自体外周血造血干细胞(APBSC)动员采集及冻存的研究

目的评价自体外周血造血干细胞(APBSC)的动员、采集及冻存方法。方法18例病例中，恶性淋巴瘤16例(NHL14例，HD2例)，睾丸肿瘤2例。病人行诱导化疗完全缓解后，采用大剂量联合化疗加小剂量粒细胞集落刺激因子(G—CSF)进行外周造血干细胞动员。用CS-3000，Plus血细胞分离机采集外周血造血干细胞，将分离的单个核细胞(MNC)经程序降温仪降至-80℃后，冻存-196℃液氮。冷冻前及解冻后分别行MNC计数和粒单系祖细胞集落(CFU—GM)培养。结果动员后外周血WBC及MNC总数明显增加，与动员前比较，差异有显著性。冷冻前后，MNC计数，CFU—GM集落数无明显差异。结论大剂量联合化疗加小剂量G—CSF动员方案是安全有效的。冷冻保存APBSC及复苏过程对细胞损伤较小，值得推广使用。     

环磷酰胺联合G-CSF动员外周血造血干细胞的实验和临床观察

目的评价环磷酰胺(CTX)联合G-CSF(粒细胞集落刺激因子)对自体外周血造血干细胞(PBSC)的动员效果和毒性反应.方法CTX 3.5～4g/m2第1、2天静滴,WBC降至最低点时开始注射G-CSF 4.5(3.5～5)μg/kg@天,至PBSC采集结束.当WBC恢复至(1.9～3.0)×109/L以上,以及MNC(单个核细胞)≥20%～30%和外周血CD34+≥1%时采集APBSC,当累计采集MNC≥2.0×108/kg和CD34+细胞≥2.0×106/kg时停止采集.结果23例患者经CTX+G-CSF动员后第9(7～10)天WBC最低,为0.65(0.25～0.9)×109/L,G-CSF给药开始时间为动员后第10(8～11)天,持续6.5(5～11)天,第13(11～20)天开始采集PBSC,持续2天,采集得MNC 2.5(1.3～8.9)×108/kg,CFU-GM 6.8(2.8～11.6)×105/kg,CD34+细胞4.9(2.5～8.9)×106/kg,1例患者出现心包炎,无其他严重毒性反应;21例接受自体外周血干细胞移植支持下超大剂量化疗均获得满意造血重建.结论CTX联合G-CSF是高效和安全的PBSC动员方案,值得临床广泛应用.     

化疗联合单一剂量rhG-CSF用于自体外周血造血干细胞移植的临床研究

背景与目的:总结广东省干细胞多中心研究协作组自1999年6月至2001年12月间55例自体外周血造血干细胞移植治疗造血系统恶性疾病的资料,对化疗联合单一剂量rhG-CSF用于自体外周血造血干细胞移植前动员及移植后造血重建的效果进行研究和评价。方法:全部病例(急性髓细胞性白血病28例,急性淋巴细胞性白血病9例,非霍奇金淋巴瘤14例,其他4例)采用化疗+重组粒系集落刺激因子(rhG-CSF,格拉诺赛特)联合动员方案,其中白血病患者主要采用EA方案,恶性淋巴瘤患者主要采用以CTX为主的方案。rhG-CSF用量为250μg/d,WBC升至>4×109/L后,连续1～2天采集PBSC。移植后+3天开始使用rhG-CSF250μg/d,并观察造血重建情况。结果:动员所需的时间即自化疗开始至采集的平均时间为(18.08±3.63)天,rhG-CSF平均应用剂量为4.15μg·(kg·d)-1,应用时间平均7.12天。55例患者平均采集1.38次,采集到的MNC细胞数为(4.09±1.69)×109/kg,CD34+细胞平均值为8.5×106/kg,CFU-GM平均为(6.1±5.8)×105/kg。WBC恢复至>1.0×109/L及中性粒细胞绝对值>0.5×109/L的中位天数分别为10天和10.5天,全部移植患者均获满意的造血重建。结论:我们采用的EA和以CTX为主的化疗联合单一剂量rhG-CSF,是一种安全有效的动员自体外周血造血干细胞的方法,单一剂量rh     

