Diagnosis of Intestinal Graft-versus-Host Disease and Thrombotic Microangiopathy after Allogeneic Stem Cell Transplantation

Abstract

Severe diarrhea is a serious complication after allogeneic hematopoietic stem cell transplantation (HSCT). Acute graft-versus-host disease (GVHD) has been one of the major causes of diarrhea after HSCT, which is triggered by donor-derived cytotoxic T-lymphocytes. On the other hand, intestinal thrombotic microangiopathy (TMA) sometimes coexists with acute GVHD, and intensified immunosuppression to treat acute GVHD could exacerbate intestinal TMA, presumably through the vascular endothelial cell damage. The differential diagnosis between intestinal TMA and acute GVHD of the gut has mainly relied on the pathological findings, as clinical diagnosis of intestinal TMA has not been established. Therefore, we aimed to assess the feasibility of our clinical diagnosis for the patients with diarrhea after HSCT. We made tentative clinical criteria for intestinal TMA and acute GVHD of the gut, based on the clinical manifestations, laboratory data and colonoscopic findings, and started treatment before pathological diagnosis were made. Subsequently, a pathologist retrospectively assessed the accuracy of clinical diagnosis in a blind manner. In this study, we enrolled 19 patients complicating watery diarrhea after HSCT, and diagnosed as having acute GVHD (n = 10), intestinal TMA (n = 3), or both (n = 6) according to our criteria. We demonstrated that our clinical diagnosis for intestinal TMA and acute GVHD of the gut was overall correct, in terms of the response to the therapy and the pathological diagnosis. The present study may provide a clue on making clinical diagnosis of patients with watery diarrhea after HSCT, which enables us to start a prompt therapy.

Histologic Features of Intestinal Thrombotic Microangiopathy in Pediatric and Young Adult Patients after Hematopoietic Stem Cell Transplantation

“…Other studies analyzing both endoscopic and postmortem biopsies of HSCT patients with GI symptoms have shown an equal prevalence of iTMA in patient cohorts also found to have iGVHD. These publications have illustrated the importance of coinfections possibly contributing to both iTMA and iGVHD [9,10,17]. In our cohort, a majority of patients (80% or 29 of 36) with a clinical diagnosis of gut GVHD also had histologic evidence of iGVHD.…”

“…This has been a recurrent observation seen in the limited prior publications reporting on patients with histologic and clinical findings consistent with iTMA. Additionally, iTMA patients with coincident iGVHD have been shown to recover from voluminous diarrhea when treated with immunosuppressants but may continue to have clinically significant GI blood loss, extremely debilitating pain, and transfusion dependency due to ongoing microangiopathy in the bowel [8–10,17,18]. Continued bleeding is likely due to ongoing iTMA-induced ischemic colitis.…”

“…These agents have been shown to contribute to the development of systemic TMA and iTMA in both humans and animals after stem cell and solid-organ transplantation [25–30]. Some studies have shown that patients with iTMA had reversal of bleeding and abdominal pain complaints when these agents were stopped [8,10,17]. Fujino et al were able to induce and then successfully reverse histologic and clinical signs of iTMA in rats exposed to tacrolimus [28].…”

Változások az őssejt-transzplantációhoz társult thromboticus microangiopathia diagnosztikus kritériumrendszerében

“…Az immunhiányos, thrombocytopeniás betegeknél nagy nehézséget jelent a biopszia kivitelezése. Az őssejt-transzplantációt követő súlyos hasmenés komoly szö-vődmény, amelynek egyik fő oka a bélérintettséggel járó graft versus host betegség [27]. Az intestinalis TMA sokszor együtt jelentkezik a GVHD-val, amelynek egyik oka, hogy a GVHD terápiájaként adott immunszuppresszió triggerelheti az endothelkárosodást [27].…”

“…Az őssejt-transzplantációt követő súlyos hasmenés komoly szö-vődmény, amelynek egyik fő oka a bélérintettséggel járó graft versus host betegség [27]. Az intestinalis TMA sokszor együtt jelentkezik a GVHD-val, amelynek egyik oka, hogy a GVHD terápiájaként adott immunszuppresszió triggerelheti az endothelkárosodást [27]. A szö-vettani elkülönítést megnehezíti, hogy a graft versus host betegség és a thromboticus microangiopathia által okozott bélelváltozások jelei nem specifikusak.…”