本文選題：異基因造血干細(xì)胞移植　切入點(diǎn)：急性白血病　出處：《鄭州大學(xué)》2017年碩士論文

【摘要】：背景異基因造血干細(xì)胞移植(allogenetic hematopoietic stem cell transplantation,allo-HSCT)是治療急性白血病(acute leukemia,AL)的重要手段之一。雖然移植技術(shù)在不斷進(jìn)步,但移植后移植物抗宿主病(graft versus host disease,GVHD)的發(fā)生仍是其最主要、最嚴(yán)重的并發(fā)癥,特別是急性GVHD,影響了allo-HSCT的療效,也是移植后非復(fù)發(fā)死亡(non-relapse mortality,NRM)的主要原因之一。目前急性GVHD的診斷主要是依靠受累靶器官的臨床癥狀,而臨床表現(xiàn)缺乏特異性,故在發(fā)病早期很難與藥物對(duì)靶器官的毒副作用、感染等相互區(qū)分。因此,尋找可以在臨床癥狀出現(xiàn)前診斷或預(yù)測(cè)急性GVHD發(fā)生的生物標(biāo)志物或危險(xiǎn)因素,對(duì)降低急性GVHD發(fā)生率,提高移植后總生存率至關(guān)重要。目的探討急性白血病患者行allo-HSCT后發(fā)生急性GVHD的危險(xiǎn)因素,為及早預(yù)測(cè)急性GVHD的發(fā)生提供更多依據(jù)。方法收集2012年1月至2016年9月于鄭州大學(xué)第一附屬醫(yī)院行allo-HSCT的符合入組條件的急性白血病患者103例,人類白細(xì)胞抗原(Human Leukocyte Antigen,HLA)全相合組采用“改良BU/CY”預(yù)處理方案,單倍體組采用“改良BU/CY+ATG”預(yù)處理方案。采用“環(huán)孢素A、嗎替麥考酚酯聯(lián)合短程甲氨蝶呤”方案預(yù)防急性gvhd的發(fā)生。分析患者移植前血清β2-微球蛋白(β2-mg)濃度、乳酸脫氫酶(ldh)水平、白蛋白濃度、移植前是否合并感染、造血干細(xì)胞移植共患病指數(shù)(hct-ci)等因素對(duì)急性白血病患者行allo-hsct后發(fā)生急性gvhd的影響。結(jié)果103例患者中,36例發(fā)生了急性gvhd(34.95%),總計(jì)共發(fā)生了54次急性gvhd,皮膚型27次(50%),胃腸道型18次(33.33%),肝臟型9次(16.67%)。急性gvhd發(fā)生率在單倍體組為60.47%(26/43),相較全相合組發(fā)生率16.67%(10/60)高(p0.001)。急性t淋巴細(xì)胞白血病(t-all)患者的急性gvhd發(fā)生率為75%(9/12),高于急性b淋巴細(xì)胞白血病(b-all)的34.15%(14/41)和急性髓系白血病(aml)組的26%(13/50)(p=0.008)。移植當(dāng)日中性粒細(xì)胞(anc)缺乏組、非anc缺乏組分別為45.10%(23/51)和25%(13/52)(p=0.04)。患者移植前血生化指標(biāo)(β2-mg、ldh、白蛋白)、anc植入時(shí)間、單個(gè)核細(xì)胞(mnc)計(jì)數(shù)、cd34陽(yáng)性細(xì)胞數(shù)(cd34+)、移植前是否合并感染、hct-ci、性別、年齡、供受者血型是否相同、供受者性別差異等方面的差異無(wú)統(tǒng)計(jì)學(xué)意義(p0.05)。將p0.1的因素:al類型、hla配型、回輸當(dāng)日是否處于粒缺狀態(tài)、白蛋白濃度、cd34+計(jì)數(shù)納入logistic多因素回歸分析顯示t-all組、單倍體組更易發(fā)生急性gvhd(p0.05)。cox回歸分析顯示,發(fā)生0-Ⅰ度急性gvhd組的無(wú)白血病中位生存期為22(3-49)月,較Ⅱ-Ⅳ度急性gvhd組的中位生存期8(2-40)月長(zhǎng)(p=0.023)。結(jié)論1.急性gvhd的發(fā)生以皮膚型多見(jiàn),其次為胃腸道型、肝臟型。2.急性白血病患者行allo-hsct后,單倍體、t-all患者更易發(fā)生急性gvhd,對(duì)此可以加強(qiáng)預(yù)防措施,降低急性gvhd的發(fā)生率。3.急性白血病患者行allo-hsct后發(fā)生急性gvhd可能與移植前血清β2-mg、ldh、白蛋白水平、hct-ci、移植前是否合并感染等因素?zé)o關(guān)。4.Ⅱ-Ⅳ度急性gvhd的發(fā)生影響了al患者移植后的無(wú)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. 鍥犵礌瀵規(guī)，

本文編號(hào)：1691844