彩色多普勒超声评价自体外周血干细胞移植治疗糖尿病下肢动脉闭塞症:与血管造影结果吻合吗?

背景:糖尿病下肢动脉闭塞的传统治疗方法如药物、介入等效果不佳,干细胞移植是近几年治疗该病变的新方法,临床取得了较好的效果.评价干细胞移植的治疗效果造影检查损伤大,费用高,所以采用彩色多普勒超声进行下肢动脉无创性检查具有重要的临床价值.目的:应用彩色多普勒超声评价自体外周血干细胞移植后下肢动脉病变的改善情况,并与血管造影结果相比较.方法:纳入确诊糖尿病下肢动脉闭塞症患者41例,经重组人粒细胞集落刺激因子150 μg皮下注射,1次/d进行外周血干细胞动员,第5天用血细胞分离机采集分离干细胞,配成干细胞悬液,将干细胞悬液肌肉注射进行双下肢移植(3×109细胞/肢).干细胞移植后观察3个月至1年,同时进行各项指标的综合评估.结果与结论:干细胞移植后,患肢疼痛、冷感、间歇性跛行、溃疡明显好转,踝臂指数明显升高(P＜0.01),彩色多普勒超声测量足背动脉血流速度明显增加(P＜0.01).移植后下肢动脉管腔血流有不同程度改善,闭塞动脉周围、肌肉内的侧支血管增多;螺旋CT血管造影显示新生侧支血管明显增多.41例患者均未发生并发症和不良反应.提示彩色多普勒超声可准 确、快速地检测和评价干细胞移植后下肢血运改善情况,和血管造影结果相吻合,在评价干细胞移植治疗糖尿病下肢动脉 闭塞症的疗效方面能为临床提供可靠的诊断依据.     

自体外周血干细胞移植治疗下肢缺血性疾病14例

背景:血管病变引起的肢体缺血性疾病不仅仅是肢体动脉主干发生病变,还常常伴有微循环障碍,通常所采用的动脉搭桥或动静脉转流术只能解决主干动脉阻塞,不能改善微循环障碍,因而其临床效果并不十分理想.近年来,基于内皮祖细胞的自体外周血干细胞移植已成成为治疗此类疾病的新办法.目的:观察自体外周血干细胞移植对下肢缺血性疾病的治疗效果.方法:选择2004-09/2006-07在沪州医学院附属医院住院经下肢血管造影确诊的下肢动脉症闭搴患者14例,共23条患肢,临床表现为患肢痛,冷感,间歇件跛行,皮温降低,足背动脉搏动减弱或消失,皮色发生变化及皮肤溃疡,严重者趾或足坏死破溃.采用血细胞分离机采集自身外周血单个核细胞制成干细胞混悬液,于患肢一次性按4cm ×4cm间距做干细胞混悬液肌肉注射,每点注射1mL,沿缺血下肢动脉走行采取多点肌肉注射.12个月后对移植前后临床症状土观指标和辅助检台客观指标进行评估.结果与结论:自体外周血干细胞移植后12个月患者肢体疼痛、患肢冷感明显减轻,皮肤温度升高,间歇跛行距离延长.5例缺血性足溃疡患者的足部创面基本愈合.9例实施了下肢血管造影检查.其中7条患肢侧支血管丰富.末见骨髓动员并发症.1例患者发生外周血单个核细胞移植并发症,患肢移植部位剧烈疼痛,所有疼痛均干移植后第3人缓解.提示自体外周血干细胞移植对于下肢缺血性疾病是一种安全、可行、可选择的治疗方式.     

