Clinical Update on Current Management of Thalassemia

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Highlights:

• Thalassemia and sickle cell society of Bangalore was host to a presentation on the clinical updates on thalassemia by leading hematology specialist, Dr. M B Agarwal from Mumbai
• The event held on 1st October 2017 drew nearly 200 patients and parents who benefited from the expertise
• Thalassemia is a complex genetic blood disorder and optimal management of thalassemia is absolutely essential
• With newer information and knowledge on thalassemia being added by the day, it is essential for patients and parents to get updated on the know-how of best practices

Thalassemia is a complex genetic blood disorder where the beta-globin gene responsible for producing normal hemoglobin is defective. This means that the body does not produce sufficient hemoglobin for survival. People with thalassemia require life-long blood transfusions to survive. Since blood transfusions add excess iron into the body which can accumulate in vital organs, like the heart and liver causing permanent damage and even death, it has to be removed with the help of medications. These medications known as iron chelators come in the form of injections and tablets and can be used singly or in combination. Due to the complexity of thalassemia, there are several gray areas with lack of clarity of clinical management. New knowledge is being added every day and if patients have to get the best out of clinical management practices, they need to be updated regularly. The thalassemia and sickle cell society, Bangalore organized an important clinical update for thalassemia patients and parents on 1^st October at the Chancery Hotel, Bangalore. Many patients registered with the society can hardly afford regular visits to a hematologist. Arranging an event where masses get access to top specialists can help patients improve the quality of their lives with regular updates. The motivation behind this event was to enable as many people to learn and understand about the diseases and its latest treatment.

Dr. MB Agarwal is one of India’s top hematologists. He is currently the Head of the Department of Hematology at the Bombay Hospital Institute of Medical Sciences at Mumbai, and also the Director of the Hematology Centre located on Dr. Ambedkar Road, Dadar, in Mumbai. He also consults at reputed hospitals like Breach Candy and Lilavati hospital, Mumbai. Many patients from Bangalore who are able to make the time and afford the resources seek the consultation of Dr. Agarwal for thalassemia. Those who are under his care and guidance have been leading quality lives with minimal complications. To make this possible for all patients, the society arranged for Dr. Agarwal to come to Bangalore and update the patients and parents. The event was coordinated and managed by office bearers of the society like Gagandeep Singh Chandok, Masood, Prathima and others who supported the organization.

Dr. Agarwal began the information session with a brief description of thalassemia. To motivate the patients he also spoke about thalassemia patients who have normal lives and careers. He said thalassemia is no longer a life-threatening disorder if managed well and there are doctors, doctorates and other professionals among patients who are living well.

The main session was divided into important sections which included:

• blood transfusion practices
• blood-acquired viral infections and vaccines
• chelation therapies and options
• complications of iron overload
• curatives and the future
• prevention of thalassemia and prenatal testing
• life with thalassemia

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Blood transfusion practices

Blood banking and transfusion medicine is critical in the life of a child/adult with thalassemia. The reason many children and adults abhor going for blood transfusion is the sheer effort and complexity involved with it. Dr. Agarwal explained that better developments in blood banking and transfusion services mean one need not spend the whole day in a hospital. There are centers in India offering hassle-free transfusions with better facilities like reclining chairs instead of hospital beds. This means that children and adults can do any work during the transfusion time.

The doctor explained the optimal level at which hemoglobin has to be maintained and the need to be regular with blood transfusions. Irregular transfusions can lead to excessive bone marrow hyperplasia and ultimately bone deformities in the face and body. Patients and parents alike were informed that 10 grams were the optimal level after which the next transfusion must be planned.

Safe blood transfusion practices include washing and centrifuge of the cells and using a filter to remove unwanted white blood cells (WBCs). People with thalassemia only require red blood cells and hence WBCs can cause problems like antibody-antigen reactions. Dr. Agarwal warned the group that patients should not be taking blood from their parents or near relatives since the antibody-antigen reactions can damage their chances of bone marrow transplant in future. This was an extremely useful bit of information as patients often take blood from parents, siblings, cousins, aunts and uncles.

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Blood-acquired viral infections and vaccines

Blood transfusions are a must for a person with thalassemia. However, blood-acquired viral infections are a threat with blood which has not be tested properly. Human Immunodeficiency Virus (HIV), Hepatitis B (HBV) and Hepatitis C (HCV) are real threats. Many thalassemia patients have been affected by one or more of these viruses. Dr. Agarwal clearly informed the group that every unit of blood must be tested with NAT (nucleic acid test) to rule out HIV, HBV and HCV. NAT is currently the most sensitive test for these viruses.

Apart from rigorous testing, it is important for people with thalassemia to be vaccinated against HBV. Currently there is not vaccination for HCV; so one has to rely solely on robust testing to avoid this virus. However, there are anti-viral treatments for HIV, HBV and HCV. HIV and HBV require lifelong medications but HCV is a short course of medications for around 6 months.

