Determining risk in patients with myelofibrosis can be achieved by using a prognostic scoring system called the Dynamic International Prognostic Scoring System + (DIPSS +), which assesses a variety of laboratory and clinical features. Patients are categorized as low, intermediate-1, intermediate-2, or high risk.2

Mr M is older than 65 and is symptomatic due to his disease, placing him in the intermediate risk category.  The splenomegaly associated with myelofibrosis has caused secondary effects on the hepatopulmonary system, and treatment should be started. Additionally, Mr M has leukocytosis with a WBC greater than 25,000. These 3 features lead to categorization as intermediate-2 disease.  Although not incorporated into the DIPSS +, the presence of an ASXL1 mutation indicates the patient is at higher risk for disease progression. 

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Identifying goals of treatment are important when determining appropriate treatment. In this case, Mr M would benefit from spleen reduction, WBC control, and symptom improvement. Ruxolitinib, a JAK1/2 inhibitor, is currently the only FDA-approved therapy for intermediate and high-risk myelofibrosis. This therapy was granted FDA approval based on phase 3 clinical trials that showed significant reduction in spleen size and improvement in symptoms, among other benefits.This would be the choice of therapy for Mr M. Of note, clinical trial enrollment for patients with myelofibrosis should be considered, especially for those who are ineligible for ruxolitinib therapy. 

Starting Ruxolitinib Therapy 

For patients with myelofibrosis, ruxolitinib dose is based on the patient’s platelet count. Reductions in WBC, RBC, and PLTs are expected due to the agent’s suppressive effect on cellular production signaling pathways. For patients whose platelets are between 100,000 and 150,000, the starting dose would be 15 mg twice daily.4

Mr M is started on ruxolitinib 15 mg twice daily, and has improvement in splenomegaly and reduction in WBC to 12×109/L. With a hemoglobin level of less than 8.0, he receives a blood transfusion 2 weeks after starting therapy for symptomatic anemia. Fatigue and shortness of breath improve after PRBC transfusion. Laboratory assessment after 4 weeks of therapy show worsening thrombocytopenia (75,000 × 2 weeks). Due to the platelets falling and staying at approximately 75,000 on 2 occasions, the ruxolitinib dose is reduced to 10 mg twice daily. The platelets can fluctuate fairly frequently in these patients, and since Mr M was right on the border for dose reduction, laboratory tests were repeated to confirm and avoid unnecessary dose reductions. 

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