ABSTRACT
Allogeneic hematopoietic stem cell transplantation (HSCT) has become the treatment of
choice for many hematopoietic malignant disorders and also for certain solid tumors (1).
The clinical outcome and success of allogeneic HSCT rely on the extensive knowledge of
the HLA system and its accurate definition by serological and molecular typing. The appli-
cation of DNA typing methods has allowed a better definition of the diversity of HLA class I
and class II genes (2-5). Better HLA matching between donor and recipient may result in
a lower rate of graft failure and graft rejection as well as graft-vs.-host disease (GVHD)
(6). However, despite the use of immunosuppressive drugs for GVHD prophylaxis, in
20-30% of the patients clinically significant grades II-IV GVHD invariably occurs
even when fully HLA-matched transplants are performed (7). These clinically significant
alloreactive immune responses have been hypothesized to be due to mismatching for
polymorphic genes outside the major HLA complex. Some of these genes defined as minor
histocompatibility antigens (mHags) have been characterized and have been shown to act
as targets for specific allo recognition by donor T cells (8-10). Such an immune activity of
donor T cells is responsible not only for the detrimental GVHD but also for the therapeutic
graft-vs.-leukemia (GVL) effect observed after allogeneic HSCT. The antileukemic effect
of alloreactivity has been indicated by the observation that patients developing acute and/ or chronic GVHD had a significantly lower probability of leukemia relapse (11,12). More-
over, when comparing allogeneic HSCT with unmodified grafts versus T-cell-depleted
allogeneic or syngeneic HSCT, the decreased risk of acute or chronic GVHD coincided
with a higher rate of leukemic relapse (13,14). On the basis of these observations the
crucial antineoplastic role played by immunocompetent T cells against leukemia became
evident. Further conclusive evidence for the GVL effect of donor T cells after allogeneic
HSCT came from the success of donor lymphocyte infusion (DLI) used as a sole procedure
to reinduce a complete remission (CR) in relapsed patients (15,16). The potent capacity of
donor T cells to fully eradicate massive tumor loads has prompted several investigators to
challenge this dramatic therapeutic activity of the donor immune system by performing
allogeneic HSCT with reduced intensity conditioning regimens (17,18).