供者单采外周血中幼稚粒细胞检测的研究

目的 :探讨异基因外周血干细胞移植 ( Allo-PBSCT)供者经细胞集落刺激因子动员后 ,采集的外周血干细胞 ( PBSC)移植物中的幼稚粒细胞与单个核细胞 ( MNC)及 CD+ 3 4 细胞数之间相关性和移植的剂量标准。方法 :对 6例 Allo-PBSCT供者用 G-CSF或 G-CSF+GM-CSF进行动员 ,于动员前及动员后 ,对外周血及收集的MNC收集物中幼稚粒细胞及 CD+ 3 4 细胞进行检测计数 ,并计算出输给患者每公斤体重的 MNC、幼稚粒细胞及 CD+ 3 4细胞数。结果 :动员后外周血中的幼稚粒细胞与 CD+ 3 4 细胞数同步增加 ,外周血 MNC中幼稚粒细胞数与 CD+ 3 4 细胞数之间有较好的相关性。 6例患者全部植活恢复造血功能 ,并为染色体核型或血型转为供者型所证实。结论 :Allo-PBSCT供者经 G-CSF或 G-CSF+GM-CSF动员之后 ,外周血 MNC中幼稚粒细胞与 CD+ 3 4 细胞数有较好的相关性。因此 ,MNC与幼稚粒细胞数结合可作为 Allo-PBSCT的剂量标准 ,该法检测方便快速 ,稳定性好 ,便于推广     

环磷酰胺联合G-CSF动员慢性粒细胞白血病患者外周血造血干细胞

 目的 评价环磷酰胺（Cy）联合粒细胞集落刺激因子（G-CSF）动员慢性粒细胞白血病（CML）患者外周血造血干细胞的动员、采集效果及不良反应。方法 选择符合诊断的CML患者7例,无心、肺、肝、肾等重要脏器功能损害。动员方案为Cy+人基因重组粒细胞集落刺激因子（rhG-CSF）,于化疗后WBC降至1.0×109／L时开始用rhG-CSF,用CS3000 plus血细胞分离机采集干细胞,-80 ℃低温冰箱冻存,并作单个核细胞（MNC）计数及CD+34细胞测定。结果 Cy平均剂量为4.0（3.0 ~ 5.0）g,rhG-CSF的剂量均为300 μg／d,平均5.8（3 ~ 9）d;其中仅1例患者动员2次,余6例均动员1次;共采集2次,每次循环血量为10 ~ 13 L;采集的MNC达（2.94 ~ 5.45）×108／kg,CD+34细胞数达（2.15 ~ 6.59）×106／kg ;患者能耐受整个动员和采集过程,无一例因化疗的不良反应而中止动员;移植后全部患者均迅速恢复了造血功能。结论 Cy联合G-CSF的动员方案对CML患者是安全、有效的。     

《中国肿瘤临床》文章推荐:普乐沙福用于外周血干细胞动员的研究进展

大剂量化疗联合自体外周血干细胞(PBSC)移植是淋巴瘤和多发性骨髓瘤(MM)的有效治疗手段。PBSC的常规动员方案包括粒细胞集落刺激因子(G-CSF)单用或联合化疗。部分患者使用常规动员方案无法采集到目标剂量的CD34+细胞,无法进行造血干细胞(HSC)移植治疗。因此,针对动员不佳患者以及降低具有危险因素患者动员失败的风险,根据个体情况有效调整动员策略十分必要。     

