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A new class of drug known as tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia (CML) has been tested in Newcastle-led international clinical trials. One of these drugs, imatinib, was found to almost double five-year survival rates and significantly improve quality of life with few side effects. Subsequent follow up studies found an estimated eight-year overall survival of 85%. Imatinib is now recommended in national and international guidelines and is used increasingly to treat patients with CML.
Chronic myeloid leukaemia (CML) is a rare blood cancer, with around 560 new cases diagnosed in the UK each year. Research conducted by Professor Tessa Holyoake's team at the University of Glasgow has led drug development and stimulated clinical trials of therapies targeting CML stem cells at two major pharmaceutical companies (Novartis and Bristol-Myers Squibb). The researchers are listed as co-inventors of a novel compound (LDE225) and have promoted two further therapies targeting CML stem cells (BMS-833923 and hydroxychloroquine) into clinical trials as treatments for CML. Holyoake also had a key role in establishing the Paul O'Gorman Leukaemia Research Centre in May 2008, funded by more than 1,800 charitable donations totalling around £2.6 million and giving patients unprecedented access to the latest clinical trials.
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.
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.
Acute promyelocytic leukaemia (APL) is of interest because it is the first cancer that can be cured with drugs that target a unique molecular abnormality. KCL research has developed accurate molecular techniques which are essential to diagnose the disease, guide treatment, and monitor for relapse. Sub-microscopic levels of leukaemic cells remaining in the patient's bone marrow after treatment (referred to as `minimal residual disease') give an early warning of re-occurrence of the disease. Our laboratory has developed sensitive tests for these cells, allowing treatment to be tailored to individual patient needs. This has had a major impact on APL diagnosis and monitoring and has been incorporated in national and international disease-treatment guidelines.
Ataxia telangiectasia (A-T) is an inherited disease affecting multiple systems in the body, causing severe disability and death. Work led by Professor Malcolm Taylor at the University of Birmingham has been central to the biological and clinical understanding of this disease, from the identification of the gene responsible to the clarification of related conditions with different underlying causes. As a result of this work, within the 2008-13 period, his laboratory has been designated the national laboratory for clinical diagnosis of A-T — a service also offered internationally — and has also changed national screening policy for breast cancer, following his confirmation of the increased risks of A-T patients and those who carry a single copy of the gene for this type of tumour. Furthermore, he has contributed in a major way to patient support for this condition.
Clinicians and scientists at UCL have been central to the design and management of single centre and multi-centre lymphoma trials within the UK and internationally. The trials have enabled a balanced approach to the non-Hodgkin lymphomas (NHL), supporting more conservative strategies in certain well-defined situations but also providing evidence for the value of very intensive therapy in appropriate patients. These trials have contributed to patient survival, quality of life and appropriate resource utilisation.
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 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.