无关供者与亲缘供者异基因造血干细胞移植治疗SAA疗效比较

目的比较无关供者异基因造血干细胞移植(Allo-HSCT)与亲缘供者Allo-HSCT治疗重型再生障碍性贫血(SAA)的疗效。方法根据供者来源不同,将移植患者分为无关供者组(A组)18例和亲缘供者组(B组)27例。两组均行Allo-HSCT治疗。预处理方案:A组10例采用兔抗人T淋巴细胞球蛋白(ATG)+环磷酰胺(CTX)+低剂量全身照射(TBI),8例采用ATG+CTX+氟达拉滨(Flud);B组中13例采用ATG+CTX+Flud,余14例采用ATG+CTX。结果两组造血功能恢复时间及造血干细胞植入情况相近(P均>0.05)。A组移植后发生感染12例(75%),B组发生13例(50%),两组相比,P<0.05。A组移植后5例死亡,余13例治愈,2年无病生存率(DFS)为72.2%;B组移植后7例死亡,余20例存活,其中19例治愈,1例明显进步,DFS为70.4%。两组DFS比较,P>0.05。A组发生急性移植物抗宿主病(GVHD)9例,慢性4例,B组分别为5、3例,两组相比,P均<0.05。结论无关供者与亲缘供者Allo-HSCT治疗SAA疗效相近,前者急、慢性GVHD发生率均高于后者。     

非清髓异基因造血干细胞移植治疗重型再障1例

2004年8月我们应用HLA—A、B、DR位点相合亲属外周造血干细胞移植治疗再生障碍性贫血(重再Ⅱ型)1例获得成功，报告如下。     

异基因造血干细胞移植治疗重症再生障碍性贫血的评价

目的 评价以环磷酰胺(CTX)为预处理方案行异基因造血干细胞移植(Allo-HSCT)治疗重症再生障碍性贫血(SAA)的疗效.方法 对1例SAA患者行同胞供者Allo-HSCT治疗.预处理方案为CTX 50 mg/kg-1*d-1×4 d;干细胞来源采用外周血+骨髓;输注单个核细胞数(MNC)为10.41×108/kg,CD34+细胞计数为6.86×106/kg.预防移植物抗宿主病(GVHD)采用环孢素A(CsA)加短程甲氨蝶呤(MTX)加霉酚酸酯(MMF).结果 患者获得造血重建,第14天中性粒细胞数(ANC)≥0.5×109/L、血小板计数(PLT)≥20×109/L,第96天血型转变为供者型(B→O).患者出现Ⅳ度急性GVHD(aGVHD),经积极治疗后控制.150 d内患者出现急性化脓性扁桃体炎、口腔溃疡、急性支气管炎、带状疱疹病毒感染、巨细胞病毒血症、肺炎,经积极治疗后均好转.随访24个月,患者无病存活.结论 以CTX为预处理方案allo-HSCT是治愈SAA的一种有效方法.     

异基因造血干细胞移植后纯红细胞再生障碍

ABO血型不合不影响异基因造血干细胞移植的成功进行。许多研究表明 ,与 ABO相合的移植相比 ,两者在植活时间 ,GVHD发生以及无病生存等方面差异不显著 〔1〕。尽管如此 ,在 ABO主要血型不合的异基因造血干细胞移植中 ,红系造血延缓甚至发生纯红细胞再生障碍 ( PRCA)时有发生。本文就异基因造血干细胞移植后 PRCA的特点 ,发病机理和防治措施作一综述。1　发病情况纯红细胞再生障碍性贫血是指因红系祖细胞受损衰竭而导致骨髓红系细胞显著减少 ,且不累及粒细胞和血小板的一种贫血。移植后 PRCA绝大多数发生于 ABO血型主要不合的骨髓…     

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     

非清髓性异基因干细胞移植结合供者干细胞输注治疗重型再生障碍性贫血

异基因干细胞移植是目前治疗重型再生障碍性贫血 (SAA)的主要方法之一 ,而植入失败或移植排斥是影响其长期生存的主要因素。供者干细胞输注 (DSI)作为一种加强供者细胞植入的方法已逐渐受到重视。我院于 1 998～ 1 999年用非清髓性异基因外周血干细胞移植治疗 SAA 2例 ,均经短暂植入后排斥 ,予再次 DSI,1例成功植入并无病生存1 5个月 ,1例失败 ,现报告如下。1　材料与方法1 .1 　 供受者一般情况例 1　男 ,40岁。因高热伴牙龈出血 2周于1 998年 7月入院。 3个月前曾患急性黄疸性肝炎治愈 ,既往有全身顽固性银屑病 3年。入院体检 :体温3…     

