造血干细胞移植与非移植治疗重型再生障碍性贫血的比较

背景:造血干细胞移植是公认的重型再生障碍性贫血最好的治疗办法。国内外已经开始进行了多种造血干细胞来源的移植,包括亲缘单倍体移植、非血缘移植,而联合间充质干细胞移植提高疗效的报道多为单独个案报道。目的:回顾性对比分析造血干细胞移植与非移植治疗重型再生障碍性贫血的疗效。方法:2008-04/2010-04住院的17例重型再生障碍性贫血患者,年龄3～53岁,8例患者接受造血干细胞移植,9例患者接受了非移植治疗。移植组的8例患者分别接受了亲缘HLA半相合(4例)、HLA相合(2例),非血缘(2例)的造血干细胞移植,在所有移植的患者中有4例在造血干细胞输注的同时静脉输注体外培养扩增的间充质造血干细胞。非移植治疗组9例患者主要采用免疫抑制剂和促造血治疗。结果与结论:移植组除1例45岁患者接受过非移植方法治疗11个月无效,合并肾功能衰竭、肺部真菌感染时才行造血干细胞移植,死于移植合并症外,余7例患者移植后染色体及DNA指纹检测等说明造血干细胞移植完全供者植入,造血功能恢复快,中性粒细胞达到0.5×109L-1,血小板计数≥20×109L-1中位时间分别为12d和14d;其中接受间充质干细胞输注的4例患者平均中性粒细胞达到0.5×109L-1,血小板计数≥20×109L-1的中位时间均为11.6d。移植患者发生Ⅰ,Ⅱ度急性移植物抗宿主病4例,局限慢性移植物抗宿主病者4例,移植后生活质量良好,无需血制品输注,无严重感染和出血。而非移植组患者治疗后造血功能均未恢复正常,1例死于脑出血和感染,余患者生活质量低下,需要反复住院对症治疗,长期间断的血制品输注;治疗后出现多种严重的合并症。结果表明造血干细胞移植是高效的治疗重型再生障碍性贫血的方法,患者造血恢复快,移植物抗宿主病可以预防和控制,生活质量高,疗效明显优于非移植治疗。     

造血干细胞移植治疗重型再生障碍性贫血

异基因造血干细胞移植是治疗重型再生障碍性贫血患者的有效方法,预处理方案是影响移植疗效最重要的因素,Cy+ATG是基本的预处理方案,无关供者移植患者需在此基础上加用低剂量TBI以促进造血植入,减少移植物排斥,此外,供受者HILA高分辨配型也是影响无关供者移植疗效的关键因素.     

单倍体造血干细胞移植治疗儿童重型再生障碍性贫血

本研究分析非体外去T细胞亲缘单倍体造血干细胞移植(hi-HSCT)治疗儿童重型再生障碍性贫血(SAA)的疗效。我院于2010年10月-2013年3月对2例SAA/极重型再生障碍性贫血(VSAA)患儿进行了非体外去T淋巴细胞的父亲2个HLA位点不合的HSCT。2例在病程4个月内用环孢素A(CsA)+粒细胞集落刺激因子(G-CSF)治疗无效,有活动或重症感染,输血依赖,无HLA全合的同胞供者或非血缘供者。移植前预处理用福达拉滨(Flu)+环磷酰胺(Cy)+抗胸腺细胞球蛋白(ATG)。移植物为G-CSF动员的外周血造血干细胞(PBHSC)和骨髓(BM)。移植物抗宿主病(GVHD)预防用CsA+骁悉(MMF)+短程甲氨蝶呤(MTX)。结果2例患儿均达到100%供者植入,粒细胞植入时间分别为移植后12 d、18 d,血小板植入时间分别为移植后17 d、26 d。2例均出现I度急性GVHD(aGVHD),1例发展为可控制的局限性慢性GVHD(cGVHD)。2年随访期间,2例患儿保持稳定的100%供者植入并有免疫功能的重建。结论:小数量临床研究结果提示在没有同胞HLA全合供者或非血缘HLA全合供者时,亲缘单倍体造血干细胞移植对儿童SAA是适宜的选择,总体生存率(OS)的提高还有待大规模前瞻性临床研究的开展。     

