ET is caused by abnormal production of platelets by the bone marrow which can lead to coagulopathy complications including thrombus, stroke, heart attack and pulmonary embolism. PV occurs when too many red blood cells are produced in the marrow; although it’s a chronic disorder, when well managed it’s often nonproblematic. However, it can precede other hematologic malignancies, including myelodysplastic syndrome and acute myeloid leukemia. MF has the worst prognosis of the MPNs and is associated with a buildup of fibers and scar tissue in bone marrow. Over time, the fibrotic tissue impedes the marrow’s ability to produce stem cells, impairing red blood cell, platelet, and white blood cell production as well as driving hematopoiesis outside of the bone marrow, particularly in the spleen.

Symptoms and Clinical Presentation

MPNs have no known screening and prevention methods. The disease typically presents as abnormal blood results during routine physicals or as myriad symptoms from abnormal production or collection of blood or stem cells.

After ruling out other causes, clinicians will conduct a blood examination and bone marrow aspirate and biopsy with cytogenetics and molecular testing to confirm the diagnosis.

Biomarkers

After testing for BCR-ABL1 to rule out chronic myeloid leukemia, molecular testing with a blood sample should be done to check for the JAK2, CALR, and MPL somatic driver variants, which are all mutually exclusive. Approximately 95%–98% of patients with PV, 50%–60% with MF, and 50%–60% with ET have a JAK2 variant. It is the most common variant found in MPNs and is linked to overproduction of red blood cells. CALR is altered in 16% of patients with MF.

Other biomarkers are serum erythropoietin levels and iron studies to diagnose and prognose. Advanced-stage disease will see increased loads of JAK2 variant. JAK2 may be monitored throughout treatment for patients with MF or PV taking a JAK1 or JAK2 inhibitor. If the cancer progresses, conduct molecular testing for acute myelogenous leukemia–associated variants.

Treatment

People can live with MPNs for years without experiencing symptoms, and watchful waiting may be a reasonable treatment approach. The JAK1/JAK2 inhibitor ruxolitinib has been evaluated for all MPNs with some success, and the U.S. Food and Drug Administration approved its use in MF and OV.

Other treatment modalities depend on the type of MPN:

MF: Treatment includes managing the symptoms associated with the disease. In addition to ruxolitinib, hydroxurea is often used for cytoreduction, but other drugs such as interferon, thalidomide, and lenalidomide may improve enlarged spleen, bone pain, and thrombocytosis associated. Other treatment strategies include splenectomy and radiation therapy. Hematopoietic stem cell transplantation is the only curative therapy, but it is associated with a high degree of complication, morbidity, and mortality. Fewer than 10% of patients are referred for transplantation.

ET: Treatment involves minimizing symptoms and reducing risk of thrombotic events. Aspirin, hydroxyurea, anagrelide, interferon, and plateletpheresis are commonly used.

PV: Low-risk patients are treated with aspirin and therapeutic phlebotomy, whereas higher-risk patients are managed with the former as well as cytoreductive therapies such as hydroxyurea, interferon, ruxolitinib, or busulfan.

Because the conditions are rare, we are still learning about best treatment pathways. Patients requiring treatment should be referred to clinical trials.

Side Effects

JAK1/JAK2 inhibitors are associated with myelosuppression and infection, bruising, headache, dizziness, and diarrhea. Hydroxyurea is associated with myelosuppression and infection and can produce dose-limiting toxicities in white blood cell and platelet counts.

Survivorship

Symptom management and quality of life are a strong focus. MPNs can progress to secondary malignancies; patients should keep scheduled appointments and focus on follow-up care. If patients received stem cell transplantation, survivorship considerations expand to include organ toxicities and acute graft-versus-host disease for the remainder of life.