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Monitoring Iron Levels in Transfusion-Dependent MDS

Panelists:James M. Foran, MD, FRCPC, Mayo Clinic Cancer Center; Azra Raza, MD, Columbia University Medical Center; David P. Steensma, MD, Dana-Farber Cancer Institute
Published: Friday, Apr 15, 2016


Transcript:

James M. Foran, MD, FRCPC:
Do you use transferrin saturation then instead of ferritin or do you still follow ferritin? Or do you use testing like, for instance, MRI testing or T2* sequence testing and MRI to look for iron overload? Do you do more detailed testing on patients?

Azra Raza, MD: It is a very important practical issue. So for time immemorial, we have been using ferritin. It’s inexpensive, it’s available everywhere, easy to use. The only problem is it’s an acute phase reactant. So ferritin levels could be high if a patient is infected, has inflammation, or has something going else going on. And suddenly you have a high ferritin level. So, I regularly use [the] serum ferritin level as my first line measurement of iron overload. But it has to be consistently elevated over a certain level, which is 1000 mg of ferritin consistently in the presence of at least 10 transfusions. So it isn’t a ferritin level of 1200 without a transfusion. That, I would think, is ineffective hematopoiesis. But if they have a history of at least 10 transfusions or 20 units of blood combined with a ferritin level of 1000, then I know there is iatrogenic iron overload.

The second issue is, can we make iron overload measurements more accurate by more modern technology? And certainly you can by using these T2* MRIs both for the liver and heart, which can very accurately document the deposition of iron in these organs. These are highly sophisticated measures, and they are confined to only specialized centers. Now, I believe they've become more common, but still they may not be the most common test that a community hematologist would have access to the minute they thought of iron overload. So, I do think that we should definitely universally utilize the serum ferritin level, just making sure that we are interpreting it properly in the background of having no inflammation, no infection, etc.

We revert to T2* MRI use only in special conditions, such as when suddenly unexplained problems start occurring with liver function tests or there are cardiac issues and the patient has now received at least 20, 25, 30 transfusions. You start worrying that their iron deposition, ferritin is going up; the patient is not following the regime of iron chelation that you prescribe. In those settings, it is very important to even refer a patient to a specialized center for these MRIs.

James M. Foran, MD, FRCPC: This is not the same as a liver MRI. They needed a dedicated sequence. It’s not like a fibroscan, it’s not like some other liver workup. You have to have the software for it, so you have to request it. I think we use it a lot less in adult hematology than the pediatric hematologist. I think that they use this much more commonly than we do. I suspect it will become more and more important as we get better therapies for iron overload. Do you ever use the T2* to follow the patients or do you just follow the serum ferritin once you address that?

Azra Raza, MD: I think judicious use of both.

James M. Foran, MD, FRCPC: I see. Well, I’ll come back to that point. This may sound like kind of a facile question, but what happens to your MDS patients? What do they die of?

Azra Raza, MD: MDS patients have very heterogeneous scores. So the lower-risk MDS patients will have increasing profundity of their cytopenias until a time comes when we can’t keep up with transfusions. If they have iron overload, they can die of cardiac events. One of the problems with iron overload is that certain pathogens can use iron for their proliferation, especially fungi. And many fungi are siderophores, so they will grow in the presence of iron and they’ll blossom. In fact, infectious disease experts, when they are treating fungal infections, now recommend iron chelation therapy along with antifungal therapy so that you’re taking away the nutrition from the fungus as well. So what do lower-risk MDS patients die of? Eventually they really will die of the consequences of their increasing profundity of cytopenia. Thirty percent of the time, high-risk MDS patients will develop acute myeloid leukemia and die from it, and 70% of the time, they will also die from the consequences of cytopenias.

Transcript Edited for Clarity
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Transcript:

James M. Foran, MD, FRCPC:
Do you use transferrin saturation then instead of ferritin or do you still follow ferritin? Or do you use testing like, for instance, MRI testing or T2* sequence testing and MRI to look for iron overload? Do you do more detailed testing on patients?

Azra Raza, MD: It is a very important practical issue. So for time immemorial, we have been using ferritin. It’s inexpensive, it’s available everywhere, easy to use. The only problem is it’s an acute phase reactant. So ferritin levels could be high if a patient is infected, has inflammation, or has something going else going on. And suddenly you have a high ferritin level. So, I regularly use [the] serum ferritin level as my first line measurement of iron overload. But it has to be consistently elevated over a certain level, which is 1000 mg of ferritin consistently in the presence of at least 10 transfusions. So it isn’t a ferritin level of 1200 without a transfusion. That, I would think, is ineffective hematopoiesis. But if they have a history of at least 10 transfusions or 20 units of blood combined with a ferritin level of 1000, then I know there is iatrogenic iron overload.

The second issue is, can we make iron overload measurements more accurate by more modern technology? And certainly you can by using these T2* MRIs both for the liver and heart, which can very accurately document the deposition of iron in these organs. These are highly sophisticated measures, and they are confined to only specialized centers. Now, I believe they've become more common, but still they may not be the most common test that a community hematologist would have access to the minute they thought of iron overload. So, I do think that we should definitely universally utilize the serum ferritin level, just making sure that we are interpreting it properly in the background of having no inflammation, no infection, etc.

We revert to T2* MRI use only in special conditions, such as when suddenly unexplained problems start occurring with liver function tests or there are cardiac issues and the patient has now received at least 20, 25, 30 transfusions. You start worrying that their iron deposition, ferritin is going up; the patient is not following the regime of iron chelation that you prescribe. In those settings, it is very important to even refer a patient to a specialized center for these MRIs.

James M. Foran, MD, FRCPC: This is not the same as a liver MRI. They needed a dedicated sequence. It’s not like a fibroscan, it’s not like some other liver workup. You have to have the software for it, so you have to request it. I think we use it a lot less in adult hematology than the pediatric hematologist. I think that they use this much more commonly than we do. I suspect it will become more and more important as we get better therapies for iron overload. Do you ever use the T2* to follow the patients or do you just follow the serum ferritin once you address that?

Azra Raza, MD: I think judicious use of both.

James M. Foran, MD, FRCPC: I see. Well, I’ll come back to that point. This may sound like kind of a facile question, but what happens to your MDS patients? What do they die of?

Azra Raza, MD: MDS patients have very heterogeneous scores. So the lower-risk MDS patients will have increasing profundity of their cytopenias until a time comes when we can’t keep up with transfusions. If they have iron overload, they can die of cardiac events. One of the problems with iron overload is that certain pathogens can use iron for their proliferation, especially fungi. And many fungi are siderophores, so they will grow in the presence of iron and they’ll blossom. In fact, infectious disease experts, when they are treating fungal infections, now recommend iron chelation therapy along with antifungal therapy so that you’re taking away the nutrition from the fungus as well. So what do lower-risk MDS patients die of? Eventually they really will die of the consequences of their increasing profundity of cytopenia. Thirty percent of the time, high-risk MDS patients will develop acute myeloid leukemia and die from it, and 70% of the time, they will also die from the consequences of cytopenias.

Transcript Edited for Clarity
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