异基因造血干细胞移植后重度肠道移植物抗宿主病的临床研究

Clinical study of Severe intestinal graft-versus-host disease following allogeneic hematopoietic stem cell transplantation

目的探讨异基因造血干细胞移植(allo-HSCT)后发生重度肠道移植物抗宿主病(GVHD)的临床特点和治疗方法。方法2例慢性髓性白血病-慢性期(CML-CP)及1例急性髓性白帆病M_2(AML-M_2)行allo-HSCT。干细胞分别来自血缘HLA相合、非血缘HLA相合及血缘HLA一个位点不合的供者。1例采用氟达拉滨+马利兰+抗胸腺淋巴细胞球蛋白(ATG)作为预处理,另2例预处理采用改良的马利兰/环磷酰胺(Bu/Cy)+ATG。均以环孢素A(CsA)联合短疗程甲氨蝶呤(MTX)的基础上加用霉酚酸酯(MMF)预防急性GVHD(aGVHD)。结果3例患者分别于移植后60、105、116 d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,诊断为肠道GVHD。予以免疫抑制剂为主的治疗,1例最后死于肺部结核杆菌及白色念珠菌感染,2例得到有效控制。结论allo-HSCT后并发GVHD所致肠炎,诊断有赖于肠镜和病理活检,治疗采用以免疫抑制剂为主的综合治疗。

Objective To study clinical features of severe intestinal graft - versus - host disease （GVHD） following allogeneic hematopoietic stem cell transplantation（allo - HSCT） , and to explore its treatment. Methods 2 patients in chronic phase of chronic myelocytic leukemia （ CML - CP） and one with acute myelocytic leukemia - M2 （ AML - M2） were pre - conditioned by fludarabin ＋ busulfan ＋ anti- thymocyte globulin （ATG） and improved busulfan / cyclophosphamide ＋ ATG. The stem cells respectively came from HLA - identical related donor, unrelated donor and one locus mismatched related donor. The prevention of acute GVHD （ aGVHD） included cyclosporine A （ CsA） , mycophenolate mofetil （ MMF） and short course methotrexate（ MTX）. All regular supportive care was used. Results 3 patients respectively had the complications of severe enteritis in 60, 105 and 116 days after allo - HSCT. 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 were observed in biopsy tissues. Immunosuppressants were basically administered to all the patients. One patient died of tuberculosis and candida albicans infection of lung, and two other patients were controlled. Conclusions Enteroscopic investigation and biopsy are useful for the diagnosis of intestinal GVHD following allo - HSCT, and early treatment of immunosuppressant is required for better outcome.