Stem Cell Transplantation
The first allogeneic stem cell transplant was performed in the Department of Haematology in 1975 and over the past 35 year 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 chronic myeloid leukaemia, acute leukaemia, lymphoma, myeloma, and the haemoglobinopathies. The clinicians involved in this programme include Professor Jane Apperley, Professor Francesco Dazzi, Dr Josu de la Fuente, Dr Ed Kanfer, Dr Donald MacDonald, Dr David Marin, Dr Amin Rahemtulla and. Dr Katy Rezvani. Current and previous members of the department have been elected as Presidents 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 is the current President of the pan-European JACIE system of accreditation of clinical, collection and processing facilities. She has developed and supervised at the Hammersmith an adult clinical programme which is one of the largest and most innovative in Europe, and 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 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. The laboratories of both Professor Francesco Dazzi and Dr Katy Rezvani work on the dissection of the immune effector and regulatory mechanisms underlying these reactions. Dr Karadimitris’s work on CD1d is also directed to the investigation of its role in the presentation of glycolipids to T cells, which may be an alternative mechanism of development of GvHD.
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 Professor Dazzi has contributed internationally to the understanding of the mechanism of action and safe administration of these cells. More recently we have begun to dissect the effects of various lymphocyte sub-populations such as T-regulatory, NK and NKT cells and are planning Phase I/II clinical studies to manipulate GvHD and GvL. Dr Rezvani has a long-standing interest in tumour vaccination and two clinical studies for vaccination of candidate antigens in situations of minimal residual disease will commence in 2010.
Haemopoietic and non-haemopoietic stem cells derived from adult human bone marrow and umbilical cord blood have potential use in a wide variety of degenerative conditions and we are working across disciplines to understand and optimise these approaches. Mesenchymal stromal cells (MSC) have been used in a number of disorders and in SCT to promote engraftment and treat GvHD. Professor Dazzi is currently conducting a multicentre Phase I/II trial of MSC generated under GMP conditions in our purpose built facility and will extend these studies in regenerative medicine in 2010.
