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Transfusion Dependence in MDS: The Risk for Iron Overload

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: Tuesday, Apr 05, 2016


Transcript:

James M. Foran, MD, FRCPC:
What do you think about the impact of the transfusion burden on the patient’s quality of life? That’s a hard one to answer, actually.

Azra Raza, MD: No, it just brings so many faces in front of me. When you ask a question like that, what is a transfusion burden on a patient? I have a gallery of patients that come to my mind—some who have a physical burden, some who have psychological burden, some who have an emotional burden, some who have a financial burden, and some who have all of the above or any combination of the above. It is not a good thing to be getting transfusions for any reason, and it kind of also presents itself as a milestone by which patients judge the intensity of their disease.

They were getting a CBC every so often in my clinic, and now suddenly I’d say, “Well, now your disease is serious enough to require a transfusion.” Some patients can really have a meltdown almost because they think, ‘now I’m going to die.’ No, it’s a very mild thing. So I’m just trying to emphasize that it’s not just a physical debilitating thing, but we are dealing with an older population and you have to understand that at that age, you are already very anxious about mortality; you’re already very scared. And then even a little milestone like this where you have reached a transfusion requirement can prove to be quite a serious event for them. I don’t want, for a second, for anybody to think that getting transfusions is an easy thing. You just go, get a transfusion, everything is hunky-dory and now you’re jumping up and down because you have so much energy. It is not that at all, James.

James M. Foran, MD, FRCPC: No, I agree. It’s about subsistence rather than existence sometimes.

Azra Raza, MD: Yes, well said.

James M. Foran, MD, FRCPC: I like the fact that you put a face to the disease, and that you associate this with people’s faces, and with the people you see in clinic. I think that’s a critical point. This is not an abstract discussion. And it is truly a burden in their lives. At our institution, we can give a blood transfusion 7 days a week as an outpatient. I’m sure it’s the same for you. But I know that in community practice, that’s not always easy for them. They often have to prepare it a day or two in advance. We can do it same day, but that’s not always the case. So I think that’s a difficulty for people as well, that they then have to go to a hospital to get it as an outpatient 2 or 3 days later. I don’t even think it’s easy for the practices to coordinate, let alone for the patients to go through.

Azra Raza, MD: By the way, one of the questions I’m often asked, and I’m sure you are too, is by family members. “Can I give my blood?” Especially by grandchildren, they really want to do something for their grandma or grandpa. They always ask, “Dr. Raza, can we give our blood to grandma?” No, it’s okay, darling. You go give your blood to someone else. Let somebody else get it.

But I love that. I mean, many people ask me, James, “Don’t you get depressed seeing the patients with myelodysplastic syndromes every day?” For 30 years, I’ve been doing that. I see 40 to 50 MDS patients every week, and my answer is two-fold. One, there are no 2 patients with MDS who are alike. And, secondly, many people have jobs where they see the worst face of humanity, especially in public service. You are standing behind a counter of some sort and everyone wants to break the line and come and be angry with you. On the other hand, I’m in a field where I see the noblest face of humanity 10 times a day; like a child saying, can I help my grandmother by giving my blood? Or okay, I’ll give my blood to some stranger. So, blood transfusion is something from which I learned so much about the patient, their mental status, their psychological burdens, and then the family’s commitment. There are all kinds of issues, not just the practical issue of getting.

James M. Foran, MD, FRCPC: You keep bringing this back to the individual and I think that’s a critical point that’s harder and harder for us in practice with the pressures we’re under. But we have to make it about the person. It’s really a disease you treat one at a time, person by person. I wanted to switch gears a little bit, or at least extend things, to ask about the risk for iron overload or the development of iron overload and what are the strategies to prevent iron overload? How do you try to reduce that risk?

Azra Raza, MD: Iron overload in myelodysplastic syndromes is a very interesting problem because first of all, the means we have by which we measure iron overload—the most common being serum ferritin level—is high in the vast majority of MDS patients at diagnosis without ever having received a transfusion. So we know that there is some disturbance of iron metabolism in this disease already, and that because of which their iron level is high despite never having received a transfusion. In other words, ineffective hematopoiesis and expanding clone of cells in the bone marrow by itself disturbs the hepcidin, transferrin, ferroportin—all these pathways in such a way that iron is not being metabolized. Take the example of refractory anemia with ringed sideroblasts. Here you have paucity and poverty in the presence of plenty. The erythroid cells are filled with iron, which is now trapped in mitochondria surrounding the nucleus, and yet this cell cannot utilize the iron to make heme, which will bind with globin to make hemoglobin. And you know that the fate of ringed sideroblasts is just going to undergo apoptosis and die because it cannot become a fully mature red cell.

So how do I think about this issue of iron overload in MDS? It’s a complicated issue. The fact that a patient was presenting with a ferritin level of 800 at diagnosis doesn’t mean they have iron overload. They have iron metabolism disturbance. Iron overload that we can deal with more effectively is that which we are creating in the disease by giving transfusions. So, with every unit of blood, we are putting in 200 mg of iron. With one transfusion or two units of blood, we are giving 400 mg of iron, which is more than a year’s requirement of iron for the body.

