造血干细胞移植治疗重型再生障碍性贫血

造血干细胞移植治疗重型再生障碍性贫血北京首都医科大学宣武医院田丁，北京１０００５３再生障碍性贫血（ａｐｌａｓｔｉｃａｎｅｍｉａ，ＡＡ）是由多种原因引起的造血功能障碍性疾病，表现为全血细胞减少以及由其并发症引起的一系列症状，已知造血干细胞（ｈａｅｍｏｐ...     

造血干细胞移植治疗重型再生障碍性贫血临床研究

对10例重型再生障碍性贫血（SAA）患者行造血干细胞移植（HSCT），骨髓移植（BMT）1例，外周血干细胞移植（PBSCT）7例，脐血移植（CBT）2例。结果1例BMT及5例PBSCT完全植入；2例PBSCT嵌合植入者分别在移植后3、12个月发生宿主排斥移植物反应，分别用再次外周血造血干细胞输注、免疫疗法后血象恢复正常；2例CBT未成功植入，但均重建造血功能。随访6～44个月，9例存活，1例死于急性心功能衰竭。     

HLA配型相合的造血干细胞移植治疗重型再生障碍性贫血的临床研究

目的 评价HLA配型相合的异基因造血干细胞移植(allo-HSCT)治疗重型再生障碍性贫血(SAA)的疗效.方法 2000年1月至2008年11月采用allo-HSCT治疗SAA患者20例,其中同胞相合移植17例,非血缘关系移植3例.预处理采用环磷酰胺(Cy)50 mg·kg~(-1)·d~(-1)4 d加抗淋巴细胞免疫球蛋白(ATG)2.5 mg·kg~(-1)·d~(-1)或20 mg·kg~(-1)·d~(-1) d.移植物抗宿主病(GVHD)的预防方案为经典的环孢素A(CsA)联合短程甲氨蝶呤(MTX)及霉酚酸酯(MMF).同胞供者采集经重组人粒细胞集落刺激因子(G-CSF)动员的骨髓及外周血干细胞,非血缘供者单纯采集外周血干细胞.结果 回输单个核细胞中位数为7.89(4.00-14.21)×10~(8)/kg,所有患者均获供者造血重建,粒细胞植活中位时间14(11～20)d;血小板植活中位时间12(8～108)d.但1例患者发生晚期排斥,行另一供者二次移植后植活.21例次移植后共发生6例次急性GVHD(I度3例,Ⅱ度皮肤3例),发生率16%.19例生存期>100 d的患者中有7例发生慢性GVHD,其中4例为局限型,3例为广泛型.截至2009年2月28 日,经过中位18(2.0～106.8)个月的随访,共有17例患者无病生存,总生存率为82.5%.结论 采用Cy+ATG的预处理方案对SAA患者进行HLA配型相合HSCT,植活率高,可以获得良好的疗效.     

外周血造血干细胞移植治疗重型再生障碍性贫血23例分析

目的:探讨外周血造血干细胞移植(HSCT)治疗重型再生障碍性贫血(SAA)的疗效。方法:回顾性分析23例接受外周血HSCT治疗的SAA患者的植活情况、移植物抗宿主病(GVHD)和移植相关并发症发生情况及影响预后的因素等。结果:23例患者中,22例造血重建,白细胞和血小板中位植活时间分别为移植后15(7～21)d、19(7～32)d,其中4例患者出现急性GVHD,发生率为18.2%(4/22),3例出现慢性GVHD,发生率为13.6%(3/22);1例未植活死亡,总体生存率为95.7%(22/23)。22例造血重建患者中,移植后发生巨细胞病毒感染4例,有出血表现8例,出血性膀胱炎1例,肺部感染7例,口角疱疹1例,化脓性扁桃体炎1例。另外,移植前有无感染及诊断到移植的间隔时间是影响患者预后的危险因素。结论:HSCT是治疗SAA的有效方法,加强移植前后的免疫抑制剂治疗,预防和控制感染,能有效地减少GVHD的发生,改善预后。     

无关供者外周血造血干细胞移植成功治疗重型再生障碍性贫血1例

目前治疗重型再生障碍性贫血(SAA)患者重要的、疗效最好的方法是造血干细胞移植[1].本文报道应用无关供者异基因造血干细胞移植成功治疗重型再生障碍性贫血1例.     

异基因外周血造血干细胞移植治疗重型再生障碍性贫血1例

异基因造血干细胞移植是治疗重型再生障碍性贫血 ( SAA)的最有效方法之一。因此 ,我们尝试用异基因外周血造血干细胞移植 ( peripheral bloodstem cell transplantation,PBSCT)治疗 SAA 1例 ,获得成功 ,现报告如下。1　资料与方法1 .1 　 临床资料女 ,35岁。 1 999年 7月出现头晕伴发热 ,在当地医院检查血常规示血红蛋白 49g/ L,白细胞 2 .3× 1 0 9/ L,血小板 1 1× 1 0 9/ L;骨髓检查有核细胞增生极度低下 ,淋巴细胞占 0 .96,拟诊断为 SAA。给予达那唑、丙酸睾丸酮、细胞生长因子及输全血 12 0 0 ml等支持治疗 3个月。于同年 1 0月…     