《中国肿瘤临床》文章推荐:普乐沙福用于外周血干细胞动员的研究进展

大剂量化疗联合自体外周血干细胞(PBSC)移植是淋巴瘤和多发性骨髓瘤(MM)的有效治疗手段。PBSC的常规动员方案包括粒细胞集落刺激因子(G-CSF)单用或联合化疗。部分患者使用常规动员方案无法采集到目标剂量的CD34+细胞,无法进行造血干细胞(HSC)移植治疗。因此,针对动员不佳患者以及降低具有危险因素患者动员失败的风险,根据个体情况有效调整动员策略十分必要。     

自体和供者外周血干细胞动员效果观察

 目的 探讨自体和供者外周血造血干细胞动员的方法及其效果。方法 自体干细胞移植者,采用化疗加G-CSF方案动员,WBC降至最低点又回升至2×109／L以上时,开始皮下注射G-CSF 5 μg·kg-1·d-1到采集结束前1天,采集日予地塞米松（DEX）10 mg／d。当WBC上升到>10×109／L时,用CS 3000 plus或MCS +血细胞分离机采集外周血干细胞,连续采集2 d。6名供者予G-CSF 10 μg·kg-1·d-1皮下注射共6 d,动员第5,6天采集外周血干细胞,采集当天清晨给予DEX 10 mg静脉滴注。结果 自体和供者均连续采集2次,采集单个核细胞（MNC）数分别为（3.72±2.17）×108／kg 和（6.07±1.64）×108／kg ,CD+34细胞总数分别为（6.22±2.38）×106／kg和（13.33±1.72）×106／kg。均无严重不良反应。结论 化疗联合G-CSF方案动员自体外周血干细胞和单用G-CSF进行供者干细胞动员是一种简便、经济、高效、低毒的方法。     

应用细胞集落刺激因子动员外周血干细胞移植治疗白血病研究

本文报告30例外周血干细胞移植,应用细胞集落刺激因子动员干细胞后,采集外周血干细胞进行外周血干细胞移植治疗白血病.男性20例,女性10例,年龄3.7～40岁,急性髓细胞白血病(AML)20例、急性淋巴细胞白血病(ALL)10例,第一次缓解(CR_1)20例,第二次缓解(CR_2)10例.方法:应用动员剂前先联合化疗,待白细胞回升后,采用粒单细胞因子(GM-CSF)动员11例,粒细胞刺激因子(G-CSF)19例、药物剂量3～6μg/kg体重,皮下或静脉注射3～7次,每天1次,在用药后4～7天用血细胞分离机、分高采集2～3次.结果:移植前获得单个核细胞(MNC)数为6.23±2.03×10~8/kg重.GM-CSF数为5.83±0.31×10~4/kg体重CD34~ 细胞5.11±0.61×10~6/kg体重(10例).对照组未动员者15例,分离采集5～7次,获得MNC数1.84±0.83×10~8/kg.GM-CSF数为2.73×10~4/kg.造血功能恢复:白细胞>1.0×10~9/kg中位数时间18天(14～46天),血小板>20×10~9/L为21天(14～64天),骨髓增生活跃所需中位时间为36天(18～90),远     

低剂量粒细胞集落刺激因子动员健康供者造血干细胞的研究

 目的　探讨低剂量（5 μg·kg-1·d-1）粒细胞集落刺激因子（G-CSF）对健康供者CD+34细胞动员的效果及造血干细胞最佳采集时间。方法　对2006年2月至2009年4月108例健康供者给予G-CSF 5 μg·kg-1·d-1,在动员后的第4天至第6天收集标本,检测相应时间点的外周血白细胞（WBC）计数、采集物单个核细胞（MNC）计数、采集物中CD+34细胞的比例、粒-巨噬细胞集落形成单位（CFU-GM）培养。结果　动员后采集物中第4天至第6天CD+34细胞比例分别为（0.71±0.08）%、（1.09±0.09）%、（0.57±0.08）%,第4天至第6天CFU-GM产率分别为：（93.33±44.51）／105 MNC、（124.61±57.85）／105 MNC和（80.25±49.24）／105 MNC。CD+34细胞比例和CFU-GM产率均在第5天达到峰值（P＜0.05）,第4天次之（P＜0.05）,第6天再次之（P＜0.05）。动员后采集物中第4天至第6天CD+34细胞量分别为（3.33±1.36）×106／kg、（4.14±1.67）×106／kg、（2.79±1.47）×106／kg,第5天达到峰值（P＜0.05）,第4天次之（P＜0.05）,第6天再次之（P＜0.05）。108例供者采集2次（第4天、第5天）均可满足移植标准。所有供者均无严重不良反应发生。结论　单一低剂量G-CSF能够有效动员健康供者造血干细胞。动员后于第4、第5天行干细胞采集优于第5、第6天。     

