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The Effects of Blood Transfusions on Iron Accumulation

Insights From:Thomas Prebet, MD, PhD, Yale Cancer Center; Heather Leitch, MD, PhD, St. Paul’s Hospital;Vinod Pullarkat, MD, City of Hope Medical Center
Published: Tuesday, Oct 11, 2016


Transcript:

Thomas Prebet, MD, PhD:
The question of transfusions in myelodysplastic syndromes, especially red blood cell transfusion, is a very crucial one. Firstly, because it’s the type of treatment that is most commonly used worldwide for patients with myelodysplastic syndromes. And in several countries, that’s the only treatment that we can have for these patients. Regular transfusion is the basis of the treatment for most of the patients with anemia.

We can discuss about this threshold of transfusion that we are using between 7 g and 9 g. Basically, anemia will be important and transfusion will be important, because they will define the survival, but also the quality of life, of all patients. It’s really important when we deal with the management of a patient with myelodysplastic syndromes to have a plan of management for the transfusion by itself. That’s what will then show the patient the best quality of life. That’s important because we’re talking about years, potentially, of transfusion for this patient. So, that’s one thing: taking care of the quality of life of the patient. But also having a management plan for transfusion is important because with this long-term transfusion, we know that there could be some consequences—infections, transfusion reaction, but also long-term transfusion-related iron overload, for example.

Heather Leitch, MD, PhD: Transfusions can impact dramatically on a patient’s quality of life. It’s very inconvenient for them to come in for transfusions. It may take a whole day; they may have transfusion reactions. Many of these patients are elderly. Their children have to take time off work to bring them in because their spouse may not be able to. And it can have an economic impact not only on the family, but also, if the patient’s still working, on the patient themselves. So, I think that we do need to weigh quality of life. And is there an adverse impact of quality of life of transfusion dependence? Absolutely. That needs to be weighed against the adverse effect that some treatments can have on quality of life, as well if patients experience side effects, for example.

Thomas Prebet, MD, PhD: If we think about transfusion and iron overload, we need to think that with every transfusion bringing red cells, we bring iron to the body of the patient. Basically, we know that the iron we bring with transfusion is not something we can get rid of so easily. And transfusion after transfusion, these patients with myelodysplastic syndromes will develop and stock some iron mostly in some critical organs, like the liver and heart. This accumulation may, at the end, lead to significant consequences for the body of the patient.

Heather Leitch, MD, PhD: For MDS patients, the patients that are most at risk of iron overload are those that are transfusion-dependent, because that’s the most significant amount of iron that’s taken onboard. However, there have been a couple of studies done in various different MDS subtypes looking at hepcidin levels. And hepcidin, of course, feeds back on ferroportin and affects iron absorption through the GI track, but also iron release from the reticular endothelium system and hepatocytes. It’s been found that the hepcidin levels vary greatly between MDS subtypes. The lowest hepcidin levels are in RARS (refractory anemia with ringed sideroblasts) in both studies, and this can help to explain why patients at diagnosis, with RARS, may have very elevated iron stored, even in the absence of red blood cell transfusions. So, I think we need to understand the iron pathways more in the different MDS subtypes and also in other acquired anemias as well, particularly those that are transfusion-dependent.

Vinod Pullarkat, MD: Transfusion support is an integral part of the management of a patient. Low-risk patients and intermediate 1-risk patients sometimes are transfusion-dependent, and they can have a long life expectancy and be transfusion-dependent for a long time. Strategies to decrease transfusion requirements are critical to prevent iron overload and its complications. Use of growth factors, for example: if a patient responds, the transfusion requirements will come down. Interestingly, iron chelation itself has been shown in studies to decrease. In about 15% of MDS patients, there may be improvement in hematopoiesis when they are chelated using deferasirox. And those patients could have a decrease in transfusion requirements. So, in a subset of patients, we still don’t know how to define that subset, but iron chelation could have the beneficial effect of improving hematopoiesis.

Transcript Edited for Clarity
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Transcript:

Thomas Prebet, MD, PhD:
The question of transfusions in myelodysplastic syndromes, especially red blood cell transfusion, is a very crucial one. Firstly, because it’s the type of treatment that is most commonly used worldwide for patients with myelodysplastic syndromes. And in several countries, that’s the only treatment that we can have for these patients. Regular transfusion is the basis of the treatment for most of the patients with anemia.

We can discuss about this threshold of transfusion that we are using between 7 g and 9 g. Basically, anemia will be important and transfusion will be important, because they will define the survival, but also the quality of life, of all patients. It’s really important when we deal with the management of a patient with myelodysplastic syndromes to have a plan of management for the transfusion by itself. That’s what will then show the patient the best quality of life. That’s important because we’re talking about years, potentially, of transfusion for this patient. So, that’s one thing: taking care of the quality of life of the patient. But also having a management plan for transfusion is important because with this long-term transfusion, we know that there could be some consequences—infections, transfusion reaction, but also long-term transfusion-related iron overload, for example.

Heather Leitch, MD, PhD: Transfusions can impact dramatically on a patient’s quality of life. It’s very inconvenient for them to come in for transfusions. It may take a whole day; they may have transfusion reactions. Many of these patients are elderly. Their children have to take time off work to bring them in because their spouse may not be able to. And it can have an economic impact not only on the family, but also, if the patient’s still working, on the patient themselves. So, I think that we do need to weigh quality of life. And is there an adverse impact of quality of life of transfusion dependence? Absolutely. That needs to be weighed against the adverse effect that some treatments can have on quality of life, as well if patients experience side effects, for example.

Thomas Prebet, MD, PhD: If we think about transfusion and iron overload, we need to think that with every transfusion bringing red cells, we bring iron to the body of the patient. Basically, we know that the iron we bring with transfusion is not something we can get rid of so easily. And transfusion after transfusion, these patients with myelodysplastic syndromes will develop and stock some iron mostly in some critical organs, like the liver and heart. This accumulation may, at the end, lead to significant consequences for the body of the patient.

Heather Leitch, MD, PhD: For MDS patients, the patients that are most at risk of iron overload are those that are transfusion-dependent, because that’s the most significant amount of iron that’s taken onboard. However, there have been a couple of studies done in various different MDS subtypes looking at hepcidin levels. And hepcidin, of course, feeds back on ferroportin and affects iron absorption through the GI track, but also iron release from the reticular endothelium system and hepatocytes. It’s been found that the hepcidin levels vary greatly between MDS subtypes. The lowest hepcidin levels are in RARS (refractory anemia with ringed sideroblasts) in both studies, and this can help to explain why patients at diagnosis, with RARS, may have very elevated iron stored, even in the absence of red blood cell transfusions. So, I think we need to understand the iron pathways more in the different MDS subtypes and also in other acquired anemias as well, particularly those that are transfusion-dependent.

Vinod Pullarkat, MD: Transfusion support is an integral part of the management of a patient. Low-risk patients and intermediate 1-risk patients sometimes are transfusion-dependent, and they can have a long life expectancy and be transfusion-dependent for a long time. Strategies to decrease transfusion requirements are critical to prevent iron overload and its complications. Use of growth factors, for example: if a patient responds, the transfusion requirements will come down. Interestingly, iron chelation itself has been shown in studies to decrease. In about 15% of MDS patients, there may be improvement in hematopoiesis when they are chelated using deferasirox. And those patients could have a decrease in transfusion requirements. So, in a subset of patients, we still don’t know how to define that subset, but iron chelation could have the beneficial effect of improving hematopoiesis.

Transcript Edited for Clarity
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