异基因外周血干细胞移植治疗慢性髓系白血病17例

目的探讨异基因外周血干细胞移植治疗慢性髓系白血病(CML)的临床疗效及移植并发症的情况.方法对17例CML患者进行异基因外周血干细胞移植,其中慢性期15例,加速期、急变期各1例.供者均为同胞兄妹,16例为HLA全相合,1例为2个位点不合.预处理方案采用BU/CY方案,应用CsA、MMF和短程MTX预防GVHD.结果全部患者造血功能均获得快速重建,中性粒细胞绝对值≥0.5×109/L的平均时间为移植后+11(+9～+13)天,血小板≥20×10/9L的平均时间为移植后+16(+14～+21)天.16例HLA全相合移植中发生急性Ⅰ度GVHD 1例(6.25%),慢性GVHD 4例(25.00%);1例HLA 2个位点不合移植患者发生急性Ⅱ度GVHD.中位随访时间19个月(2～43个月),15例CP期患者均无病生存,2例AP期及BP期患者分别于移植后9个月及6个月死亡.结论Allo-PBSCT是治疗CML的有效方法,CsA/MMF/MTX三联方案可以有效地预防急性GVHD.     

人白细胞抗原不合异基因造血干细胞移植治疗难治性重型再生障碍性贫血的临床研究

目的 探讨人白细胞抗原(HLA)不合供者异基因造血干细胞移植治疗难治性重型再生障碍性贫血(SAA)的可行性.方法 2008年5月至2009年9月,对7例SAA患者进行了8次移植,其中女3例,男4例,中位年龄14.5岁(1.4～29.0岁);从确诊至移植的中位时间为13个月(5.5 ～87.0个月);移植前均接受过1种以上的免疫抑制剂[抗胸腺细胞球蛋白(ATG)、环孢素(CsA)等]治疗3个月以上无效,完全依赖输血生存.移植前仅有2例无感染并发症,其余5例均有1个以上感染部位.预处理方案:第1例首次非血缘移植时采用环磷酰胺(CTX)加200 cGy的全身放疗,另有1例非血缘患者及1例半相合患者均采用CTX+ATG的预处理方案,其他5例(次)患者均采用CTX+氟达拉滨(Flu)+ ATG方案.造血干细胞来源:非血缘全合外周血供者2例,HLA8/10相合供者1例,均来自中华骨髓库;HLA半相合供者5例(来自母亲供者3例、父亲及胞兄各1例),均为3/6位点相合.移植物抗宿主病(GVHD)预防:自预处理开始即加用CsA及吗替麦考酚酯(MMF);移植后短暂应用甲氨蝶呤(MTX).结果 3例非血缘移植的患者中,1例稳定植入,2例被完全排斥,其中1例在排斥后半个月(+50天)再次由其母亲提供髓血混合干细胞进行移植,稳定植入,已随访11个月余,血象完全恢复正常,嵌合体检查100％供者型造血.半相合移植母供子患者中,1例白细胞和血小板稳定植入,但于+52天死于颅内真菌感染,另有1例+3天死于肺部感染.父供子的患者+11天死于败血症.胞兄供妹的患者到+30天时血象无改进,2次骨髓穿刺检查均无植入倾向,家长选择放弃治疗.GVHD发生情况:植入成功者均有Ⅰ～Ⅱ度皮肤排异,但都得到有效控制.结论 对无理想供者、免疫抑制治疗失败的SAA患者,采用CTX+Flu+ATG预处理方案行HLA不合的异基因造血干细胞移植是一种选择,值得进一步探索.     

激素治疗ABO血型不合异基因造血干细胞移植后纯红细胞再生障碍性贫血--1例报告及文献复习

目的 探讨异基因造血干细胞移植后纯红细胞再生障碍性贫血(PRCA)的发生机制。方法 报道1例病例并进行文献复习。结果 1例诊断为骨髓增生异常综合征(MDS—RAEBT)组织配型相合、ABO血型不合的患者进行造血干细胞移植获得成功，但移植后出现PRCA，经红细胞生成素治疗失败，改用激素治疗后血红蛋白恢复正常。结论 免疫因素及a抗体是ABO血型不合造血干细胞移植后致PRCA的最可能原因；糖皮质激素(泼尼松)是治疗ABO血型不合造血干细胞移植后PRCA的有效、经济、安全的药物。     

