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Predicting graft versus host disease in bone marrow transplantation using in vitro techniques

Obiettivo




Graft versus host disease (GVHD) is the most serious complication following bone marrow transplantation(BMT)-incidence 40-60% and can be fatal in 50% of cases. Two BMT centres in Europe have unique assays for predicting acute GVHD, a human skin explant model (Partner 1) and minor histocompatibility antigen (Hag) typing for HAl (Partner 2). Both centres have established these techniques by former research and publication. The aim now is to demonstrate the ability to predict GVHD in different cohorts of patients across Europe in large BMT centres . To date predicting GVHD and then modifymg therapy has not yet been achieved. An important step forward would be to demonstrate an accurate prediction of GVHD so that future studies could prevent and regulate GVHD more effectively. This cannot be achieved at a single centre level and requires this type of demonstration project across BMT Centres. Measurable objectives (every 6 months) would include co-ordination of clinical results (transplant outcome) with the results of both predictive models for GVHD. Specific objectives will include:
1. Partner 1 to aid other BMT Centres (Partners 3 and 5) in the use of the skin explant assay for predicting GVHD in adult and paediatric transplant recipients 2. To use the mHAl typing (HLA-identical sibling transplants only) results to further substantiate and strengthen the results obtained from the skin explant model and 3. To assess and evaluate the model in several BMT centres (Partners 1,2 and 5) to predict which patients will develop GVHD. This will influence the selection of donors and in the future enable therapy to be modified on an individual patient basis. Partner 1 is the only centre in Europe which has established this model as a useful and important predictive test for GVHD. This novel method has been used in a single BMT centre (Partner 1) for 9-10 years and has been demonstrated to be better than other cellular tests for predicting GVHD, especially in HLA-identical sibling transplants. The major aim will be to reduce mortality and morbidity of BMT recipients by more careful selection of donors and ultimately reduce in-patient hospital stay and cost of treatment. Whilst improving results another significant outcome of the demonstration project may be an additional reduction m treatment cost if prolonged chronic GVHD is also reduced.
Results from this demonstration project will contribute a significant step forward beyond the state of the art .This is due to the novel techniques used which when demonstrated within the larger European Bone Marrow Transplant ( BMT) community will significantly influence treatment modalities and modes of graft versus host disease ( GVHD) prevention.
The importance of demonstrating these techniques within the European BMT community lies with the potential benefit to larger numbers of transplant cases. In 1995, a total of 3287 allogenic bone marrow transplants were perforrned in Europe by 343 teams from 31 countries and data were reported to the European group for Blood and Marrow Transplantation (EBMT). The main indications being leukaemias, lymphomas and certam inherited haematological disorders. The EBMT and the International Bone Marrow Transplant Registry (IBMTR) document annual transplant activity and have bi-annual and annual meetings respectively. The numbers of transplants occurring in Europe and Worldwide is rising expotentially with still the main cause of mortality being GVHD.
Results demonstrated would be quickly and easily disseminated to BMT groups within the European community with the aim of influencing EBMT workshops for further participation, multilateral co-operation and involvement in potential new clinical trials for modifying GVHD therapy and prophylaxis based on results obtained from our multi-centre study.

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Coordinatore

UNIVERSITY OF NEWCASTLE UPON TYNE
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Indirizzo
Queen Victoria Road Royal Victoria Infirmary
NE1 7RU NEWCASTLE UPON TYNE
Regno Unito

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