Johansson J E, Brune M, Ekman T
Department of Haematology, Sahlgrenska University Hospital, Faculty of Medicine, University of Göteborg, Göteborg, Sweden.
Bone Marrow Transplant. 2001 Oct;28(8):737-42. doi: 10.1038/sj.bmt.1703230.
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.
异基因造血干细胞移植(HSCT)的疗效受到伴随毒性的限制。这促使了毒性较小的减低强度预处理(RIC)方案的发展,其治疗益处很大程度上与相关的免疫介导的移植物抗恶性肿瘤效应有关,而非细胞毒性治疗本身。小鼠HSCT模型表明,急性移植物抗宿主病(GVHD)会随着肠道黏膜屏障完整性丧失介导的预处理方案强度增加而增加。本研究旨在调查接受RIC的异基因HSCT期间的胃肠道(GI)通透性。在17例患者中(9例接受清髓性预处理,8例接受RIC),在干细胞输注前一天(第-1天)开始细胞毒性治疗前以及干细胞输注后4、7和14天,通过(51)铬-乙二胺四乙酸(Cr-EDTA)吸收试验评估肠道通透性。接受RIC的患者在移植过程中肠道通透性没有任何显著增加,但在接受清髓性预处理的患者中,与基线相比,在干细胞输注前一天(P<0.005)、第4天(P<0.005)、第7天(P<0.01)和第14天(P<0.005)肠道通透性有显著增加。与RIC相比,清髓性预处理在第7天也显示出肠道通透性增加(P<0.05)。结合胃肠道损伤可能是GVHD重要起始事件的假说,讨论了接受RIC的异基因HSCT期间肠道屏障功能得以保留的这一发现。