ABO血型不合异基因造血干细胞移植后单纯红细胞再生障碍性贫血二例并文献复习

 【摘要】　目的　分析ABO血型不合异基因造血干细胞移植（allo-HSCT）后发生单纯红细胞再生障碍性贫血（PRCA）造血功能紊乱的发病机制,了解造血干细胞移植过程中特殊的免疫功能状态。方法　回顾性分析2例急性髓系白血病（AML）行allo-HSCT后发生PRCA患者的临床资料并复习相关文献。结果　停用环孢素A（CsA）、加用糖皮质激素、丙种球蛋白等治疗该患者后血型转化,造血恢复。结论　ABO血型不合allo-HSCT易出现红系造血延迟及PRCA,应用糖皮质激素、丙种球蛋白治疗有效。     

髓腔内造血干细胞移植联合供者淋巴细胞输注对GVHD和GVL的影响

 目的　观察髓腔内供者淋巴细胞输注（IBM-DLI）对急性淋巴细胞白血病小鼠异基因外周造血干细胞移植（allo-PBSCT）后移植物抗宿主病（GVHD）和移植物抗白血病效应（GVL）的影响。方法　雌性C57BL／6小鼠为受鼠建立白血病模型,接受全身照射(TBI)预处理后,输注雄性BABL/C小鼠来源的经rhG-CSF动员后的外周造血干细胞,分别经尾静脉（IV）和髓腔内进行DLI,2天后腹腔注射环磷酰胺（CTX）,观察移植后小鼠的生存状态和GVHD发生情况,应用流式细胞仪检测受鼠体内嵌合体形成和CD+4 CD+25调节性T细胞（Treg）比例。结果　IBM-DLI组的受鼠GVHD发生比例和死于白血病的小鼠比例均较IV-DLI组明显减低（P＜0.01）;移植后第7天各组受鼠骨髓中供鼠来源的细胞比例均在95 ％以上;与IV-DLI组比较,脾细胞中Tregs比例在IBM-DLI组明显升高（P＜0.01）。结论　与IV-DLI相比,IBM-DLI有利于减轻GVHD的发生,并保留GVL效应,其机制可能与受鼠体内Tregs细胞比例增高有关。     

急性淋巴细胞白血病异基因造血干细胞移植后合并急性大疱剥脱性Ⅳ度皮肤移植物抗宿主病一例并文献复习

 【摘要】　目的　探讨急性淋巴细胞白血病异基因造血干细胞移植（allo-HSCT）后合并急性大疱剥脱性Ⅳ度皮肤移植物抗宿主病（GVHD）的临床治疗效果。方法　1例急性淋巴细胞白血病患者行allo-HSCT,预处理方案为TBI+Cy,回输HLA相合同胞供者外周血造血干细胞。应用环孢素A（CsA）、短程甲氨蝶呤（MTX）预防GVHD。结果　患者移植后+15天造血重建,+32天诊断为急性大疱剥脱性Ⅳ度皮肤GVHD,给予无菌环境保护、加强局部皮肤护理,应用甲泼尼龙（MP）+MTX联合CsA控制GVHD,未发生皮肤感染。结论　急性淋巴细胞白血病allo-HSCT后合并急性大疱剥脱性Ⅳ度皮肤GVHD临床少见,发展迅速,早期联合用药及局部预防感染等可取得满意疗效。     

异基因造血干细胞移植治疗白血病的临床研究

目的探讨异基因造血干细胞移植治疗白血病。方法脐血移植治疗儿童白血病3例,异基因外周血造血干细胞移植治疗白血病3例。结果6例患者完全植入,+15～+25天白细胞(WBC)>1.0×109/L,+35天～+51天血小板(Plt)>20×109/L。例1出现急性GVHDⅠ度,例5出现急性GVHDⅣ度,例6出现肝静脉闭塞综合征(VOD)、急性GVHDⅠ度、出血性膀胱炎(HC),例2移植后6个月复发,放弃治疗死亡。余5例正常生活或工作。结论异基因造血干细胞移植治疗白血病是安全有效的方法。     

