Recent advancements in management and treatment of thalassemia

Dr Gaurav Kharya, Clinical Lead, Centre for Bone Marrow Transplant and Cellular Therapy, Senior Consultant, Paediatric Haematology, Oncology and Immunology, Indraprastha Apollo Hospitals, New Delhi gives detailed insights into how treatment for thalassemia at the right can save patients, importance of tests to detect the disorder and preventive measures to be taken

Thalassemia is an inherited blood disorder that causes your body to have less haemoglobin than the normal levels. It is mostly caused by mutations in the DNA of cells that make haemoglobin and carries oxygen throughout the body. The mutations associated with thalassemia are passed from parents to children. Diagnosis of thalassemia can be made by simple test either Hb electrophoresis or preferably high performance liquid chromatography (HPLC). The test should be conducted before any blood transfusion otherwise they become difficult to interpret. Subsequently, a confirmatory genetic test should be done wherever possible. Over the past few years treatments for thalassemia major have evolved:

1. Ensuring extraction and transfusion of blood with utmost safety: Regular blood transfusion (to be precise red cell transfusion) is the lifeline for patients of thalassemia major. This is the only way to keep them alive as soon as they are diagnosed with thalassemia major. This highlights the importance of red cell transfusion in management of TM. Over the years significant advances have been made in offering safe blood to patients in need. Universal leucodepletion is one such way where the harmful white cells from the donors are removed immediately after the donation. This helps in minimising reactions at the time of transfusion and also decreases the risk of antibody sensitisation. Over the years the infections screening of blood products has also improved to a great extent further decreasing the risk of transfusion transmittable infections.
2. Optimal chelation: Chelation or removing excess iron from body is the next most important thing in patients on regular blood transfusion. We all know, with each unit of blood, some amount of iron is deposited in the body. If not removed optimally it causes damage to various organs eventually leading to organ failure and death. Over the years we have moved from subcutaneous chelation to thrice daily oral drugs to one daily drug. Even with once daily dosing it was difficult to have compliance especially from smaller kids. Of late defrasirox (once daily chelator) can just be sprinkled on the food of the patient and kids can consume it even without having any idea of medicine being taken. This ensures better patient compliance thus optimising chelation.
3. Newer drugs to decrease the frequency of blood transfusion: In recent years some very promising molecules have come into the market which helps in decreasing the frequency of blood transfusions. Luspatercept is one such drug which is approved for use in beta thalassemia major. It is given subcutaneously once every three weeks. (Only after being prescribed by a medical practitioner)
4. Advances in bone marrow transplant: As we are aware bone marrow transplant is the only possible cure for thalassemia major in current scenario. Conventionally HLA identical sibling donors were the only possible choice for BMT, thus limiting the usage of this modality. The medications used to kill the defective marrow in the past were also quite toxic leading to long term complications. In recent years, due to availability of much safer medications and better supportive care the outcome of HLA identical transplants has improved significantly and is more than 90 per cent if done at the right age. Apart from this HLA identical unrelated donors are also now available out of the family which increases the applicability of this procedure. An important progress made in last decade is advancement in success rates of haploidentical or half HLA match family donors. If done at the right age at experienced centres, the success rate of haploidentical transplant is also very encouraging and is more or less same as HLA identical donor transplants. This means that any child diagnosed with thalassemia major can undergo BMT using one or other donor (HLA identical related / HLA identical unrelated / haploidentical donor).
5. Advancements expected in the future: There is lot of enthusiasm and expectations about gene therapy / gene editing for thalassemia and related disorders. Initial trials done in the US and the UK are very encouraging and gives hope that gene therapy might be the future for thalassemia major patients. Phase III trials are ongoing, the results of which shall be available in next five years and hopefully in next 10 years it will be available for larger clinical usage. Despite its slight advantage over BMT, cost of gene therapy might be prohibitory in the initial years.