Ask the Experts – Sandra Kurtin Nurse

Oncology Nurse Advisor (ONA): What is the role of phlebotomy in the treatment of patients with polycythemia vera (PV)?

Dr Kurtin: PV is a disease that is primarily characterized by erythrocytosis. This increase in blood volume, together with the inflammatory nature of PV, places the patient at an increased risk for thrombosis. Phlebotomy, together with low-dose aspirin, is the treatment of choice in newly diagnosed patients. The goal is to maintain the hematocrit below 45%. The frequency and duration of phlebotomy will depend on the individual patient’s response and tolerance.

ONA: What options are available if phlebotomy does not provide adequate hematocrit control?

Dr Kurtin: Some of it will depend on the patient. The most common presentation is a high hemoglobin and hematocrit (erythrocytosis), but some patients may have elevated white blood cells (lymphocytosis) and elevated platelets (thrombocytosis). Phlebotomy does not effectively control lymphocytosis or thrombocytosis, both of which contribute to the risk of bleeding or clotting. If phlebotomy is not adequate in controlling the hematocrit or if the patient has significantly elevated white blood cells or platelets, cytoreductive therapy is recommended. In the United States, hydroxyurea is the most common cytoreductive therapy used. Interferon may also be used as cytoreductive therapy but is less common in the United States.

ONA: What are the signs and/or symptoms that indicate the patient may have persistent disease or is intolerant to treatment? What are your tactics for monitoring patients from diagnosis and throughout treatment?

Dr Kurtin: The JAK-STAT pathway is associated with hematopoiesis and inflammatory cytokines. Mutations in this pathway cause upregulation of the hematopoiesis and an increase of the inflammatory cytokines resulting in the elevated blood counts and the disabling symptoms patients with PV may experience. The most common disease-related symptoms include fatigue, pruritic, bone pain, fevers, early satiety (due to splenomegaly), and abdominal pain. Reducing these symptoms, along with reducing the elevated blood counts, is the primary goal of therapy in PV.

First, we typically start patients on phlebotomy and aspirin to reduce the clotting potential. Again, the goal is to maintain the hematocrit below 45%. We also want to maintain the WBC below 10,000 and the platelets below 400,000. If a patient has splenomegaly, we expect that to decrease by at least 50%. We start hydroxyurea, together with aspirin, based on the patient’s counts and how many cell lines are involved. We will gradually increase the dose of hydroxyurea if we find that the treatment is not effective in reaching the milestones. If the patient continues to require phlebotomy despite cytoreductive therapy at the maximum dose (> hydroxyurea 2gm/day) or does not reach the milestones after 3 months at that dose, we will consider a change in therapy like ruxolitinib, a JAK2 inhibitor. We know that 95% of people with PV are JAK2-positive.

In some patients, the hydroxyurea may cause the WBC or platelet count to go too low, placing the patient at an increased risk of infection or bleeding. Other patients may have difficulty tolerating the hydroxyurea, or in some cases may develop leg ulcers that are painful and are difficult to heal. Patients receiving interferon often experience profound fatigue and may have psychological changes or hyperglycemia. In both cases, the patient would be intolerant to cytoreductive therapy.

Monitoring depends on the type of treatment that a patient is receiving. If a patient is on hydroxyurea and is well controlled the strategy would just be to follow them. In some patients, this approach can be used for many years. The frequency of visits will depend on their response (meeting milestones) and the presence or absence of symptoms of clinical findings. In patients with well-controlled disease, visits might be every 6 months after they have reached their milestones. For patients whose disease is less well controlled it is necessary to schedule follow up visits more frequently. We work closely with the patient to provide them with the information needed to contact us for any changes in their symptoms. If major changes occur, we may need to schedule a bone marrow biopsy to make sure that their disease isn’t moving toward myelofibrosis.

ONA: What are the risks for patients with persistent/intolerant PV?

Dr Kurtin: The biggest risks of not controlling the disease are clotting and bleeding. Quality of life (QOL) is also very important. If we are not able to control the symptoms associated with PV, this will have a negative impact on QOL. Patients who develop neutropenia or thrombocytopenia due to cytoreductive therapy or progressive bone marrow failure will be at risk for infection or bleeding. The patients that develop hydroxyurea-associated ulcers are also at an increased risk of infection and often experience ulcer-related pain that is difficult to treat.

ONA: What are the criteria for initiating treatment with ruxolitinib in patients with PV? Do you follow a particular protocol to identify appropriate patients?

Dr Kurtin: The National Comprehensive Cancer Network (NCCN) guidelines have been recently updated and provide specific criteria for determining if the patient is resistant or intolerant to hydroxyurea. I mentioned many of these previously. Criteria for defining resistance include the continuing need for phlebotomy despite cytoreductive therapy, meaning a patient’s hematocrit levels can’t be kept below 45%, and not controlling disease-related symptoms, including those associated with splenomegaly. Criteria for defining intolerance include the development of cytopenias due to cytoreductive therapy (ANC < 1000, platelets < 100,000), and treatment-related adverse events including hydroxyurea-associated leg ulcers. Patients that meet any of these criteria should be considered for treatment with ruxolitinib.