G-CSF联合化疗动员外周血干细胞过程中某些生物因子的动态变化

目的　探讨IL 8、可溶性血管细胞粘附分子 1 (sVCAM 1 )及可溶性细胞间粘附分子 1(sICAM 1 )在自体造血干细胞动员过程中的变化及其意义。方法　采用酶联免疫吸附实验方法动态分析患者造血干细胞动员过程中血浆IL 8、sICAM 1及sVCAM 1水平的变化 ;通过免疫荧光标记和流式细胞仪检测CD3 4+细胞 ;体外半固体培养CFU GM集落及血细胞计数法观察白细胞和血小板数量变化。结果　①在动员过程中 ,外周血IL 8[(2 4 7.4± 84.2 ) μg L]、sICAM 1 [(530 .3± 2 86 .1 ) μg L]及sVCAM 1[(575 .3± 350 .4) μg L]含量均较动员前和正常人显著升高 (P <0 .0 1 ) ;②患者外周血中IL 8、sVCAM 1水平与CD3 4+细胞和CFU GM集落数呈正相关 (P <0 .0 0 1 )。结论　在自体干细胞动员过程中 ,血浆IL 8和sVCAM 1的含量与患者CD3 4+细胞数和CFU GM集落形成有显著的相关性 ,分析这些生物因子的变化具有临床实用价值     

外周血胞苷脱氨酶活性检测对类风湿关节炎活动期的意义

目的探讨外周血胞苷脱氨酶(CDA)活性检测对类风湿关节炎(RA)活动期的临床意义.方法用分光光度法测定46例RA活动期、32例RA缓解稳定期患者及50名正常对照者外周血CDA活性,同时测定血沉(ESR)和C-反应蛋白(CRP)的浓度.结果RA活动期组患者的外周血CDA活性[(15.36±2.27)U/ml]、CRP[(48.67±22.37)mg/L]和ESR[(86.80±27.63)mm/h]明显高于RA缓解稳定期组[(5.16±1.56)U/ml、(4.83±2.43)mg/L、(14.36±4.11)mm/h]及正常对照组(P均＜0.01),而RA缓解稳定期组外周血CDA活性、CRP和ESR与正常对照组间差异无显著性(P＞0.05);RA活动期组患者的外周血CDA活性与CRP、ESR均呈正相关(r=0.538、0.763,P＜0.01).结论外周血CDA活性检测可作为判断RA活动的指标之一.     

自体骨髓干细胞原位移植对急性心肌梗死后梗死面积和心功能的影响

目的探讨应用粒细胞集落刺激因子( granulocyte-colony stimulating factor,G-CSF)动员自体骨髓干细胞进入心肌梗死部位原位移植以修复梗死心肌组织,对急性心肌梗死患者心肌梗死面积及心功能的影响. 方法 25例初次急性心肌梗死患者在入院后随机分为干细胞原位移植组( n=12)和对照组( n=13).干细胞原位移植组于入院后在常规治疗基础上加用 G-CSF 动员自体骨髓干细胞进行心肌梗死原位移植;对照组按急性心肌梗死常规方法治疗.于入院第 1,28 d描记常规 12导联心电图,采用 Wagner的 QRS波群记分法评价心功能,于入院后 7, 28 d行核素心肌灌注断层显像,测量心肌梗死面积. 结果 G-CSF治疗 4周,干细胞原位移植组 QRS记分值明显降低( 2.14± 0.21),显著低于对照组 (5.07± 0.31)( t=5.2, P< 0.05);心肌梗死面积由 (36± 8) %下降至 (18± 6) %,显著小于对照组 (33± 7)%( t=12.6, P< 0.05). 结论用 G-CSF动员自体骨髓干细胞来修复坏死心肌组织的"干细胞原位移植"疗法,能减小心肌梗死的范围,改善心功能.     

