4.5 Review

Novel approaches for preventing acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

Journal

EXPERT OPINION ON INVESTIGATIONAL DRUGS
Volume 25, Issue 8, Pages 957-972

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1080/13543784.2016.1182498

Keywords

Acute graft-versus-host disease; anti-IL-6 receptor antibody; histone deacetylase inhibitors; demethylating agents; JAK inhibitors; mesenchymal stem cells; mTOR inhibitors; proteasome inhibitors; regulatory T cells; T-cell depletion

Funding

  1. FNRS from the University of Liege
  2. Belgian Foundation against Cancer (FBC) from the University of Liege
  3. Anti-Cancer Center from the University of Liege
  4. Leon Fredericq Foundation from the University of Liege
  5. Terry Fox Foundation from the Belgian Government
  6. Plan Cancer from the Belgian Government

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Introduction: 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.Areas covered: 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.Expert opinion: 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.

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