HLA不全相合脐血造血干细胞移植成功1例报告

异基因骨髓移植是白血病等致死性血液病的根治方法,然而因我国的具体国情所致,儿童极难有骨髓移植供体。故此,我们探索性应用HLA不全相合同胞脐血造血于细胞移植(CBT)治疗小儿急性淋巴性白血病1例,获得成功。现病人造血恢复,存活40余天,现将结果简要报告如下。     

非清髓异基因造血干细胞移植治疗急性白血病的临床研究

采用非清髓预处理（环胞霉素A、环磷酰胺、阿糖胞苷及CD3单克隆抗体或抗淋巴细胞球蛋白）的异基因外周造血干细胞移植治疗急性白血病5例。5例病人均顺利度过造血抑制期并移植成功。2例例经嵌合性植入转为完全植入,另3例为嵌合性植入。5例中2例发生Ⅱ～Ⅲ度GVHD,经治疗后治愈。5例中4例仍无病存活。结果表明,非清髓异基因造血干细胞移植简便安全,并发症少,疗效较好,为急性白血病的治疗提供了新手段。     

含照射与纯化疗的移植预处理方案治疗儿童白血病：Meta分析

目的观察含照射与纯化疗的两种不同的移植预处理方案对儿童造血干细胞移植的治疗效果。方法计算机检索循证医学数据库、美国国立医学图书馆医学文献分析和联机检索系统、中国学术期刊网全文数据库、中国生物医学文献光盘数据库在199042007年期间发表的关于儿童白血液病移植中对比不同预处理方案的研究文献。从干细胞植入、移植后的治疗相关病死率、长期生存率等方面进行对比分析。采用Review Manager软件进行Meta分析。结果检索出4012篇文献，最终纳入9个试验共2333例患者。全身照射加环磷酰胺与白消安加环磷酰胺组相比植入失败率和移植后的复发率无明显区别：白消安加环磷酰胺组治疗相关病死率明显升高，而全身照射加环磷酰胺组长期无病生存率则明显优于白消安加环磷酰胺组。结论目前有限文献表明，全身照射加环磷酰胺预处理方案是儿童白血病移植的有效方案，而全身照射对儿童生长发育的长期不良影响有待进一步探讨。     

非清髓异基因外周造血干细胞移植治疗高龄血液病临床研究

目的 探讨非清髓异基因外周造血干细胞移植(NAST)在治疗高龄血液病中的作用。方法 采用NAST、治疗高龄血液病患者5例。5例患者平均年龄55岁(53～59岁)。预处理方案主要由环孢素、抗淋巴细胞球蛋白和环磷酰胺等组成。结果 5例患者均顺利度过移植后造血抑制期，3例供者细胞完全植入，2例为供受者混合嵌合体。2例出现移植物抗宿主病(GVHD)，治疗后好转。结论 NAST简便安全，并发症少，疗效好，为高龄血液病的治疗开辟了新途径。     

外周血造血干细胞移植治疗恶性血液病21例报告

目的：观察外周血造血干细胞移植（PBHSCT）治疗恶性血液病的疗效和并发症。方法：21例恶性血液病中8例行自体PBHSCT（auto-PBHSCT）,13例行异基因PBHSCT（allo-PBHSCT）。结果：21例全部获得造血重建,随访7～42月,10例（47.6%）存活,其中：auto-PBHSCT 5例,allo-PBHSCT5例。11例（52.4%）死亡,其中：auto-PBHSCT：3例复发死亡;allo-PBHSCT：5例复发死亡,2例移植相关死亡,1例死于第二肿瘤。结论：PBHSCT是治疗恶性血液病的有效方法,但如何有效减少复发、提高长期无病生存率需要进一步研究。     

亲代间单倍体相合造血干细胞移植治疗血液病45例临床分析

目的观察亲代间单倍体相合造血干细胞移植治疗血液病的临床疗效。方法第三军医大学新桥医院血液科自2007年7月-2011年1月,对45例患者实施父母供子女的亲代间单倍体相合造血干细胞移植,观察其临床疗效及并发症。结果 43例患者造血重建成功,2例患者植入失败。移植物抗宿主病(GVHD)发生率为62.2%,其中急性GVHD发生率为40.0%,慢性GVHD发生率为22.2%。与母亲作为供者相比,父亲作为供者时患者GVHD的发生率较低。GVHD的发生率与供者年龄、HLA配型相合位点数目有关。移植后并发的感染中以血源性巨细胞病毒感染和肺部感染为多。随访6个月~4年,移植成功的43例患者中共死亡6例,主要死因为感染和原始疾病复发,患者存活率86.7%。7例患者采用联合脐血移植,与单纯采用亲代间单倍体造血干细胞移植者相比,其造血重建时间提前,GVHD发生率占总发生率的7.14%。结论亲代间单倍体造血干细胞移植对治疗血液病有效,应选择HLA配型相合位点数目较多、男性、年轻供者。亲代间单倍体相合造血干细胞移植联合脐血移植,造血重建较快、GVHD发生率较低。     

