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Clinical research from UCL established `salvage therapy' and autologous transplantation protocols for use in relapsed and resistant Hodgkin lymphoma and demonstrated the efficacy of such approaches. These treatments are now widely used standards of care. A reduced intensity transplant (RIT) regimen, incorporating alemtuzumab to reduce graft-versus-host disease, was also developed and a potent graft-versus-tumour effect was demonstrated. RIT treatments are now increasingly used in patients failing an autologous transplant and in those patients deemed to have a high risk of autograft failure, as determined by pre-transplant CT/PET scanning. We estimate that 5,000 patients have been cured in the REF period as a result of our research.
Alemtuzumab, a humanised therapeutic antibody, is a major addition to the repertoire of immunosuppressive agents used for organ and stem cell transplants. Administered as an induction agent in a short course of treatment, alemtuzumab reduces the incidence of graft rejection without preventing recovery of the patient's ability to fight infection. Alemtuzumab also decreases graft versus host disease, a vital factor in the treatment of aplastic anaemia and acute leukaemias. Furthermore, its important role in minimising immunosuppressive therapy helps prevent treatment-associated problems for the patient. Currently used off-licence for transplants, alemtuzumab improves patient survival and healthcare.
Research conducted at UCL/UCLH over the last 20 years has enabled the identification of adults with acute leukaemia who are most likely to benefit from the use of stem cell transplantation, i.e. those with acute leukaemia in first remission. The treatment is highly intensive, potentially toxic and expensive high-dose chemotherapy followed by haemopoietic stem cell transplantation, and is inappropriate for some patients. The work has made a major contribution to the development of guidelines worldwide for the treatment of this disease. Improved patient selection for transplantation results in improved survival, less toxicity with improved overall quality of life, and a more appropriate use of NHS resources.
Research led by University of Oxford scientists has resulted in widespread use of the humanised therapeutic antibody, Campath (alemtuzumab), in patients with chronic lymphocytic leukaemia (CLL). Licensed by both the European and American regulatory authorities in 2004 for the treatment of CLL, Campath is used as first-line treatment for patients with aggressive forms of the disease and following relapse. It can induce long-term clinical remission even in cases resistant to other drugs. Campath has now been used in approximately 15,000 patients, and has generated revenues of approximately £750 million from the licensed treatment of CLL.
Research at UCL pioneered B cell depletion to treat rheumatoid arthritis (RA) and also stimulated the development of B-cell-directed therapies for other autoimmune rheumatic, haematological and neurological diseases. Now NICE approved, B cell depletion (based on rituximab) in RA is as effective as the alternative (anti-TNFα drugs) and an option for patients unable to gain benefit from anti-TNFα drugs. Rituximab offers drug-cost savings of up to £5,000/annum/patient and for many is a more convenient therapy, being given as an infusion only every five months apart, or more. B cell depletion has also proved to have an excellent safety profile, with many receiving repeated courses of treatment. As a consequence of UCL research, rituximab has brought substantial benefit to patients with many autoimmune diseases, including over 200,000 who have been treated with rituximab for RA so far.
Research conducted by a multidisciplinary team of oncologists and scientists at the University of Southampton has driven major advances in lymphoma care, leading to the development and standardisation of effective new antibody treatments and optimal drug regimens. Through their direction of international clinical trials, they have influenced care for Hodgkin and Burkitt lymphoma in the UK and internationally, affecting all stages of patient-experience from diagnosis to treatment. Their findings underpin significant improvements in survival and quality of life for the 14,000 people affected by lymphoma in the UK each year.
Research at UCL firmly established tacrolimus as the optimal calcineurin inhibitor to use in immunosuppressive regimens following liver transplantation. Compared to ciclosporin its use improved graft survival by 6% and patient survival by 7%. Assuming 550 liver transplants per year in the UK since 2008, we can estimate that, with 90% of patients treated with tacrolimus and 10% ciclosporin, tacrolimus-based immunosuppression has resulted in 165 grafts and 192 lives being saved during the period 2008-13.
The change in outcome for patients with chronic myeloid leukaemia (CML) is the outstanding cancer success story of the 21st century. All newly diagnosed patients now receive highly effective targeted life-long therapy with tyrosine kinase inhibitors and their response is monitored by a molecular test invented at Imperial College in the 1990s, to monitor patients after transplant. Improvements in methodology pioneered by Imperial staff, refined the test such that it is now a robust and accurate quantitative reflection of residual disease, and now in 2013 it is routinely used in both developed and developing countries to diagnose, determine management and predict outcome in CML.
Seven patients with avascular necrosis of the femoral head and bone cysts have been treated successfully with skeletal stem cell therapy, developed by Southampton researchers, resulting in an improved quality of life. This unique multi-disciplinary approach linking nano-bioengineering and stem cell research could revolutionise treatment for the 4,000 patients requiring surgery each year in the UK and reduce a huge financial burden on the NHS. The work has been granted three patents and the team are in discussions on development of the next generation of orthopaedic implants with industry.
Researchers at the University of Bristol have developed tests to track low-level leukaemia — `minimal residual disease' (MRD) — in children with acute lymphoblastic leukaemia (ALL) down to levels thousands of times lower than detectable by light microscopy. These tests have become the gold standard for monitoring of leukaemic response in clinical trials. MRD testing has been shown in 2013 to allow safe de-intensification of treatment for one-fifth of patients treated nationally, with substantial savings in toxicity and treatment-related expense. The same techniques have also improved worldwide understanding of how disease clearance is related to success after haemopoietic stem cell transplantation.