Ireland’s first successful bone marrow transplant
By Professor McCann
Image credit: Hospital by stux. Public Domain via Pixabay.
The idea of bone marrow transplantation as a treatment for bone marrow failure and leukaemia is a direct result of experiments carried out in Los Alamos, New Mexico, where the Manhattan project was researching the atomic bomb in the early 1940s. Bone marrow transplantation was championed by E Donal Thomas as treatment for leukaemia, for which he shared the Nobel Prize with Joseph E Murray. By the 1980s bone marrow transplantation had become an accepted form of treatment for leukaemia and related diseases.
I carried out the first successful bone marrow transplant for leukaemia (read this freely available chapter) in 1984 in St James’ Hospital, Dublin, having learnt the technique in the Fred Hutchinson Cancer Research Centre in Seattle Washington, under the direction of Dr Thomas. The philosophy of bone marrow transplantation involved the delivery of lethal doses of chemotherapy or chemotherapy and total body irradiation (TBI) to a patient, usually in remission from leukaemia, and the ‘rescue’ of that patient with the administration of stem cells from a healthy (HLA matched sibling at that time) donor. This was the opposite of what we were trained to do as doctors and unfortunately, the outcome was not always successful.
There were many complications for the recipient including infection, severe damage to the lining of the GUT (mucositis), and the requirement for isolation. Coupled with those was the possibility of a new disease, Graft versus Host Disease (GvHD), which was the opposite of graft rejection and, in spite of treatment, could be fatal or produce a chronic illness associated with very poor quality of life.
Although the transplant procedure is relatively straight forward the complications involve all body systems and thus require the input of colleagues from all specialities. This requires a lot of discussion and persuasion.
Happily, things have improved since the early days of transplant. A number of sources of stem cells are now available (peripheral blood and umbilical cord blood); the spectrum of possible donors has been widened to include so-called unrelated matched donors and now haploidentical donors (parents). The technology of tissue typing has undergone many developments. Conditioning therapy has been altered (reduced intensity transplant), to reduce toxicity and make transplantation available to older patients. However, we have made little progress in the treatment of GvHD.
The number of recipients of bone marrow transplantation, or as it is now called stem cell transplantation, continues to increase globally, with the unit in St James’ Hospital having carried out over 2000 transplants since 1984.
The use of ‘targeted therapy’, for example, the use of tyrosine kinase inhibitors in chronic myeloid leukaemia, has removed the need for stem cell transplantation in the majority of patients. Whether a similar approach to other forms of leukaemia will prove effective or not remains to be seen. Some predict that the use of checkpoint inhibitors, CAR T cells (Gene-engineered autologous T cells with chimeric antigen receptors), monoclonal antibodies, and other forms of immunotherapy will eventually replace stem cell transplantation. Time will tell.
Shaun R. McCann was Professor of Academic Medicine in the University of Dublin, Trinity College from 2005-2011 and was a consultant haematologist, George Gabriel Stokes Professor of Haematology and head of department in St James's hospital, Dublin from 1984 until 2009. He performed the first stem cell transplant for leukaemia in Ireland in 1984. Appointed Medical Director of the Irish Blood Transfusion Service in April 1995 by the Minister for Health during the Hepatitis C crisis. He was the first President of the Haematology Association of Ireland.
Professor McCann has published over 150 medical articles, numerous book chapters and a number of textbooks for undergraduate medical students. He was Editor-in-Chief of the European Hematology Association Newsletter from 2006-2012 and was Chair of the European Hematology Association (EHA) Training on line Unit. Professor McCann is currently member of the 'Online and Case Unit' and the Communications Committee of the EHA, and has made over 200 podcasts for EHA.
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