Recipient organisationGuy's and St Thomas' NHS Foundation Trust
Funding£2.8M
PeriodApr 2010 — May 2020
In plain English
AI plain-English summary
Around 2,000 people in the UK are diagnosed with acute myeloid leukaemia each year, and doctors need a better way to decide who should receive a gruelling stem cell transplant and who can safely be treated with chemotherapy alone. The problem is that current treatment guidelines are too blunt. Some patients receive a transplant they may not need, exposing them to high toxicity and cost, while others relapse because they were undertreated. This research aims to solve that by developing a standardised panel of molecular tests that can detect tiny amounts of leukaemia cells—minimal residual disease—long before conventional methods would spot them. The team has already proven this approach works in one subtype of leukaemia, where monitoring guides treatment and reduces both relapse and chemotherapy side effects. If successful, the programme will extend that precision to all major subtypes of acute myeloid leukaemia. The potential impact is a more personalised, cost-effective NHS service: fewer unnecessary transplants, lower treatment toxicity, and better survival rates—all without requiring new drugs, just smarter use of existing molecular diagnostics.
View original technical description
Acute myeloid leukaemia (AML) affects around 2,000 people a year in the UK, with an increasing incidence as the population ages. Curative treatment is highly intensive, which is arduous for the patient, expensive (over £50k/patient) and requires prolonged hospital admissions, representing a significant cost to the NHS. The UK runs the largest AML clinical trials in the world which have led to major improvements in survival, but still at least half of patients die, mostly due to relapse, but also treatment-related toxicity. Allogeneic stem cell transplantation (alloSCT) provides a powerful approach to reduce relapse, but is costly (£40-80k/ transplant) and associated with significant toxicity, with a mortality rate of 10-25%. AlloSCT is currently widely applied in standard and poor risk AML. However, it is becoming clear that some patients subject to transplant could have been cured with chemotherapy alone, whilst standard AML therapy represents overtreatment for a proportion with favourable disease. Therefore, to improve quality of care, survival rates and cost-effectiveness there is a critical need to define more precisely the optimal consolidation therapy for any given AML patient, particularly identifying those most (and least) likely to benefit from transplant.Over the last 20 years there have been major advances in understanding the molecular basis of AML with identification of an increasing number of prognostically and therapeutically relevant mutations. This information has been embraced in the recently updated WHO classification, which carries significant implications for guidance on the optimal diagnostic work-up and management of AML. This places demands on the NHS to develop a standardized validated panel of laboratory assays and to evaluate their clinical utility. Better molecular and immunophenotypic characterisation of AML also offers the opportunity to define markers in individual patients which can be used to monitor disease, to identify very low levels of leukaemic cells (minimal residual disease, MRD) before any conventional method.The potential of molecular diagnostics and MRD monitoring has prompted a number of service laboratories to develop their own assays, which are now being applied around the UK in a piecemeal non-standardized fashion, such that the clinical utility of these expensive technologies has not been validated. However, work pioneered by this research team in the MRC/NCRI AML trials involving 155 UK hospitals has shown that rigorous evaluation of standardized quantitative polymerase chain reaction (Q-PCR) assays in the acute promyelocytic leukaemia (APL) subtype of AML can be used to guide treatment according to the needs of the individual patient. Molecular diagnostics and monitoring in APL have been approved as cost-effective in a health economic report commissioned by the Australian Government and are recommended in national and international guidelines. Accordingly, this has been implemented as an NHS service by Blood Sciences at Guy’s and St. Thomas’ acting as the national reference centre performing high-throughput monitoring to direct management of APL patients across the UK. In APL (accounting for ~12% of AML), where effective molecularly targeted therapies are available, MRD monitoring has produced tangible benefits, reducing rates of disease relapse through early treatment intervention and determining the extent to which chemotherapy can be safely reduced, thereby substantially decreasing treatment toxicity and inpatient care. Having established proof of principle and technology transfer in APL in which over 80% of patients are now cured, this programme will develop a comprehensive panel of molecular diagnostic assays for the other subtypes of AML encompassing the new WHO classification, evaluating their predictive value in patients recruited to the NCRI AML17 trial (http://aml17.cardiff.ac.uk). This will be complemented by systematic evaluation of standardized MRD assays to establ
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