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Predicting outcome and developing new therapeutic strategies for
haematological stem cell transplant recipients using in vitro techniques.
Topic : Therapeutic Strategies
Project No : QLRT 2001 01936
European Commission Funded 2002 – 2005 FP5 Project
Allogeneic stem cell transplantation (SCT) is the only means of cure for haematological malignancies , as well as inherited anaemias and immunodeficiency disorders. The current poor rate of survival of only 30-50% is due to post transplant complications, including infections, relapse (recurrence of disease) and graft versus host disease GvHD. Tools to predict acute and chronic GvHD and or GvL (graft versus leukaemia) following different types of allogeneic SCT would enable new clinical protocols and therapeutic strategies to be developed based on individual patient expected risk. By the use of in vitro (in the lab) biotechnology, genetic and clinical risk assessment, we aim to predict out come following therapy and SCT and develop new European –wide common clinical protocols improving current therapeutic strategies. The 2.1m Euro (£1.8M) European Commission funded project involves the development of an important European –wide tissue bank for research use within the transplant community.
We Aim to
A patient tissue bank for use within the European community for transplant related research. This will aid the development of standardized diagnostic criteria for GvHD. By investigating and predicting the effect of current therapeutic protocols we aim to develop new therapeutic strategies and European –wide common clinical protocols.
Functional therapeutic risk analysis studies will improve the outlook for SCT patients by ultimately reducing the occurrence of GvHD.
Improved therapeutic protocols developed from the knowledge gained in the project will ultimately reduce health care costs and improve quality of life.
Due to the relatively small number of transplants carried out at each SCT centre within Europe a collective network of participants interacting at all levels from the clinic to the laboratory is an indispensable necessity. The project is multidisciplinary, involving molecular biologists, immunologists, transplant clinicians, pathologists and those in the treatment and care of autoimmune disease.
The importance of the TRANS-EUROPE project lies in
innovative strategies for monitoring
standard and new
transplant therapies including GvHD treatment
permitting statistical analyses on large patient groups.
TRANS-EUROPE will also develop a European-wide
tissue bank for transplant related research .
Predicting outcome following SCT and GvHD therapy will be carried out by the aid of an in vitro human skin explant assay (tissue sample), on-going genetic risk analysis, including non HLA immunogenetics studies (e.g.cytokine gene polymorphism analysis) and clinical assessments. The skin explant assay can predict the occurrence and severity of acute GvHD in pediatric and adult patients undergoing SCT. The results are used to modify GvHD therapy on an individual patient basis and aid in the design of therapeutic protocols.
The assay will be used to predict GvHD in different cohorts of transplant patients on varying conditioning regimes, where increased GvHD is problematic. Predicting this effect will be an important step forward in SCT management. The assay can be used to study the immunobiology of GvHD.
Extracorporeal photochemotherapy (ECP); an important new therapy for use in steroid-resistant patients is also being studied in the project.