正常人骨髓、脐血及动员后外周血CD^＋34细胞粘附分子的研究

目的探讨正常人骨髓、脐血及动员后外周血CD34+细胞粘附分子的表达及外周血干细胞动员的可能机制.方法采用CD34+MultiSortKit免疫磁珠分离系统,分离纯化出正常人骨髓、脐血及动员后外周血CD34+细胞,流式细胞术检测其纯度,选择与CD34+细胞相关的粘附分子CD44、CD11a、CD18、CD49d、CD54、CD58及CD62L,进行免疫荧光标记及短期液体培养后再行免疫荧光标记,流式细胞术检测.结果动员后外周血CD34+细胞粘附分子表达CD44为(92.7±2.2)%[骨髓(93.1±2.3)%]、CD11a为(56.3±6.0)%[骨髓(61.8±7.8)%]、CD18为(65.2±6.0)%[骨髓(70.6±7.5)%]、CD49d为(39.4±7.2)%[骨髓(66.9±5.1)%]、CD54为(20.9±4.1)%[骨髓(24.1±3.8)%]、CD58为(77.9±5.8)%[骨髓(81.9±5.6)%]及CD62L为(45.9±5.6)%[骨髓(63.9±4.3)%],其表达均较骨髓为低,尤以CD49d和CD62L为著.脐血CD34+细胞CD11a为(55.5±6.5)%、CD18为(66.7±7.5)%、CD44为(90.3±4.0)%、CD49d为(63.7±6.7)%、CD62L为(50.8±5.9)%,其表达亦较骨髓为低,尤以CD62L为著,但脐血CD54的表达[(29.1±4.9)%]较骨髓及动员后外周血为高,尤较动员后外周血为著.结论不同来源CD34+细胞粘附分子表达存在差异,外周血细胞动员的机制可能与粘附分子的表达下调有关.     

正常人骨髓、脐血及动员后外周血CD_(34)~ 细胞粘附分子的研究

目的　探讨正常人骨髓、脐血及动员后外周血CD3 4 细胞粘附分子的表达及外周血干细胞动员的可能机制。方法　采用CD3 4 MultiSortKit免疫磁珠分离系统 ,分离纯化出正常人骨髓、脐血及动员后外周血CD3 4 细胞 ,流式细胞术检测其纯度 ,选择与CD3 4 细胞相关的粘附分子CD4 4、CD11a、CD18、CD4 9d、CD54 、CD58及CD62L,进行免疫荧光标记及短期液体培养后再行免疫荧光标记 ,流式细胞术检测。结果　动员后外周血CD3 4 细胞粘附分子表达CD4 4为 (92 .7± 2 .2 ) % [骨髓 (93.1± 2 .3) % ]、CD11a为 (5 6 .3± 6 .0 ) % [骨髓 (6 1.8± 7.8) % ]、CD18为 (6 5 .2± 6 .0 ) % [骨髓 (70 .6± 7.5 ) % ]、CD4 9d为 (39.4±7 2 ) % [骨髓 (6 6 .9± 5 .1) % ]、CD54 为 (2 0 .9± 4.1) % [骨髓 (2 4.1± 3.8) % ]、CD58为 (77.9± 5 .8) % [骨髓(81.9± 5 .6 ) % ]及CD62L为 (4 5 .9± 5 .6 ) % [骨髓 (6 3.9± 4.3) % ],其表达均较骨髓为低 ,尤以CD4 9d和CD62L为著。脐血CD3 4 细胞CD11a为 (5 5 .5± 6 .5 ) %、CD18为 (6 6 .7± 7.5 ) %、CD4 4为 (90 .3± 4.0 ) %、CD4 9d为 (6 3.7± 6 .7) %、CD62L为 (5 0 .8± 5 .9) % ,其表达亦较骨髓为低 ,尤以CD62L为著 ,但脐血CD54 的表达[(2 9.1± 4.9) % ]较骨     

自体外周血干细胞移植治疗下肢动脉闭塞症的护理与康复

目的探讨对下肢动脉闭塞症的患者采用将分离提取的自体造血干细胞悬液,在双下肢进行肌肉注射移植的护理与康复。方法15例下肢动脉闭塞症患者,给予rhG-CSF皮下注射,每天两次进行外周血动员,第5天用血细胞分离机单采干细胞,进行双下肢肌肉注射移植。观察患者症状改善情况并进行各项指标综合评估。结果术后患者疼痛、冷感、间歇性跛行症状改善,彩色多普勒超声检查提示小动脉血流速度有所增快,有彩色血流。结论提出严密监测生命体征、血糖的变化,进行患肢的护理与康复,严格控制感染,是保证治疗成功的重要因素。     