非血缘脐血移植治疗儿童复发难治性急性白血病

目的 观察非血缘脐血移植对儿童急性白血病的治疗效果，从其移植并发症、长期造血及免疫重建等方面了解脐血作为干细胞来源的移植效果。方法 2例均为难治复发的急性白血病患儿，行人自细胞抗原一个位点不相合的无关脐血移植。予处理，例1采用马利兰，环磷酰胺2 氟达拉滨方案；例2用全身照射 马法兰 抗胸腺球蛋白，移植物抗宿主疾病的预防用环胞菌素A 骁悉或甲泼尼松。移植后联合应用粒细胞集落刺激因子及促红细胞生成素以加速造血重建。结果 例1于 26天粒系植入， 21天出现Ⅱ度移植物抗宿主病，加用甲泼尼松治疗后控制， 120天血小板植入，于 30天人自细胞抗原配型示为供者型，随访1．5年，患者各项检查正常，未发生慢性移植物抗宿主疾病。例2于 27天粒系植入， 73天血小板植入，于 137天血型转为B型， 48天发生Ⅳ度肠道移植物抗宿主病，用CD25单抗治疗后控制。结论 脐血移植适合我国国情且对儿童高危白血病较为适宜，但移植后移植物抗宿主病并未明显减弱，移植前有必要进行人白细胞抗原基因分型。移植后血小板的植入延迟仍是需要解决的问题。     

异基因外周血造血干细胞移植治疗极重度骨髓型和肠型急性放射病的临床报告

目的 探讨异基因外周血造血干细胞移植在肠型和极重度骨髓型放射病救治中的作用和地位.方法 山东"10·21" 60Co 辐射事故中2例病人受到意外照射,病例A受照射剂量20～25Gy,诊断为"肠型放射病",病例B受照射剂量9～15Gy,诊断为"极重度骨髓型放射病".经联合环磷酰胺、抗淋巴细胞球蛋白和氟达拉滨预处理,2例分别行HLA半相合及全相合外周血造血干细胞移植.采用环孢霉素A和骁悉方案(病例A加用CD25单抗和供者间充质干细胞)预防移植物抗宿主病(GVHD).结果 2例均移植成功,供体完全存活,移植后9～11天白细胞开始恢复,2周后白细胞恢复正常、骨髓造血重建成功.2例均未发生移植排斥和GVHD.病例A照射后33天死于败血症和多器官功能衰竭.病例B照射后75天死于心衰为主的多器官功能衰竭.结论 HLA相合及半相合外周血造血干细胞移植救治极重度骨髓型和肠型急性放射病是完全可能和可行的,联合免疫抑制剂预处理对促进供体稳定植入是必要的,环孢霉素A、骁悉和CD25单抗及供者间充质干细胞对预防GVHD有重要作用.     

同胞脐血移植治疗儿童急性白血病(2例临床报告)

目的:观察同胞脐血移植对儿童急性白血病的治疗效果,从其移植并发症、长期造血及免疫重建等方面了解脐血作为干细胞来源的移植效果.方法:2例急性白血病患儿,例1为急性单核细胞白血病患儿,体重30 kg,例2为急性淋巴肉瘤白血病患儿,体重50 kg;行HLA相合的同胞脐血移植,予处理采用BU/CY2方案:马利兰(BU)lmg/kg,每6 h一次,用4共16次,环磷酸胺(CY)60 mg/kg,d,用2天.分别输入脐血有核细胞3.7×10~7/kg及1.60×10~7/kg,CD34~ 分别为3.9×10~5/kg及1.6×10~7/kg,移植物抗宿主反应(GVHD)的预防单用环胞菌素A.移植后联合应用G-CSF及EPO以加速造血重建.结果:例1于 18天粒系植入, 33天血小板植入,例2于 13天粒系植入, 35天血小板植入,细胞因子的应用可以加速造血重建,例1于 30天DNA指纹图示骨髓全部为供者型,移植后2个月外周血T细胞亚群恢复正常.随访10个月,患者各项检查正常,未发生急、慢性GVHD.例2于 33天外周血性染色体分析证明为供者型,于 7天.发生急性Ⅱ度GVHD,用激素后控制,无其它并发症.结论:脐血移植适合我国国情且对儿童高危白血病较为适宜,应尽快建立和完善脐血库以促进脐血移植的发展.     