High-dose chemotherapy with autologous peripheral blood stem cell transplantation for the treatment of multiple myeloma refractory to conventional chemotherapy

High-dose chemotherapy with autologous peripheral blood stem cell transplantation was administered to five patients with refractory myeloma. To collect peripheral blood stem cells, apheresis was done by administering doxorubicin 40 mg/m2 on the first day, and etoposide 60 mg/m2 on the first, second, and third days, followed by G-CSF administration to harvest cells. The high-dose chemotherapy consisted of melphalan 60 mg/m2 administered for 4 days and infusion of mononuclear cells. No serious side effects were observed during the clinical course. After transplantation, complete or partial responses were achieved. APBSCT is considered to be a useful method because it had an antitumor effect against multiple myeloma that is refractory to conventional chemotherapy, as well as against multiple myeloma that is sensitive to chemotherapy, and it can be safely performed.     

聚乙二醇重组人粒细胞集落刺激因子在复发难治恶性淋巴瘤自体外周血造血干细胞动员中的应用研究

  目的  比较聚乙二醇重组人粒细胞集落刺激因子（pegylated recombinant human granulocyte colony stimulating factor,PEGrhG-CSF）与粒细胞集落刺激因子（granulocyte colony stimulating factor,G-CSF）在复发难治恶性淋巴瘤自体外周血造血干细胞动员（peripheral blood stem cell mobilization,PBSCM）及自体外周血造血干细胞移植（autologous peripheral stem cell transplantation,APBSCT）后造血重建中疗效及药物经济学差异。  方法  选择2014年7月至2016年10月上海交通大学附属第一人民医院收治的复发难治恶性淋巴瘤患者15例,应用PEG-rhG-CSF动员（试验组）;选择2013年1月至2015年8月上海交通大学附属第一人民医院收治的复发难治恶性淋巴瘤患者15例,应用G-CSF动员（对照组）,进行回顾性分析。  结果  两组患者外周血造血干细胞均动员采集成功,其中试验组和对照组采集物的中位CD34+细胞计数分别为16.2×106/kg和8.9×106/kg（P=0.414）;中位总单核细胞（mononuclear cell,MNC）数量分别为12.4×108/kg和9.9×108/kg（P=0.519）。试验组和对照组的平均动员时间分别为（10.66±1.45）d和（9.33±1.83）d（P=0.234）。动员期间,试验组和对照组的平均粒缺时间分别为（4.20±2.17）d和（3.80±2.04）d（P=0.608）。干细胞回输后,试验组和对照组粒系重建的平均时间分别为（10.14±1.29）d和（10.93±2.69）d（P=0.327）。血小板重建平均时间分别为（10.36±2.27）d和（12.27±3.38）d（P=0.121）。两组在干细胞动员和造血系统重建方面无显著差异。在药物经济学方面,PEG-rhGCSF平均费用明显低于G-CSF,分别为3 960元和（11 479.3±2 401.3）元（P < 0.001）。  结论  PEG-rhG-CSF在复发难治恶性淋巴瘤的自体PBSCM中疗效与传统的G-CSF相当,且可明显降低患者费用,应用前景广泛。      

The administration of 10 microg/kg granulocyte colony-stimulating factor (G-CSF) alone results in a successful peripheral blood stem cell collection when previous mobilization with chemotherapy and hematopoietic growth factor failed.

