PubMed · 16040388
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M Cavazzana-Calvo, I André-Schmutz. 2005. Selective allodepletion.. https://doi.org/10.1080/14653240510027127
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Acute lower gastrointestinal GVHD (aLGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Although the intestinal microbiota is associated with the incidence of aLGI-GVHD, how the intestinal microbiota impacts treatment responses in aLGI-GVHD has not been thoroughly studied. In a cohort of patients with aLGI-GVHD (n = 37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and a disrupted fecal microbiome characterized by reduced abundances of Bacteroides ovatus. In a murine GVHD model aggravated by carbapenem antibiotics, introducing B. ovatus reduced GVHD severity and improved survival. These beneficial effects of Bacteroides ovatus were linked to its ability to metabolize dietary polysaccharides into monosaccharides, which suppressed the mucus-degrading capabilities of colonic mucus degraders such as Bacteroides thetaiotaomicron and Akkermansia muciniphila, thus reducing GVHD-related mortality. Collectively, these findings reveal the importance of microbiota in aLGI-GVHD and therapeutic potential of B. ovatus.
Haploidentical stem cell transplantation is an alternative transplant strategy for patients without an human leucocyte antigen-matched donor. The historical experience with haploidentical stem cell transplantation has been characterised by the immunological consequences of crossing a major histocompatibility barrier, namely graft-versus-host disease (GVHD), graft rejection and impaired immune reconstitution. Ex vivo T-cell depletion of the graft may reduce the risk of GVHD, but at the expense of a higher risk of engraftment failure and relapse of the underlying malignancy. Myeloablative transplant strategies using vigorously T-cell-depleted 'megadose' stem cells appear to have improved the outcomes of selected patients with acute leukaemia. Non-myeloablative stem cell transplantation strategies, in which mixed chimaerism as a platform for adoptive cellular immunotherapy is intentionally induced, show promise for limiting GVHD and lessening transplant-related mortality. Future approaches, based on promising preclinical and early clinical observations, may include selective allodepletion of the graft, and manipulation of the cellular environment post-transplant using selected cellular populations or immunomodulatory soluble factors.
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