Ruben A. Mesa, MD:A continued need for phlebotomy well into the management of polycythemia vera can be problematic on a variety of levels. Individuals may have difficulty tolerating it, such as this individual, with issues such as fatigue, dizziness, and lightheadedness each time they have phlebotomy. For the individual in which phlebotomy works well, we typically see that the need for a number of phlebotomies goes down relatively rapidly and that we are inducing an iatrogenic state of iron deficiency to try to control the erythrocytosis that individuals have with polycythemia vera.
Now, that iron deficiency has its own toxicity, and this individual is experiencing that toxicity. Appropriately, they begin on cytoreductive therapy, and that hydroxyurea is indicated for individuals who are tolerating phlebotomy as the sole management of polycythemia vera. I think their management has been appropriate and that we should begin with hydroxyurea, but the dose of hydroxyurea that we use is really balanced against its effectiveness. We want to decrease that number of phlebotomies to a minimal level and try to monitor for any progression, as well as any toxicity related to hydroxyurea, whether it be neutropenia, thrombocytopenia, or other difficulties.
This individual continues on hydroxyurea based on the need for continued phlebotomies, and now he develops progressive pruritus, a common symptom of polycythemia vera. His dose of hydroxyurea is increased to 2000 mg per day. While on that dose, he continues to have significant pruritus, as well as a need for phlebotomies. In many ways, this individual now meets the criteria established by the European LeukemiaNet that defines hydroxyurea resistance for an individual with polycythemia vera. The goals of the use of hydroxyurea are control of the hematocrit so that phlebotomies are not needed, control of the other counts, avoidance of symptoms, and tolerability of the therapy itself.
Hydroxyurea, as I share with patients, is a drug where individuals typically take between 10 and 20 tablets per week, 500 mg at a timeso, 20 or 21 tablets a week; that’s about 3 pills, or 1500 mg, a day. The individual who needs significantly more than that is really an outlier and, in many ways, is not really having an adequate response to hydroxyurea.
The maximum tolerated dose of hydroxyurea depends a bit on its goal, and we use it in a variety of settings. In the setting of polycythemia vera, a very chronic indication, I would be reluctant to go above 2000 mg per day. We will certainly consider it in higher doses in more acute settings at the time of presentationin the setting of extreme thrombocytosis or in individuals with an increase in blast cells who are moving towards acute leukemia. But in this setting, I would consider 2000 mg to be the top dose for any extended period of time.
Transcript edited for clarity.