造血干细胞移植治疗重型再生障碍性贫血Ⅰ型和Ⅱ型的临床比较

目的：总结非清髓性造血干细胞移植治疗2种类型重型再生障碍性贫血的临床经验,为临床治疗提供安全有效的治疗方案及经验。方法：对32例重型再障患者进行非清髓性造血干细胞移植,预处理主要采用小剂量环磷酰胺、抗淋巴细胞球蛋白或抗胸腺细胞球蛋白;移植后采用环孢菌素、骁悉预防移植物抗宿主病。结果：重型再生障碍性贫血Ⅰ型患者较重型再生障碍性贫血Ⅱ型患者造血重建迅速、植入率高、并发症少且轻,预后佳,生存率高。结论：非清髓性造血干细胞移植是治疗重型再生障碍性贫血Ⅰ型患者及一般情况良好且输血制品次数少的重型再生障碍性贫血Ⅱ型患者的治疗首选。     

异基因造血干细胞移植治疗儿童再生障碍性贫血

再生障碍性贫血(aplastic anemia,AA)是一组由于化学、物理、生物因素及不明原因引起的骨髓造血功能衰竭,以造血干细胞损伤、外周血全血细胞减少为特征的异质性疾病,包括先天性和获得性AA。临床上,绝大多数儿童AA属于后天获得、原因不明的原发性AA,常表现为较严重的贫血、出血和感染。部分AA可最终演变成骨髓增生异常     

改良非清髓性异基因造血干细胞移植治疗SAA疗效观察

目的探讨非清髓性异基因造血干细胞移植(NAST)治疗重型再生障碍性贫血(SAA)的方法及疗效。方法对20例急性SAA患者进行NAST,预处理采用小剂量环磷酰胺、抗淋巴细胞球蛋白或抗胸腺细胞球蛋白;移植后采用环孢菌素、骁悉、抗CD25预防移植物抗宿主病(GVHD)。采用短串联重复序列复合扩增技术检测供者植入情况。结果10例异基因外周血造血干细胞移植患者造血功能获得快速重建;8例脐血造血干细胞移植患者均未植入,但自身造血亦获得安全重建。发生急性GVHD1例,慢性GVHD2例,严重感染性休克、间质性肺炎、败血症各1例均治愈,突发心衰死亡1例,造血重建失败并发感染死亡2例。结论改良NAST疗效肯定、植入率高、并发症少、造血功能恢复快,是治疗SAA的有效方法。     

非血缘异基因脐血移植治疗SAA可行性研究

目的评价非血缘脐血移植(UCBT)治疗急性重型再生障碍性贫血(SAA)的疗效。方法SAA患者6例,采用环磷酰胺和抗胸腺细胞球蛋白预处理方案;移植方式为HLA不全相合UCBT;应用环孢素A和骁悉预防移植物抗宿主病(GVHD)。随访时间为60~1358d。结果移植后l2~38d造血重建。短串联重复序列-聚合酶链反应分析显示移植后l7~150d基因型表现为完全性患者型,未发生GVHD。血常规、骨髓象检查正常。结论非血缘HLA配型不合的脐血用于治疗SAA是可行的。     

Disseminated Rhizopus microsporus infection following allogeneic hematopoietic stem cell transplantation in a child with severe aplastic anemia

Disseminated Rhizopus microsporus infections are uncommon in children and are resistant to echinocandin and azole antifungal agents. We describe a child with severe aplastic anemia who developed disseminated R. microsporus infection following allogeneic hematopoietic stem cell transplantation. R. microsporus was identified microscopically in the hepatic drain culture and was confirmed on the basis of 18S rRNA and 28S rRNA sequence analyses. The patient was treated successfully with hepatic drainage and amphotericin B deoxycholate.     

HLA位点不全相合的异基因干细胞移植治疗白血病的临床分析

目的：探讨HLA不完全相合的造血干细胞移植治疗白血病的新方法.方法：将8例白血病患者接受FBC预处理方案后行异基因粒细胞集落刺激因子（G-CSF）动员的骨髓和外周血干细胞联合移植，观察造血重建和移植相关的并发症情况.结果：1例2位点不合患者植入失败，其余7例完全植入，白细胞恢复时间13.5 d，血小板恢复15.1 d，7例患者Ⅰ～Ⅱ度急性移植物抗宿主病（GVHD）发生率57.1%（4/7），局限性慢性GVHD发生率83.3%，未出现严重的心、肝和肺脏并发症.移植后6个月生存率62.5%.结论：用FBC预处理方案和GCSF动员后的骨髓和外周血干细胞联合移植的方法对于HLA不相合的移植安全有效。     

Long-term follow up after allogeneic stem cell transplantation in patients with severe aplastic anemia after cyclophosphamide plus antithymocyte globulin conditioning

Background

Due to increased rates of secondary solid organ cancer in patients with severe aplastic anemia who received an irradiation-based conditioning regimen, we decided some years ago to use the combination of cyclophosphamide and antithymocyte globulin. We report the long-term follow up of patients who underwent hematopoietic stem cell transplantation from an HLA-matched sibling donor after this conditioning regimen.