异基因造血干细胞移植治疗恶性血液病20例临床疗效观察

 【摘要】　目的　探讨异基因造血干细胞移植（allo-HSCT）治疗恶性血液病的疗效,观察造血重建、移植物抗宿主病（GVHD）发生、移植相关并发症及疾病的转归。方法　回顾性分析allo-HSCT治疗恶性血液病患者20例,男15例,女5例,中位年龄39岁（8～59岁）。供者于移植前3 d采用重组人粒细胞集落刺激因子（rhG-CSF）行干细胞动员;预处理方案：人类白细胞抗原（HLA）亲缘全相合移植患者采用改良Bu／Cy方案;HLA亲缘不全相合者采用改良Bu／Cy+ATG方案;急性T淋巴细胞白血病（T-ALL）和多发性骨髓瘤（MM）患者采用Flu+Bu／Cy方案。GVHD预防方案：麦考酚酸酯+环孢素+短疗程甲氨蝶呤。结果　20例患者均成功获得造血重建,中性粒细胞计数＞0.5×109／L的中位时间为13 d（12～17 d）,血小板＞20×109／L的中位时间为16 d（12～23 d）,且供者CD+34 细胞采集量＞2.5×106／kg（受者体质量）或单个核细胞采集量＞5.0×108／kg（受者体质量）所移植的患者造血重建较快。12例供受者血型不合,移植后未出现严重溶血反应;11例（55 %）发生急性GVHD（aGVHD）,包括Ⅰ度4例,Ⅱ度4例,Ⅲ度2例,Ⅳ度1例,均经治疗后好转。移植后所有患者均达到完全缓解（CR）,中位随访6个月（2～14个月）,1例白血病患者移植后5个月复发死亡,1例移植后4个月因自行停用环孢素发生自身免疫性溶血、慢性GVHD（cGVHD）、多器官衰竭死亡,其余患者仍处于CR状态。结论　allo-HSCT是治疗恶性血液病的有效方法。造血重建与采集物中造血干细胞的数量密切相关。ABO血型不合不是移植的障碍。复发、GVHD、感染是移植后死亡的重要原因。     

非清髓异基因外周造血干细胞移植治疗老年重型再障报告

目的 :探讨非清髓异基因外周造血干细胞移植 (NAST)治疗老年重型再生障碍性贫血 (SAA)的方法及疗效。方法 :采用非清髓预处理的异基因外周造血干细胞移植治疗老年 SAA患者1例。供受者 HL A配型及红细胞 ABO血型完全相合。预处理方案主要由环胞霉素 A(Cs A)、抗淋巴细胞球蛋白 (ATG)和环磷酰胺组成。用环胞霉素 A和霉酚双酯 (MMF)预防移植物抗宿主病(GVHD)。采用 STR- PCR定量方法检测供者细胞植入情况。结果 :该例老年 SAA患者顺利度过移植后造血抑制期 ,于移植后第 8天外周血 WBC升至 0 .8× 10 9/ L,第 14天血象三系恢复 ,于移植后第 14天、30天、90天及 180天时检测供者细胞植入率均为完全植入。患者未出现移植物抗宿主病 ,现己无病存活 31个月。结论 :非清髓异基因外周造血干细胞移植简便安全 ,并发症少 ,疗效好 ,为老年 SAA的治疗提供了新手段     

