New Protocol for Treatment of Thalassemia Major

Chelation along with amlodipine drug was found to benefit patients with thalassemia major - an inherited blood disorder.

Highlights

Thalassemia major is an inherited blood disorder in which the body makes an abnormal form of hemoglobin.
Iron accumulation in myocardial cells results in heart failure or fatal arrhythmia in patients with thalassemia major
Anti-hypertensive drug amlodipine along with chelation resulted in effective reduction of cardiac iron

Daily dose of amlodipine along with chelation therapy resulted in a more effective reduction of cardiac iron in a clinical trial involving 62 patients with thalassemia major, a hereditary disease also known as Mediterranean anemia.

Amlodipine drug is prescribed for the treatment of high blood pressure (hypertension). Amlodipine is an inexpensive drug with few side effects.

Thalassemia - Symptoms, Diagnosis, Treatment, Future Therapies
Thalassemia is an inherited blood disorder passed on through parental genes causing the body to produce abnormal hemoglobin.

‘Amlodipine (anti-hypertensive drug) in conjunction with chelation therapy helps combat problems caused by the buildup of iron in organs in patients with thalassemia.’

"The drug has been used clinically for decades and is considered safe for adults and children. As an adjunct to standard treatment, it can be greatly beneficial to patients and has few side effects," said Juliano de Lara Fernandes, a researcher at José Michel Kalaf Research Institute in Campinas, São Paulo State, Brazil, and principal investigator for the project.

The clinical trial was conducted in partnership with researchers at the University of Campinas Blood Center (Hemocentro UNICAMP), Boldrini Child Cancer Center, and São Paulo Blood Center (CHSP), among others.

"The iron in red blood cells is normally reused when new red cells are produced, but transfusions introduce a lot of extra iron into the patient. The concentration of iron can double after ten transfusions," Fernandes said.

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In Thalassemia major condition the body lacks mechanisms to excrete the excess iron, which builds up in the cells of several organs, especially the heart and liver. The chelating drugs help treat the accumulation process; the chelating agents bind with the excess iron to produce compounds that are excreted in urine or feces.

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One of the serious complication of thalassemia is the accumulation of non-transferrin bound iron (NTBI) in myocardial cells. NTBI proves to be toxic and causes cell death. Myocardial dysfunction is the main cause of death among thalassemia patients and can emerge in kids from the age of ten. NTBI enters the heart via the channel which is involved in the calcium transport into the cells.

"It occurred to us that drugs capable of blocking the calcium channel could also prevent NTBI from entering the heart and therefore increase the efficacy of chelation therapy," Fernandes said. "Calcium-channel blockers are widely used to treat problems such as high blood pressure and irregular heart beat."

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The trials were tested in 62 patients with thalassemia major. Peripheral venous blood samples were collected for chemistry and hematology analyses, and MRI scans were performed on patients before enrollment. The study participants were divided into two groups; both the groups were given chelation therapy but amlodipine was administred to group 1 and group 2 received oral placebo.

Depending on the iron concentrations found in their organs, each group was subdivided into those with and without initial cardiac iron overload. MRI scans were repeated a year later. The study results revealed the following

Myocardial iron concentration drops 21% in patients with initial iron overload who were treated with chelation plus amlodipine
Whereas it increased by 2% in those with initial overload who were treated with chelation plus placebo

"Perhaps we would have needed to monitor these patients for a longer period to see the benefits of preventive therapy with amlodipine for people who don't have excess iron in their organs," Fernandes said. "For those who do, however, the results show it's worth using amlodipine. There's no need to change the existing therapy. It's enough to administer the anti-hypertensive orally every day."

Thalassemia:

Thalassemia results in a low red blood cell count, which in turn leads to chronic anemia. Patients with thalassemia require blood transfusions every three to four weeks. Thalassemia is of two types

1. Alpha thalassemia occurs when the genes related to alpha globin protein are missing.

2. Beta thalassemia occurs when genes related to beta globin protein are affected.

Hemoglobin is made up of alpha and beta globin proteins.

Forms of Thalassemia

Thalassemia Major occurs when the child inherits two mutated genes one from each parent.

Thalassemia Minor occurs if the child receives faulty gene from only 1 parent.

References

Juliano L. Fernandes et al. A Randomized Trial Of Amlodipine In Addition To Standard Chelation Therapy In Patients With Thalassemia Major; Blood; (2016) DOI: http://dx.doi.org/10.1182/blood-2016-06-721183
General Information About Thalassemia - (https://medlineplus.gov/ency/article/000587.htm)

Source-Medindia