低剂量环磷酰胺对肺癌肿瘤血管生成的影响

目的研究低剂量环磷酰胺(CTX)对肺癌肿瘤血管生成的影响,观察其抑瘤效果及对生存期影响.方法以荷Lewis肺癌的C57/BL6小鼠为模型,分别给予低剂量CTX、最大耐受剂量(MTD)CTX灌胃,免疫组化染色测定肿瘤微血管密度(MVD)、血管内皮生长因子(VEGF)和核增殖抗原表达基因(Ki-67),观察小鼠生存期.结果低剂量CTX治疗组小鼠肿瘤MVD值较对照组和MTDCTX治疗组均降低,同时低剂量CTX组VEGF及Ki-67表达也降低(P＜0.05);低剂量CTX治疗组小鼠生存期较MTD CTX治疗组延长(P＜0.05).结论持续低剂量CTX给药方式可抑制肺癌肿瘤微血管生成,具有良好抑瘤效果,动物生存期延长.     

ICE和CCE方案治疗晚期肺腺癌的疗效比较

目的探讨异环磷酰胺(IFO)联合卡铂(CBP)、足叶乙甙(Vp-16)与环磷酰胺(CTX)联合CBP、Vp-16治疗晚期肺腺癌的效果.方法应用IFO联合CBP、Vp-16(IFO组)和CTX联合CBP、Vp-16(CTX组)随机对照治疗晚期肺腺癌患者61例,其中IFO组32例,CTX组29例.治疗结束后4周评价疗效.结果 IFO组近期有效率为31.3%(10/32),CTX组为24.1%(7/29),两组比较差异无显著性(P>0.05).IFO组中位生存期7.5个月(2～24个月),CTX组7.0个月(1～18个月).IFO组镜下血尿发生率为12.5%(4/32),CTX组为0(P<0.05).其他毒性相似(P>0.05).结论 ICE和CCE 方案对晚期肺腺癌均有较好的疗效,且IFO对晚期肺腺癌的疗效较CTX为优.     

低剂量环磷酰胺对抑制性T细胞的选择性作用

从1958年Arnold等人合成环磷酰胺(CTX)以来,作为一种抗癌药物已在临床上广泛应用。随后,人们发现CTX 对机体的免疫功能具有抑制作用。近年来,人们对CTX 选择性灭活抑制性T 细胞(Ts)的作用做了不少的研究,发现在一定条件下,低剂量CTX 对动物和人的免疫功能具有放大作用,并可增强载瘤宿主的排斥反应。CTX 对迟发超敏反应的放大作用自从Maguire 等人1967年首先在豚鼠上发现CTX 对二硝基氯苯(DNCB)所致迟发性超敏反应(DTH)具有加强作用以来,不少学者对此做了进一步研究。Askenase等研究了CTX 对绵羊红细胞在不同种系的小鼠所致的DTH 影响及抗体生成的作用。先用CTX 给小鼠注射,二天后静脉给予不同剂量     

甲基莲心碱增强环磷酰胺诱导小鼠Lewis肺癌细胞凋亡的作用

目的评价甲基莲心碱(Nef)对环磷酰胺(CTX)诱导小鼠Lewis肺癌细胞凋亡作用的影响。方法Lewis肺癌移植瘤小鼠40只,雄性,体重18～22g,随机分成CTX+Nef、CTX、Nef、NS4个组,每组10只。通过检测瘤重抑制率及瘤细胞凋亡率,观察Nef联合CTX对小鼠Lewis肺癌的疗效和诱导癌细胞凋亡的影响。结果CTX+Nef、CTX组的瘤重抑制率分别为80.08%、58.95%,明显高于Nef组(6.78%),P<0.01;而CTX+Nef组较CTX组也有增高(P<0.05);流式细胞术检测CTX+Nef、CTX组的癌细胞凋亡率分别为53.50%、25.92%,明显高于Nef、NS组(7.09%,5.63%),P<0.01;CTX+Nef组也高于CTX组(P<0.05);TUNEL法检测CTX+Nef、CTX组的癌细胞凋亡指数分别为(10.24%±11.08%),(5.36%±6.24%),较Nef、NS组明显增加(1.45%±1.98%,1.03%±1.65%),P<0.05;CTX+Nef组的凋亡指数较CTX组也有明显增加(P<0.05)。结论甲基莲心碱能增强环磷酰胺诱导的小鼠Lewis肺癌细胞凋亡作用,且两者具有协同效应。     

