3.0 BACKGROUND AND RATIONALE 
3.1 Viral Infections After Unrelated or Mismatched BMT 
When allogeneic BMT is undertaken using a donor other than a matched 
sibling the increased alloreactivity between donor and recipient results in 
increased incidences of graft rejection and GVHD.(l-3). The risk of rejection 
can be reduced by increasing the conditioning to eliminate residual recipient 
alloreactive T cells and the risk of GVHD can be reduced by depleting the 
donor marrow of mature alloreactive T cells (4-7). Both these manoeuvres are 
effective and in the 24 St Jude patients receiving mismatched or unrelated 
donor BMT for leukemia in the last 2 years the Day 50 survival has been 
100%. However as a consequence of GVHD and rejection prevention other 
problems occur in these patients. 
Since August 1990, 24 transplants using mismatched family and closely 
matched unrelated donors, with in vitro T cell depletion, in patients with 
leukemia have been performed at St Jude. Thirteen of these patients have 
died and in nine (38%) the cause of death was a documented viral infection 
(4 with CMV pneumonitis, 3 with EBV lymphoproliferative syndrome, 1 with 
adenovirus hepatitis, 1 with bronchiolitis obliterans organizing pneumonia and 
positive culture for parainfluenza). In another two the cause of death was 
pneumonitis with no virus isolated. In addition many of these patients had 
other viral infections and the eleven surviving patients have also experienced 
considerable morbidity from viral infections. This experience is repeated at 
almost every other center performing these transplants (8). This increased risk 
of infection may be partly due to the immunosuppressive regimens these 
patients receive and to delayed immune recovery but may also relate to 
greater genetic disparity resulting in defective interactions between antigen 
presenting cells and immune system effector cells. 
In most cases viral infection post BMT results from reactivation of latent 
virus. CMV has historically been the major cause of morbidity and mortality 
but the incidence of CMV pneumonitis has decreased since the advent of 
Ganciclovir and IVIG prophylaxis regimens (9,10). However the incidence of 
EBV lymphoproliferation post BMT is increasing as more transplants are 
performed from mismatched or unrelated donors and is now between 5 and 
30% in this group. 
3.2 EBV Biology in Normals 
EBV is an ubiquitous human herpes virus which infects over 90% of normal 
individuals. In primary infection the main route of entry is the oropharyngeal 
epithelium. Replication of the virus in epithelial cells allows infection of B 
lymphocytes resulting in a polyclonal proliferation of transformed B cells. 
These B cells express a number of EBV gene products including the nu^r 
Recombinant DNA Research, Volume 17 