自体外周血干细胞移植降低下肢缺血性疾病患者截肢率及截肢平面:30例报告

目的:观察自体外周血干细胞移植对下肢缺血性疾病截肢率及截肢平面的影响。方法:选择2003-11/2004-07解放军第四六三医院30例下肢缺血性疾病患者,已行单侧下肢截脚术3侧,均经药物治疗疼痛及创面无改善,经彩色超声多普勒和血管造影检查显示有不同程度的下肢血管闭塞,临床已诊断以闭塞部位确定截肢平面。施行自体外周血干细胞移植治疗,观察移植治疗后截肢率和截肢平面的降低情况,以及经自体外周血干细胞移植治疗后足部皮温,踝脓比、经皮氧分压、疼痛的改善及创面愈合情况。结果:按实际处理分析,30例患者均进入结果分析。①降低截肢率情况:27例患者移植后截肢8例,截肢率为30%(8/27),截肢率降低了70%。②截肢患者降低截肢平面情况:3例已截肢患者行再次截肢,8例移植后截肢,移植术后截肢患者11例中拟截肢平面为大腿6例、小腿2例、足3例,实际截肢平面为大腿3例、小腿4例、足趾3例、趾1例。降低截肢平面者8例。③移植前后患足皮温和经皮氧分压变化情况:移植后患者皮温较移植前明显升高[(325±1.3],(28.1±1.5)℃,P<0.011,移植后经皮氧分压测定较移植前明显增高[(4.0±0.80),(3.2±0.53)kPa,P<0.01]。④移植后3个月局部疼痛及创面愈合情况随访;疼痛消失、剖面愈合11例;疼痛减轻,创面面积减少5例;疼痛减轻,创面面积无明显变化7例;无效7例。结论:外周血干细胞移植治疗下肢缺血性血管病,可促进剖面愈合,降低截肢率和降低截肢平面,无明显副作用及并发症,可望成为一种简单的、有效的治疗下肢动脉缺血性疾病的方法。     

加用亚胺培南-西司他丁的抗生素预防方案对预防造血干细胞移植后早期感染的作用--附12例临床观察

目的了解在常规抗生素预防方案基础上加用亚胺培南-西司他丁对预防移植早期感染的作用.方法观察亚胺培南-西司他丁预防组(观察组,12例)和常规抗生素预防组(对照组,12例)造血干细胞移植患儿移植的早期感染发生情况.结果所有患儿首次感染均发生在中性粒细胞绝对计数超过0.5×10 9/L之前.移植后早期感染最常见为呼吸道感染和口腔炎、胃肠炎等.观察组发生首次感染的时间[(9±5)日]较对照组[(5±2)日]明显推迟;且观察组发生感染时外周血白细胞均数显著高于对照组(P＜0.05).结论移植前在常规抗生素预防方案基础上加用亚胺培南-西司他丁可推迟移植后早期感染的发生时间,对移植早期感染的预防有一定的效果.     

Mobilization of peripheral blood stem cells with paclitaxel and rhG-CSF in high-risk breast cancer patients

