There is no staging system for this disease.
Prognostic factors include:[8,9,10,11,12]
- 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 the adverse features, excluding age, have a median survival of more than 10 to 15 years, but the presence of any two of the adverse features lowers the median survival to less than 4 years.[13,14] International prognostic scoring systems incorporate the aforementioned prognostic factors.[13,15]
Karyotype abnormalities can also affect prognosis. In a retrospective series, the 13q and 20q deletions and trisomy 9 correlated with improved survival and no leukemia transformation in comparison with the worse prognosis with trisomy 8, complex karyotype, -7/7q-, i(17q), inv(3), -5/5q-, 12p-, or 11q23 rearrangement.[7,16]
Asymptomatic low-risk patients (based on the aforementioned prognostic systems) should be followed with a watchful-waiting approach. The development of symptomatic anemia, marked leukocytosis, drenching night sweats, weight loss, fever, or symptomatic splenomegaly would warrant therapeutic intervention.
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:[4,17,18,19]
- Erythropoietic growth factors. Erythropoietin and darbepoetin are less likely to help when patients are transfusion dependent or manifest a serum erythropoietin level greater than 125 U/L.[20,21]
- Prednisone (40–80 mg/day).
- Danazol (600 mg/day).
- Thalidomide (50 mg/day) ± prednisone. Patients on thalidomide require prophylaxis for avoiding thrombosis and careful monitoring for hematologic toxicity.
- Lenalidomide (10 mg/day) ± prednisone.[23,24,25] In the presence of del(5q), lenalidomide with or without prednisone, can reverse anemia and splenomegaly in most patients.[23,24,25] However, patients on lenalidomide require prophylaxis for avoiding thrombosis and careful monitoring for hematologic toxicity.
- Pomalidomide. Patients on pomalidomide require prophylaxis for avoiding thrombosis and careful monitoring for hematologic toxicity.
Ruxolitinib, an inhibitor of JAK1 and JAK2, can reduce the splenomegaly and debilitating symptoms of weight loss, fatigue, and night sweats for patients with JAK2-positive or JAK2-negative primary myelofibrosis, post–essential thrombocythemia myelofibrosis, or post–polycythemia vera myelofibrosis. In two prospective, randomized trials, 528 higher-risk patients were randomly assigned to ruxolitinib or to best available therapy or placebo; at 48 weeks, patients on ruxolitinib had a decrease of 40% to 60% in mean palpable spleen length or in spleen volume compared with an increase of 1% to 4% with best available therapy.[Level of evidence: 1iiDiv]; [Level of evidence: 1iDiv] Ruxolitinib also improved overall quality-of-life measures with low toxic effects in both studies but with no benefit in overall survival. Discontinuation of ruxolitinib results in a rapid worsening of splenomegaly and recurrence of systemic symptoms.[28,29,30] Other JAK2 inhibitors are currently being studied in clinical trials.