Polycythemia vera is a type of slow-growing neoplasm, localized to the bone marrow, whose chief manifestation is an excessive production of red blood cells. While polycythemia vera is not curable, with good medical management, people who have this condition will commonly live for decades.
One of the therapies that has been used to treat polycythemia vera is interferon alpha. It is administered as an injection.
Polycythemia Vera
Polycythemia vera is one of the eight types of myeloproliferative neoplasms (MPN), a family of disorders in which the bone marrow produces excessive amounts of certain kinds of cells (for instance, polycythemia vera produces too many red cells, and essential thrombocythemia produces too many platelets) or excessive fibrosis (primary myelofibrosis). Polycythemia vera can occur at any age, but is much more common in people over 60.
While interferon alpha is usually not considered a first-line treatment for polycythemia vera, and while side effects can limit its use, a majority of people with this condition who are treated with interferon alpha have favorable results.
While the MPN disorders, including polycythemia vera, are not considered malignancies, if untreated they can lead to fatal complications, and at times they can develop into malignant cancers.
With polycythemia vera, the red blood cell counts become higher than normal—often much higher than normal. Polycythemia can lead to an increased risk of bleeding. Also, if the red cell count is high enough, blood flow can become sluggish and blood clotting can increase, leading to venous or arterial blockages and consequences such as heart attack, stroke, and pulmonary embolism.
People with polycythemia vera may also develop an enlarged spleen and gastrointestinal ulcers. In addition, they may have a host of troublesome or disabling symptoms, including weight loss, headaches, dizziness, severe pruritus (itchy skin—classically after a hot shower), easy bruising, weakness, fatigue, blurred vision, and erythromelalgia (burning pain in the hands or feet).
Gout is also a common problem in people with this condition, and a small number of people can eventually develop malignant leukemia.
There is no cure for polycythemia vera. However, a number of treatments are available that can reduce the red blood cell count and diminish or eliminate the symptoms caused by this condition. Among these treatments is interferon alpha.
Uses of Interferon Alpha
The interferons comprise a family of small signaling proteins, made by virtually every tissue in the body, whose chief function is to defend against (that is, “interfere” with) viral infections. When a cell is infected with a virus, interferons signal the cell to begin producing substances that can prevent the virus from replicating.
Interferons also have actions which can help to fight certain bacterial infections and can inhibit the growth of neoplasms. Specifically, interferons can inhibit the growth of abnormal cells and enhance the activity of white cells that can attack and kill tumor cells.
Three types of interferons—alpha, beta, and gamma—are produced by different types of cells in the body, and they have somewhat different actions. Researchers have developed all of them into drugs that are being used to treat various types of infections, neoplasms, and other conditions.
Interferon alpha has proven useful in the treatment of chronic hepatitis B or C, genital warts, and for certain cancers including malignant melanoma, Kaposi’s sarcoma associated with AIDS, and follicular lymphoma.
Another use for interferon alpha is in the treatment of polycythemia vera. While interferon alpha is not currently considered a first-line treatment for this condition, it is nonetheless an important therapy for many people with polycythemia vera.
Treating Polycythemia Vera
Given that no cure exists at this time, the goal of treating polycythemia vera is to control symptoms and prolong survival.
Treatment is based on whether the patient is judged to be at high or low risk. People who are under 60 years of age and have no history of abnormal blood clots are considered to be at low risk. Those who are 60 years old or above, or who have a history of blood clots, are considered to be at high risk.
Low-risk patients are generally treated with phlebotomy (blood drawing) to reduce the red blood cell count and low-dose aspirin to prevent blood clots. Aspirin is also reasonably effective in reducing two symptoms that are peculiar to polycythemia vera—pruritus and erythromelalgia.
Phlebotomy is usually required weekly, aiming to keep the hematocrit (a measure of the proportion of blood volume accounted for by red blood cells) under 45%. Once it is under 45%, phlebotomy is required every two to four weeks or less.
High-risk patients are also treated with phlebotomy and aspirin, but in addition they are given “cytoreductive” therapy, which is drug treatment aimed at inhibiting the bone marrow’s ability to produce excessive red blood cells.
In addition to inhibiting red cell production, cytoreductive therapy often improves many of the symptoms caused by polycythemia vera. For this reason, cytoreductive therapy is commonly used even in low-risk patients who have troublesome and persistent symptoms.
Several cytoreductive drugs are used in treating polycythemia vera, including hydroxyurea, busulfan, ruxolitinib, and interferon alpha. Most experts consider hydroxyurea to be the best first-line option, because it has been used for decades, is relatively inexpensive, and is reasonably well tolerated.
Busulfan has fallen out of favor for the treatment of polycythemia vera because it has been weakly associated with persistent bone marrow suppression and the development of leukemia. Today, it is used chiefly when other drugs have been tried and have failed.
Ruxolitinib is FDA approved for the treatment of polycythemia vera as a second-line drug, specifically in people who have failed with hydroxyurea. It is not a first-line drug mainly due to its expense, and because its long-term effectiveness and toxicities are not fully known. In practice, most experts reserve its use for people with polycythemia vera who have marked enlargement of the spleen, because ruxolitinib is particularly effective in reducing splenic enlargement.
Interferon Alpha for Polycythemia Vera
Interferon alpha is possibly the most favored second-line drug for polycythemia vera, as it is quite effective in treating this condition.
Up to 80% of patients treated with interferon alpha achieve control of their red blood cells, a reduction in symptoms (including pruritus), and a reduction in spleen size. Some studies suggest that interferon alpha may produce somewhat better disease control than hydroxyurea.
However, interferon alpha is more difficult to tolerate than hydroxyurea and is also substantially more expensive.
A newer form of interferon alpha, called PEGylated interferon alpha-2a (sold under the brand name Pegasys) currently appears to be the most favorable type of interferon alpha for treating polycythemia vera.
“PEGylated” refers to the fact that a polyethylene glycol chain has been added to the interferon alpha. PEGylation reduces the side effects of the drug, making it more tolerable, and prolongs its activity which reduces the frequency of injections. Studies are ongoing comparing the efficacy of PEGylated interferon alpha-2a with hydroxyurea.
PEGylated interferon alpha-2a is administered as a subcutaneous injection, beginning with a dose of 45 micrograms (mcg) weekly and increasing to a maximum of 180 mcg weekly as tolerated, while monitoring the hematocrit and symptoms.
Side Effects
Common side effects of PEGylated interferon alpha-2a include nausea, vomiting, flu-like sickness, fever, insomnia, irritability, muscle pain, and appetite loss.
Less common but more severe side effects include the induction of autoimmune diseases including psoriasis, lupus and rheumatoid arthritis; serious mood disorders and depression, which may include hallucinations, mania, and aggressive behavior; increased susceptibility to infections; and an increase in blood pressure that may lead to stroke.
A Word From Verywell
Interferon alpha is a drug derived from human cells that modulates the immune system, fights certain infections, and has anti-tumor activity. It is useful in treating polycythemia vera, a form of neoplasm. Currently it is considered a second-line drug for this condition.
Newer formulations of interferon alpha, aimed at reducing toxicity and increasing its duration of action, are being evaluated in randomized trials to determine whether it might eventually become a first-line drug for polycythemia vera.
