Jamile M. Shammo, MD:I think the dose that this patient has receivedbeing 500 mg initially, 1 tablet—that’s really remarkable that it did result in symptom control. So, in a way, I’m not surprised that the dose had to be taken up to 1000 mg, and frankly, if you wanted to exactly assess or categorize the response of the 1000 mg of Hydrea, even if it were to suboptimal, you can argue that it may be because the dose wasn’t sufficient. Because again, let’s remember, the guidelines for Hydrea resistance demand that the patient needs to be taking at least 2 g of Hydrea for at least 3 months, without any optimization of the hematological parameters. In which case, you can say that, “Well, maybe you had a patient who has actually developed Hydrea-resistance.” But if she hasn’t even taken 1000 mg, or even 1500 mg, then it would hard to argue or make a case for resistance to Hydrea.
So, I will probably increase the dose and then see how the patient is tolerating the higher dose. It’s possible that they may develop intolerance, in which case you try to control the symptoms. You’re trying to optimize the hematocrit to reduce the risk of thrombotic events, but then your patient develops heme toxicity. In which case, you are forced to interrupt the dose because you want to present symptoms of consequences of things like neutropenia, etc. Then it becomes an issue of tolerability to the medicine.
Whether or not the increased need for phlebotomy can be associated with worse outcomeand she was not clear up until a recent study that looked at patients who required greater than 3 phlebotomies in a year’s time—they demonstrated that those patients had the worse outcome actually. So, I think this needs to be looked into in a prospective fashion to actually get confirmation that people who do have increased rate of phlebotomy do have a worse outcome ultimately. All we have is, to some extent, retrospective data from Alvarez-Larrán, who looked at basically patients who met the criteria for resistance and intolerance, and demonstrated that lack of response is associated with survival and higher chance of transformation. But when it comes to phlebotomy itself, I think there is a suggestion that it may be associated with worse outcome, but we don’t have concrete data. Nonetheless, there are data relative to thrombosis. So, if you want to reduce the chances of thrombosis, then it would be important to keep the hematocrit below 45%. But I think the question about frequency of phlebotomy is still out there.
I think that monitoring the iron parameter is extremely important, especially when you are dealing with someone who has a high phlebotomy. The whole idea of phlebotomy is so that you would make a patient iron deficient to the point where they basically cannot make hemoglobin, and their hematocrit, therefore, is well controlled. Therefore, when I have a patient who all of a sudden decided to have high hematocrit, other than the fact that we discussed compliance with the medication, I also check their iron stores. Because it may very well be that they need to be phlebotomized so that you can optimize or make them iron deficient again. Again, there’s some suggestion that making patients iron deficient may, by itself, create a whole set of new symptoms akin to what patients with iron deficiency develop. But that’s a topic for a different discussion.
I do check their iron parameters, but I think another extension, or I should say, an element to this is, what are their other counts doing? Do they have evidence of myeloproliferation? Is their white count increasing? Because let’s face it, phlebotomy is not going to optimize a high white blood cell count. So, I think as physicians, we need to evaluate the extent of myeloproliferation, and not just elevation of hematocrit in this patient population, and determine whether higher cytoreduction or just simply phlebotomy will be sufficient for those patients.
Transcript edited for clarity.