Scientists at the University of the West of England and the Bone Marrow Transplant Unit at the Bristol Children's Hospital have just won funding for a two-year project aimed at improving the outcome of bone marrow stem-cell transplants in young leukaemia patients.
After a stem cell transplant there is a significant risk that grafted donor white blood cells, known as T-cells, will attack the recipient and may cause a fatal complication called graft versus host disease (GvHD). In Bristol a monoclonal antibody called Campath is used to kill donor T-cells, reducing the chance of GvHD. A side effect of Campath therapy is delayed recovery of the immune system after the transplant which may be associated with leukaemic relapse.
UWE vice-chancellor Sir Howard Newby commented:
“Medical research is important to us all and especially to children. Basic scientific research cannot guarantee cures but in the longer term this important study could help children unfortunate enough to have to undergo a transplant and their families and friends. This award is evidence of the excellence of scientific research in our city.”
The UWE project will monitor the patient’s immune system to see how quickly it recovers following transplantation. In particular, the researchers are focussing on the role played by ‘natural killer T-cells’ (NKT-cells), which form a tiny but important population of white cells present in the blood of normal individuals including stem cell donors. The UWE group hypothesise that NKT-cells play a vital role killing remaining leukaemic cells in the patient’s system after the transplant thus leading to a higher probability of cure.
After an initial year of successful investigations researchers at UWE have discovered that NKT-cells possess the target antigen for Campath, already known to be present on the surface of T-cells. This means that unfortunately NKT-cells are also likely to be removed by Campath treatment. To investigate this important observation further the UWE researchers have just been awarded £97,000 additional funding by the charity CHILDREN with LEUKAEMIA.
Project leader Dr Craig Donaldson explains, “Initially, the treatment with Campath means the graft ‘takes’ better but unfortunately a significant proportion of transplant patients relapse over time and eventually die of leukemia. An important part of this project is to study the rate of repopulation of vital NKT-cells in patients who have received Campath treated grafts in comparison with patients who do not receive Campath treatment.”
“Patients who have consented to take part in this study will have a research blood sample taken at the same as their routine blood tests before transplant and at 3, 6 and 12 months after transplant. When the stem cell donor is a family member they will also be asked whether they wish to participate by consenting to having a research blood sample being taken when they attend the transplant unit for their routine pre-transplant blood check.”
The Bone Marrow Transplant unit based in the Paul O’Gorman wing of the new Bristol Children’s Hospital has an international reputation for developing novel methods of improving the results of stem cell transplants in young patients with leukaemia. Laboratory studies are being carried out at the Centre for Research in Biomedicine at the University of the West of England by Barbara Rees under the supervision of Dr Craig Donaldson and Professor Jill Hows.