Some heavily pretreated cancer patients fail to mobilize enough peripheral blood stem cells (PBSC) after stimulation with chemotherapy and hematopoietic growth factors. For these patients the best way to obtain an adequate PBSC collection is unknown. Here we report 6 heavily pretreated cancer patients who failed to mobilize sufficient PBSC after stimulation with chemotherapy and G-CSF 5 microg/kg/day. In these cases, we used G-CSF 10 microg/kg/day alone for six days at least 3 weeks after the last chemotherapy. After three consecutive leukaphereses starting on day 5, five patients had adequate PBSC collections. With 6 days of G-CSF 10 microg/kg/day alone, 2.8 x 10(6) (+/- 1) CD34+ cells/kg were collected. This was significantly higher than the number of CD34+ cells/kg collected after chemotherapy and G-CSF 5 microg/kg 0.3 x 10(6) (+/- 0.1) [P = 0.05]. Four patients received high-dose chemotherapy with PBSC support. Hematologic recovery observed in these patients was as expected. In conclusion, G-CSF 10 microg/kg alone can mobilize progenitor cells into peripheral blood when previous mobilization with chemotherapy and G-CSF 5 microg/kg fails.     

高龄血液恶性肿瘤患者自体外周血造血干细胞动员采集的临床研究

目的探讨高龄血液恶性肿瘤患者外周血干细胞动员采集的疗效及影响因素。方法对32例高龄患者和57例中青年患者经化疗＋生长因子动员后,使用CS3000Plus血细胞分离机（Baxter公司）进行外周血干细胞采集,并进行临床观察和分析。结果所有病例均采集成功。高龄患者动员获得单个核细胞（MNC）数为（6．47±7．04）×10^9／L,中青年患者获得MNC数为（10．89±9．50）×10^9／L,差异有显著性。高龄患者采集获得的MNC及CD34^＋细胞分别为（5．24±1．05）×10^8／kg和（2．74±1．04）×10^6／kg,中青年患者采集获得MNC及CD34^＋细胞分别为（6．71±2．62）×10^8／kg和（4．82±2．62）×10^6／kg,差异具有显著性。高龄患者在采集过程中不良反应发生率明显高于中青年患者。高龄患者与中青年患者移植后造血重建时间相当。结论做好采集前的充分准备,注意并发症的预防和处理,一般会成功地动员采集高龄患者自体外周血造血干细胞。     

Filgrastim fails to improve haemopoietic reconstitution following myeloablative chemotherapy and peripheral blood stem cell rescue.

The morbidity of high-dose chemotherapy has been considerably reduced by the use of autologous peripheral blood progenitor cell reinfusion. Most studies have used myeloid colony-stimulating factors after stem cell reinfusion, making it difficult to determine the relative contribution of each of these variables to the early recovery of blood cells. The financial implications of colony-stimulating factor use are an area of concern as dose intensification in chemosensitive malignancies is increasingly employed. We have studied 19 consecutive patients receiving high-dose chemotherapy with and without filgrastim (Amgen, granulocyte colony-stimulating factor, G-CSF) after stem cell infusion to examine its effect on the kinetics of blood cell recovery, the complications of myelosuppression and the associated costs. Analysis of the two treatment groups reveals that administration of filgrastim 10 micrograms kg-1 day-1 following stem cell reinfusion does not further accelerate haemopoietic recovery, fails to reduce the incidence of neutropenic fever or antibiotic usage and significantly increases the cost of the procedure. The results of this study do not support the routine use of filgrastim after high-dose chemotherapy and peripheral blood stem cell reinfusion.     