HLA全相合异基因造血干细胞移植与免疫抑制剂治疗重型再生障碍性贫血的比较

背景：国外有报道显示异基因造血干细胞移植和免疫抑制疗法治疗急性重型再生障碍性贫血的有效率及总生存期相当,但两种疗法治疗后的生活质量及治疗费用方面的差异报道较少。目的：回顾性分析同胞HLA全相合异基因造血干细胞移植与免疫抑制疗法治疗急性重型再生障碍性贫血的疗效。方法：入选2004-07/2010-10在南京鼓楼医院血液科行同胞HLA全相合异基因造血干细胞移植的7例及行免疫抑制疗法的16例急性重型再生障碍性贫血患者,每3个月定期进行随访。结果与结论：异基因造血干细胞移植组在粒细胞和血小板恢复时间,脱离输血时间,治疗后3个月总有效率及治疗后12个月完全缓解率均优于免疫抑制疗法组,但治疗后12个月总有效率差异无显著性意义。异基因造血干细胞移植组与免疫抑制疗法组的总生存率分别为86%与81.3%,两组比较差异无显著性意义。治疗1年后两组患者总体健康状况及功能健康状况均提示良好,两组住院费用差异无显著性意义。     

HLA全相合异基因造血干细胞移植与免疫抑制剂治疗重型再生障碍性贫血的比较

背景:国外有报道显示异基因造血干细胞移植和免疫抑制疗法治疗急性重型再生障碍性贫血的有效率及总生存期相当,但两种疗法治疗后的生活质量及治疗费用方面的差异报道较少.目的:回顾性分析同胞HLA全相合异基因造血干细胞移植与免疫抑制疗法治疗急性重型再生障碍性贫血的疗效.方法:入选2004-07/2010-10在南京鼓楼医院血液科行同胞HLA全相合异基因造血干细胞移植的7例及行免疫抑制疗法的16例急性重型再生障碍性贫血患者,每3个月定期进行随访.结果与结论:异基因造血干细胞移植组在粒细胞和血小板恢复时间,脱离输血时间,治疗后3个月总有效率及治疗后12个月完全缓解率均优于免疫抑制疗法组,但治疗后12个月总有效率差异无显著性意义.异基因造血干细胞移植组与免疫抑制疗法组的总生存率分别为86%与81.3%,两组比较差异无显著性意义.治疗1年后两组患者总体健康状况及功能健康状况均提示良好,两组住院费用差异无显著性意义.     

单倍体造血干细胞联合脐带间充质干细胞移植治疗重型再生障碍性贫血-Ⅱ型的临床观察

本研究探讨单倍体相合造血干细胞移植联合脐带血间充质干细胞（hUC—MSC）治疗重型再生障碍性贫血-Ⅱ型（SAA—Ⅱ）的安全性、有效性及相关并发症的发生情况。对8例重型再生障碍性贫血-Ⅱ型均进行单倍体造血干细胞移植,移植物选用G—CSF动员的外周血干细胞加骨髓干细胞混合移植方案,并加入脐带间充质干细胞作为第3方细胞;预处理方案采用兔抗人T淋巴细胞球蛋白（ATG）＋环磷酰胺（CTX）方案＋福达拉滨（Flu）方案,其中2例患者加用马法兰（Bu）;移植物抗宿主病（graft—versus—hostdisease,GVHD）的预防方案采用环孢菌素A＋ATG＋霉酚酸酯（MMF）＋短程甲氨喋呤（MTX）＋CD25单克隆抗体。结果表明,8例患者全部获得造血重建,血象好转：中性粒细胞〉0．5×10^9／L平均时间11．9d;血小板〉20×10^9／L平均时间14．6d。Ⅰ-Ⅱ度急性移植物抗宿主病（aGVHD）发生率25％,Ⅲ-Ⅳ度aGVHD发生率12．5％。移植相关死亡率为25％。结论：联合脐带MSC的单倍体异基因造血干细胞移植治疗sAA—Ⅱ安全可行,疗效显著,临床可以对其进一步尝试。     

