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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.
Since 2000, the tyrosine kinase inhibitor (TKI) imatinib has transformed CML from a fatal disease for half of patients within 5 years, to a chronic disease whereby ~ 90% of patients lead normal lives for at least 9 years. This remarkable transformation has spawned a second phase of clinical and translational research aiming to cure CML. The University of Liverpool (UoL) CML research group headed by Prof Richard Clark has been integral in both phases, particularly in the development of the second generation TKI nilotinib. Important contributions have also shed light on CML biology and the possible mechanism of acute leukaemic transformation (blast crisis).
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.
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.
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.
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.
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.
Questions about the benign or malignant nature of liver tumours are common and pressing since they determine how the patient is managed. Benign masses are frequently encountered; they usually do not require intervention but are easily mistaken for malignancies with conventional imaging methods. Work at Imperial College demonstrated that microbubble contrast agents have the special property of lingering in both normal liver tissue and in benign solid masses, whereas malignancies do not retain microbubble. The discovery of this property at Imperial has led to their use worldwide as a diagnostic tool. In 2012 NICE recommended their use as being cost-effective for this use.
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.
HIV associated plasmablastic multicentric Castleman's disease (MCD) has emerged as an uncommon disease over the last decade that is a significant cause of mortality in people living with HIV infection. Advances in our understanding of the epidemiology, virology and immunology of this disease led Professor Bower to recognise the potential for using targeted monoclonal antibody therapy. This has dramatically improved the survival of patients with MCD and is now advocated in the national treatment guidelines and is widely adopted in clinical practice globally. Moreover, the use of plasma Kaposi's sarcoma herpesvirus virus levels as a tumour marker for MCD has been developed.