Allogeneic bone marrow transplantation: Recent developments and the potential expansion of the donor pool

Graft versus host disease is a preventable complication of allogeneic bone marrow transplantation. A complex biological manoeuvre has enabled us to achieve this. Unfortunately T-cell depletion of the donor marrow shifts the delicate immunological balance in favour of the recipient immune system. The consequence has been an increased risk of graft rejection and leukaemia relapse. It is necessary to shift this balance back in favour of the donor (derived) immune system. This can be achieved by increasing the immunosuppressive power of the 'conditioning' chemoradiotherapy. Toxicity considerations limit our scope although single fraction fast dose rate radiotherapy appears to diminish the risks inherent with T-cell depletion. Logically an approach with greater promise will be to use specific immunological means of eliminating the recipient T lymphocytes in vivo. Early experience with a monoclonal anti-lymphoid antibody in vivo in an HLA matched unrelated donor programme suggests that this approach has great promise whilst lacking toxicity. We hypothesise that a shift in immunological superiority to the donor derived immune system will not only allow T-cell depletion whilst minimising the risk of graft rejection, but also enhance the anti-leukaemic properties of the graft. Of further interest will be the potential for application of lymphokines (e.g. IL2) without increasing the risk of lethal graft versus host disease.