Why was this study done?
Iron overload is the buildup of iron in the body as a result of many blood transfusions. If iron builds up in important organs such as the heart and the liver, these organs may not work well. The iron in the body needs to be measured to figure out if it is time to begin a treatment to get rid of the iron from the body. Researchers wanted to find new ways to measure iron overload. This is usually done with a liver biopsy. But that procedure has risks that include pain, bleeding and infection. If we can measure iron overload by another way without a biopsy that would be important for patients.
In this study, we used MRI imaging (magnetic resonance imaging, a way to obtain pictures of internal organs) and compared it to a liver biopsy to measure iron overload. T2* MRI has shown promise as a test to replace liver biopsy for this purpose. We wanted to compare the results of the T2* MRI with the results of the same patient’s liver biopsy.
The study's main goals:
- Compared T2* MRI and biopsy measurements of iron in the liver
- Compared T2* MRI and biopsy measurements of iron in the heart
- Compared T2* MRI of the liver and the heart to the ferritin tests we do in the blood
- Find out if a stronger MRI machine (3 Tesla MRI scanner) is better than the traditional MRI machine (1.5 Tesla MRI scanner)
- Find out if the MRI can measure how well the heart works, compared with other heart tests (echo, EKG, MUGA scan)
- Find out if new MRI tools (called “dark blood” and phantom) can help measure the iron in the heart and liver
- Find out if increased pressure in the lungs can be linked to iron overload in the heart
- Find out if genes in the liver are important in iron buildup
When was this study done?
The study opened in October 2005 and closed in June 2008.
What did the study consist of?
- MRI T2* and T2 of the liver and the heart
- Optional T2* liver scan on a 3 Tesla MRI (after the 1.5 Tesla MRI exam)
- Blood tests
- Liver biopsy
- Heart tests
What did we learn from this study?
Iron overload and the heart: Diastolic dysfunction is a disorder that occurs when the chambers in the lower part of the heart do not work correctly. We learned that this problem is not caused by transfusions or iron deposits in the heart. Instead, it’s likely caused by sickle cell disease itself.
Iron overload and the liver: In patients who receive many transfusions, the amount of liver damage depends on the rate and pattern of iron deposits. We learned more about these patterns. We found out that chelation therapy (a process to remove metals like iron from the body) may be underused and that mutations in certain genes, such as GSTM-1, may increase the iron accumulation in the liver by impairing how chelation medications work. We also learned that liver damage related to transfusions may begin earlier than we knew before.
MRI vs. liver biopsy: We found strong evidence that an MRI T2* can predict iron content in the liver without the patient having to undergo a liver biopsy.
What are the next research steps as a result of this study?
Scientists will continue to research the genetic and disease-related processes that affect iron buildup.
How does this study affect my child?
Every individual with sickle cell disease should receive life-long follow-up care. Please speak with your St. Jude doctor about specific guidelines that apply to your child.
For more information
Please talk with your child’s St. Jude doctor about questions or concerns you have as a result of this study.
Publications generated from this study:
Ventricular diastolic dysfunction in sickle cell anemia is common but not associated with myocardial iron deposition. Hankins JS, McCarville MB, Hillenbrand CM, Loeffler RB, Ware RE, Song R, Smeltzer MP, Joshi V. Pediatr Blood Cancer. 2010 Sep;55(3):495-500.
https://www.ncbi.nlm.nih.gov/pubmed/20658621
Patterns of liver iron accumulation in patients with sickle cell disease and thalassemia with iron overload. Hankins JS, Smeltzer MP, McCarville MB, Aygun B, Hillenbrand CM, Ware RE, Onciu M. Eur J Haematol. 2010 Jul;85(1):51-7.
https://www.ncbi.nlm.nih.gov/pubmed/20374273
R2* magnetic resonance imaging of the liver in patients with iron overload. Hankins JS, McCarville MB, Loeffler RB, Smeltzer MP, Onciu M, Hoffer FA, Li CS, Wang WC, Ware RE, Hillenbrand CM. Blood. 2009 May 14;113(20):4853-5.
https://www.ncbi.nlm.nih.gov/pubmed/19264677
Microarray analysis of liver gene expression in iron overloaded patients with sickle cell anemia and beta-thalassemia. Flanagan JM, Steward S, Hankins JS, Howard TM, Neale G, Ware RE. Am J Hematol 2009 Jun;84(6):328-34.
https://www.ncbi.nlm.nih.gov/pubmed/19384939
GSTM1 and Liver Iron Content in Children with Sickle Cell Anemia and Iron Overload. Puri L, Flanagan JM, Kang G, Ding J, Bi W, McCarville BM, Loeffler RB, Tipirneni-Sajja A, Villavicencio M, Crews KR, Hillenbrand CM6 Hankins JS. J Clin Med. 2019 Nov 5;8(11).
https://www.ncbi.nlm.nih.gov/pubmed/31694285