Emerging drugs for prevention of graft failure after allogeneic hematopoietic stem cell transplantation

Abstract

Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the treatment of choice for many patients suffering from hematological malignancies, severe hemoglobinopathies, bone marrow failures or severe primary immunodeficiencies. Graft rejection/failure (GF) is a life-threatening complication following allo-HSCT that is most commonly caused by the reactivity of recipient T cells, natural killer (NK) cells or antibodies against donor grafted hematopoietic cells. The increasing use of allo-HSCT following reduced-intensity conditioning (RIC) and the increasing use of alternative donors (unrelated cord blood and human leukocyte antigen (HLA)-mismatched donor) have resulted in higher frequency of GF.

Areas covered: This review describes the pathogenesis and current prevention and treatment of GF as well as agents in development for GF prevention or treatment.

Expert opinion: The risk of GF may be reduced in the future by optimizing the conditioning regimens and post-grafting immunosuppression, increasing the number of hematopoietic stem cells (HSCs) and/or immune cells transplanted, optimizing HSC homing and better detecting patients at high risk of GF by searching for pre-transplant donor-specific anti-HLA antibodies in patients given grafts from HLA-mismatched donors, or by closely monitoring donor T- and/or NK-cell chimerism after allo-HSCT following RIC.

Keywords::

• alemtuzumab
• anti-thymocyte globulin
• chimerism
• costimulation
• CTLA4
• fludarabine
• graft failure
• graft rejection
• hematopoietic cell transplantation
• mesenchymal stromal cells
• reduced-intensity conditioning
• total body irradiation
• treosulfan

Acknowledgement

The authors would like to acknowledge Pharmaprojects database for providing drug information.

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