自体造血干细胞移植治疗恶性血液病

为探讨恶性血液病的有效治疗方法,应用自体骨髓移植(ABMT)38例,自体外周血造血干细胞移植(ABSCT)13例,自体外周血造血干细胞与自体骨髓联合移植15例。治疗白血病54例,恶性淋巴瘤11例,多发性骨髓瘤1例。外周血造血干细胞采用化疗加多抗甲素或C—CSF动员。移植物采用微波、阿克拉霉素净化处理。结果:两组动员方案均有良好动员效果。ABSCT组及联合移植组造血功能恢复比ABMT组快(P<0.05),合并症少。66例中,45例仍呈持续缓解(CCR),中位CCR时间32(5～98)个月,复发21例。3年无病生存率及复发率分别为68.5％及26.1％。结果表明:自体造血干细胞移植是根治恶性血液病的有效手段。ABSCT及联合移植具有造血功能恢复快,合并症少等优点。微波和阿克拉霉素体外净化移植物是一种简便、有效的净化方法。     

骨髓基质细胞输注对外周血干细胞移植造血恢复的影响

为观察骨髓基质细胞输注对外周血干细胞移植（PBSCT）后造血恢复的影响，经放、化疗预处理的BALB／c小鼠，分别输入动员的外周血干细胞（PBSCT组）、外周血干细胞联合扩增的骨髓基质细胞（实验组），观察受体鼠4周的生存率、骨髓有核细胞（BMNC），粒细胞巨噬细胞集落形成单位（CFU－GM）、成纤维细胞集落形成单位（CFU－F）、外周血白细胞计数等指标。结果显示，实验组的生态率，BMNC、CFU－GM、CFU－F较PBSCT组显著升高（P＜0．005）；白细胞的最低值较PBSCT组高（P＜0．01），白细胞恢复较PBSCT组块（P＜0．01）。提示骨髓基质细胞输注有促进外周血干细胞移植造血恢复的作用。     

MR-Charakterisierung der Zusammensetzung hämatopoetischen Knochenmarks Befunde bei generalisierten Neoplasien und Monitoring der Therapie

PURPOSE: Methodological work was performed in the field of magnetic resonance imaging (MRI) and spectroscopy (MRS) in order to develop suitable tools for non-invasive characterization of hematopoietic bone marrow. The methods were applied for the assessment of normal values in healthy persons and to examine patients with generalized hematological diseases or to monitor effects of therapies influencing the composition of bone marrow. METHODS: Besides standard techniques of MRI as T1- or T2-weighted methods, chemical shift techniques for selective visualization of water or lipid components were applied. The method of magnetization transfer (MT) contrast was used with the intention to differentiate between multiple water containing tissue compartments (intra- vs. extracellular space). A further approach was the determination of the magnetic field distribution within spongy bone marrow. Besides investigations in healthy volunteers, prospective clinical studies were carried out in patients suffering from acute leukemia during their initial treatment and in patients who underwent high-dose therapy with following peripheral blood stem cell transplantation (PBSCT). RESULTS: Especially MR techniques for selective imaging of water of fat signals and proton spectroscopy yielded a high sensitivity to primarily pathological or therapeutically induced changes of hematopoietic bone marrow. Application of MT allowed an improved differentiation of the tissue compartments under PBSCT, which might result in temporary edema. Storage of hemosiderin in bone marrow after blood transfusions and simultaneous hematopoietic insufficiency could be revealed by methods sensitive to magnetic field inhomogeneities. CONCLUSIONS: Methods of MRI and MRS allow to non-invasively characterize hematopoietic bone marrow in the course of hematological diseases and during therapy. Marked changes in the composition of hematological bone marrow are detectable for extensive marrow areas. The prognostic relevance of the findings has to be evaluated in future follow-up studies.     

外周血造血干细胞移植后造血重建的细胞学动态观察

目的：了解自体外外周血造血干细胞移植（APBSCT）与异基因外周血造血干细胞移植（alloPBSCT)后骨髓重建造血功能的规律与差异。方法：观察了两组13例外周血造血干细胞移植（PBSC）后骨髓造血重建的细胞学特点,其中,APBSCT6例,allPBSCT7例,结果：两组人在移植后在白细胞（WBC）、血小板（PLT）、血红蛋白（Hb)下降与回升有一定规律,不受年龄、性别的影响。两组之间无明显差异,P＞0．05。结论：重建造血的速度与输入单个细胞（MNC）数有一定相关性,移植时病人状态及适时的对症支持治疗也是决定重建速度的重要因素。     

Repopulation of marrow after transplantation: MR imaging with pathologic correlation