移植物抗宿主病对26例血液肿瘤患者异基因造血干细胞移植后长期生存的影响

背景与目的:移植物抗宿主病(graft-versus-hostdisease,GVHD)是异基因造血干细胞移植的一个主要并发症,亦是影响移植结果的重要因素。一些研究显示,不管是急性GVHD或慢性GVHD,都伴随有较强的移植物抗白血病(graft-versus-leukemia,GVL)作用,这种正向效应与降低异基因造血干细胞移植后白血病复发率及延长受者无病生存密切相关。本研究探讨GVHD的发生及其对异基因造血干细胞移植结果的影响。方法:回顾分析1995年3月至2005年10月26例血液肿瘤患者接受异基因造血干细胞移植术后GVHD的发生、肿瘤复发及生存情况,分析GVHD与血液肿瘤复发率、生存率的关系。结果:异基因造血干细胞移植后中位随访时间为20个月(2～127个月),20例患者术后发生GVHD(76.9%),其中1例受者复发(1/20),6例未出现GVHD的受者3例复发(3/6),两组复发率比较差异有显著性(P<0.05);移植后无病生存16例,死亡10例,Kaplan-Meier生存曲线示3年无病生存率为60%;发生GVHD的受者其无病生存率(15/20)较无GVHD受者(1/6)高(log-rank=7.30,P<0.05),发生GVHD时移植患者发生死亡的风险明显下降(RR值为0.20,P<0.05)。20例发生GVHD的受者,经治疗17例达完全缓解(completeresponse,CR),3例未达CR。17例CR受者中,无病生存15例;而未达CR的3例受者则无一例生存,两组生存率比较差异有显著性(P<0.05)。结论:GVHD是影响异基因造血干细胞移植结果的重要因素。GVHD治疗效果与移植受者无病生存密切相关,早期识别急性GVHD并予及时处理是治疗成功的关键。     

Prognostic Significance of Inflammation-associated Blood Cell Markers in Nonmetastatic Clear Cell Renal Cell Carcinoma

ObjectivesOur objective was to evaluate the effect of the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), and red blood cell distribution width (RDW) on the survival outcomes of nonmetastatic clear cell renal cell carcinoma (ccRCC).Materials and MethodsWe accessed our single-center, urologic-oncologic registry to extract the data for patients who had undergone nephrectomy for nonmetastatic ccRCC. The optimal cutoff for these markers was determined using X-tile software, and survival analyses using Cox regression were performed.ResultsA total of 687 patients had undergone nephrectomy. The optimal cutoffs for NLR, PLR, LMR, and RDW were 3.3, 210, 2.4, and 14.3%, respectively. The NLR, PLR, LMR, and RDW were significantly associated with a larger pathologic tumor size, and stage, more aggressive Fuhrman grade, and the presence of tumor necrosis. After adjusting for age, baseline Eastern Cooperative Oncology Group, pathologic tumor and nodal stage, and Fuhrman grade, only PLR remained an independent prognostic marker for both cancer-specific survival (hazard ratio, 2.69; 95% confidence interval, 1.36-5.33; P = .004) and overall survival (hazard ratio, 2.19; 95% confidence interval, 1.36-3.50; P = .001). When the PLR was included with the Leibovich score and University of California, Los Angeles, integrated staging system, the Harrell’s c-index increased from 0.854 to 0.876 and 0.751 to 0.810, respectively, for cancer-specific survival at 5 years after nephrectomy. When risk stratified by the Leibovich risk group and UCLA integrated staging system, PLR was a significant prognostic factor only within the intermediate- to high-risk groups.ConclusionsPLR is a robust prognostic marker in nonmetastatic ccRCC that clearly outperforms other inflammatory indexes in those who had undergone nephrectomy. However, its prognostic effect was limited in the low-risk category of ccRCC.     

Cell kinetics

Cell kinetic concepts have pervaded radiation therapy since the early part of the 20th century and have been instrumental in the development of modern radiotherapy. In this review, the fundamental radiobiological concepts that have been developed based on cell kinetic knowledge will be revisited and discussed in the context of contemporary radiation therapy. This will include how the proliferation characteristics, variation in sensitivity during the cell cycle and the extent of radiation-induced cell cycle delay translate into a variable time for the expression of damage, how cell kinetics interacts with hypoxia and how the response to fractionated radiation schedules is influenced by cell kinetics in terms of repair, redistribution, reoxygenation and repopulation. The promise of combining radiation with new biologically targeted agents and the potential of non-invasive positron emission tomography imaging of proliferation are areas where cell kinetics will continue to influence radiotherapy practice.     

Cell Size Following Irradiation in Relation to Cell Cycle

The cell volume of Ehrlich ascites tumour cells was studied following a radiation dose of 5.0 Gy. The cell volume increased 12 to 30 hours after irradiation by about 20 per cent, was normal at about 50 hours, and increased again at 72 hours. In order to explain these changes the composition of the cells in cell cycle was studied. In addition, the cell volume of irradiated cells from the various parts of the cell cycle, separated by centrifugal elutriation, was measured. The changes in the mean cell volume of unseparated cells could be explained by variations in the cell cycle composition of the cell population. Irradiated cells from the various parts of the cell cycle did not deviate from the volume of non-irradiated cells. The cell volume doubled during the cell cycle. This increase was, however, not linear.     

