Dr Sunil Udgire, Consultant Haematologist, Paediatric Oncologist and Bone Marrow Transplant Physician, SPARSH Hospital emphasises on the evolution and upcoming trends in bone marrow transplantation
The first human bone marrow transfusion was given to a patient with aplastic anemia in 1939. However, the first allogeneic stem cell transplant was not performed until 1957 by E. Donnall Thomas, who focused mainly on acute leukemia. The process of selecting a donor using HLA(Human leukocyte antigen) typing had not yet evolved during this time.
Evolution of HLA typing
By the 1980s, more sophisticated transplants were being performed, and HLA typing had become a critical factor in selecting a donor. When a patient matches with a donor at 10/10, it is considered a fully matched family donor, making the donor eligible for donation. Over the years, HLA typing has continued to evolve.
Initially, bone marrow transplantation was mainly used to treat blood cancers or acute leukemia. However, medical professionals soon realised that it could be used to treat other diseases such as thalassemia and aplastic anemia, where stem cells are affected due to genetic causes. The use of bone marrow transplantation has also been expanded to treat benign hematological disorders, metabolic disorders, and immunodeficiency.
Evolution of conditioning treatment and donor availability
The conditioning treatment used to prepare the bone marrow for transplantation has also evolved over the years. Currently, a lot of research is being conducted on graft vs leukemia effects to control cancer, which has resulted in lower intensity chemotherapy. Previously, myeloablative conditioning chemotherapy was used, which was highly toxic and resulted in transplant-related mortality due to infection and chemotherapy toxicity. However, Reduced Intensity Conditioning chemotherapy (RIC) has now been introduced, which reduces the toxicity and intensity of chemotherapy. Non-myeloablative chemotherapy is also used in some cases where toxicity is much lower. This has allowed for allogeneic transplants in elderly patients up to 70 years of age.
Donor availability has also been extended due to the introduction of unrelated donor transplants. Initially, patients had to find a family donor for allogeneic transplants, which was challenging since only 30 per cent of siblings were fully matched to the patient. With the advent of HLA typing, several stem cell registries were established where donors voluntarily provided their buccal swab or blood sample for HLA typing. Patients in need of a transplant then searched for donors with matching HLA typing in the registry. This led to the discovery of unrelated donors, who were not related to the patient’s blood. In India, there are currently three unrelated donor registries: BMST-DKMS (joint registries), DATRI, and MDRI.
In India, however, donor representation is low compared to Western countries, resulting in only a 20 per cent chance of patients getting unrelated donors. Therefore, it is important to create awareness about these unrelated donor registries and encourage people to become stem cell donors. Anyone can become a stem cell donor by giving their HLA, which is added to the registry. This will increase the chances of patients finding a matching donor and ultimately save their lives.
What does the future hold?
The future of transplantation is moving towards haploidentical transplants, which have grown in popularity in the last 5-6 years. Haploidentical transplants are used when there is no match-family donor or unrelated donor available. Haploidentical means at least a 50 per cent match, and although there is a risk of Graft Versus Host Disease (GVHD) due to the mismatched transplant, advances in manipulating the graft have led to a newer technique involving the depletion of the bad T cells (TCR alpha beta) responsible for GVHD. This technique, using immuno magnetic beads, has improved transplant outcomes and made the donor problem easier to solve.
Another change is in nomenclature, now the term ‘bone marrow transplantation’ is replaced by hematopoietic stem cell transplantation (HSCT). Stem cells can be collected from bone marrow or directly from blood, and now 80 per cent of cases involve peripheral blood stem cells. Additionally, transplantation is becoming just one part of treatment, with a focus on cellular therapy and targeted cellular therapy, such as the upcoming CAR-T cell therapy. Clinical trials have already been approved in India, and this therapy may be available within the next 1-2 years for refractory leukemia/lymphoma that does not respond to any transplant or chemotherapy. This immunotherapy is considered the future of curing cancer.