Preclinical studies have demonstrated the rapid and efficient mobilization of hematopoietic peripheral blood stem cells (PBSC) in a mouse model using the combination of paclitaxel with recombinant human granulocyte colony-stimulating factor (rhG-CSF). On the basis of these results, a clinical trial was initiated using rhG-CSF with paclitaxel for PBSC mobilization in high-risk breast cancer patients. The mobilized PBSC were evaluated for CD34(+) cell number, mononuclear cell content, and clonogenic potential. One-hundred and seventeen breast cancer patients received paclitaxel (300 mg/m(2)) administered as a 24-h continuous intravenous infusion. Forty-eight hours after completing paclitaxel, rhG-CSF (5 microg/kg) was initiated and continued until completion of PBSC collection. Leukapheresis was initiated once the white blood cell count reached 1.0 x 10(9)/L. Each collection was evaluated for the numbers of mononuclear cells (MNC) and CD34(+) cells. Clonogenic potential was enumerated using colony-forming units-granulocyte-macrophage (CFU-GM) and burst-forming units-erythroid (BFU-E). Patients receiving paclitaxel with rhG-CSF mobilized a large number of mononuclear cells/apheresis (mean, 3.7 x 10(8); range, 3.3-4.1) and CD34(+) cells/apheresis (mean, 7.2 x 10(6); range, 6.1-8.4). The average number of leukophereses needed was 1.8 (mean, range 1.6-2.0). Colony growth was normal with 178.9 x 10(5) and 214.8 x 10(5) colonies counted in CFU-GM and BFU-E assays, respectively. Patients engrafted platelets and neutrophils on day 10 following transplantation. In conclusion, PBSC mobilization with paclitaxel and rhG-CSF results in a large number of mononuclear cells and CD34(+) cells with normal clonogenic potential. The cells engraft normally following high-dose chemotherapy and autologous stem cell transplantation in high-risk breast cancer patients. These results demonstrate that paclitaxel with rhG-CSF is an efficient mobilizing agent in high-risk breast cancer patients.     

重组人白介素11联合粒细胞集落刺激因子动员的自体外周血造血干细胞移植

本研究旨在探索重组人白介素11（rhIL—11）联合重组人粒细胞集落刺激因子（rhG—CSF）动员外周血造血干细胞进行自体外周血干细胞移植的作用。16例预行自体外周血干细胞移植的非霍奇金淋巴瘤及急性髓系白血病患者随机分为实验组（rhIL-11联合rhG—CSF动员）及对照组（rhG—CSF动员），两组均在动员性化疗后血象下降至最低值有回升迹象时应用rhIL—11及rhG—CSF；rhG—CSF5μg/（kg·d）动员中位时间5．5天，rhIL—1150μg/（kg·d）动员中位时间4天；动员后观察外周血白细胞和血小板计数，以及干细胞采集物单个核细胞、CD34^＋细胞、CFU—GM集落数的变化；按常规进行自体外周血干细胞移植后，观察粒细胞及血小板植活时间及单采血小板输注量。结果显示：实验组及对照组动员后外周血白细胞和血小板计数，以及干细胞采集物单个核细胞、CD54^＋细胞及CFU—GM集落数无显著性差异（P〉0．05）。自体外周血干细胞移植后，实验组中性粒细胞数≥0.5×10^9／L的中位时间为10．5天，对照组中为13天．实验组比对照组提前2.5天（P〈0．05）。实验组血小板数≥20×10^9／L的中位时间为11.5天，对照组为13天，实验组比对照组提前1.5天（p〈0．05）。实验组输注单采血小板中住数为3.5单位，对照组为5单位，实验组比对照组减少1．5单位（P〈0．05）。实验组使用动员剂的不良反应主要有低热、乏力、感冒样症状、食欲不振、头晕、肌肉酸痛等，对照组仅出现低热，患者对以上症状均可以耐受，停药后症状自行消失。结论：rhIL—11联合rhG—CSF动员外周血造血干细胞安全有效，在自体外周血干细胞移植后造血重建较快，单采血小板输注量少。     

