Possible Implication of Bacterial Infection in Acute Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Graft-versus-host disease (GVHD) is still one of the major causes of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (HSCT). In the pathogenesis of acute GVHD, it has been established that donor-derived T-cells activated in the recipient play a major role in GVHD in initiation and maintenance within an inflammatory cascade. To reduce the risk of GVHD, intensification of GVHD prophylaxis like T-cell depletion is effective, but it inevitably increases the risk of infectious diseases and abrogates beneficial graft-versus-leukemia effects. Although various cytokines are considered to play an important role in the pathogenesis of GVHD, GVHD initiation is such a complex process that cannot be prevented by means of single inflammatory cytokine inhibition. Thus, efficient methods to control the whole inflammatory milieu both on cellular and humoral view are needed. In this context, infectious diseases can theoretically contribute to an elevation of inflammatory cytokines after allogeneic HSCT and activation of various subtypes of immune effector cells, which might in summary lead to an aggravation of acute GVHD. The appropriate treatments or prophylaxis of bacterial infection during the early phase after allogeneic HSCT might be beneficial to reduce not only infectious-related but also GVHD-related mortality. Here, we aim to review the literature addressing the interactions of bacterial infections and GVHD after allogeneic HSCT.

Attenuation of graft‐versus‐host‐disease in NOD scid IL‐2Rγ−/− (NSG) mice by ex vivo modulation of human CD4+ T cells

“…Most patients who receive cells from matched unrelated donors, non-HLA-identical siblings or UCB and up to 30% of the recipients of stem cells or bone marrow transplants from HLA-identical related donors develop acute GvHD (>Grade II) despite immunosuppressive prophylaxis (2,7). T cells play a major role in the development of GvHD and mechanisms other than direct T-cell-mediated cytotoxicity have been shown to be important in the pathogenesis (2,10,11). GvHD is initiated by immune-competent T cells from the donor recognizing host antigens in the recipients, which leads to their activation, expansion, and the release of pro-inflammatory factors (2,12,13).…”

Potential protective effect of Helicobacter pylori on the development of gastrointestinal GvHD

“…Considering the fact that prevalence of HP infection is decreasing in developed countries because of eradication treatments, regular and widespread use of broad-spectrum antibiotics during HCT and that intestinal flora is reduced and changed after chemotherapy, 40 we could observe a slowly progressive increase in the incidence of gastrointestinal GvHD in the future as it has already been observed in some studies. 41 Microbiota injury (because of antibiotics use, oral intake modifications and transplants characteristics), could impact on the GvHD development and our results.…”

Hyperglycemia as a possible risk factor for mold infections—the potential preventative role of intensified glucose control in allogeneic hematopoietic stem cell transplantation

“…60,61 The development of infectious diseases during the early post-transplant period might lead to an increased risk of subsequent complications. 62,63 In a small prospective study designed to assess the feasibility and effectiveness of intensive glycemic control (IGC) after allogeneic HSCT, there were significantly fewer documented infections in patients undergoing IGC compared with the matched-control group, although the study population was too small to assess the impact of IGC on the incidence of mold infections. 64 Although a multicenter clinical trial incorporating IGC for patients treated with allogeneic HSCT using myeloablative conditioning regimens is ongoing in Japan (UMIN000001189), it is also too small to assess the impact of IGC on the incidence of mold infections.…”