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Looking Beyond Hematocrit Control in Polycythemia Vera

Insights From: Srdan Verstovsek, MD, PhD, University of Texas MD Anderson Cancer Center; Daniel J. DeAngelo, MD, PhD, Dana-Farber Cancer Institute; Kim-Hien T. Dao, DO, PhD, Oregon Health & Science University
Published Online: Wednesday, Jan 04, 2017



Transcript:

Srdan Verstovsek, MD, PhD:
In patients that have a high risk of thrombosis and have polycythemia vera, we will introduce cytoreductive therapy. And hydroxyurea is traditionally the first choice, particularly here in the United States, with the goal of decreasing and maintaining hematocrit below 45%. That has been proven in a prospective randomized study to be the goal of the therapy. However, we have been cognizant of other issues that people with polycythemia vera may have, not only increased hematocrit. I’m talking about increase in white blood cells, increase in platelets, enlargement of the spleen, and bad quality of life. Even with good control of hematocrit, these other factors can be present. And, experts in the field, in general, community physicians, are cognizant that we are not only treating the number of red blood cells, we need to look beyond that.

So, once we settle on a cytoreductive therapy, hydroxyurea as a first choice, usually, we should be looking beyond the red blood cell control. One would like to have control of all the other factors: control the red blood cells, platelets, white cells, spleen, and symptoms. This is how we would like to assess the response to therapy, and particularly in a development of new drugs to be able to fully comprehend the benefit of the new therapy that we are developing.

The hydroxyurea traditionally has been used over decades to control the red blood cells. And, now, with our understanding of complexity of the disease, sometimes it’s not easy to really say how well hydroxyurea does in controlling these 5 factors. But, attempts have been made in a retrospective way to assess the utility of hydroxyurea, and it is very active, in fact. In many patients, it can control all these 5 factors, but in about 20% to 25%, it does not really work at all. About 10% to 12% of the patients will not respond, they’re refractory, and about 10% to 12% would also be intolerant. There will be toxicities to hydroxyurea. It’s interesting to analyze what kind of toxicities we are talking about. The first and most common, 90% of the toxicities related to hydroxyurea, are related to the ulcers. Are these skin ulcers or mouth ulcers, particularly skin ulcers on the lower part of the legs around the ankle? Then, you have can have GI upset with diarrhea, low-grade fevers, hair loss, and skin rash. Those are relatively rare. But, about 10% to 12% of the patients do have intolerance to hydroxyurea, and it should be recognized as such.

Kim-Hien T. Dao, DO, PhD: When I put a patient on hydroxyurea, I carefully evaluate for intolerance. And some of these intolerances are symptoms such as nausea, vomiting, night sweats, and fevers. The other thing that providers have to be very careful in evaluating when they see the patients is also development of mucocutaneous ulcers. That is another common reason for patients to not tolerate hydroxyurea. And so, you have to examine their oral cavity and also their skin, especially on their feet. The other scenario where I carefully watch for intolerance is patients who have poor wound healing from other medical conditions such as cellulitis, or an ulcer from diabetes, or post-surgery wounds. In those situations, you have to monitor the wound healing very carefully while on hydroxyurea because they may not be healing well because of the hydroxyurea. Although generally well tolerated, everyone should be assessing their patients for signs of intolerances to hydroxyurea.

One additional intolerance of hydroxyurea I should mention is the development of cytopenias. We may be using hydroxyurea to reduce the hematocrit, but sometimes our limitation is not so much the dose, but actually that the white cell count or the platelets are going too low in order to control the hematocrit. So, this is another consideration for evaluating hydroxyurea failure or intolerance.

Transcript Edited for Clarity
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Transcript:

Srdan Verstovsek, MD, PhD:
In patients that have a high risk of thrombosis and have polycythemia vera, we will introduce cytoreductive therapy. And hydroxyurea is traditionally the first choice, particularly here in the United States, with the goal of decreasing and maintaining hematocrit below 45%. That has been proven in a prospective randomized study to be the goal of the therapy. However, we have been cognizant of other issues that people with polycythemia vera may have, not only increased hematocrit. I’m talking about increase in white blood cells, increase in platelets, enlargement of the spleen, and bad quality of life. Even with good control of hematocrit, these other factors can be present. And, experts in the field, in general, community physicians, are cognizant that we are not only treating the number of red blood cells, we need to look beyond that.

So, once we settle on a cytoreductive therapy, hydroxyurea as a first choice, usually, we should be looking beyond the red blood cell control. One would like to have control of all the other factors: control the red blood cells, platelets, white cells, spleen, and symptoms. This is how we would like to assess the response to therapy, and particularly in a development of new drugs to be able to fully comprehend the benefit of the new therapy that we are developing.

The hydroxyurea traditionally has been used over decades to control the red blood cells. And, now, with our understanding of complexity of the disease, sometimes it’s not easy to really say how well hydroxyurea does in controlling these 5 factors. But, attempts have been made in a retrospective way to assess the utility of hydroxyurea, and it is very active, in fact. In many patients, it can control all these 5 factors, but in about 20% to 25%, it does not really work at all. About 10% to 12% of the patients will not respond, they’re refractory, and about 10% to 12% would also be intolerant. There will be toxicities to hydroxyurea. It’s interesting to analyze what kind of toxicities we are talking about. The first and most common, 90% of the toxicities related to hydroxyurea, are related to the ulcers. Are these skin ulcers or mouth ulcers, particularly skin ulcers on the lower part of the legs around the ankle? Then, you have can have GI upset with diarrhea, low-grade fevers, hair loss, and skin rash. Those are relatively rare. But, about 10% to 12% of the patients do have intolerance to hydroxyurea, and it should be recognized as such.

Kim-Hien T. Dao, DO, PhD: When I put a patient on hydroxyurea, I carefully evaluate for intolerance. And some of these intolerances are symptoms such as nausea, vomiting, night sweats, and fevers. The other thing that providers have to be very careful in evaluating when they see the patients is also development of mucocutaneous ulcers. That is another common reason for patients to not tolerate hydroxyurea. And so, you have to examine their oral cavity and also their skin, especially on their feet. The other scenario where I carefully watch for intolerance is patients who have poor wound healing from other medical conditions such as cellulitis, or an ulcer from diabetes, or post-surgery wounds. In those situations, you have to monitor the wound healing very carefully while on hydroxyurea because they may not be healing well because of the hydroxyurea. Although generally well tolerated, everyone should be assessing their patients for signs of intolerances to hydroxyurea.

One additional intolerance of hydroxyurea I should mention is the development of cytopenias. We may be using hydroxyurea to reduce the hematocrit, but sometimes our limitation is not so much the dose, but actually that the white cell count or the platelets are going too low in order to control the hematocrit. So, this is another consideration for evaluating hydroxyurea failure or intolerance.

Transcript Edited for Clarity
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