自体外周血干细胞移植治疗糖尿病下肢缺血效果观察

目的 探讨自体外周血干细胞(PBSC)移植治疗糖尿病性下肢缺血的疗效。方法 应用自体PBSS移植治疗18例30条糖尿病性下肢缺血。采用主观、客观评价指标对疗效进行观察评定。结果 自体PBSC移植后1个月患者疼痛、冷感、麻木症状明显改善,改善率分别为96.7％ (29/30)、100％(30/30)、95.8％ (23/24);间歇性跛行明显缓解,总有效率为76.9％ (10/13)。3个月后踝肱指数(ABI)升高,由术前的0.60±0.11增加到术后的0.71±0.12,差异有统计学意义(t=-6.882,P＜0.01)。93.3％(28/30)的患者皮氧分压不同程度地升高;同时患者的足部感染得到控制,溃疡或足趾坏疽好转或愈合。移植后所有患者均未出现并发症和明显不良反应。结论 自体PBSC移植治疗糖尿病性下肢缺血是一种相对简单、安全、有效的方法。     

Application of peripheral blood stem cells (PBSC) mobilized by recombinant human granulocyte colony stimulating factor for allogeneic PBSC transplantation and the comparison of allogeneic PBSC transplantation and bone marrow transplantation.

Recombinant human granulocyte colony stimulating factor (rhG-CSF)-mobilized peripheral blood stem cells (PBSC) are now widely used for allogeneic PBSC transplantation (alloPBSCT). Large numbers of hematopoietic progenitor cells mobilized by rhG-CSF would be considered equivalent or better than bone marrow (BM) cells and would be used as an alternative to BM for allogeneic hematopoietic stem cell transplantation. The complications associated with the administration of rhG-CSF and apheresis in PBSC collection in formal donors are well tolerated and usually acceptable in the short term but some hazardous adverse events such as splenic rupture and cardiac arrest are reported although the incidence is very low. Protective means and stopping rules for safe donation in the collection of PBSC are established. The characteristics of PBSC were clarified; the expression of some adhesion molecules such as CD49d on CD34 positive cells of PBSC have been shown to be low compared to BM stem cells. In alloPBSCT compared with allogeneic BM transplantation (alloBMT), the incidence and frequency of graft versus host disease (GVHD) is of concern because high number of T lymphocytes are infused in alloPBSCT. The incidence and severity of acute GVHD are not increased but chronic GVHD is higher in alloPBSCT compared with alloBMT. The outcome of alloPBSCT and BMT are almost equivalent and conclusive results regarding survival are not yet available.     

Peripheral blood stem cell collection from healthy donors for allogeneic transplantation

There is great interest in the use of peripheral blood stem cells (PBSC) for allogeneic transplantation, based on the good results seen with autologous PBSC infusion. Reasonable caution exists regarding the use of allogeneic PBSC for transplantation because of donor toxicities due to rhG-CSF administration and the risk of graft-versus-host-disease (GVHD) in the recipient because of the large number of T-cell infused. We present preliminary data on allogeneic PBSC collections and transplantation in ten patients affected by advanced leukemia (eight patients), severe aplastic anemia (one patient) and sickle cell anemia (one patient). Seven donors were HLA-identical siblings, while the other three were mismatched for three, two and one locus, respectively. All donors received rhG-CSF at a dose of 12 micrograms/kg for a mean of 5 days. Leukaphereses were performed with the aim of collecting a minimum of 5 x 10(6)/kg (recipient's weight) CD 34+ cells. Collection timing was determined by monitoring CD 34+ cells in the donor's peripheral blood from the second day of rhG-CSF therapy. The PBSC collections yielded a mean of 10.05 x 10(8) MNCs/kg and of 10.48 x 10(6) CD 34+ cells/kg (recipient's weight). PBSC were immediately infused after collection in patients given myeloablative therapy. Engraftment was observed in each patient at a mean of 13.2 days for an absolute neutrophil count (ANC) more than 0.5 x 10(9)/L and of 26.5 days for a platelet count of more than 20 x 10(9)/L. Eight patients experienced no or moderate acute GVHD, whereas two patients died of grade 4 GVHD, notwithstanding GVHD prophylaxis with cyclosporine and prednisone. Two other patients died of viral and fungal infections, respectively, despite prophylaxis. The remaining six patients are alive between 58 and 430 days after transplant. Our results document that allogeneic PBSC are capable of engraftment after a myeloablative regimen. Controlled trials are necessary to compare the potential benefits of this approach with the results obtained in allogeneic bone marrow transplantation.     