单倍体相合造血干细胞联合脐带血间充质干细胞移植治疗急性重型再生障碍性贫血的疗效观察

本研究探讨单倍体相合造血干细胞移植联合脐带血间充质干细胞治疗重型再生障碍性贫血(SAA)的方法和疗效。对5例SAA的患者进行了单倍体相合造血干细胞移植。移植物选择单倍体相合供者骨髓或外周造血干细胞加脐带血间充质干细胞。观察移植后临床造血重建时间及近期并发症。结果显示,所有SAA患者移植后均获得造血重建,白细胞计数大于2×109/L的平均时间是13.8天,血小板计数大于20×109/L的平均时间是17.8天,第30天行患者外周血STR-PCR检测显示为完全供者的基因型。除1例发生癫痫失去联系外,其余4例均无病存活至今,仍在继续随访中。总之,单倍体相合造血干细胞联合脐带血间充质干细胞移植是治疗急性SAA有效可行的方法,但还须大样本的研究。     

外周血造血干细胞移植治疗重型再生障碍性贫血一例

我们最近为１例重型再生障碍性贫血（ＳＡＡ）患者成功进行了同基因外周血造血干细胞移植（ＰＢＳＣＴ）,报告如下。病例和方法１病例患者,女,２７岁。因头晕、乏力、牙龈出血、月经量多１５天,伴发热４天,于１９９８年２月１０日入院。查体：体温３８．５℃,重度贫...     

多种来源造血干细胞移植治疗重型再生障碍性贫血

背景:造血干细胞移植是年轻重型再生障碍性贫血患者首选方法,但在中国多数重型再生障碍性贫血患者无合适的供者,单倍体相合或非血缘造血干细胞移植国内外目前还处于探索阶段,联合间充质干细胞移植报道少见.目的:观察不同干细胞来源造血干细胞移植治疗重型再生障碍性贫血的疗效.方法:10例(3～52岁)重型再生障碍性贫血患者,分别接受了亲缘HLA相合(2例),单倍体相合(5例),非血缘(3例)的外周血和/或骨髓造血干细胞移植,其中5例患者同时联合了间充质干细胞共移植.预处理方案主要为环磷酰胺、氟达拉滨和抗人胸腺球蛋白,以霉酚酸酯、环孢素A加短疗程的甲氨蝶呤预防移植物抗宿主病,单倍体相合移植的患者在此基础上加马利兰和CD25单克隆抗体;同基因的例5患者预处理方案为抗人胸腺球蛋白+甲基泼尼龙.输注间充质干细胞的量为(0.27～1.85)×106/kg.接受和未接受间充质干细胞组的患者回输的造血干细胞有核细胞分别为(7.4～17.38)×108/kg和(6.09～13.68)×108/kg.结果与结论:除1例单倍体相合患者移植未成功,+36 d死于并发症外,余患者移植后染色体及DNA指纹检测等说明造血干细胞移植完全供者植入.移植后中性粒细胞达到0.5×109 L-1,血小板计数≥20×109 L-1中位时间分别为12 d和13 d;其中造血功能恢复快慢的趋势是同基因移植>外周血或/和骨髓+间充质干细胞移植>单纯外周血或/和骨髓干细胞移植,而亲缘HLA全相合的52岁患者造血恢复最慢.非血缘移植例1、6患者发生了Ⅰ度急性移植物抗宿主病,单倍体相合移植的例2和例10患者发生了Ⅱ度急性移植物抗宿主病后出现了局限性的慢性移植物抗宿主病,余下患者移植后生活质量良好,无慢性移植物抗宿主病;除未接受间充质干细胞的例3患者移植后出现严重感染外,其余患者移植后再未出现严重的感染和出血.结果提示造血干细胞是安全,高效治疗重型再生障碍性贫血的方法,联合应用间充质造血干细胞者患者造血恢复快,移植并发症少.     

