By Dr Revathi Raj
For 6-year-old Ayesha (name changed), hailing from southern Tamil Nadu, the travel difficulties of the pandemic almost turned into a death sentence. A thalassemia patient, Ayesha needs monthly blood transfusions to ensure her body has enough haemoglobin to supply oxygen through the body. Without access to Apollo Cancer Centre in Chennai, Ayesha’s mother was forced to arrange for her transfusions locally. Unfortunately, problems with these transfusions led Ayesha’s immune system to attack the transfused blood cells dropping her haemoglobin levels to less than half the normal for a child her age.
“Giving optimal blood transfusions month after month may seem simple on paper, but maintaining this process is a massive challenge,” says Dr Revathi Raj, Senior Consultant for Paediatrics and Haematology Oncology at Apollo Cancer Centre.
For patients and their families the monthly transfusions mean significant disruptions to their everyday lives. Then there are the logistics of ensuring sufficient supply of high-quality, properly matched donor blood, as was the case for Ayesha. Even done optimally, frequent transfusions lead to an overload of iron in the body causing heart and liver problems among others. Preventing this requires further expensive medication for iron chelation. Added to the emotional toll of such precarious health conditions is also the stigma surrounding thalassemia. “This is particularly difficult in adolescence, because puberty is often delayed for thalassemia patients,” observes Dr Revathi. In adulthood, these difficulties are further strengthened due to the significant lack of marriage and job opportunities for such patients.
As bleak as the picture often looks, however, several medical advances in the last decade that are being honed to optimum efficiency in labs and hospitals around the world offer thalassemia patients new horizons of hope. “There are a lot of exciting things happening in the treatment and prevention of thalassemia now,” says Dr Revathi.
Thalassemia is an inherited blood disorder in which the absence of certain genes leads to reduced haemoglobin in the body. This shortage of haemoglobin means a reduction in the capacity of the blood to supply oxygen to the different parts of the body. A fundamental symptom of this condition is prolonged and intense fatigue or tiredness, along with others such as frequent infections, poor appetite and so on. This condition can also lead to deformations in marrow-producing bones and the spleen, as these tissues are forced into making greater number red blood cells to make up for the shortage in oxygen.
Based on the extent of mutation, cases of thalassemia can be classified into thalassemia minor and thalassemia major. The former refers to persons who carry at least one faulty gene, but do not show any other symptoms and do not require treatment. The chief concern in such cases is the ability to pass on the condition to one’s children. Thalassemia major, on the other hand, arises when the patient inherits the faulty genes from both sets of parents, involves much more serious symptoms and results in a drastically shortened lifespan for patients without significant medical intervention.
Thalassemia awareness is crucial because it is one of the most common genetic disorders in the world, with India reporting the highest numbers of new patients each year. Reports suggest that there are over 1.5 lakh people with thalassemia in India, and 10,000-15,000 new patients being born each year.
Given the significant complications that come with frequent blood transfusions, doctors and researchers have consistently sought out ways to reduce the frequency of transfusions. Finally, in 2019, a new drug called luspatercept received approval for use as a boost to blood production so that transfusions can be conducted once in 120 instead of 30 days. “This is the first time that we have a drug available in the market that reduces the burden of transfusions for thalassemia patients,” says Dr Revathi.
While blood transfusions help manage thalassemia, the only curative process for this condition is bone marrow transplantation. Here, the deficient bone marrow cells of a thalassemia patient are replaced with healthy stem cells. For many years in the past, such transplantation was only possible in a small number of cases where a donor whose marrow type fully matched the patient’s could be found. “Just as we have different blood groups, bone marrow also gets grouped into types based on certain genes called human leukocyte antigens (HLAs). These genes help the body decide what marrow cells belong to the body and what cells are foreign objects to be broken down by immune system,” explains Dr Revathi.
The techniques practiced in the past required a match across 10 HLAs in order to ensure successful transplantation. However, more recently, advanced techniques have been developed where marrow transplantation can be done even when a family member’s marrow matches across only 5 HLAs. “For nearly half of patients, there were no marrow donors available,” observes Dr Revathi. The development of Half-Match Transplant techniques has made this process accessible to a much wider set of patients, as we all inherit half of our HLAs from each parent, she adds.
However, such marrow transplantation is only advisable for children with thalassemia. For adult patients, the next frontier is gene therapy, explains Dr Revathi. “In gene therapy, we extract a patient's own bone marrow cells, and process them in the lab to incorporate the missing gene and give the cells back to them. This ensures that the patient’s body does not reject the new stem cells,” says Dr Revathi. Such a procedure received FDA approval in the US in August 2022, but it is yet to become widely accessible as an affordable treatment protocol.
When two thalassemia carriers have a child together, there is a 25% chance that the child may develop thalassemia major. However, recent advances in reproductive technologies have meant that two such carriers can have a child together without risking the possibility of that child inheriting the faulty genes. “There is a set of techniques called pre-implementation genetic diagnosis (PGD), where doctors examine 8 early-stage embryos created through IVF to discover which embryos are healthy and which carry the genes for thalassemia major. Accordingly, only the healthy embryos are implanted,” explains Dr Revathi. What’s more, for families that already have a child with thalassemia, PGD also allows for choosing the embryos that fully match with the sibling, so that bone marrow donation for the first child can be assured.
Even as we are seeing exciting advances in the field of management and cure of thalassemia, says Dr Revathi, many of these techniques, tools and drugs are currently far too expensive to be affordable for the majority of people. “These are all very new therapies, and so they are prohibitively costly. There are groups in India advocating for making these procedures more accessible to patients,” she says.
However, meaningful and viable alternatives already exist in terms of prenatal testing and counselling for couples to make informed decisions regarding having a child who has inherited thalassemia. “It’s actually a very simple blood test that can be done in the third month of pregnancy. If a woman is pregnant and knows herself to be carrier, the first step is to get the spouse tested. If the spouse also is a carrier, then the foetus can also tested, based on which the parents could take a call on whether to terminate the pregnancy or carry it to term,” explains Dr Revathi. Evidence that such preventive techniques can help cut down the incidence of thalassemia comes from several countries that have widespread premarital testing and counselling for thalassemia such as Dubai, Cypress, Italy, Thailand and Maldives, points out Dr Revathi.
With such broad-based screening and cutting-edge techniques for curing or managing thalassemia, this condition need not anymore consign patients to bleak and all-too-short life journey, says Dr Revathi.
For more details on Thalassemia, please refer https://apollocancercentres.com/cancers/thalassemia-cancer/
Dr Revathi Raj
Senior Consultant – Paediatric Haematology Oncology
This article was published in association with Apollo Cancer Centre.