新型外周血CD34+细胞动员剂--抗CD49d单克隆抗体的实验研究

为了探讨外周血干细胞动员的新途径，用抗CD49d单克隆抗体和rhG-CSF及二者联合给小鼠皮下注射，动态观察小鼠外周血的白细胞总数和CD34^ 细胞数的变化，并将各种动员方法所获得的干细胞分别进行干细胞移植。结果发现，给予动员剂后小鼠的外周血白细胞总数和CD34^ 细胞比例明显升高，以rhG-CSF和抗CD49d单克隆抗体联合给药效果最佳。移植后各组小鼠均获造血重建，以联合动员组造血恢复速度最快。结论：抗CD49d单克隆抗体能有效动员小鼠外周血干细胞，与rhG-CSF具有协同作用。     

Peripheral blood stem cells differ from bone marrow stem cells in cell cycle status,repopulating potential,and sensitivity toward hyperthermic purging in mice mobilized with cyclophosphamide and granulocyte colony-stimulating factor

Peripheral blood stem cells (PBSCs) are increasingly used in autologous stem cell transplantations. We investigated the mobilizing effect of a combined cyclophosphamide (CTX) and granulocyte colony-stimulating factor (G-CSF) treatment on progenitor cells (STRA) and primitive stem cells (LTRA) in normal and splenectomized CBA/H mice. This combined treatment not only resulted in mobilization but also in expansion of hematopoietic stem cell subsets. The latter phenomenon was somewhat suppressed in splenectomized animals, but in these mice an enhanced mobilization of STRA and LTRA cells into the peripheral blood was observed. Furthermore, we studied the engraftment potential of mobilized PBSCs. Mice transplanted with PBSCs engrafted significantly better compared to mice transplanted with bone marrow stem cells from control and mobilized mice. The repopulation curve was characterized by a less-deep nadir indicating that the differences occur during the initial phase after transplantation. Contamination of autologous PBSC transplants with malignant cells is noticed frequently and is the basis for urging the use of purging modalities. Here we used hyperthermia and found that the mobilized progenitor cells in peripheral blood are more resistant to hyperthermia than those in the bone marrow (i.e., a survival of 11 +/- 5% after 90 min at 43 degrees C for peripheral blood progenitors, compared to 0.5 +/- 0.4% in bone marrow of mobilized animals and 1.6 +/- 0.5% in normal animals, respectively). Hyperthermic purging does not eliminate the superior repopulating features of a PBSC graft, as is demonstrated by an increased median survival time of lethally irradiated mice transplanted with purged PBSCs. In conclusion, our data demonstrate that CTX + G-CSF-mobilized PBSCs have an enhanced engraftment potential concomitantly with a decreased cycling activity and hence a decreased hyperthermic sensitivity. These findings support the use of these mobilized PBSCs for autologous stem cell transplantation and strengthen the basis for using hyperthermia as a purging modality.     

FLAG巩固治疗急性髓系白血病对自体外周血造血干细胞动员的影响

本研究探讨以大剂量阿糖胞苷（Ara—C）联合氟达拉滨（Flud）和粒细胞集落刺激因子（G—CSF）即FLAG方案巩固治疗急性髓系白血病（AML）对自体造血干细胞动员的影响。对15例AML患者在诱导缓解后采用FLAG方案巩固治疗（氟达拉滨，50mg／d，第1-5天；Ara—C2g／（m^2·d），第1—5天；G—CSF300μg／d，皮下注射，化疗前1天至中性粒细胞〉1．0×10^9／L）。15例中男10例，女5例，中位年龄36（14—51）岁，13例为初发AML，2例为复发难治AML。12例FLAG观固2个疗程，3例巩固3个疗程。动员方案为：9例为FLAG，6例大剂量足叶乙甙（VP16）＋G—CSF。结果表明：15例患者中11例（73．3％）被证实有足够的造血干细胞（CD34’细胞〉2．0×10^6／kg），CD34细胞中位数为3．52×10^6／kg[（2．2—4．6）×10^6／kg]。在4例仅采集到足够的单个核细胞（MNC），而CD34^＋细胞含量却较低。结论：2个疗程的FLAG巩固治疗对AML患者的造血干细胞影响不明显，毒副作用不明显且不影响自体外周血造血干细胞的动员。     

