Graft failure after allogeneic hematopoietic cell transplantation

Area of Science:

• Immunology
• Hematology
• Transplantation Medicine

Background:

• Graft failure is a major complication following allogeneic hematopoietic cell transplantation (alloHCT).
• It can arise from recipient immune responses involving T cells, natural killer (NK) cells, or antibodies.
• Risk factors include HLA-mismatched or unrelated grafts, T cell-replete transplants, patient sensitization, and reduced-intensity conditioning (RIC).

Purpose of the Study:

• To review the causes and contributing factors of graft failure in alloHCT.
• To discuss potential strategies for overcoming graft failure.
• To highlight the increasing incidence of graft failure with evolving transplant practices.

Main Methods:

• Review of existing literature and recent data on alloHCT graft failure.
• Analysis of factors associated with increased graft failure rates.
• Examination of therapeutic interventions to mitigate graft failure.

Main Results:

• Graft failure is associated with HLA-mismatched, unrelated, and T cell-replete grafts, particularly in sensitized patients or those on RIC.
• Major ABO blood group mismatched transplants in unrelated recipients show increased graft failure (P = .008).
• Donor-specific antibodies targeting CD34(+)/VEGFR-2(+) cells may contribute to graft failure.

Conclusions:

• Graft failure remains a significant challenge in alloHCT, influenced by graft type, recipient factors, and conditioning intensity.
• Intensified conditioning, higher cell doses, or improved immunosuppression may overcome graft failure.
• The increasing use of RIC, cord blood, and HLA-mismatched grafts necessitates strategies to address rising graft failure rates.