Current and Future Treatments for the Management of Myelodysplastic Syndrome - Episode 11
Comprehensive insight on potential complications that can occur during transfusion therapy for myelodysplastic syndrome.
Bart Scott, MD, MS: Many patients wonder about what the complications are of transfusions. Transfusions, for the most part, are tolerated well, but they are not without [adverse] effects. We can take them 1 by 1. We’ll begin with the most controversial, which would be neutrophil infusions. They are controversial because there is disagreement among medical experts about whether they’re beneficial.
Most neutrophils are collected either through administration of GCFS [granulocyte-colony stimulating factor] or steroids, 2 donors. We collect the neutrophils, and they can be infused into patients. There was a randomized study evaluating the use of neutrophils in patients, not just in MDS [myelodysplastic syndrome], but all kinds of patients who had neutropenia. This randomized phase 3 trial showed no benefit, and we consider randomized phase 3 trials to be the gold standard of medical evidence. As always, the devil is in the details, and one of the issues with this RING study is that many patients didn’t receive an adequate dosing of the neutrophil infusions.
There are some who still believe in this intervention who would argue that, if we are able to give an adequate dose of the neutrophils, then they would be effective. With the neutrophils, there is not general agreement that they work, but if they did work, they’re hard to get. Thirdly, they don’t have a very long half-life. They have a short duration of half-life, so you have to give the neutrophil infusions quite frequently. My general feeling of the neutrophil infusions is not to use them, but I acknowledge some of my colleagues may disagree with that.
Then, in regard to platelets, that’s more of an established pattern, and we generally get platelets when counts are less than 10,000, or at a higher number if patients have bleeding, bruising, or other symptoms. There are some patients who can have symptoms, but their counts may not be very low because the blood counts themselves don’t work well, because MDS is not only a disease of numbers; it’s also a disease of function. It’s both a qualitative and quantitative defect.
In regard to the platelets, they have specific [adverse] effects. They tend to be more immunogenic, so patients can have more allergic reactions like fevers, chills, and hives. Platelets can also only be stored for shorter durations of about 5 days, and they can’t be frozen and thawed very well because they’re sensitive to the freezing and thawing. Their storage procedure increases the risk of bacterial contamination, so platelets are more likely to lead to problems with infections, generally bacteria that can occur in the platelets.
The platelet transfusions have a shorter half-life on average. In a normal circumstance, a platelet has a half-life of about 10 days. They have a shorter duration of half-life, so you have to transfuse the patients more frequently with platelets, and because they’re so immunogenic, patients can frequently become immunized and they can develop reactions against the platelets. Eventually, patients can become refractory to platelets where they develop antibodies, and you have to search for matched donors for them.
Red cells are the most frequently transfused product for MDS patients. Anemia is the most frequently presenting cytopenia. Many patients with MDS require red cell transfusions. They have unique [adverse] effects, and one of the unique [adverse] effects of red cell transfusions is iron overload. Since patients may go many years with red cell transfusion dependence, they can develop problems with iron overload. The iron can accumulate in the liver and cause liver damage in the pancreas, leading to diabetes. It can also accumulate in the bones, leading to osteoporosis. It can affect the gonads and lead to hypogonadism with low testosterone levels. Iron overload has a lot [adverse] effects.
We generally think that patients with MDS are at risk for iron overload if they’ve received at least 20 units of red cells and have a ferritin level of greater than 1500µg/L, which is a blood test that we use to determine iron levels. Red cells can also transmit viruses, but the risk of viral transmission is actually very low. The risk of HIV, for instance, is about 1 in 6 million, although people are concerned about that. It’s understandable given the history of what’s happened during the AIDS epidemic, for instance. The risk of viral transmission with red cell transfusion is actually low.
The most common problem that patients can get with red cell transfusions is allergic reactions with fevers, chills, and hives; they can be more severe. There is something called TRALI, which is transfusion-related acute lung injury, where patients can get fluid in their lungs. Then patients may also have delayed transfusion reactions, which can occur up to 2 weeks after transfused red cell products, where patients have fatigue, jaundice, and a flu-like illness.