Design and Methods

We analyzed 61 consecutive patients transplanted from June 1991 to February 2010, following conditioning with cyclophosphamide (200 mg/kg) and antithymocyte globulin (2.5 mg/kg/day × 5 days).

Results

Median age was 21 years (range 4–43); 41 of the 61 patients were adults. Median duration of the disease before hematopoietic stem cell transplantation was 93 days. All but 2 patients received bone marrow as the source of stem cells and all but 2 engrafted. Cumulative incidence of acute grade II–IV graft-versus-host disease was 23% (95%CI 13–34) and 18 developed chronic graft-versus-host disease (cumulative incidence 32% at 72 months, 95% CI 20–46). In multivariate analysis, a higher number of infused CD3 cells was associated with an increased risk of developing chronic graft-versus-host disease (P=0.017). With a median follow up of 73 months (range 8–233), the estimated 6-year overall survival was 87% (95% CI 78–97). At 72 months, the cumulative incidence of avascular necrosis was 21% and 12 patients presented with endocrine dysfunction (cumulative incidence of 19%). Only one patient developed a secondary malignancy (Hodgkin’s lymphoma) during follow up.

Conclusions

Cyclophosphamide and antithymocyte globulin is an effective conditioning regimen for patients with severe aplastic anemia and is associated with low treatment-related mortality. Long-term complications include avascular necrosis and endocrine dysfunction.     

非清髓无关供体外周血干细胞移植治疗重型再生障碍性贫血

目的 探讨无关供体造血干细胞移植治疗重型再生障碍性贫血(SAA)的方法 和疗效.方法 对1例SAA的患者进行了无关供体HLA高分辨4/6相合的外周血干细胞移植.采用环磷酰胺(100 mg/kg) 氟达拉宾(150 mg/m2) 抗人淋巴细胞球蛋白(100 mg/kg)的非清髓性预处理后,回输粒细胞集落刺激因子(G-CSF)动员的外周血干细胞,共输注单个核细胞(MNC)6.77×108/kg,CD 34细胞1.95×106/kg.预防移植物抗宿主病(GVHD)采用环胞菌素A(CsA)联合短疗程甲氨蝶呤(MTX)的基础上加用霉酚酸酯(MMF)的方案.结果 患者移植后造血恢复顺利,于移植后第6天WBC植入,第8天PLT植入,第30天行患者骨髓STR-PCR检测显示为完全供者的基因型,第150天血型转变为供者型(O→A).未发生急性GVHD(aGVHD)及慢性GVHD(cGVHD),随访至移植后8个月,造血功能恢复良好,仍在继续随访中.结论 以氟达拉宾、环磷酰胺和抗人淋巴细胞球蛋白组成的非清髓性预处理方案用于无关供体外周血干细胞移植治疗SAA,能够获得稳定的植入,且并发症少,是有效移植方法之一.     

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造血干细胞移植(HSCT)是目前惟一能治愈先天性溶血性贫血(如重型地中海贫血和鐮状细胞贫血)的治疗方法。HLA相合同胞供者移植治疗儿童患者的总生存(OS)率超过90%,无事件生存(EFS)率超过80%。无关供者移植使更多无HLA相合同胞供者的患者获得移植机会。     

Unrelated donor stem cell transplantation in acquired severe aplastic anemia: a systematic review

Acquired severe aplastic anemia is a rare disease characterized by an immune-mediated functional impairment of hematopoietic stem cells. Transplantation of these cells from unrelated donors is a treatment option frequently offered to patients after failed immunosuppressive therapy. The aim was to investigate the outcome of these patients treated with unrelated donor transplants. Systematic literature searches were performed in MEDLINE, EMBASE, and The Cochrane Library. All databases were searched from inception to June 2009. Only full-text publications and studies including at least 10 patients were considered. The primary outcome was 5-year overall survival from the day of transplantation and the secondary outcomes were graft failure and graft-versus-host disease. A meta-analysis of survival estimates was conducted and heterogeneity was investigated. A total of 18 studies, one controlled trial and 17 case series were identified. The overall survival at five years and the corresponding confidence interval was stated in 8 studies and ranged from 28% to 94%. A meta-analysis revealed considerable heterogeneity between the studies that could not be explained and was also present in subgroups of the studies. The proportion of acute graft failure was 45% in one study using only umbilical cord blood, and it was reported to be 0–26% in 15 studies using mainly bone marrow as stem cell source after different follow-up periods. Acute GVHD grade II–IV was reported for 8–86% and extensive chronic GVHD for 0–38% of the evaluated patients in 16 studies. Recipient age, human leukocyte antigen match, performance status, year of transplantation, and conditioning with serotherapy were identified as significant factors for improved survival. Unrelated donor hematopoietic stem cell transplantation in patients with acquired severe aplastic anemia after failure to immunosuppressive therapy is a treatment option. A stable physical condition of the patients before receiving the transplant (for example, performance and age) may be associated with a better survival. Detailed HLA-matching facilitated by DNA-based typing, among other factors, may have contributed to recent improvements on survival after unrelated donor HSCT as a second-line treatment.