Stem cell transplantation

The first allogeneic stem cell transplant was performed in the Department of Haematology in 1975, and over the past 40 years the group has built an international reputation in the management of haematological disorders by allogeneic and autologous stem cell transplantation (SCT). More than 140 transplants are performed each year principally for acute and chronic leukaemia, myelodysplastic syndromes, lymphoma, myeloma, germ cell tumours and the haemoglobinopathies. The programme is headed by Dr Eduardo Olavarria and other clinicians involved in this programme include Professor Jane Apperley, Dr Holger Auner, Dr Josu de la Fuente, Dr Dragana Milojkovic, Dr Jiri Pavlu, and Dr Aristeidis Chaidos. Current and previous members of the department have been elected as Presidents and/or Working Party Chairs of the British, European and International Blood and Marrow Transplant Societies (BSBMT, EBMT and CIBMTR) and the World Donor Marrow Association (WMDA) and have instigated measures to ensure both patient and donor safety and thereby improve transplant outcome. Professor Apperley was also the President of the pan-European JACIE system of accreditation of clinical, collection and processing facilities. The stem cell transplant programme is supported by a state-of-the-art facility for cell collection and manipulation. The pediatric transplant programme, initiated by Professor Irene Roberts and now under the directorship of Dr de la Fuente is the leading UK transplant unit for children and adolescents with haemoglobinopathies.

The John Goldman Centre for Cellular Therapy comprises two separate units each with two clean rooms. The Centre processes and stores human cells for transplantation and is fully accredited by JACIE, the Human Tissue Authority (HTA) and the Medicines and Healthcare products Regulatory Agency (MHRA). The Centre has a license to develop investigational and advanced medicinal cellular products (IMP/ATMP) and routinely produces mesenchymal stromal cells for the treatment of post-transplant complications such as refractory graft versus host disease, engraftment failure and other degenerative and autoimmune disorders. The JGCCT has recently acquired the technology to manufacture virus specific T-cells for the management of viral infections in post-transplant patients. 

Manipulating graft versus host disease with cellular interventions

The clinical department has strong links with several research groups in both haematology and immunology. Successful allogeneic SCT (allo-SCT) requires a profound understanding of the allo-immune responses resulting in host-versus-graft (HvG) and graft-versus-host (GvH) reactions.

Professor Anastasios Karadimitris’s group investigates the biology of glycolipid-specific T cells, their role in haematological disease and their therapeutic potential. The group are particularly interested a) in the role of invariant NKT (iNKT) cells in allogeneic stem cell transplantation and their therapeutic potential for CD1d-expressing B cell malignancies and b) in the role of gycosylphosphatidylinositol-specific T cells in the pathogenesis of paroxysmal nocturnal haemoglobinuria.

Together with Dr Aristeidis Chaidos, the group is currently studying the potential modulatory effect of iNKT cells on the immune responses involved in the pathogenesis of aGVHD and is developing novel protocols for clinical scale expansion of iNKT cells for the purpose of adoptive immunotherapy to prevent aGVHD. A new and exciting endeavour is the development and validation of chimeric antigen receptor-modified iNKT cells as therapeutic agents to target B &T cell non-Hodgkin lymphoma.

Much of the therapeutic effect of allo-SCT is mediated via durable immune responses and our transplant focus has led to a strong research platform in tumour immunology. Clinical exploitation of this graft versus tumour (GvT) effect has hitherto used infusions of donor derived lymphocytes to prevent relapse or restore remission after transplant and while at Imperial College, Professor Francesco Dazzi (now Honorary Chair) contributed internationally to the understanding of the mechanism of action and safe administration of these cells. More recently he has focussed his group on a better understanding of the immunoregulatory role of mesenchymal stromal cells. MSC have been used in a number of disorders and in SCT to promote engraftment and treat GvHD. The John Goldman Centre for Cellular Therapy is currently supplying MSC generated under GMP conditions to centres throughout the UK for use in bone marrow failure and steroid refractory GvHD.