HLA半相合非清髓异基因造血干细胞移植治疗难治性急性白血病1例

目的探讨HLA半相合非清髓异基因造血干细胞移植(NAST)在治疗难治性急性白血病中的作用。方法2002-06采用非清髓预处理的NAST治疗军事医学科学院附属307医院难治性急性髓性白血病患者1例。预处理方案主要由抗淋巴细胞球蛋白(ATG)、阿糖胞苷(Ara-C)、氟达拉滨(Flu)和环磷酰胺(CTX)等组成。移植物抗宿主病(GVHD)的预防采用环孢素A(CSA)、霉酚双酯(MMF)、甲氨蝶呤(MTX)和CD25单抗。结果患者移植过程顺利,于移植后第100d转为完全供者型植入。患者于移植后出现皮肤Ⅰ度GVHD,经治疗后好转。结论应用HLA半相合NAST治疗难治性急性白血病患者,简便安全,疗效好,为无HLA相合供者的白血病患者治疗开辟了新的治疗手段。     

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。     

间充质干细胞在HLA半相合移植中的应用

造血干细胞移植是治愈恶性血液系统疾病的唯一方法,但寻找HLA完全相合的供者越来越难,HLA半相合移植显示出它独特的优势。骨髓间充质干细胞是骨髓微环境中具有自我更新和多向分化的非造血干细胞,在造血干细胞移植中发挥重要的作用,它能够促进造血重建,与造血干细胞共输注能增强造血干细胞的植入。     

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.     

非亲缘HLA不相合脐血移植治疗再生障碍性贫血

目的 :观察HLA位点不相合的非亲缘脐血细胞移植治疗重型再生障碍性贫血 (SAA)的疗效。方法 :采用 5～ 6个HLA位点相合的非亲缘脐血移植治疗SAA患者 1例。输入脐血单个核细胞数为 4.72× 10 7/kg。预处理方案为环磷酰胺 (5 0mg/kg·d-1× 4)、抗淋巴细胞球蛋白 (2 0mg/kg·d-1× 4)和全身照射 (3Gy)。用环胞素、骁悉和泼尼松预防移植物抗宿主病 (GVHD)。结果 :移植后白细胞下降至零 ,持续 12d ,中性粒细胞分别于移植后第 2 4天和第 2 6天恢复至 0 .5× 10 9/L和 1.0× 10 9/L ,血小板分别于移植后第 2 8天和第 82天达到 2 0× 10 9/L和 5 0× 10 9/L ,DNA短串重复序列PCR检测证实为持续稳定的供者造血。随访 12个月未发生急慢性GVHD。结论 :非亲缘脐血移植是治疗重型再障的一种有效的方法。     

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。     

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     

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.     

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.     

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...     

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.     

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。     

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.     

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.     

Unmanipulated haploidentical haematopoietic stem cell transplantation for children with severe aplastic anaemia

Haploidentical haematopoietic stem cell transplantation (haplo‐HSCT) used to be a third‐line treatment option for childhood severe aplastic anaemia (SAA). We conducted this retrospective study of 36 children (38 transplants) who received haplo‐HSCT from human leucocyte antigen (HLA)‐mismatched related donors between July 2002 and November 2013 at five HSCT centres in China, including 17 cases that were 5/6 HLA matched (Group 1) and 21 that were 4/6 or 3/6 HLA matched (Group 2). Although patients in Group 2 had a higher incidence of grade II‐IV acute graft‐versus‐host disease (57·9% vs. 5·9%, P = 0·001), they had similar rates of graft failure (5·3% vs. 5·9%, P = 0·742) and overall survival (80·8% vs. 93·8%, P = 0·234) as Group 1. Unmanipulated haplo‐HSCT is an effective treatment for SAA children with satisfactory outcome of this cohort, especially in the 5/6 HLA‐matched group. For patients in critical situations, such as unresponsive to immunosuppressive therapy, refractory infection and failing first HSCT, to bring forward the timing of haplo‐HSCT is a feasible salvage strategy with better and faster donor accessibility.     

Supplemental peripheral blood stem cells to decrease marrow rejection in adult patients with severe aplastic anemia

Twenty-two multi-transfused patients with a long duration of severe aplastic anemia (SAA) received a transplant from an HLA-matched donor after cyclophosphamide (CY) plus antithymocyte globulin plus procarbazine using CD34(+) enriched blood stem cells + fresh marrow. Peripheral blood stem cells (PBSC) were collected on days 5 and 6 of G-CSF (10 microg/kg/day), and T cells were depleted using an immunoadsorption column (n = 15) or magnetic cell sorting (n = 7). Marrow harvesting was performed 48 hr after the last leukapheresis. Two patients (9.1%) that developed graft failure had a successful engraftment again using unpurged PBSC. Median time to neutrophils > or = 0.5 x 10(9)/l and platelets > or = 20 x 10(9)/l without platelet transfusions were 12 days and 17 days, respectively. Acute graft-versus-host disease (GVHD) grade II occurred in four of 22 patients. No patient developed grade III or IV acute GVHD. Four of the evaluable 21 patients had chronic GVHD. One patient developed extensive disease. Three patients (13.6%) died from CY-induced heart failure, extensive-type chronic GVHD, and sepsis of unknown cause. The Kaplan-Meier estimate of survival was 83.9% (95% CI, 70.1-95.2%) with a median follow-up duration of 33.5 (6-44) months. CD34(+)-enriched PBSC in combination with unmanipulated marrow seem to play a role in overcoming the sensitization to histocompatibility antigens without an apparent increase in GVHD. The stem cell component therapy may be feasible for the high-risk SAA adult patients.     

再生障碍性贫血患者骨髓间充质干细胞成脂和成骨分化能力的变化

目的 通过观察再生障碍性贫血(再障)患者间充质干细胞(MSCs)成脂肪和成骨能力的变化,研究骨髓MSCs成脂分化的异常在再障患者红髓脂肪化中的作用.方法 分离培养再障患者及正常人的骨髓,观察其一般生物学特性,并在体外诱导其向脂肪、成骨细胞分化,同时用RT-PCR方法检测成脂肪、成骨特异基因的表达时间,比较再障患者和正常对照MSCs向脂肪细胞、成骨分化能力的不同.结果 原代培养7 d,再障组贴壁细胞克隆形成率为(19.30±4.77)/(5×105 MNCs),较正常对照组明显降低(47.72±3.46)/(5×105 MSCs)(P＜0.05).在培养初期,再障组MSCs与正常对照MSCs增殖能力相似,但在连续传8代后,其增殖能力降低.再障组MSCs体外诱导成脂滴早,诱导分化的脂肪细胞leptin(瘦素)基因表达早.再障组MSCs体外诱导成骨形成钙化结节少,碱性磷酸酶活性低,诱导的成骨细胞osteocalcin(骨钙素)基因表达晚.结论 再障患者MSCs成脂分化能力增强而成骨分化能力降低,可能在再障的病程中起一定作用.