多种来源造血干细胞移植治疗重型再生障碍性贫血

背景：造血干细胞移植是年轻重型再生障碍性贫血患者首选方法,但在中国多数重型再生障碍性贫血患者无合适的供者,单倍体相合或非血缘造血干细胞移植国内外目前还处于探索阶段,联合间充质干细胞移植报道少见。目的：观察不同干细胞来源造血干细胞移植治疗重型再生障碍性贫血的疗效。方法：10例（3～52岁）重型再生障碍性贫血患者,分别接受了亲缘HLA相合（2例）,单倍体相合（5例）,非血缘（3例）的外周血和/或骨髓造血干细胞移植,其中5例患者同时联合了间充质干细胞共移植。预处理方案主要为环磷酰胺、氟达拉滨和抗人胸腺球蛋白,以霉酚酸酯、环孢素A加短疗程的甲氨蝶呤预防移植物抗宿主病,单倍体相合移植的患者在此基础上加马利兰和CD25单克隆抗体;同基因的例5患者预处理方案为抗人胸腺球蛋白＋甲基泼尼龙。输注间充质干细胞的量为（0.27～1.85）×106/kg。接受和未接受间充质干细胞组的患者回输的造血干细胞有核细胞分别为（7.4～17.38）×108/kg和（6.09～13.68）×108/kg。结果与结论：除1例单倍体相合患者移植未成功,＋36d死于并发症外,余患者移植后染色体及DNA指纹检测等说明造血干细胞移植完全供者植入。移植后中性粒细胞达到0.5×109L-1,血小板计数≥20×109L-1中位时间分别为12d和13d;其中造血功能恢复快慢的趋势是同基因移植〉外周血或/和骨髓＋间充质干细胞移植〉单纯外周血或/和骨髓干细胞移植,而亲缘HLA全相合的52岁患者造血恢复最慢。非血缘移植例1、6患者发生了Ⅰ度急性移植物抗宿主病,单倍体相合移植的例2和例10患者发生了Ⅱ度急性移植物抗宿主病后出现了局限性的慢性移植物抗宿主病,余下患者移植后生活质量良好,无慢性移植物抗宿主病;除未接受间充质干细胞的例3患者移植后出现严重感染外,其余患者移植后再未出现严重的感染和出血。结果提示造血干细胞是安全,高效治疗重型再生障碍性贫血的方法,联合应用间充质造血干细胞者患者造血恢复快,移植并发症少。     

造血干细胞移植治疗重型再生障碍性贫血

Objective To evaluate the therapeutic effects of allogeneic hematopoietic stem cell transplantat (allo-HSCT) for severe aplastic anemia (SAA). Methods Four patients of SAA underwent allo-HSCT at the bonemarrow transplant unit in our hospital from March 2003 to May 2009. Stem cell source was an HLA (human leukocyte antigen) matched related donor (MRD) in 3, HLA 1 (B) mismatched related donor in 1 patient A retrospective analysis was performed on interval from diagnosis to transplant,HSCT manners,conditioning regimens, hematopoiesis reconstitution, effectiveness and complication. Results The interval from diagnosis to transplant was 70 (19 - 180) days. Three patients (MRD) underwent BM + PBSCT, one was undergone BM + PBSC + CBSCT. Conditioning regimens of all patients were CY/ATG. Hematopoiesis reconstitution was achieved in 4 patients (100%). The median time of neutrophils which reached 0. 5 x 109/L and platelets reached 20 × 109/L were 14. 5 (9-28) and 16(9 -28) days. Two cases developed grade Ⅰ acute graft-versus-host diseaes (aGVHD), chronic local GVHD occurred in one patient. Four patients are alive with a median time of 40. 6(2 -63) months at the end of the following-up. Conclusions Allo-HSCT are an efficient and safe therapy for the patient with SAA,not only for patients with HLA matched related donor,but also for those only HLA mismatched related donor available.     