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…     

单倍体HLA不相合非清髓性异基因造血干细胞移植治疗血液病临床研究

目的:探讨组织相融抗原(HLA)不相合,主要血型不合的非清髓性异基因外周造血干细胞移植(NASCT)治疗血液病的可行性。方法:对7例血液病患者接受2～3个位点不合,ABO主要血型不合的未去T细胞NASCT,连续接受免疫抑制治疗。其中男3例,女4例,中位年龄41(21～58)岁。7例中,急性白血病第1次完全缓解(CR1)3例,CR2 1例,骨髓增生异常综合征(MDS)1例,极重症再生障碍性贫血(SSAA)1例,再障-阵发性睡眠性血红蛋白尿(AA-PNH)1例。结果:7例患者均取得三系重建造血,移植后粒细胞>0．5×109／L及血小板>20×109／L的中位时间分别为移植后第14天和第21天,植入直接证据检测证实完全供者造血,2例发生急性移植物抗宿主病,2例发生慢性移植物抗宿主病。结论:经粒细胞集落刺激因子动员的外周造血干细胞采用NASCT及持续性免疫抑制剂应用特别是ATG应用于未去T细胞的NASCT成功率高,疗效好,为扩大供者来源治愈血液病提供了新手段。     

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。     

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.     

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.     

Successful treatment with allogeneic peripheral blood stem cell transplantation and granulocyte transfusion for severe aplastic anemia with sinusitis

A 43-year-old woman with severe aplastic anemia (SAA) received anti-thymocyte globulin and cyclosporin A (CyA) and achieved hematological remission. Although she had maintained hematological remission, the disease relapsed 10 months after arbitrary discontinuance of maintenance therapy with CyA. Resumption of CyA therapy was not effective, and her condition became complicated with progressive sinusitis with bone destruction, which was refractory to antibiotics, antifungal agents, granulocyte colony-stimulating factor, and surgical drainage. Because of the necessity for early neutrophil recovery (to resolve the infection), we proceeded with a combination therapy using allogeneic peripheral blood stem cell transplantation (PBSCT) promptly followed by granulocyte transfusion (GTX) from the same human leukocyte antigen-identical donor rather than carrying out a second immunosuppressive therapy. The patient showed temporal resolution of infection on the second day after a single GTX. Although the patient had pneumonia on day 11, it was resolved promptly after engraftment on day 16. This report suggests the clinical utility of a salvage therapy with allogeneic PBSCT followed by GTX in a particular case of recurrent SAA with refractory infections.     

Primary transplantation of allogeneic peripheral blood stem cell for severe aplastic anemia

 Primary allogeneic peripheral blood stem cell transplantation (allo-PBSCT) has not been previously described in the treatment of severe aplastic anemia (SAA). We report a patient with SAA who underwent primary allo-PBSCT with cells from her HLA-identical sibling and achieved rapid bone marrow reconstitution. The patient has been in complete remission with normal blood counts for 9 months following allo-PBSCT. This suggests that primary allo-PBSCT is a safe and effective alternative in the treatment of SAA. Received: 13 November 1996 / Accepted: 29 January 1997     

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.     

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.     

Improved outcome of patients older than 30 years receiving HLA-identical sibling hematopoietic stem cell transplantation for severe acquired aplastic anemia using fludarabine-based conditioning: a comparison with conventional conditioning regimen

Older age is a limitation for HLA-identical sibling hematopoietic stem cell transplantation (HSCT) as first-line therapy for severe acquired idiopathic aplastic anemia (SAA). Fludarabine (Flu)-based conditioning might improve outcome in older patients. We analyzed retrospectively 30 patients older than 30 years receiving such reduced-intensity conditioning HSCT according to recommendations of the European Group for Blood and Marrow Transplantation (EBMT) and compared their outcome to a control group receiving the standard regimen (cyclophosphamide+/−antithymocyte globulin) over the same study period (1998–2007). Patients conditioned with Flu had a higher probability of overall survival than the control group (p=0.04) when adjusting for recipient’s age. This might be related to a trend towards a reduced incidence of graft failure in patients receiving Flu (0% vs. 11%, p=0.09), while no difference was observed regarding graft-versus-host disease incidence. Flu-based conditioning regimen may reduce the negative impact of age in older patients with SAA receiving an HLA-identical sibling HSCT.     

HLA半相合非清髓性造血干细胞与间充质干细胞共移植治疗重症再生障碍性贫血1例

目的:观察HLA半相合非清髓性造血干细胞与间充质干细胞(MSC)共移植治疗重症再生障碍性贫血(SAA)的疗效及安全性。方法:1例24岁男性SAA患者。应用非清髓性预处理方案,进行HLA半相合异基因外周血造血干细胞和MSC共移植。移植rhG-CSF动员的供者外周血单个核细胞9.22×108/kg,CD34 细胞8.56×106/kg,及体外扩增培养的供者骨髓MSC2.12×105/kg。结果:移植后 12d中性粒细胞数>0.5×109/L, 21d WBC4.5×109/L,Hb99g/L,PLT108×109/L。经HLA配型,红细胞亚型和VNTR检测,为供者型完全嵌合体。随访14个月,无急、慢性移植物抗宿主病(GVHD)发生。结论:HLA半相合非清髓性造血干细胞与MSC共移植治疗SAA是安全有效的方法。