Tohoku J. Exp. Med., 2012, 227(1)

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

MINAMI YAMADA-FUJIWARA,1,4 KOICHI MIYAMURA,1,6 TOHRU FUJIWARA,2 YASUO TOHMIYA,5 KATSUYA ENDO,3 YASUSHI ONISHI,1 KENICHI ISHIZAWA,2 JUNICHI KAMEOKA,1 MASAFUMI ITO7 and HIDEO HARIGAE1

1Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, Japan
2Department of Molecular Hematology and Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan
3Department of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
4Department of Hematology, Sendai Medical Center, Sendai, Japan
5Department of Hematology, Miyagi Cancer Center, Sendai, Japan
6Department of Hematology, Japanese Red Cross First Hospital, Nagoya, Japan
7Department of Pathology, Japanese Red Cross First Hospital, Nagoya, Japan

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.

keywords —— acute graft-versus-host disease; colonoscopy; hematopoietic stem cell transplantation; intestinal thrombotic microangiopathy; pathological diagnosis

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Tohoku J. Exp. Med., 2012, 227, 31-37

Correspondence: Minami Yamada-Fujiwara, Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, 2-1 Seiryomachi, Aoba-ku, Sendai 980-8575, Japan.

e-mail: yminami@snh.go.jp