The use of monoclonal antibodies in graft versus host disease prevention.

One of the most important causes of procedure related death after bone marrow transplantation (BMT) is graft versus host disease (GvHD) in which donor T-lymphocytes recognise alloantigens in the recipient and attack and damage the cells bearing them. Even when donor and recipient are matched at all loci of the major histocompatibility complex (MHC) 40%-70% of recipients develop severe graft versus host disease after conventional BMT: in a third of those affected the outcome is fatal. When donor and recipient are less than identical at the MHC the incidence and severity of acute graft versus host disease are correspondingly higher. The morbidity and mortality associated with acute GvHD has limited the application of bone marrow transplantation in two ways: first by restricting the procedure to patients with serious haematological disease and second by excluding individuals who might benefit from BMT but who lack an MHC identical sibling. In this review we discuss briefly the theoretical work that led us to our protocol for T-cell depletion for GvHD prevention and then describe the results of our own and other groups undertaking T-cell depleted bone marrow transplants. Finally, we discuss some of the new problems--and benefits--associated with T-cell depletion and outline the improvements in techniques now taking place.