Professor Eduardo Olavarria

This was my first research interest and culminated in a series of publications that have served as benchmarks for the implementation of minimal residual disease (MRD) monitoring after allogeneic stem cell transplantation. It also developed further the field of PCR for fusion genes as means of monitoring leukaemia response to therapy, which has become even more prominent in the era of Tyrosine Kinase Inhibitors in Myeloproliferative Neoplasms. From here, my research involved the use of different methods of minimal residual disease combined with chimaerism to define relapse after stem cell transplantation. This culminated in two joint publications from the NCI First International Workshop on the Biology, Prevention and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation

The manipulation of the stem cell graft offers multiple possibilities for improving outcomes after allogeneic stem cell transplantation. Our research in this field has focussed on immunomagnetic methods of T-cell depletion with a near total abrogation of the risk of Graft versus Host Disease after transplant. More recently we are researching the use of different methods for selective depletion of only allo-reactive T-cells.

In collaboration with St John’s Institute of Dermatology at St Thomas’ Hospital in London, we have established the largest Transplant Program for Cutaneous T-cell Lymphomas in the UK and one of the largest in Europe. We have sequentially developed three different protocols over the years with over 50 patients with this rare disease treated and contributed to several publications in the field and the production of the UK National Guidelines

In collaboration with the University of Navarra, Spain, my group has developed a new method of monitoring anti-viral T-cell constitution culminating in several publications over the past 3 years. Following from this, we are now manufacturing viral-specific T-cells to treat patients with refractory viral infections after transplant. We are able to treat several viral infections (CMV, EBV, AdV, Polyoma BKV) with adoptive T-cell therapy.

Multiple sclerosis is a chronic immune mediated disease of the central nervous system affecting ~0.1% of Caucasians and characterised by a variety of symptoms including visual impairment, limb weakness, sensory disturbance, balance and postural problems, sphincter dysfunction, cognitive impairments, pain and fatigue. Most patients become disabled as the disease progresses with ~50% requiring walking aids or the use of wheelchairs within 15 years of onset. In the majority of patients, the illness runs an initial relapsing remitting (RRMS) course characterised by episodes of acute neurological dysfunction followed by full or partial recovery, usually culminating in a secondary progressive (SPMS) course during which disability progresses inexorably.

The main common pathogenic pathway in multiple sclerosis involves an immune-mediated cascade targeting CNS myelin. In patients failing immunosuppressive treatment, autologous hematopoietic system cell transplantation has been shown to be a potent modifier of disease activity, reflected by stabilisation of disease and a reduction of abnormal magnetic resonance imaging activity. The SCT team at Imperial College led by Professor Olavarria and Dr Ian Gabriel and in collaboration with Professor Paolo Muraro and Dr Richard Nicholas from the Department of Neurology have established an active programme with over 100 patients transplanted. More recently, we have been successful in securing a £2.3 Million NIHR-EME grant to set up a national clinical trial (STAR-MS) in collaboration with Sheffield University and King’s College.

We routinely produce 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.  

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 the group at Imperial College contributed internationally to the understanding of the mechanism of action and safe administration of these cells. More recently the SCT unit has focussed on better understanding 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 (JGCCT) is currently supplying MSC generated under GMP conditions to centres throughout the UK for use in bone marrow failure and steroid refractory GvHD.

A patient at Imperial College Healthcare NHS Trust achieved a sustained remission from HIV-1 after ceasing antiretroviral treatment – becoming only the second person globally to do so. The patient, who has requested to remain anonymous, was treated with a stem cell transplant at the Hammersmith Hospital, similarly to the ‘Berlin Patient’ 11 years ago, although the strategy was not identical. Following the transplant in 2016, antiretroviral therapy was discontinued and the patient has now remained in remission for 18 months. The treatment was offered as part of collaboration by the stem cell transplant team at Imperial College London, led by Professor Eduardo Olavarria and Dr Ian Gabriel and HIV scientists at University College London led by Professor Ravindra Gupta.

The patient was diagnosed with HIV infection in 2003 and developed an AIDS defining cancer advanced Hodgkin’s Lymphoma in 2012. He received a transplant of haematopoietic stem cells from a donor carrying a genetic mutation in the HIV receptor CCR5. The patient remained on antiretroviral drugs for 16 months after the transplant, when he stopped the treatment. Using very sensitive techniques the virus cannot be identified and his new cells have shown that cannot be infected by HIV-1 nearly 3 years after the transplant. The use of donors with CCR5 mutations opens a new possibility towards the cure of HIV.