ABSTRACT
For the past 25 years, the effective prevention of graft-vs.-host disease (GVHD) has been
the primary goal of laboratory and clinical investigators studying allogeneic hematopoietic
stem cell transplantation (HSCT). GVHD, once established, can be difficult to treat. The
survival of patients who develop moderate to severe GVHD is markedly inferior to that of
patients with either mild or no GVHD (1-4). Mortality can result from direct organ
damage or from opportunistic infections promoted by the use of immune-suppressive
medications. Although the use of calcineurin inhibitors and methotrexate is somewhat
effective as prophylaxis, GVHD remains a serious problem, particularly for patients
receiving transplants from unrelated or HLA-nonidentical related donors. As the role of
donor T cells in GVHD pathogenesis became established, efforts to limit the number of
potentially allo-reactive T lymphocytes in the graft were undertaken in order to prevent
GVHD. It was hoped that T-cell depletion (TCD) would improve the safety of and,
consequently, survival after allogeneic HSCT (5). Most early trials documented that
TCD substantially limited acute GVHD. However, these reductions in GVHD were coun-
terbalanced by high rates of graft failure, immune deficiency, and disease recurrence
(Table 1). Subsequent efforts have focused on ways of successfully manipulating
allogeneic grafts without inducing these adverse complications.
