The main curative therapy for haematological malignancies is allogeneic haematopoietic stem cell transplantation (HSCT). In 2011, over 14,000 allogeneic HSCT transplants a year were carried out in Europe. However some patients can die as a result of this procedure. Complications after HSCT include relapse with the original malignancy, graft versus host disease, graft rejection and infection. Novel transplant regimens are currently being developed to improve transplant outcomes via new forms of cellular therapy.
Graft-versus-host disease (GVHD) is a severe complication that can occur after a stem cell or bone marrow transplant in which the newly transplanted donor cells attack the transplant recipient's body. Bone marrow and stem cell transplants are treatments that use very high doses of chemotherapy, sometimes with radiotherapy, this treatment kills cancer cells but it can also kill the stem cells in your bone marrow that produce your blood cells. To combat this problem, patients are “rescued” by an allogeneic transplant. This occurs after the patient has had the high dose chemo/radiotherapy treatment to destroy the malignancy. The patient then has stem cells or bone marrow from the donor transfused through a drip into their bloodstream and these donor stem cells then make their way into the patient's bone marrow and start to produce blood cells again.
GVHD happens when particular types of white blood cell (T cells) in the donated bone marrow or stem cells attack your own body cells. This happens because the donated cells (the graft) see your body cells (the host) as foreign and attack them.
This is a complex condition and it is difficult to say who will develop GVHD after a transplant. We don't know exactly, but somewhere between 1 and 4 of every 5 people (20 to 80%) having a donor transplant will develop some degree of GvHD. Some people have a very mild form which doesn't last long. However, in its acute form, GVHD can be severe where patients fail to respond to available and approved therapeutics. It may even be life threatening in a few cases.
This project will study and develop novel diagnostic tools (biomarkers) for monitoring transplant outcome and investigate Graft versus Host Disease (GvHD), which as previously mentioned is a serious transplant complication, affecting 20-80% of transplant patients.In addition, new cellular therapies will also be developed and used in clinical trials. The production of these cellular therapies will be completed using Good Manufacturing Practice techniques in collaboration with industrial partners.
The ability to predict GvHD and its severity, or the response to therapeutic strategies, will enable clinicians to tailor therapy on an individual basis to improve outcome. Considering the morbidity associated with GvHD, the availability of biomarkers for predicting or monitoring success should
Reduce the number of deaths due to this disease
Improve the quality of life of patients
Ultimately reduce health care costs
As previously mentioned new cellular therapies will also be developed and these therapies require biomarkers to enable monitoring of responses to then tailor therapy to improve outcomes.
Any new biomarker will need to be validated and qualified or evaluated prior to routine use, and usually needs to be explored or validated in a phase one clinical trial.
CELLEUROPE will train fellows in the identification, validation and use of various biomarkers for both predicting the occurrence and severity of GvHD and evaluating the potential value of such markers in influencing clinical decisions.
This will impact on the use of cellular therapies and the unmet need of industry to have access to fully trained scientists in this important area of biomarker discovery.