The MDS Beacon™

After analyzing patients diagnosed with early myelodysplastic syndromes (MDS), Czech researchers from the Institute of Hematology and Blood Transfusion have concluded that dependence on red blood cell transfusions has a significantly negative impact on the length of overall survival.

Eighty to 90 percent of MDS patients receive transfusions to treat symptoms of anemia, which is a decrease in the number of red blood cells. Symptoms commonly include chronic tiredness or fatigue, shortness of breath, heart palpitations, and chilled sensations.

Transfusions help anemic patients by supplementing the insufficient levels of red blood cells. However, transfusions also introduce approximately 200 to 250 mg of iron to the body without providing a means of removing excess iron. Proteins that normally bind iron and prevent it from reacting destructively with other cells in the body can become overloaded. This causes iron deposits that can cause cell death, tissue damage, and reduced life expectancy, especially in the heart, liver, and endocrine system.

Patients who continually receive at least two red blood cell transfusions each month are at risk of iron overload and its associated clinical complications. Iron overload is the most significant negative effect of transfusions. Iron chelation therapy, the use of molecules that bind heavy metals and remove them from the body, is needed to get rid of excess iron and keep the levels from becoming toxic.

The Czech study analyzed variables affecting the overall survival time of 137 patients in the early stages of MDS. With a median age of 49 years, the group was younger than the typical MDS patient, probably because many younger patients were referred to the study as good transplant candidates.

All patients had primary MDS without excess blasts, which are the characteristic immature blood cells that die prematurely in the bone marrow. Patients were diagnosed with one of the following: Refractory Anemia (RA), Refractory Anemia with Ringed Sideroblasts (RARS), Refractory Cytopenia with Multilineage Dysplasia (RCMD), Refractory Cytopenia with Multilineage Dysplasia and Ringed Sideroblasts (RCMD-RS), or 5q-syndrome. RA, RARS, and 5q-syndrome are caused by abnormal levels of red blood cells, while RCMD and RCMD-RS are caused by insufficient levels of more than one blood cell type.

Researchers observed length of overall survival, progression-free survival, and the percentage of patients living three, five, and 10 years after diagnosis. In this study, 87 percent of patients received at least one red blood cell transfusion during the course of the disease, with a median of two transfusions each month.

Results showed that median overall survival was decreased from 65 months to 35 months in patients who required more than two red blood cell transfusions per month. Additionally, patients with RCMD or RCMD-RS had median overall survival of 22 months, which is significantly shorter compared to patients with RA, RARS, or 5q-syndrome, who survived a median of 48 months.

Researchers acknowledged that the most important variable affecting survival throughout the experiment, regardless of dependency on transfusions, was disease progression to more advanced stages of MDS or acute myeloid leukemia (AML). Patients with RCMD, RCMD-RS, or abnormal chromosomes who experienced disease progression had significantly decreased survival.  In RA, RARS, and 5q-syndrome patients who did not  receive a transplant and who did not progress towards AML, frequent red blood cell transfusions were the only factor that negatively impacted their survival.

The study concluded that transfusion dependency has a significant negative impact on survival, most likely due to iron buildup. The authors suggest that patients with RA, RARS, or 5q-syndrome should be the main target group for iron chelation therapy, since their survival is longer and they are likely to receive more transfusions during that time.

Similar studies have shown that iron levels significantly affect survival time and support the use of iron chelation therapy to remove excess deposits.

For more information, please see the related article in Leukemia Research (abstract) and the Beacon resource article about excess iron in MDS patients.