發(fā)布時(shí)間：2018-01-20 07:17

  本文關(guān)鍵詞： 單倍體 異基因造血干細(xì)胞移植 重型再生障礙性貧血　出處：《山東大學(xué)》2017年碩士論文　論文類(lèi)型：學(xué)位論文

【摘要】：研究背景和目的再生障礙性貧血(Aplastic anemia,AA),簡(jiǎn)稱(chēng)再障,是由多種病因引起的一種骨髓造血功能衰竭綜合征。其中SAA具有病情重、死亡率高等特點(diǎn),主要治療方法為針對(duì)性支持治療、免疫抑制治療(immunosuppressive therapy,1ST)及異基因造血干細(xì)胞移植(allo-hematopoietic stem ce11 transplantation,allo-HSCT)治療。其中,1ST以抗胸腺細(xì)胞球蛋白(ATG)聯(lián)合環(huán)孢素A(CsA)為主,起效緩慢,且復(fù)發(fā)率高,治療相關(guān)不良反應(yīng)多,療效欠佳。Allo-HSCT是目前國(guó)內(nèi)外研究最多的治療領(lǐng)域,其中HLA同胞全相合allo-HSCT具有造血重建快、復(fù)發(fā)率低、療效確切、相關(guān)并發(fā)癥少等優(yōu)點(diǎn)。但國(guó)內(nèi)獨(dú)生子女政策的限制使同胞供者來(lái)源較少,尋找HLA配型全相合的無(wú)關(guān)供者耗時(shí)亦長(zhǎng),應(yīng)用單倍體相合的allo-HSCT(haploidentical stem cells transplantation,haplo-HSCT)治療SAA成為可能。供受者HLA配型中有一條染色體完全相同即可,極大地拓寬了供者的選擇范圍,為SAA及其他血液系統(tǒng)疾病的治療提供了新途徑。本研究旨在對(duì)haplo-HSCT治療SAA患者的臨床資料進(jìn)行回顧性分析,并與同期行HLA全相合的同胞和非血緣HSCT治療者對(duì)比分析臨床療效及存活情況,結(jié)合查詢(xún)文獻(xiàn),評(píng)價(jià)其臨床治療可行性和安全性。研究資料和方法本次研究收集并分析山東省千佛山醫(yī)院自2013年1月至2016年12月重型再障SAA患者資料,對(duì)其臨床治療、植入預(yù)后、隨訪情況等臨床資料進(jìn)行回顧性分析。治療組為行Haplo-HSCT治療的13例患者,其中女性4人,男性9人,年齡范圍為7—47歲。對(duì)照組為同期行HLA全相合Allo-HSCT患者11例,其中血緣供者6例,無(wú)關(guān)供者5例。預(yù)處理方案:治療組采用FLU+Bu/Cy+ATG方案,對(duì)照組采用Flu +ATG +CTX方案。并采用CsA +短程MTX + MMF方案預(yù)防及治療GVHD。隨訪觀察患者造血重建情況、植入情況、感染及GVHD等并發(fā)癥的發(fā)生率、嚴(yán)重程度及總體生存率。并對(duì)特殊病例詳細(xì)分析病史及治療療效。統(tǒng)計(jì)采用SPSS 19.0軟件進(jìn)行數(shù)據(jù)處理,生存分析采用Kaplan-Meier方法。并檢索PubMed、中國(guó)知網(wǎng)等數(shù)據(jù)庫(kù)關(guān)于haplo-HSCT治療SAA的相關(guān)報(bào)道,通過(guò)復(fù)習(xí)相關(guān)文獻(xiàn)對(duì)該疾病的治療等進(jìn)一步作總結(jié)分析。結(jié)果造血功能重建結(jié)果:植入成功率1000%。治療組13例病例Haplo-HSCT移植后均獲得造血功能重建,中性粒細(xì)胞成功植入中位時(shí)間為13天(11-20天),血小板成功植入中位時(shí)間為16天(12-23天)。對(duì)照組11例患者中性粒細(xì)胞植入中位時(shí)間為13天(11-17天),血小板植入中位時(shí)間為17天(12-22天)。P值分別為0.51、0.87(P0.05),差異無(wú)統(tǒng)計(jì)學(xué)意義。植入情況:STR-PCR檢測(cè)治療組13例移植后半月內(nèi)均獲得完全供者型植入(FDC),后多次復(fù)查12例穩(wěn)定為FDC,1例為MC。對(duì)照組11例均為FDC。供受者血型不同的均轉(zhuǎn)變?yōu)楣┱哐?未出現(xiàn)植入失敗者。至隨訪結(jié)束,治療組5例患者并發(fā)GVHD(3例Ⅰ-Ⅱ度,1例Ⅲ-ⅣV度aGVHD,1例cGVHD),GVHD發(fā)生率為38.460%;6例患者合并多重感染,感染發(fā)生率46.15%;3例患者死亡(均死于敗血癥);10例患者基本治愈或緩解達(dá)到無(wú)病生存,總體生存率(OS)為76.9%。對(duì)照組3例aGVHD(2例皮膚Ⅰ-Ⅱ度,1例肝臟Ⅱ度)GVHD發(fā)生率27.27%;6例感染并發(fā)癥,發(fā)生感染率54.54%,2例死于敗血癥,OS為81.81%。P0.05,差異無(wú)統(tǒng)計(jì)學(xué)意義。結(jié)論1.再障患者在缺乏同胞及非血緣全相合供者、免疫抑制治療效果欠佳時(shí),單倍體相合造血干細(xì)胞移植治療可以達(dá)到造血重建,是可行的、安全的、有效的治療方法。2.單倍體HSCT與HLA全相合同胞或非血緣造血干細(xì)胞移植治療重型再障相比,植入成功率與移植后并發(fā)癥發(fā)生率、死亡率無(wú)明顯差異,療效相當(dāng),在臨床上有一定的發(fā)展應(yīng)用前景。
[Abstract]:Research background and purpose of aplastic anemia (Aplastic anemia, AA), AA, is a bone marrow failure syndrome resulted from many causes. Among them, SAA has a severe illness, high mortality, the main treatment method to support therapy, immunosuppressive therapy (immunosuppressive, therapy, 1ST) and allogeneic hematopoietic stem cell transplantation (allo-hematopoietic stem ce11 transplantation, allo-HSCT) treatment. Among them, 1ST with antithymocyte globulin (ATG) combined with cyclosporine A (CsA), slow onset, and the relapse rate is high, the treatment related adverse reactions, poor efficacy of.Allo-HSCT at home and abroad is the most studied therapeutic areas, including HLA matched related allo-HSCT has rapid hematopoietic recovery and low recurrence rate, curative effect, less complications. But the one-child policy restrictions to sibling donor sources less search Looking for HLA typing matched unrelated donor is also time-consuming long, application of haploidentical allo-HSCT (haploidentical stem cells transplantation, haplo-HSCT) for the treatment of SAA possible. A chromosome identical donor to HLA typing, greatly broaden the scope of selection of donors, provides a new way for the treatment of SAA and other diseases of the blood system. The purpose of this study was a retrospective analysis of clinical data of SAA patients treated by haplo-HSCT, and compared with the same period for HLA identical sibling and unrelated HSCT treatment and survival analysis. Clinical situation, combined with the query literature, evaluate the clinical feasibility and safety. This study collected materials and methods and analysis of Shandong Province, Qianfo Hill hospital from January 2013 to December 2016 data of SAA patients with severe aplastic anemia, the clinical treatment, implantation prognosis, follow-up clinical data Were analyzed retrospectively. The treatment group was 13 cases of Haplo-HSCT patients, including 4 women, 9 men, age range 7 - 47 years old. The control group underwent HLA matched 11 Allo-HSCT patients, including 6 cases of blood donors, 5 cases of unrelated donor preconditioning regimen: treatment. Group using FLU+Bu/Cy+ATG program, the control group was treated with Flu +ATG +CTX. And the CsA + MTX + MMF shortcut scheme of prevention and treatment of GVHD. follow-up in patients with hematopoietic reconstruction, implantation, the incidence of GVHD infection and other complications, the severity and the overall survival rate. And the special cases of detailed analysis of the history and treatment effect by using SPSS 19. Statistical software for data processing, survival analysis using the Kaplan-Meier method. And the retrieval of PubMed, reports Chinese HowNet database on the treatment of haplo-HSCT SAA, through the review of the relevant literature on the treatment of diseases such as further The results were summarized and analysed. Hematopoietic reconstruction results: the treatment group of 13 cases of Haplo-HSCT achieved engraftment success rate of 1000%. implantation, neutrophils successfully implanted a median of 13 days (11-20 days), platelet engraftment at a median of 16 days (12-23 days). 11 patients in the control group were neutral granulocyte implantation of a median of 13 days (11-17 days), platelet engraftment a median of 17 days (12-22 days).P = 0.51,0.87 (P0.05), the difference was not statistically significant. The implantation of STR-PCR detection: the treatment group of 13 cases were completely within half a month after transplantation donor implantation (FDC). After repeatedly review 12 patients with stable FDC, 1 cases MC. and 11 cases in control group were all transformed into donor blood group FDC. donors and recipients of different blood types, no implant failure. At the end of follow-up, 5 cases in the treatment group (3 cases of patients with GVHD I-II, 1 cases of III - IV degree V aGVHD, cGVHD, GVH) in 1 cases The incidence rate of D was 38.460%; 6 cases of patients with multiple infections, the infection rate was 46.15%; 3 patients died (died of sepsis); 10 patients were cured or relieved to disease-free survival, overall survival (OS) for 76.9%. and 3 cases in the control group aGVHD (2 cases of skin I-II, 1 cases liver of second degree) the incidence rate of GVHD was 27.27%; 6 cases of infectious complications, infection rate was 54.54%, 2 cases died of sepsis, OS for 81.81%.P0.05, the difference was not statistically significant. Conclusion 1. AA patients matched donor in the absence of sibling and unrelated, immunosuppressive therapy is ineffective, single ploidy haploidentical hematopoietic stem cell transplantation for treatment can be achieved hematopoietic reconstruction, is feasible, safe and effective treatment of HSCT and.2. haploid HLA matched sibling or unrelated donor hematopoietic stem cell transplantation in the treatment of severe aplastic anemia, implantation success rate and incidence of complications after transplantation, no significant differences in mortality, treatment It has the same effect, and has a certain development and application prospect in clinical.

【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R457.7;R556.5

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 余U，

本文編號(hào)：1447341