造血干细胞移植治疗重型再生障碍性贫血

Objective To evaluate the therapeutic effects of allogeneic hematopoietic stem cell transplantat (allo-HSCT) for severe aplastic anemia (SAA). Methods Four patients of SAA underwent allo-HSCT at the bonemarrow transplant unit in our hospital from March 2003 to May 2009. Stem cell source was an HLA (human leukocyte antigen) matched related donor (MRD) in 3, HLA 1 (B) mismatched related donor in 1 patient A retrospective analysis was performed on interval from diagnosis to transplant,HSCT manners,conditioning regimens, hematopoiesis reconstitution, effectiveness and complication. Results The interval from diagnosis to transplant was 70 (19 - 180) days. Three patients (MRD) underwent BM + PBSCT, one was undergone BM + PBSC + CBSCT. Conditioning regimens of all patients were CY/ATG. Hematopoiesis reconstitution was achieved in 4 patients (100%). The median time of neutrophils which reached 0. 5 x 109/L and platelets reached 20 × 109/L were 14. 5 (9-28) and 16(9 -28) days. Two cases developed grade Ⅰ acute graft-versus-host diseaes (aGVHD), chronic local GVHD occurred in one patient. Four patients are alive with a median time of 40. 6(2 -63) months at the end of the following-up. Conclusions Allo-HSCT are an efficient and safe therapy for the patient with SAA,not only for patients with HLA matched related donor,but also for those only HLA mismatched related donor available.     

造血干细胞移植治疗重型再生障碍性贫血

目的 评价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 2003年3月至2009年5月接受Allo-HSCT治疗SAA患者4例,其中HLA位点全相合同胞供者3例,HLA 5个位点相合同胞供者1例.回顾性分析从诊断到移植时间、HSCT方式、预处理方案、植入时间、HSCT并发症和疗效等.结果 诊断到移植时间平均70(19-180)d.HLA位点全相舍HSCT采用骨髓+外周血干细胞移植3例,HLA 5个位点相合HSCT采用骨髓+外周血+脐血干细胞移植1例,预处理方案均为环磷酰胺/抗人胸腺细胞球蛋白(CY/ATG).4例患者均植活,中性粒细胞绝对值(ANC)≥0.5×109/L和血小板(BPC)≥20 × 109/L中位时间分别为移植后14.5(9～28)d、16(9～28)d,其中2例患者发生Ⅰ度急性移植物抗宿主病(aGVHD),1例患者发生局限性慢性移植物抗宿主病(cGVHD).至随访截止日无死亡病例,中位生存40.6(2～63)个月.结论 Allo-HSCT是治愈SAA的有效方法,并且对于HLA位点不全相合同胞供者的Allo-HSCT,同样是安全有效的.     

单倍体相合造血干细胞移植治疗儿童重型再生障碍性贫血

背景：目前治疗儿童再生障碍性贫血的主要方法为强化免疫抑制治疗或干细胞移植,后者由于供者来源少而受到限制,HLA单倍体相合的异基因造血干细胞在白血病治疗中常见应用,在再生障碍性贫血治疗中较少应用。目的：探讨单倍体相合的造血干细胞移植联合胎盘来源的间充质干细胞移植治疗重型儿童再生障碍性贫血的疗效。方法：患儿,女,7岁,确诊重型再生障碍性贫血1年半,2012-07-09接受HLA单倍体相合的异基因骨髓及外周血单个核细胞联合胎盘来源间充质干细胞移植,供者为母亲。预处理采用氟达拉滨联合环磷酰胺和抗胸腺细胞球蛋白方案。结果与结论：移植后＋9 d中性粒细胞〉0.5×109 L-1,＋12 d完成造血重建,＋100 d查STR提示植入完成。移植后＋8个月停用免疫抑制药物,未发生急、慢性移植物抗宿主病。患儿随访18个月,无病生存。结果表明,HLA单倍体相合的造血干细胞联合胎盘来源间充质细胞移植治疗儿童重型再生障碍性贫血是一种安全有效、值得探索的方法。     

