients; this can sometimes be treated with glucocorticoids. Disease-associated anemia may occasionally respond to the following:[4,15,16,17]
JAK2 inhibitors are being evaluated in randomized trials, and patients may be eligible even in the absence of a JAK2 mutation.(COMFORT-I trial [NCT00952289])
Painful splenomegaly can be treated temporarily with chemotherapy (hydroxyurea), interferon, thalidomide, lenalidomide, or radiation therapy, but often requires splenectomy.[17,18] The decision to perform splenectomy represents a weighing of the benefits (i.e., reduction of symptoms, decreased portal hypertension, and less need for red blood cell transfusions) versus the debits (i.e., postoperative mortality of 10% and morbidity of 30% caused by infection, bleeding, or thrombosis; no benefit for thrombocytopenia; and accelerated progression to blast crisis that was seen by some investigators but not others).[4,18]
Hydroxyurea is useful in patients with this disease but may have a potential leukemogenic effect. In patients with thrombocytosis and hepatomegaly after splenectomy, cladribine has shown responses as an alternative to hydroxyurea. The use of interferon-alpha can result in hematologic responses, including reduction in spleen size in 30% to 50% of patients, though many patients do not tolerate this medication.[20,21] Favorable responses to thalidomide and lenalidomide have been reported in about 20% to 60% of patients.[15,16,17,22,23][Level of evidence: 3iiiDiv]