Thalassemia is a common genetic disorder in India, and over 10,000 children are born per year with the major form of the disease. The disease in the severe form is called Thalassemia Major. It happens when the genes for thalassemia are inherited from both the parents. Usually the child becomes listless and irritable a few months after birth. By 6-9 months, most children require blood transfusion for survival. Blood transfusion needs to be regular as in every 4-6 weeks as needed to keep the hemoglobin levels above 12 gm% and not letting it drop below 9 gm%. Such a transfusion schedule if started in time and carried out rigorously, results in normal growth and development of the child. However, this comes at a cost. Blood contains a lot of iron and our body cannot naturally get rid of the iron if in excess. In a normal individual, iron comes from the food and the body can increase or decrease the iron absorption from the gut depending on its requirement. If the same iron is injected in our body as it happens with blood transfusion, the iron cannot be excreted and it builds up. Like everything in excess is bad, so is iron. Excess iron gets deposited in the heart and the liver amongst other places and results in dysfunction and ultimately failure of these organs and death.
Getting rid of the excess iron from the body by medicines is called CHELATION. The first such drug was Desferrioxamine. This can only be injected through the veins or under the skin. The children with thalassemia needed small pumps to continuously inject the drug under the skin for 8-10 hours usually at night. As these children grow up, they resent these restrictions and often do not adhere to the chelation schedule. Even in western countries, the children developed severe iron overload during the adolescence and early adulthood which significantly reduced their lifespan. The average survival for children with thalassemia in developing countries barely exceeded the second decade.
The researchers had been toiling for two decades to find an oral drug to rid the body of the excess iron. The first such attempt produced a drug called Deferiprone. It was effective and yet had unexpected life-threatening toxicities. As a result, the drug was not approved for use in the western countries and was introduced in India due to resource constraints. The struggle continued until recently when a new drug called Deferasirox was launched which produced results similar to the injectable form of desferrioxamine with no surprising new side-effects. Can this change the future of the thousands suffering from thalassemia in our country?
We have perhaps built the perfect cart but yet struggling to find the horses. We can rid the iron by oral tablets and can live happily ever after, but can we support these children with enough blood and safe blood? Unfortunately, voluntary and dedicated blood donation cannot suffice the need of the millions of children given the poor infrastructure of blood banks in our country. More importantly, over 50% of those children transfused for over several years develop transfusion transmitted infections such as hepatitis B or C and HIV. Properly screened blood on a regular basis with continuous chelation can make these children step into their adulthood like any of us. But the reality does not allow the children with thalassemia lead a perfect life like their peers in Europe.
Allogeneic Blood and Marrow Transplantation (BMT) from a HLA-matched family donor is the only curative treatment for Thalassemia Major. Based on biological laws of inheritance, 25% of patients could find such a donor in the family. Yet such a donor is available for very few sufferers of thalassemia, largely because the parents often do not extend their family once a child with thalassemia major is born. HLA-matched unrelated donors from registries are available to very few patients and thus the curative option eludes majority of children with this condition.
In recent years, BMT from half matched or HLA-haploidentical family donor has been made possible in patients with blood cancers and selected centres in India and the rest of the world have developed Haploidentical BMT for malignant conditions. Haploidentical BMT has been tried in patients with thalassemia with less impressive results. Any attempt at carrying out haploidentical BMT in children should be carried out within the premises of a clinical trial. As one of the few groups in the world who have developed innovative approaches for haploidentical BMT in leukemia and aplastic anemia in both adults and children, we are carrying out clinical trials for haploidentical BMT in selected patients with thalassemia. Unless we and others who are conducting similar studies in other parts of the world, could conclusively demonstrate that haploidentical BMT is possible in children with thalassemia with success rates similar to matched family donor transplantation, such procedures should not be performed outside approved clinical studies. It is encouraging that the early results of gene therapy trials are promising, but it will be a while before such an approach becomes available globally.
There is a long way to go towards curing majority of children with thalassemia. Premarital screening remain the most important ways to prevent children being born with this unfortunate condition. But we should not forget that every child with thalassemia can live a near normal life with proper provision of safe blood and medicines for chelation of iron and the government and non-governmental organisations should make efforts to make this possible for every child with thalassemia and devote resources towards prevention of the same.
There might be hope of cure for every child with thalassemia in the distant future, but the present state of healthcare is failing them. Let us ponder today if should we continue to fail our children suffering from Thalassemia major.