紫杉醇联合重组人粒细胞集落刺激因子动员 乳腺癌患者外周血干细胞的效果及影响因素

 目的研究紫杉醇联合重组人粒细胞集落刺激因子（rhG-CSF）动员乳腺癌患者外周血干细胞（peripheral blood stem cell,PBSC）的效果及影响因素分析。方法2006年2月至2009年6月我科收治行紫杉醇动员的26例乳腺癌患者,紫杉醇（PTX,175 mg/m2 持续静脉滴注24 h）化疗后,白细胞降至1.0×109/L左右时使用rhG-CSF 5 μg /(kg·d) 动员至采集结束。并进一步分析患者年龄,化疗后白细胞最低数,采集前各类血细胞数,术后分期以及既往化疗等因素对采集单个核细胞（mononuclear cell,MNC）、CD34+细胞数的影响。结果白细胞计数于紫杉醇化疗后中位7d降至1.0×109/L 左右,皮下注射rhG-CSF中位4d进行外周造血干细胞采集,采集总MNC平均(7.89±1.45)×108/kg,采集总CD34+细胞平均(4.88±1.54)×106/kg。年龄与采集CD34+细胞数显著相关。而其他因素对MNC及CD34+细胞数均无显著影响（P>0.05）。所有患者均未出现严重不良反应。结论PTX（175 mg/m2 持续静脉滴注24h）联合rhG-CSF为转移性乳腺癌患者动员的有效安全方案。患者年龄显著影响CD34+细胞的采集数量。     

Bone marrow reconstitution after high-dose chemotherapy and autologous peripheral blood progenitor cell transplantation: Effect of graft size

BACKGROUND: Peripheral blood progenitor cell transplantation is rapidlyreplacing autologous bone marrow transplantation as hematologicalsupport after high-dose chemotherapy for lymphoma or solid tumors.Controversy exists concerning the number of progenitor cellsrequired for rapid and sustained bone marrow recovery, and asto which of the widely available methods for estimating thisnumber should be employed. METHODS: Forty consecutive patients with solid tumors or lymphomas receivedhigh-dose chemotherapy followed by autologous peripheral stemcell reinfusion. All stem cell harvests had been performed aftermobilization with standard-dose chemotherapy followed by 300µg G-CSF daily. Hematopoietic reconstitution was studiedin relation to pertinent patient characteristics, to the sizeof the graft (in terms of the total number of mononuclear cells(MNC), the number of granulocyte/macrophage colony-forming units(CFU-GM) and the number of CD34⁺ cells, and to the use of G-CSFafter stem cell reinfusion. RESULTS: Both the numbers of CFU-GM and CD34⁺ cells reinfused, but notthose of the MNC, correlated with granu-locyte and plateletrecovery. Patients who received at least 5 x 10⁶ CD34⁺ cells/kgbody weight achieved platelet transfusion independence on day12 after reinfusion (range: day 7–37), significantly earlierthan patients who had received less (p     

Subcutaneous administration of recombinant human granulocyte colony-stimulating factor (KRN8601) in intensive chemotherapy for patients with advanced lung cancer.

The efficacy and toxicity of recombinant human granulocyte colony-stimulating factor (rh G-CSF, KRN8601) given subcutaneously was evaluated in patients with advanced lung cancer undergoing intensive chemotherapy. Twenty-nine and 30 patients with or without prior therapy were enrolled in this study. At dose levels of 50, 90 and 130 micrograms/m2 of rh G-CSF for 14 consecutive days after chemotherapy, the mean neutrophil nadir counts, the mean neutrophil nadir ratios and the duration of neutropenia (days of less than 1000/mm3) were significantly improved. No significant differences were seen in frequency and duration of febrile episodes (greater than 38 degrees C). When rh G-CSF is given subcutaneously, the dose required for an equal effect in alleviating neutropenia is 50% of that required when it is given intravenously. The monocyte counts in the peripheral blood were also significantly increased after chemotherapy cycles with rh G-CSF. The cumulative plasma concentration of rh G-CSF showed a decrement after 7-9 days despite maintenance of the same dose of rh G-CSF for the entire 14 days. In conclusion, 50-130 micrograms/m2 of sc rh G-CSF increased the neutrophil nadir count and shortened the duration of neutropenia in patients undergoing intensive chemotherapy for lung cancer without intolerable side effects.