Novel approaches for preventing acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.
BACKGROUND
Allogeneic hematopoietic stem cell transplantation (alloHSCT) offers potential curative treatment for a wide range of malignant and nonmalignant hematological disorders. However, its success may be limited by post-transplant acute graft-versus-host disease (aGVHD), a systemic syndrome in which donor's immune cells attack healthy tissues in the immunocompromised host. aGVHD is one of the main causes of morbidity and mortality after alloHSCT. Despite standard GVHD prophylaxis regimens, aGVHD still develops in approximately 40-60% of alloHSCT recipients.


METHODS
In this review, after a brief summary of current knowledge on the pathogenesis of aGVHD, the authors review the current combination of a calcineurin inhibitor with an antimetabolite with or without added anti-thymocyte globulin (ATG) and emerging strategies for GVHD prevention.


CONCLUSIONS
A new understanding of the involvement of cytokines, intracellular signaling pathways, epigenetics and immunoregulatory cells in GVHD pathogenesis will lead to new standards for aGVHD prophylaxis allowing better prevention of severe aGVHD without affecting graft-versus-tumor effects.
a Division of Hematology, Department of Medicine , University and CHU of Liège , Liège , Belgium.|b GIGA I3 , University of Liège , Liège , Belgium.
Sophie
S
Servais
a Division of Hematology, Department of Medicine , University and CHU of Liège , Liège , Belgium.|b GIGA I3 , University of Liège , Liège , Belgium.
Yves
Y
Beguin
b GIGA I3 , University of Liège , Liège , Belgium.
Loic
L
Delens
b GIGA I3 , University of Liège , Liège , Belgium.
Grégory
G
Ehx
b GIGA I3 , University of Liège , Liège , Belgium.
Gilles
G
Fransolet
b GIGA I3 , University of Liège , Liège , Belgium.
Muriel
M
Hannon
a Division of Hematology, Department of Medicine , University and CHU of Liège , Liège , Belgium.
Evelyne
E
Willems
c Translational Immunology Laboratory , VIB , Leuven , Belgium.|d Department of Microbiology and Immunology , KUL-University of Leuven , Leuven , Belgium.
Stéphanie
S
Humblet-Baron
b GIGA I3 , University of Liège , Liège , Belgium.
Ludovic
L
Belle
a Division of Hematology, Department of Medicine , University and CHU of Liège , Liège , Belgium.|b GIGA I3 , University of Liège , Liège , Belgium.
Frédéric
F
Baron
D000818:Animals; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000627:therapeutic use; D065095:Calcineurin Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D015195:Drug Design; D006086:Graft vs Host Disease / Q000503:physiopathology / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009369:Neoplasms / Q000628:therapy
D000961:Antilymphocyte Serum; D065095:Calcineurin Inhibitors; D016207:Cytokines; D007166:Immunosuppressive Agents
Acute graft-versus-host disease; JAK inhibitors; T-cell depletion; anti-IL-6 receptor antibody; demethylating agents; histone deacetylase inhibitors; mTOR inhibitors; mesenchymal stem cells; proteasome inhibitors; regulatory T cells