急性白血病患者异基因造血干细胞移植后发生急性移植物抗宿主病的危险因素分析

发布时间：2018-03-31 18:06

  本文选题：异基因造血干细胞移植　切入点：急性白血病　出处：《郑州大学》2017年硕士论文

【摘要】：背景异基因造血干细胞移植(allogenetic hematopoietic stem cell transplantation,allo-HSCT)是治疗急性白血病(acute leukemia,AL)的重要手段之一。虽然移植技术在不断进步,但移植后移植物抗宿主病(graft versus host disease,GVHD)的发生仍是其最主要、最严重的并发症,特别是急性GVHD,影响了allo-HSCT的疗效,也是移植后非复发死亡(non-relapse mortality,NRM)的主要原因之一。目前急性GVHD的诊断主要是依靠受累靶器官的临床症状,而临床表现缺乏特异性,故在发病早期很难与药物对靶器官的毒副作用、感染等相互区分。因此,寻找可以在临床症状出现前诊断或预测急性GVHD发生的生物标志物或危险因素,对降低急性GVHD发生率,提高移植后总生存率至关重要。目的探讨急性白血病患者行allo-HSCT后发生急性GVHD的危险因素,为及早预测急性GVHD的发生提供更多依据。方法收集2012年1月至2016年9月于郑州大学第一附属医院行allo-HSCT的符合入组条件的急性白血病患者103例,人类白细胞抗原(Human Leukocyte Antigen,HLA)全相合组采用“改良BU/CY”预处理方案,单倍体组采用“改良BU/CY+ATG”预处理方案。采用“环孢素A、吗替麦考酚酯联合短程甲氨蝶呤”方案预防急性gvhd的发生。分析患者移植前血清β2-微球蛋白(β2-mg)浓度、乳酸脱氢酶(ldh)水平、白蛋白浓度、移植前是否合并感染、造血干细胞移植共患病指数(hct-ci)等因素对急性白血病患者行allo-hsct后发生急性gvhd的影响。结果103例患者中,36例发生了急性gvhd(34.95%),总计共发生了54次急性gvhd,皮肤型27次(50%),胃肠道型18次(33.33%),肝脏型9次(16.67%)。急性gvhd发生率在单倍体组为60.47%(26/43),相较全相合组发生率16.67%(10/60)高(p0.001)。急性t淋巴细胞白血病(t-all)患者的急性gvhd发生率为75%(9/12),高于急性b淋巴细胞白血病(b-all)的34.15%(14/41)和急性髓系白血病(aml)组的26%(13/50)(p=0.008)。移植当日中性粒细胞(anc)缺乏组、非anc缺乏组分别为45.10%(23/51)和25%(13/52)(p=0.04)。患者移植前血生化指标(β2-mg、ldh、白蛋白)、anc植入时间、单个核细胞(mnc)计数、cd34阳性细胞数(cd34+)、移植前是否合并感染、hct-ci、性别、年龄、供受者血型是否相同、供受者性别差异等方面的差异无统计学意义(p0.05)。将p0.1的因素:al类型、hla配型、回输当日是否处于粒缺状态、白蛋白浓度、cd34+计数纳入logistic多因素回归分析显示t-all组、单倍体组更易发生急性gvhd(p0.05)。cox回归分析显示,发生0-Ⅰ度急性gvhd组的无白血病中位生存期为22(3-49)月,较Ⅱ-Ⅳ度急性gvhd组的中位生存期8(2-40)月长(p=0.023)。结论1.急性gvhd的发生以皮肤型多见,其次为胃肠道型、肝脏型。2.急性白血病患者行allo-hsct后,单倍体、t-all患者更易发生急性gvhd,对此可以加强预防措施,降低急性gvhd的发生率。3.急性白血病患者行allo-hsct后发生急性gvhd可能与移植前血清β2-mg、ldh、白蛋白水平、hct-ci、移植前是否合并感染等因素无关。4.Ⅱ-Ⅳ度急性gvhd的发生影响了al患者移植后的无白血病的中位生存期。
[Abstract]:Background: allogeneic hematopoietic stem cell transplantation (allogenetic hematopoietic stem cell transplantation, allo-HSCT) is the treatment of acute leukemia (acute leukemia AL) is one of the important means. Although transplantation technology is in progress, but after transplantation, graft-versus-host disease (graft versus host disease, GVHD) the occurrence is the main, the most serious complications, especially acute GVHD, affecting the efficacy of allo-HSCT, but also after the transplantation of non relapse mortality (non-relapse mortality NRM) is one of the main reasons. The diagnosis of acute GVHD is mainly depend on the clinical symptoms of involved target organ, and the lack of specific clinical manifestations, so in the early period of the disease is very difficult and adverse effects on target organ drugs, infection and distinguish each other. Therefore, looking for before clinical symptoms appear diagnostic or prognostic biomarkers or risk factors of acute GVHD, to reduce acute G The incidence of VHD, improve the total survival rate after transplantation is crucial. Objective to investigate the risk factors of acute GVHD in patients with acute leukemia after allo-HSCT, to provide more evidence for early prediction of acute GVHD. Methods from January 2012 to September 2016 in the First Affiliated Hospital of Zhengzhou University were eligible for allo-HSCT in patients with acute leukemia in 103 cases, human cell antigen (Human Leukocyte Antigen, HLA) matched group using the pretreatment scheme of modified BU/CY ", using" haploid set preprocessing scheme of modified BU/CY+ATG. Using cyclosporine A, mycophenolate mofetil combined with methotrexate for prevention of acute GVHD. Analysis of patients with pre transplant serum beta 2- microglobulin (beta 2-mg) concentration, lactate dehydrogenase (LDH) levels, albumin concentration, infection before transplantation, hematopoietic stem cell transplantation comorbidity index (hct-ci) etc. 鍥犵礌瀵规，

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