Hydroxyurea Resistant Polycythemia Vera - Episode 3
Ruben A. Mesa, MD: Laboratory monitoring of a patient with polycythemia vera involves many aspects. It certainly involves monitoring the degree of erythrocytosis and, specifically, the hematocritkeeping that level under 45%, whether that be through phlebotomy, hydroxyurea, or even other cytoreductive therapies.
Now, it’s important to monitor the other blood counts themselves. For leukocytosis and thrombocytosis, we don’t want those counts to be excessively elevated, but we need to be mindful that they don’t decrease to a concerning level related to excess myelosuppression from a therapy like hydroxyurea. That individual could certainly develop neutropenia or thrombocytopenia and have a risk of infection or bleeding. We do monitor liver and kidney function. It would be uncommon for this type of intervention to have an adverse impact on either of those 2 organs, but these are important things for us to be monitoring.
Uncontrolled polycythemia vera, in the context of taking hydroxyurea, might have several different phenotypes. And I view our goals as control of symptoms; control of splenomegaly, or the resolution of splenomegaly; a control of accounts; and absence of progression. Individuals really having a breakthrough with any of those factors are probably having an adequate response to hydroxyurea. Hydroxyurea is a helpful cytoreductive drug and is frequently the most effective in controlling the counts with polycythemia vera, but if it disappoints us, it’s usually in that context of trying to control disease symptoms, splenomegaly, or other aspects of myeloproliferation that are not as count-based as strictly erythrocytosis.
This individual is now really presenting with additional symptoms. He has abdominal fullness, and on an exam, we find that the patient has splenomegaly. The individual is having some signs of toxicity on the hydroxyurea: difficulties with both appetite and foodreally not tasting appropriately—in the setting of those doses. For me, that represents some degree, really, of resistance. Particularly, the development of splenomegaly is showing me that there is really inadequate control of the myeloproliferation in the setting of that dose of hydroxyurea. But additionally, there is certainly a suggestion of intolerance of hydroxyurea, as well, based on the issues of appetite and change in taste.
This individual has inadequate control of their erythrocytosis. One can measure that in a variety of ways. Is it the need for ongoing phlebotomies well into the time of therapy? Is it an increase in the hematocrit? Is it that every time one checks the hematocrit for phlebotomy, their level is above 45%? All of these indicators in this individual demonstrate thatdespite the current level of therapy, which has been fairly aggressive with recurrent phlebotomies and the need for hydroxyurea—the degree of erythrocytosis is not adequately controlled. This helps to propagate the symptoms associated with the PV for this patient, but it also increases that risk of thrombosis or bleeding in that the patient doesn’t have the adequate protection from or control of erythrocytosis.
This individual also now has leukocytosis. That is an additional risk factor that has been identified for both risk of thrombosis in bleeding and contributing to symptomatic difficulties. Indeed, in an individual who is now found to have abdominal fullness and splenomegaly, those features of leukocytosis suggest an additional level of myeloproliferation that impacts both symptoms, as well as risk of thrombosis and bleeding. In the ideal world, it would be well controlled with a selected medical therapy, but the hydroxyurea at its current maximum tolerated dose is not achieving those goals.
Transcript edited for clarity.