Sixty-seven magnetic resonance (MR) studies of the lumbar spine were performed in 15 patients with bone marrow transplants, and the appearance of marrow regeneration on MR images was correlated with results of bone marrow biopsy and pathologic examination. After transplantation, T1-weighted MR images of vertebral marrow showed a characteristic band pattern consisting of a peripheral zone of intermediate signal intensity and a central zone of bright signal intensity. Reciprocal changes were identified on short inversion time inversion recovery images. At histologic examination the central zone corresponded to fatty marrow; the peripheral zone corresponded to a zone of regenerating hematopoietic cells. Posttransplantation T1 and T2 relaxation times of the entire vertebral marrow were calculated from the spin-echo images; no statistically significant trends in relaxation times were noted. Knowledge of the normal MR pattern of marrow regeneration after transplantation may be useful in screening for residual marrow disease, determining marrow engraftment, and differentiating marrow repopulation with normal versus malignant cells.     

Radiation dose as a factor in host preparation for bone marrow transplantation across different genetic barriers.

Engraftment of donor bone marrow in relation to total body irradiation (TBI) dose was studied in syngeneic (B6----B6), MHC-compatible (BALB.B----B6) and MHC-incompatible allogeneic (BALB/c----B6) murine bone marrow transplantation (BMT) models. For each BMT combination radiation dose-response curves were obtained from stable long-term bone-marrow chimerism using Gpi-1 phenotyping and this was compared with the growth of exogenous CFU-S. Syngeneic engraftment required the lowest TBI doses limited to ablation of host haemopoietic stem cells. Resistance against H-2-compatible allogeneic engraftment was evident at low radiation doses (less than 5.5 Gy) but at 6 Gy and above the level of chimerism was comparable to syngeneic transplants, which indicated effective immunosuppression. Higher TBI doses were needed for engraftment as the immunological barrier was increased using fully H-2-incompatible allogeneic transplants. The high TBI dose (9.5 Gy) needed for suppression of spleen endocolonies in the CFU-S assay meant that rejection of exogenous bone marrow was evident only across the larger immunological barriers. When the fully allogeneic combination was reversed (B6----BALB/c) both CFU-S and chimerism data showed less rejection. The steep dose-response relationships show how engraftment is critically dependent on TBI dose, as well as the genetic disparity between donor and host.     

The role of stem cell transplantation in the management of Non-Hodgkin's lymphoma

The role of stem cell transplantation has markedly improved the clinical outcomes of patients with aggressive and relapsed Non-Hodgkin's lymphoma (NHL), and has now become the treatment of choice. This paper examines the evidence which is resulting in the changing trends in the management of NHL, in the use of stem cell transplantation. Autologous bone marrow transplantation has been much favoured due to the reduced incidence of treatment related complications. Although allogeneic transplants have had equal success, its use has been hampered by the increasing difficulty in finding suitably matched donors. The use of peripheral blood stem cells continues to increase, although further research is required to improve the effects of priming and purging methods used in order to reduce the risk of myelodysplastic syndrome.     

造血干细胞移植治疗飞行人员急性白血病（摘要）

目的采用造血干细胞移植治疗4例空军飞行人员急性白血病,其中3例为急性非淋巴细胞性白血病,1例为急性淋巴细胞性白血病。方法自1993～2003年4例急性白血病飞行员接受造血干细胞移植治疗,3例接受自体外周血干细胞或自体骨髓移植,预处理方案为环磷酰胺（CY）／全身照射（TBI）,1例接受半相合异基因骨髓移植,预处理方案为CY／TBI／阿糖胞苷/噻替哌。     

异基因骨髓移植的植入证明

本文对我院1987年12月至1989年11月间进行的9例HLA相合的异基因骨髓移植供受者的植入情况做了分析。我们采用了国际骨髓移植登记处的移植成功指标,及常规的细胞遗传学检查,结果全部患者均有间接的临床植入证据,其中5例有直接的细胞遗传学证据。本文综合文献提示,细胞遗传学分析在移植证明中具有很重要的意义,但其缺陷也是显而易见的。DNA-RFLP的检测可弥补常规方法的缺陷,并获得准确可靠的植入依据。     

非清髓异基因外周血造血干细胞移植后供体细胞植入证据的研究

采用染色体荧光原位杂交（FISH）并结合常规染色体和染色体分带等方法,观察并比较了4例血液病人非清髓异基因外周血干细胞移植（NAPBSCT）后的植入情况。结果4例病人均有不同程度的植入,全部形成混合性嵌合体,其中2例转化为完全植入。统计结果分析表明,FISH分析中期分裂相与间期细胞的结果无统计学差异。与常规染色体检测结果相比较,FISH分析中期分裂相或间期细胞的植入率高,但无统计学差异。但FISH具有操作简单、实验周期短、结果敏感可靠等优点,适合用于性别不合的NAPBSCT后植入证据检测。