Inhibition of Glioma Cell Proliferation by Neural Stem Cell Factor

Summary Neural stem cells (NSC) have unique differentiation-, proliferation-, and motility properties. To investigate whether they secrete factors that interfere with the proliferation of glioma cells, we grew glioma cells in conditioned medium (CM) obtained from cultures of neurospheres including neural stem / progenitor cells (NSPC) isolated from embryonic (E14)- or adult mouse brain or fetal human brain. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and BrdU-labeling assays showed that CM from NSPC (NSPC/CM) contained factor(s) that inhibited the proliferation of glioma cells by 28–87%. Filter-fractionation of NSPC/CM revealed that the 50,000–100,000 nominal molecular weight limit (NMWL) fraction contained the inhibitory activity. On the basis of these observations we transplanted 203G glioma cells and/or NSPC into the intrathecal space of the cisterna magna of mice to investigate whether NSPC interfere with the proliferation of glioma cells in vivo. Mice transplanted with both 203G and NSPC survived significantly longer than did mice transplanted only with 203G. We concluded that NSPC secrete factor(s) that may control glioma cell proliferation.     

High Occurrence of Non-Clear Cell Renal Cell Carcinoma in Oman

It is conventionally accepted that renal cell carcinoma (RCC) occurs in older patients and the clear cell type is the most common histology. However, ethnic variations exist and this study was carried out to determine the epidemiological pattern of RCC in Oman. Ninety RCC patients who presented to a tertiary care center in the Sultanate of Oman from 2010 to 2014 were studied. The main findings were that the median age of presentation was low, more patients presented with localized stage, and there was a higher incidence of non-clear (especially papillary) histology. Data from other Gulf countries and possible reasons for the different profile are discussed.     

Changes in Cell Characteristics Due to Culture Conditions in Cell Lines From Human Small Cell Lung Cancer

Eight cultured cell lines were established from human smallcell lung cancers. Every cell line showed the morphologicaland biochemical characteristics of small cell cancer. Changesin cell characteristics were observed in many of these celllines when culture conditions were changed: "oat cell type"changed to "intermediate cell type" and vice versa when serum-freemedium was changed to serum-supplemented medium; a deficiencyof vitamin A in the medium caused a change to squamous cellsand vice versa; and a tumor promoter (teleocidin B) enhancedthe adherence of these cells to the surface of plastic culturedishes. These findings provide evidence that many small celllung cancer cell lines can change their morphology with changesin the environment of the cells.     

Inhibition of Natural Killer Cell Cytotoxicity by Cell Growth-related Molecules

Certain MHC class I molecules on target cells are known to inhibit the cytotoxic action of NK cells. By using monoclonal antibody (mAb) Cho-1, we have found inhibitory non-MHC class I cell surface molecules that are noncovalently-associated with 200 kDa and 40 kDa antigens. Poly I-C-induced rat NK cells were not cytotoxic to rat fetus-derived fibroblast WFB cell line. In contrast, NK cells were cytotoxic to H- ras oncogene-induced transformants of WFB, W14 and W31. FACS analysis indicated that mAb Cho-1 reacts with WFB, but not with W14 and W31 cells. Thus, this antigen may disappear concomitantly with cell growth and transformation. Cho-1 antigens were also expressed on other NK-resistant lines, such as mouse BALB3T3 fibroblast, EL-4 lymphoma and human fibroblast HEPM. However, they were not expressed on NK-sensitive mouse YAC-1 and H- ras transformant (Brash) of BALB3T3 cells. Furthermore, treatment of target cells with IFN-γ clearly induced the cell surface expression of Cho-1 antigens, and conferred a resistance to NK cytolysis on target cells. These data strongly suggest that Cho-I antigen expression may correlate with target cell susceptibility to NK cells. Indeed, treatment of NK-resistant WFB as well as HEPM cells with F(ab')₂ fragments of mAb Cho-1 resulted in the acquisition of susceptibility to NK cytolysis. Cho-1 antigens may be novel molecules that regulate the NK resistance of cells.