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How Iron Accumulation Occurs in 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: Thursday, Apr 07, 2016


Transcript:

David P. Steensma, MD:
We assess patients with myelodysplastic syndromes in several ways. The fundamental thing that we want to know when we first meet a new patient, about their MDS, is, are they a patient who has higher-risk disease where they’re likely to have progression to acute leukemia or complications of low blood counts in the short term, or are they someone with lower-risk disease. In which case, they may have a condition that smolders along for several years or is less acutely dangerous than the higher-risk patients. Assessment of that is imperfect, but it’s improving. We use the International Prognostic Scoring System, or IPSS. There’s a revised version that was published in 2012, and increasingly we’re incorporating molecular testing into the assessment, into the risk assessment, which helps refine that.

We also characterize patients by their World Health Organization classification. That tends to be less important, though, than prognostic assessment. What are the things that really drive the disease? It is a cancer, it is clonal disorder, it is a neoplasm, so it is the clonal population, whether that is cytogenetics, whether it is the blast proportion, the proportion of immature leukemic-like cells in the marrow. Those are the big determinants of the course of the disease.

Patients who have severe anemia associated with MDS are good candidates for blood transfusions. Different institutions and different clinicians have distinct thresholds for where they would consider a transfusion. Most individuals will transfuse a patient with MDS if their hematocrit is less than about 24% or their hemoglobin is less than 8. Sometimes the patients get transfused at a higher level if they have symptoms, if they have shortness of breath or chest pains, or just extreme fatigue.

The problem that we run into with repeated blood transfusions in MDS is that there can be transfusion reactions. Patients can have fevers, they can have allergic reactions, and they can have—very rarely—infections that they acquire through blood transfusions. With repeated blood transfusions, iron can accumulate and a patient can have an increase in total body iron.

And that’s because each unit of blood has about 250 mg of elemental iron. And unlike potassium or vitamin C in excess—which our bodies can very easily eliminate—we don’t have a good mechanism, we don’t have a good physiologic pathway, for eliminating iron from the body. So, iron tends to accumulate, and it then deposits in organs like the liver and the heart where it can cause organ damage, and it can cause complications that are more chronic but can really be a problem for some patients.

Transcript Edited for Clarity
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Transcript:

David P. Steensma, MD:
We assess patients with myelodysplastic syndromes in several ways. The fundamental thing that we want to know when we first meet a new patient, about their MDS, is, are they a patient who has higher-risk disease where they’re likely to have progression to acute leukemia or complications of low blood counts in the short term, or are they someone with lower-risk disease. In which case, they may have a condition that smolders along for several years or is less acutely dangerous than the higher-risk patients. Assessment of that is imperfect, but it’s improving. We use the International Prognostic Scoring System, or IPSS. There’s a revised version that was published in 2012, and increasingly we’re incorporating molecular testing into the assessment, into the risk assessment, which helps refine that.

We also characterize patients by their World Health Organization classification. That tends to be less important, though, than prognostic assessment. What are the things that really drive the disease? It is a cancer, it is clonal disorder, it is a neoplasm, so it is the clonal population, whether that is cytogenetics, whether it is the blast proportion, the proportion of immature leukemic-like cells in the marrow. Those are the big determinants of the course of the disease.

Patients who have severe anemia associated with MDS are good candidates for blood transfusions. Different institutions and different clinicians have distinct thresholds for where they would consider a transfusion. Most individuals will transfuse a patient with MDS if their hematocrit is less than about 24% or their hemoglobin is less than 8. Sometimes the patients get transfused at a higher level if they have symptoms, if they have shortness of breath or chest pains, or just extreme fatigue.

The problem that we run into with repeated blood transfusions in MDS is that there can be transfusion reactions. Patients can have fevers, they can have allergic reactions, and they can have—very rarely—infections that they acquire through blood transfusions. With repeated blood transfusions, iron can accumulate and a patient can have an increase in total body iron.

And that’s because each unit of blood has about 250 mg of elemental iron. And unlike potassium or vitamin C in excess—which our bodies can very easily eliminate—we don’t have a good mechanism, we don’t have a good physiologic pathway, for eliminating iron from the body. So, iron tends to accumulate, and it then deposits in organs like the liver and the heart where it can cause organ damage, and it can cause complications that are more chronic but can really be a problem for some patients.

Transcript Edited for Clarity
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