title: The gut mucosa barrier is preserved during allogeneic, haemopoietic stem cell transplantation with reduced intensity conditioning.
abstract: The efficacy of allogeneic, haemopoietic stem cell transplantation (HSCT) is limited by concomitant toxicity. This has led to the development of less toxic, reduced intensity conditioning (RIC) protocols, whose therapeutic benefit is largely related to an associated, immunity-mediated graft-versus-malignancy effect rather than by the cytotoxic treatment itself. Murine HSCT models suggests that acute graft-versus-host disease (GVHD) increases with the intensification of the conditioning regimen mediated by loss of integrity of the gut mucosa barrier. The present study was undertaken to investigate gastro-intestinal (GI) permeability during allogeneic HSCT with RIC. In 17 patients (myeloablative conditioning in nine, RIC in eight), intestinal permeability was assessed by a (51)Cr-EDTA absorption test before the start of cytotoxic treatment the day before stem cell infusion (day -1) and 4, 7 and 14 days after stem cell infusion. Patients receiving RIC did not develop any significant increase in intestinal permeability during the transplantation course but in myeloablatively conditioned patients there was a significant increase in intestinal permeability the day before the stem cell infusion (P < 0.005), on day 4 (P < 0.005), on day 7 (P < 0.01) and on day 14 (P < 0.005) after stem cell infusion, compared with the baseline. Myeloablative conditioning also revealed increased intestinal permeability on day 7 compared with the RIC (P < 0.05). The finding of preserved intestinal-barrier function during allogeneic HSCT with RIC is discussed, with reference to the hypothesis that GI tract damage may be an important initiating event of GVHD.
authors.affiliation: Department of Haematology, Sahlgrenska University Hospital, Faculty of Medicine, University of Göteborg, Göteborg, Sweden.
authors.forename: J E
authors.initials: JE
authors.lastname: Johansson
authors.forename: M
authors.initials: M
authors.lastname: Brune
authors.forename: T
authors.initials: T
authors.lastname: Ekman
mesh_terms: D000328:Adult; D000961:Antilymphocyte Serum; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D002066:Busulfan / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects / Q000528:radiation effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D010539:Permeability; D011446:Prospective Studies; D013601:T-Lymphocytes; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014916:Whole-Body Irradiation / Q000009:adverse effects
chemical_list: D000961:Antilymphocyte Serum; D000970:Antineoplastic Agents; D003520:Cyclophosphamide; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine