单倍体相合造血干细胞移植（Haplo-HSCT）治疗SAA的临床资料分析及文献复习

发布时间：2018-01-20 07:17

本文关键词： 单倍体异基因造血干细胞移植重型再生障碍性贫血　出处：《山东大学》2017年硕士论文　论文类型：学位论文

【摘要】：研究背景和目的再生障碍性贫血(Aplastic anemia,AA),简称再障,是由多种病因引起的一种骨髓造血功能衰竭综合征。其中SAA具有病情重、死亡率高等特点,主要治疗方法为针对性支持治疗、免疫抑制治疗(immunosuppressive therapy,1ST)及异基因造血干细胞移植(allo-hematopoietic stem ce11 transplantation,allo-HSCT)治疗。其中,1ST以抗胸腺细胞球蛋白(ATG)联合环孢素A(CsA)为主,起效缓慢,且复发率高,治疗相关不良反应多,疗效欠佳。Allo-HSCT是目前国内外研究最多的治疗领域,其中HLA同胞全相合allo-HSCT具有造血重建快、复发率低、疗效确切、相关并发症少等优点。但国内独生子女政策的限制使同胞供者来源较少,寻找HLA配型全相合的无关供者耗时亦长,应用单倍体相合的allo-HSCT(haploidentical stem cells transplantation,haplo-HSCT)治疗SAA成为可能。供受者HLA配型中有一条染色体完全相同即可,极大地拓宽了供者的选择范围,为SAA及其他血液系统疾病的治疗提供了新途径。本研究旨在对haplo-HSCT治疗SAA患者的临床资料进行回顾性分析,并与同期行HLA全相合的同胞和非血缘HSCT治疗者对比分析临床疗效及存活情况,结合查询文献,评价其临床治疗可行性和安全性。研究资料和方法本次研究收集并分析山东省千佛山医院自2013年1月至2016年12月重型再障SAA患者资料,对其临床治疗、植入预后、随访情况等临床资料进行回顾性分析。治疗组为行Haplo-HSCT治疗的13例患者,其中女性4人,男性9人,年龄范围为7—47岁。对照组为同期行HLA全相合Allo-HSCT患者11例,其中血缘供者6例,无关供者5例。预处理方案:治疗组采用FLU+Bu/Cy+ATG方案,对照组采用Flu +ATG +CTX方案。并采用CsA +短程MTX + MMF方案预防及治疗GVHD。随访观察患者造血重建情况、植入情况、感染及GVHD等并发症的发生率、严重程度及总体生存率。并对特殊病例详细分析病史及治疗疗效。统计采用SPSS 19.0软件进行数据处理,生存分析采用Kaplan-Meier方法。并检索PubMed、中国知网等数据库关于haplo-HSCT治疗SAA的相关报道,通过复习相关文献对该疾病的治疗等进一步作总结分析。结果造血功能重建结果:植入成功率1000%。治疗组13例病例Haplo-HSCT移植后均获得造血功能重建,中性粒细胞成功植入中位时间为13天(11-20天),血小板成功植入中位时间为16天(12-23天)。对照组11例患者中性粒细胞植入中位时间为13天(11-17天),血小板植入中位时间为17天(12-22天)。P值分别为0.51、0.87(P0.05),差异无统计学意义。植入情况:STR-PCR检测治疗组13例移植后半月内均获得完全供者型植入(FDC),后多次复查12例稳定为FDC,1例为MC。对照组11例均为FDC。供受者血型不同的均转变为供者血型,未出现植入失败者。至随访结束,治疗组5例患者并发GVHD(3例Ⅰ-Ⅱ度,1例Ⅲ-ⅣV度aGVHD,1例cGVHD),GVHD发生率为38.460%;6例患者合并多重感染,感染发生率46.15%;3例患者死亡(均死于败血症);10例患者基本治愈或缓解达到无病生存,总体生存率(OS)为76.9%。对照组3例aGVHD(2例皮肤Ⅰ-Ⅱ度,1例肝脏Ⅱ度)GVHD发生率27.27%;6例感染并发症,发生感染率54.54%,2例死于败血症,OS为81.81%。P0.05,差异无统计学意义。结论1.再障患者在缺乏同胞及非血缘全相合供者、免疫抑制治疗效果欠佳时,单倍体相合造血干细胞移植治疗可以达到造血重建,是可行的、安全的、有效的治疗方法。2.单倍体HSCT与HLA全相合同胞或非血缘造血干细胞移植治疗重型再障相比,植入成功率与移植后并发症发生率、死亡率无明显差异,疗效相当,在临床上有一定的发展应用前景。
[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.

【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R457.7;R556.5

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