Severe aplastic anemia and allogeneic hematopoietic stem cell transplantation

Aplastic anemia is a form of bone marrow failure that ranges in severity from mild to severe. In all cases, some degree of pancytopenia is present. The cause usually is unknown, although many drugs and viruses are associated with the disease. The pathophysiology of aplastic anemia involves either a stem cell defect or injury or an immunologically mediated hematopoietic cell destruction, which may operate in concert with abnormalities in programmed cell death. Excellent clinical care and research have dramatically improved patient survival, with 70% to 90% of sibling hematopoietic stem cell transplant recipients surviving long term. Patients with mild or moderate disease may not require immediate treatment. If and when these patients require treatment, the mainstay of therapy is immunosuppression. The initial drug regimen includes antithymocyte globulin, often in combination with cyclosporine A, followed by moderate-dose steroids and cyclophosphamide. Nurses assess and monitor patients and their progress, recognizing medication adverse effects. Nurses educate patients about their disease and its treatment, and provide necessary emotional support. Severe aplastic anemia is treated with allogeneic hematopoietic stem cell transplantation. This therapy involves complex nursing challenges. The patient goes through an extensive pretransplantation workup. Donor selection and harvesting of hematopoietic stem cells are preludes to an intensive preparative regimen. This preparative or conditioning regimen and the need for long-term immunosuppression are the reasons for many of the acute complications and adverse events that may follow the hematopoietic stem cell transplantation. Nurses must be vigilant in assessing and monitoring patients for toxicities and long-term complications that may affect almost any organ system.     

Long-term results of allogeneic peripheral blood hematopoietic stem cell transplantation for severe aplastic anemia

ObjectiveAplastic anemia (AA) is a life-threatening disorder and may be associated with significant morbidity and mortality Currently, the first treatment option is allogeneic hematopoietic stem cell transplant (allo-HSCT) for patients younger than 40 years. Bone marrow is recommended as the stem cell source due to less graft versus host disease (GVHD) risk and better outcomes than peripheral blood (PB)-derived stem cell. The aim of this study is to share the data of AA patients who have underwent PB-derived allo-HSCT in our bone marrow transplantation center.MethodsTwenty-seven patients who underwent PB-derived allo-HSCT from human leukocyte antigen matched sibling donors were analyzed retrospectively.ResultsThe median follow-up time was 95.2 months (range, 4.8–235 months). The 10-year survival was 89 %. The median neutrophil and platelet engraftment time was 11 days (range, 9–16 days) and 13 days (range, 11–29 days), respectively. Primary platelet engraftment failure was observed in 1 patient (3.7 %). Acute and chronic GVHD observed in 2 (7.4 %) and 3 (11.1 %) patients, respectively. Neutropenic fever was observed in 13 (44.8 %) of patients until the engraftment after allo-HSCT. One patient died due to CMV infections, two died due to septic shock secondary to fungal infection.ConclusionAlthough there is no prospective data directly comparing BM with PB as stem cell source in AA, observational studies indicates better OS with BM. PB can be used in certain situations such as higher risk for graft failure and donor preference. This study demonstrated that PB-derived stem cell seems to be a reasonable alternative to BM.     

Allogeneic stem cell transplantation for severe aplastic anemia and myelodysplasia

Stem cell transplantation is an effective treatment for anemia associated with stem cell disorders such as severe aplastic anemia, myelodysplastic syndrome. Long-term survival rates after transplantation for those diseases range from less than 40% to more than 80%. The rates are significantly affected by recipient's age, HLA disparity between donor and recipient, sources of stem cells, and disease status. Results are best in younger patients transplanted with bone marrow from HLA-identical sibling at the early course of the diseases. The decision of whether and at what point to proceed to transplantation should be made early after diagnosis, based upon the consideration of a survival rate with reasonable quality of life expected with transplantation and other therapeutic approaches.     

异基因造血干细胞移植治疗再生障碍性贫血16例临床观察

目的评价异基因造血干细胞移植（allo-HSCT）治疗再生障碍性贫血（AA）的疗效。方法1991至2006年共有12例重型AA（SAA）、4例慢性AA（CAA）患者接受allo-HSCT治疗，回顾性分析植入情况、并发症发生及移植疗效等。结果造血重建14例（87．50％），中性粒细胞绝对值（ANC）≥0．5×10^9／L和BPC≥120×10^9／L中位时间分别为移植后14（11～16）天、14（10～33）天；其中6例患者发生Ⅰ～Ⅱ度急性移植物抗宿主病（aGVHD），2例患者发生慢性局限型GVHD。16例AA患者中未植入死亡1例；移植排斥（GR）3例（18．75％），其中死亡1例、自身造血恢复1例；至随访截止，存活13例（81．25％），中位生存10（0．5～84）个月。结论allo-HSCT是治疗AA的有效方法之一，加强移植前后免疫抑制处理的强度，减少GR、GVHD的发生。