Peripheral Blood Stem Cell Mobilization and Engraftment after Autologous Stem Cell Transplantation with Biosimilar rhG-CSF

Introduction

Biosimilar versions of filgrastim [recombinant human granulocyte colony-stimulating factor (rhG-CSF)] are now widely available. To date, biosimilar rhG-CSF has demonstrated a comparable quality, safety and efficacy profile to the originator product (filgrastim [Neupogen^®], Amgen Inc., CA, USA) in the prevention and management of neutropenia. Biosimilar rhG-CSFs have also been used to induce peripheral blood stem cell (PBSC) mobilization in patients undergoing autologous stem cell transplantation (AHSCT). The authors have examined the effectiveness of a biosimilar rhG-CSF (Zarzio^®, Sandoz Biopharmaceuticals, Holzkirchen, Germany) in two retrospective studies across two medical centers in Hungary.

Methods

In Study 1, 70 patients with hematological malignancies scheduled to undergo AHSCT received chemotherapy followed by biosimilar rhG-CSF (2 × 5 μg) for facilitating neutrophil, leukocyte, and platelet engraftment. In study 2, 40 additional patients with lymphoid malignancies and planned AHSCT received chemotherapy followed by biosimilar rhG-CSF for PBSC mobilization. The effectiveness of treatment was assessed by the average yield of cluster of differentiation (CD) 34+ cells and the number of leukaphereses required.

Results

In Study 1 (patients undergoing AHSCT), the median age was 56 years and most patients were male (60%). The conditioning regimens were mainly high-dose melphalan (n = 41) and carmustine (BiCNU^®, Bristol-Myers Squibb, NJ, USA), etoposide, cytarabine and melphalan BEAM (n = 21). Median times to absolute neutrophil and leukocyte engraftment were 9 (range 8–11 days) and 10 (8–12) days, respectively. Median time to platelet engraftment was 10.5 days (7–19 days). In Study 2, the patients’ median age was 54 years and the majority (57.5%) were female. The median time interval between day 1 of mobilizing chemotherapy and first leukapheresis was 12 (9–27) days. In the autologous PBSC grafts, the median number of CD34+ cells harvested was 5.2 × 10⁶/kg (2.22–57.07 × 10⁶/kg). The median yield of CD34+ cells per leukapheresis product was 2.47 × 10⁶/kg. In total, 58 leukaphereses were performed in 40 successfully harvested patients.

Conclusions

In line with previous studies with originator rhG-CSF, the findings of this study indicate that biosimilar rhG-CSF following AHSCT is effective and generally well tolerated in the engraftment setting. In addition, biosimilar rhG-CSF is comparable to the originator rhG-CSF in terms of kinetics of PBSC mobilization and yield of CD34+ cells. In conclusion, the authors have demonstrated that the use of biosimilar rhG-CSF is effective and safe in autologous PBSC mobilization and engraftment after AHSCT.     

无关供者24例外周血干细胞动员和采集

目的 总结无关供者外周血千细胞(PBSC)动员和采集情况.方法 24例无关供者给予重组人粒细胞集落刺激因子(rhG-CSF)5 μμg·kg-1·d-1,每天皮下注射,第4、5天或5、6天用CS-3000PLUS血细胞分离机采集外周血干细胞,计数采集物中单个核细胞(MNC)和CD34+细胞.结果 所有供者均安全顺利完成...