Transcript Edited for Clarity
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Transcript:

James M. Foran, MD, FRCPC:
What do you think about the impact of the transfusion burden on the patient’s quality of life? That’s a hard one to answer, actually.

Azra Raza, MD: No, it just brings so many faces in front of me. When you ask a question like that, what is a transfusion burden on a patient? I have a gallery of patients that come to my mind—some who have a physical burden, some who have psychological burden, some who have an emotional burden, some who have a financial burden, and some who have all of the above or any combination of the above. It is not a good thing to be getting transfusions for any reason, and it kind of also presents itself as a milestone by which patients judge the intensity of their disease.

They were getting a CBC every so often in my clinic, and now suddenly I’d say, “Well, now your disease is serious enough to require a transfusion.” Some patients can really have a meltdown almost because they think, ‘now I’m going to die.’ No, it’s a very mild thing. So I’m just trying to emphasize that it’s not just a physical debilitating thing, but we are dealing with an older population and you have to understand that at that age, you are already very anxious about mortality; you’re already very scared. And then even a little milestone like this where you have reached a transfusion requirement can prove to be quite a serious event for them. I don’t want, for a second, for anybody to think that getting transfusions is an easy thing. You just go, get a transfusion, everything is hunky-dory and now you’re jumping up and down because you have so much energy. It is not that at all, James.

James M. Foran, MD, FRCPC: No, I agree. It’s about subsistence rather than existence sometimes.

Azra Raza, MD: Yes, well said.

James M. Foran, MD, FRCPC: I like the fact that you put a face to the disease, and that you associate this with people’s faces, and with the people you see in clinic. I think that’s a critical point. This is not an abstract discussion. And it is truly a burden in their lives. At our institution, we can give a blood transfusion 7 days a week as an outpatient. I’m sure it’s the same for you. But I know that in community practice, that’s not always easy for them. They often have to prepare it a day or two in advance. We can do it same day, but that’s not always the case. So I think that’s a difficulty for people as well, that they then have to go to a hospital to get it as an outpatient 2 or 3 days later. I don’t even think it’s easy for the practices to coordinate, let alone for the patients to go through.

Azra Raza, MD: By the way, one of the questions I’m often asked, and I’m sure you are too, is by family members. “Can I give my blood?” Especially by grandchildren, they really want to do something for their grandma or grandpa. They always ask, “Dr. Raza, can we give our blood to grandma?” No, it’s okay, darling. You go give your blood to someone else. Let somebody else get it.

But I love that. I mean, many people ask me, James, “Don’t you get depressed seeing the patients with myelodysplastic syndromes every day?” For 30 years, I’ve been doing that. I see 40 to 50 MDS patients every week, and my answer is two-fold. One, there are no 2 patients with MDS who are alike. And, secondly, many people have jobs where they see the worst face of humanity, especially in public service. You are standing behind a counter of some sort and everyone wants to break the line and come and be angry with you. On the other hand, I’m in a field where I see the noblest face of humanity 10 times a day; like a child saying, can I help my grandmother by giving my blood? Or okay, I’ll give my blood to some stranger. So, blood transfusion is something from which I learned so much about the patient, their mental status, their psychological burdens, and then the family’s commitment. There are all kinds of issues, not just the practical issue of getting.

James M. Foran, MD, FRCPC: You keep bringing this back to the individual and I think that’s a critical point that’s harder and harder for us in practice with the pressures we’re under. But we have to make it about the person. It’s really a disease you treat one at a time, person by person. I wanted to switch gears a little bit, or at least extend things, to ask about the risk for iron overload or the development of iron overload and what are the strategies to prevent iron overload? How do you try to reduce that risk?

Azra Raza, MD: Iron overload in myelodysplastic syndromes is a very interesting problem because first of all, the means we have by which we measure iron overload—the most common being serum ferritin level—is high in the vast majority of MDS patients at diagnosis without ever having received a transfusion. So we know that there is some disturbance of iron metabolism in this disease already, and that because of which their iron level is high despite never having received a transfusion. In other words, ineffective hematopoiesis and expanding clone of cells in the bone marrow by itself disturbs the hepcidin, transferrin, ferroportin—all these pathways in such a way that iron is not being metabolized. Take the example of refractory anemia with ringed sideroblasts. Here you have paucity and poverty in the presence of plenty. The erythroid cells are filled with iron, which is now trapped in mitochondria surrounding the nucleus, and yet this cell cannot utilize the iron to make heme, which will bind with globin to make hemoglobin. And you know that the fate of ringed sideroblasts is just going to undergo apoptosis and die because it cannot become a fully mature red cell.

So how do I think about this issue of iron overload in MDS? It’s a complicated issue. The fact that a patient was presenting with a ferritin level of 800 at diagnosis doesn’t mean they have iron overload. They have iron metabolism disturbance. Iron overload that we can deal with more effectively is that which we are creating in the disease by giving transfusions. So, with every unit of blood, we are putting in 200 mg of iron. With one transfusion or two units of blood, we are giving 400 mg of iron, which is more than a year’s requirement of iron for the body.

Transcript Edited for Clarity
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