New advances in acute graft‐versus‐host disease prophylaxis

Abstract

Immunocompetent donor T cells in Allogeneic Haematopoietic Stem Cell grafts mediate acute Graft versus Host Disease (GvHD), still a major cause of recipient morbidity and mortality post transplant. Despite the advent of high resolution HLA-typing and matching at HLA loci, acute GvHD remains a significant problem, even in HLA matched siblings, due primarily to minor histocompatability antigen mismatches. Treatment of GvHD remains ineffective and highly immunosuppressive and the challenge to find effective methods of prevention continues. Non selective removal of donor T cells from the graft has been proven to be effective in preventing GvHD but the beneficial effects of donor T cells, namely effective immune reconstitution and anti tumour activity, are lost. This review considers mechanisms by which acute GvHD may be prevented in the context of the current model of GvHD immunopathogenesis, with a special emphasis on the recent techniques of selective removal or destruction of donor allogeneic T cells that have been described.

Factors associated with optimized tacrolimus dosing in hematopoietic stem cell transplantation

“…5 Additional factors, including patient adherence and other immunosuppression agents used, should be considered when evaluating the incidence of GVHD. Importantly, the small sample size in this study limited the ability to assess this relationship with certainty.…”

“…The incidence of acute GVHD (aGVHD) reaches 40–60% in patients transplanted from HLA-identical sibling donors and 75% in patients receiving stem cells from HLA-matched unrelated donors. 5 Chronic GVHD (cGVHD) occurs in 40–70% of patients and is responsible for 20–25% of late deaths following alloHSCT. 6,7 The incidence of graft failure is up to 25% in recipients of nonmyeloablative alloHSCT compared to 3% in recipients of myeloablative transplants.…”

Prophylaxis regimens for GVHD: systematic review and meta-analysis

“…They are biologically different as tacrolimus is associated with more pronounced inhibition of the production of IL-2 by T-lymphocytes, a major mediator in the pathogenesis of GVHD. 1,46 This might be an explanation for its advantage over CsA in the reduction of GVHD. Although limited by their sample size, RCTs constitute a better platform to assess the overall survival, adjusting for risk factors that cannot be foreseen or adjusted for in observational studies.…”

“…Despite prophylactic measures, the incidence of acute GVHD (aGVHD) is estimated to be 40-60% among patients receiving transplants from HLA-identical sibling donors and reaches 75% in patients receiving HLAmatched unrelated (MUD) transplants. 1 The incidence of chronic GVHD (cGVHD) ranges between 40 and 70% and is one of the leading causes of death in Allo-HSCT survivors, estimated to cause 20-25% of late deaths. 2,3 Other major causes are relapse and infection, which are estimated to cause around 30% and 10% of deaths, respectively.…”

Key factors in experimental mouse hematopoietic stem cell transplantation

“…The critical role of host antigen-presenting cells in the development of the disease was already mentioned and targeting of these cells could therefore be a prospective strategy for the suppression of GVHD [35,75,119]. Comprehensive reviews discussing modern strategies of GVHD prevention and treatment have also been recently published [23,24].…”