Graft failure is a significant complication following allogeneic hematopoietic cell transplantation (AHCT). It may be due to rejection caused by recipient T-cells, NK-cells or antibodies. It is increased in HLA-mismatched grafts, unrelated grafts, T-cell replete transplants, sensitized patients and in patients treated with reduced intensity conditioning (RIC). In recipients of unrelated grafts, graft failure is increased in patients receiving major AB0 blood group mismatched transplants (p=0.008). Recent data also suggest that donor-specific antibodies to CD34+/VEGFR-2+ cells may be involved in graft failure after AHCT. Graft failure may be overcome by more intensified conditioning, increased cell dose, or more effective immunosuppression. With more frequent use of RIC, cord blood grafts and other HLA-mismatched transplants, graft failure is an increasing problem after AHCT.
In this presentation, will distinguish two different entities, the graft failure (GF) and the poor graft function (PGF), and review the current understanding of the interactions between the immune and hematopoietic compartments in these conditions. First discuss how GF occurs as the result of classical alloreactive immune responses mediated by residual host cellular and humoral immunity persisting after conditioning and prevented by host and donor regulatory T cells. Next summarize the current knowledge about the contribution of inflammatory mediators to the development of PGF. In situations of chronic inflammation complicating Allo-HSCT, such as graft-versus-host disease (GVHD) or infections, PGF seems to be essentially the result of a sustained impairment of hematopoietic stem cells self-renewal and proliferation caused by inflammatory mediators, such as IFN-γ and TNF-α, and induction of apoptosis through Fas/Fas ligand pathway. Finally, Better understanding of immunological mechanisms responsible for GF after Allo-HSCT may lead to the development of more efficient immunotherapeutic interventions.
Correspondence: Dr. Dilshad Jahan, Specialist, Department of Haematology and SCT, Apollo Hospitals Dhaka. E-mail: [email protected].