Chelation therapies and options

Chelation therapy has always had the problem of compliance for people with thalassemia. The oldest chelator Deferoxamine (Desferal) is a subcutaneous infusion that is used with a pump. The infusion is usually taken in the night over 10-12 hours almost 5 days a week. Children and adults alike find it painful and tedious. However, there are newer oral tablets and options like sprinkles. This has made life easier for a lot of people with thalassemia. Most of these oral tablets can be taken in a combination with the infusion, which means one can take Desferal 2 nights per week along with 5 days of oral tablets. The oral tablets are:

• Deferiprone (Kelfer)
• Deferasirox (Asunra, Desirox, Defrijet)
• Deferasirox advanced (Oleptis)

It must be remembered that oral chelators can have side effects in some people. Some of the side effects include:

• Joint pains
• Nausea and vomiting
• Gastrointestinal irritation
• Liver and renal dysfunction
• Bone marrow depression

Dr. Agarwal recommended using a chelator which best suits the patient’s body.

Complications of iron overload

The single biggest cause of morbidity and mortality in people with thalassemia is complications of iron overload. Iron due to blood transfusions accumulates in the heart, liver, bones and almost all endocrine glands (reproductive system, pancreas, thyroid and pituitary). Iron overload can cause the following co-morbidities:

• Heart failure, cardiac arrests and heart attacks
• Acute liver failure or chronic liver disease due to scarring
• Osteopenia /osteoporosis
• Diabetes
• sexual and reproductive dysfunction
• Hyper- or hypothyroidism
• Pituitary disorders

While some of these can be reversed to some extent, endocrine damage is permanent and irreversible which is why it is best to prevent such issues. Dr. Agarwal recommends iron chelation (to remove excess iron in the body) as a non-negotiable need in the life of a person with thalassemia. It demands lifelong commitment and discipline but this can go a long way in maintaining a good quality life with minimal complications. The recommended serum ferritin level for thalassemia is <500 Ng/Ml.

Curatives and the future

Currently, bone marrow transplant (BMT) is the only permanent cure for thalassemia. It is usually done with a matched sibling and this is the best type of transplant. However, with advancing medical technologies and sophisticated drugs, it is also possible to carry out BMT using matched relatives, a haploidentical parent or unrelated matches (through bone marrow registries). BMT is best done before the child is 10 years of age.

For adults, the current hope is lentiviral vector-mediated globin gene transfer which can insert a normal hemoglobin producing gene into the body thus eliminating the need for lifelong blood transfusions. The therapy is currently in trials across the world and Dr. Agarwal informed the group that it would be around 5 years before the therapy becomes available with all safety and efficacy parameters.

Another hope is the drug Luspatercept which can be used by thalassemia intermedia and majors. This drug has the potential to reduce or eliminate the need for lifelong blood transfusions by promoting healthy red cell production. Dr. Agarwal believes this drug will be a boon for the lives of many with thalassemia since it is already in phase 3 clinical trials.

Prevention and prenatal testing

The best way to deal with thalassemia is to prevent it! With medical technologies, it is possible to carry out prenatal testing on a pregnant mother to determine if the fetus has thalassemia major. Chorionic Villi Sampling or CVS is the test to determine the thalassemia status of the unborn baby. Dr. Agarwal strongly recommends carrier screening of partners before marriage. This will enable the couple to take a decision on prenatal testing when the woman becomes pregnant. If both partners are thalassemia major there is 25% chance of the baby becoming a thalassemia major. If one partner is a minor, there is no need to do prenatal testing since the baby cannot become a thalassemia major.

Life with thalassemia

Dr. Agarwal infused hope and lifted the spirits of the patients and parents present by informing the group that a child/adult with thalassemia can have a perfectly normal life if he/she receives regular blood transfusions and iron chelation. People with thalassemia can play any sport, go to the gym, trek, hike, swim and participate in all physical activities. There is no bar on eating good food and he encouraged parents to allow their children to have a pizza or pav bhaji occasionally. He recommended a high-protein diet with sufficient calcium and vitamin c for optimal growth and health.

There is no bar from studying anything which a person with thalassemia aspires. People with thalassemia can become doctors or aeronautical engineers or whatever they chose to be. It is a myth that people with thalassemia cannot work hard or achieve success in life. Dr. Agarwal gave the example of doctors, medical researchers, architects, engineers, IAS officers and accountants who have thalassemia and yet scaled great heights. On the social front, Dr. Agarwal gave the examples of people with thalassemia who are married and have children as well.

These examples had a very positive impact on the patients and parents who felt that they can do whatever other “normal” people usually do in their life. The event was an eye-opener for many patients and parents as they received critical information on clinical management along with hope for future cures.

Reference:

1. Thalassemia - (https://medlineplus.gov/ency/article/000587.htm)

Source-Medindia