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

Abstract

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.ARTICLE HISTORY

PRMT5 regulates T cell interferon response and is a target for acute graft-versus-host disease

“…Epigenetic modifiers are appealing targets for aGVHD not only because of the role epigenetics has in immune regulation but also because many epigenetic modifying agents are used as treatments against hematopoietic neoplasms (72,73). A variety of epigenetic modifiers are currently being evaluated as potential aGVHD therapeutics in phase I and phase II clinical trials, primarily as combinatorial therapies with other well-established aGVHD treatments (74,75). DNA methyltransferase inhibitors, such as 5-azacitidine and 5-aza-2′-deoxycytidine (decitabine), have shown great promise in ameliorating GVHD in both preclinical and clinical studies by increasing Treg production and impairing effector T cell proliferation (76)(77)(78)(79)(80)(81).…”

In Vitro Th17-Polarized Human CD4+ T Cells Exacerbate Xenogeneic Graft-versus-Host Disease

“…Acute graft-versus-host disease (aGVHD) remains a major cause of transplantation-related mortality after allogeneic hematopoietic stem cell transplantation (alloHSCT). The immunobiology of aGVHD is complex and involves an intricate network of immune cells [1][2][3]. Among these cells, donor T cells are considered the main drivers and effectors of aGVHD reactions, as demonstrated by the low incidence of aGVHD observed in patients who undergo T cell-depleted alloHSCT [4].…”

Infusion of bone marrow derived multipotent mesenchymal stromal cells for the treatment of steroid-refractory acute graft-versus-host disease: a multicenter prospective study

“…Allogeneic hematopoietic cell transplantation (alloHCT) offers potential curative treatment for a number of hematological malignancies [ 1 ]. However, its outcome is compromised by the occurrence of acute graft-versus-host disease (aGVHD), a systemic syndrome in which donor immune cells attack tissues (mainly skin, gut and liver) of the immunocompromised host [ 2 , 3 ]. It is estimated that 30–60% of transplanted patients develop clinically significant grade II-IV aGVHD after alloHCT [ 4 ].…”