非亲缘异基因骨髓移植术后重症肠道急性移植物抗宿主病的临床分析

Study of severe intestinal graft-versus-host disease following unrelated donor allogeneic bone marrow transplantation

目的分析非亲缘异基因骨髓移植术后并发重度肠炎临床和病理特征及治疗情况。方法3例慢性粒细胞白血病慢性期及1例骨髓增生异常综合症患者接受非亲缘异基因骨髓移植术,预处理方案为马利兰/环磷酰胺,以霉酚酸酯(MMF)和环孢霉素(CsA)加短程氨甲蝶呤(MTX)预防急性移植物抗宿主病(aGVHD)。结果4例患者分别于移植后的后22、56、55、47d并发重度肠炎,肠镜和病理活检示肠黏膜充血水肿或上皮层坏死脱落,肠腔正常结构消失,直、结肠多发性溃疡,见较多淋巴细胞和浆细胞浸润,未见巨细胞病毒(CMV)包涵体和巨细胞,诊断为肠道aGVHD。予以糖皮质激素为主的治疗,其中1例予FK506、抗CD3单克隆抗体治疗。3例出现血CMV抗原血症,给予更昔洛韦/磷甲酸钠治疗。1例治疗无效死亡,3例得到有效控制。结论非亲缘异基因骨髓移植后并发aGVHD所致肠炎,诊断有赖于肠镜和病理活检并为正确治疗提供依据。

Objective To study the pathological and clinical features of severe enteritis following unrelated donor allogeneic bone marrow transplantation,and to explore its treatment.Methods Three patients in chronic phase of chronic myelogeneous leukemia and another one with myelodysplastic syndrome were pre-conditioned by cyclophosphamide and busulfan regimen. The prevention of acute graft versus host disease(aGVHD) included cyclosporine A, mycophenolate mofetil and short-course methotrexate. All regular supportive care was used. Results All patients developed severe enteritis charaterized by profuse diarrhea with intermittent abdominal pain and hemorrahge within 60 days. Enteroscopy and biopsy showed mucosal congestion and edema, apoptosis and shedding of epithelial cells, disruption of normal laminal structure, multiple ulcers in colon and rectum with massive infiltration of lymphocytes and plasma cells. No cytomegalo virus(CMV) inclusions and megalocytes were observed in biopsy tissues. Corticosteroids were administered to all patients while FK506 and anti-CD3 monoclonal antibody were additionally used in one patients. CMV antigen was detected positive in three patients and treatment of ganciclovir and foscamet was used. Three patients were controlled while one died.Conclusion Enteroscopic investigation and biopsy could be extremely critical for diagnosis of intestinal aGVHD following allogeneic bone marrow transplatation,and early treatment is required for better outcome.