Transfusion-Dependent Iron Overload: A Handbook for Patients

Published by the Myelodysplastic Syndromes Foundation

Many patients in the early stages of MDS experience anemia, a condition in which the body’s red-blood-cell count, or hematocrit, falls below normal levels. Some patients receive periodic blood transfusions as supportive therapy. While such therapy can be helpful in treating anemia, it has a downside: red blood cells carry iron, and after repeated transfusions a patient may end up with elevated levels of iron. Iron overload is a potentially dangerous condition. Fortunately, it can be treated.1

Am I at Risk of Iron Overload?
Iron overload is not a risk unless you receive a series of transfusions, usually over several years’ time or after a total of approximately 20 transfusions, whichever comes first. People who are candidates for regular blood transfusion typically have pale skin and experience fatigue and shortness of breath. They include patients in the International Prognostic Scoring System’s low-risk group or intermediate-risk group I who are severely anemic, that is, with a hematocrit consistently less than 25 percent. Repeated transfusions are also given to patients who are classified under the French-American-British system as having sideroblastic anemia. Sideroblastic anemia is a condition characterized by red blood cells that are incapable of utilizing iron for the production of hemoglobin, a blood protein that carries oxygen from the lungs to the body tissues.1,2

What Exactly Is Iron Overload?
People on transfusion therapy typically receive two units of blood every two to six weeks. Each unit carries about 250 milligrams of iron. Over the course of therapy iron builds up in the body’s tissues, and after approximately twenty transfusions a patient may end up with toxic levels.1,3

Iron has powerful oxidant activity that can damage tissue. When excessive iron accumulates in the heart, liver, lungs, bone marrow and endocrine organs, the stage is set for a broad array of possible diseases, including heart failure, diabetes, arthritis, cirrhosis and fibrosis of the liver, gallbladder disorders, depression, impotence, infertility, and cancer.3,4

How Is Iron Overload Treated?
For MDS patients who experience transfusion-dependent iron overload, only one treatment is currently available: chelation therapy. The drug deferoxamine (Desfera®) is used to chelate or bind to iron for removal. Desferal, given separately from blood infusion, is administered anywhere from three to seven times a week. Some patients receive twice-daily 2 subcutaneous injections. Others receive slow intravenous infusion by way of a portable, battery-operated pump worn over a period of about eight hours, often at night.2,3,4

Patients can expect to receive up to two grams of Desferal for each unit of blood transfused. Typically, a physician will initiate treatment with one gram, gradually adjusting the dose upward until it reaches no more than three grams a day. Urine samples reveal how much iron the patient is excreting and help the physician adjust the dose of Desferal to maintain negative iron balance.3,4

Though Desferal is slow acting—removing only 6 to 10 mg of iron per infusion—it can maintain negative iron balance even when blood transfusions continue. Success depends on early initiation of therapy. If significant iron overload exists before chelation therapy is begun, the patient may succumb to progressive heart disease or fibrosis of the liver. Better timed chelation therapy, begun within two years of the initiation of blood transfusion, can prevent or reverse these diseases.3,4

In addition to early initiation of therapy, patient compliance is critical to the success of iron chelation. Some patients discontinue Desferal treatment because of the discomfort of repeated needlesticks, a hypersensitive reaction at the site of infusion, or the regimen’s inconvenience. Strong supportive care should be given to encourage patients to continue treatment. Those who balk at the discomfort of needles should ask for a topical anesthetic cream; this can be applied an hour ahead of the needlestick to alleviate pain. Many patients find intravenous delivery by way of a slow-infusion pump the most tolerable form of treatment, because the needle remains in for a week, eliminating the need for frequent needlesticks. Furthermore, intravenous chelation is more effective than subcutaneous chelation, often requiring fewer days of therapy.4

Can I Have an Adverse Reaction to Iron-Overload Treatment?
Some patients experience side effects while on iron chelation therapy. Possible side effects include bloody urine, blurred vision, rash, hives, itching, vomiting, diarrhea, stomach or leg cramps, fever, rapid heart beat, dizziness, or pain or swelling at the infusion site. Potential long-term adverse reactions include kidney or liver damage, loss of hearing, or cataracts.3

There is a rare chance of Desferal injuring the retina of the eye. As such, patients should have an exam by an opthamologist prior to starting Desferal therapy and yearly thereafter. Your doctor should also examine your hearing periodically and have tests done to measure your liver enzymes, kidney function, hematocrit, ferritin, and transferrin iron saturation percentage. You should report any adverse symptoms immediately to your attending physician, who will either adjust your dose of Desferal or, in case of severe abnormalities, discontinue it altogether. If severe reactions resolve, your physician may reintroduce iron chelation cautiously.3,4,5 On the upside, there have been reports of the hematocrit improving after MDS patients have been “de-ironed”.

Transfusion- Dependent Iron Overload What Practical Measures Can I Take to Help Reduce Iron Overload?
While iron chelation is the only available treatment for MDS patients who experience transfusion-dependent iron overload, there are a few everyday guidelines you can follow to decrease your dietary intake of iron. To impede the absorption of iron, it helps to consume milk products, certain high-fiber foods, and tea. You shouldn’t eat raw shellfish, which may carry bacteria that can cause death in people suffering from iron overload. Last but not least, avoiding alcohol and tobacco smoke might help prevent further increase of iron levels.5

Most important, if you’re receiving iron chelation therapy, is to ensure that your attending physician is closely monitoring iron accumulation in your tissues. If not, you are at increased risk of disease associated with iron overload. It is also critical that you comply with the Desferal regimen. If you’re feeling discouraged, don’t give up—seek outside support.

References

1. Kouides P, Bennett JM. Understanding myelodysplastic syndromes: 1997; The MDS Foundation.

2. Stevens ML, ed. Fundamentals of Clinical Hematology. Philadelphia, PA: W.B. Saunders Company, 1997.

3. ID Insight. Transfusion-Dependent Iron Overload. Quarterly Publication, Iron Disorders Institute, Inc. Greenville, S.C.

4. Rakel RE. Conn’s Current Therapy. Philadelphia, PA: W.B. Saunders Company, 1999;371–372.

5. Iron: Friend or Foe. Iron Disorders Institute, Inc. Greenville, S.C.