美洲大蠊提取物CⅡ-3对肝癌H22荷瘤小鼠作用研究

目的 美洲大蠊提取物CⅡ-3在体内外有抑制肿瘤生长和改善免疫功能的作用.本研究在前期研究的基础上观察CⅡ-3单药对比联合环磷酰胺(cycolophosphamide,CTX)对小鼠肝癌H22移植性实体瘤的治疗效果,探讨C Ⅱ-3在肿瘤治疗中的作用.方法 建立Balb/c小鼠H22腋下实体瘤模型,并将80只小鼠随机分为对照组、CTX组(20 mg/kg)、CTX +CⅡ-3联合给药组(CTX 20 mg/kg,CⅡ-3 50、100和200 mg/kg)、CⅡ-3给药组(50、100和200 mg/kg).连续给药12 d后,测定其抑瘤率脏器指数,外周血细胞数量,T、B淋巴细胞转化功能及NK细胞杀伤活性.结果 对照组的瘤块质量为(1.21±0.28) g,CTX组为(0.73±0.27) g,CTX联合C Ⅱ-3低、中、高剂量给药后的瘤块质量为(0.40±0.21)、(0.43±0.11)和(0.41±0.19) g,C Ⅱ-3低、中、高剂量组的瘤块质量分别为(0.93±0.39)、(0.94±0.31)和(0.96±0.16) g,与对照组和CTX组相比,联合给药组肿瘤生长速度明显减慢,差异有统计学意义,F=8.916,P<0.05.CTX组白细胞的数量为(1.56±0.64)×109 L-1,CTX联合C Ⅱ-3低剂量组为(4.47±0.91)×109 L-1,显著改善外周血象,F=2.476,P<0.05.对照组小鼠肝脏指数为(6.101±0.412) mg/10 g,CTX组为(5.112±0.463) mg/10 g,中剂量C Ⅱ-3联合CTX给药后肝脏指数可高达(5.882±0.548) mg/10 g,减轻了CTX对肝脏的损伤,F=4.225,P<0.01.对照组小鼠脾脏指数为(0.659±0.148) mg/10 g,CTX组的脾脏受到严重损伤,其指数为(0.314±0.092) mg/10g,联合给药后可以显著地减轻CTX对脾脏的损伤,其指数为(0.569±0.033) mg/10 g,F=5.667,P<0.05;对照组小鼠的胸腺指数为(0.060±0.018) mg/10 g,给予CTX后小鼠的脏器受到严重的损伤,胸腺指数为(0.024±0.004) mg/10 g,C Ⅱ-3联合CTX给药后胸腺指数为(0.056±0.014) mg/10 g,减轻了CTX对胸腺的损伤,对胸腺有一定的保护作用,F=4.729,P<0.05.荷瘤小鼠在给予CTX治疗后,T、B淋巴细胞的转化功能及NK细胞杀伤力显著地降低(P<0.05,P<0.01),C Ⅱ-3联合CTX可提高T、B淋巴细胞的转化功能及NK细胞杀伤力(P<0.05,P<0.01),从而增强机体的免疫功能.结论 C Ⅱ-3联合CTX治疗H22荷瘤小鼠可提高抑瘤率,具有提高CTX治疗效果的作用,其增效作用是通过提高T、B淋巴细胞的转化功能及NK细胞杀伤力实现的.除此之外C Ⅱ-3还具有减毒作用,其减毒作用是通过改善白细胞、红细胞和血小板的数量,提高脏器指数实现的.     

广西眼镜蛇蛇毒细胞毒素的抗肿瘤作用

目的 了解广西眼镜蛇毒细胞毒素(CTX)的抗肿瘤作用。方法 采用MTT法检测CTX对人鼻咽癌细胞株(CNE)、淋巴瘤细胞株(YAC)、S180癌细胞株、人宫颈癌细胞株(HELA)和卵巢癌细胞株(Ho8990)体外细胞毒作用，同时应用动物移植性肿瘤的体内试验法，观察CTX对S180载瘤小鼠(S180)和CNE的抑瘤作用及其生命延长率。结果 CTX对上述体外培养的肿瘤细胞有明显的细胞毒效应，作用24h的半数抑制浓度分别为1．04，0．50，1．82，1．76和1．05μg／ml；CTX对小鼠肿瘤有明显的抑制作用，抑瘤率为12％～37％，呈明显量效关系。结论 CTX对体外培养的癌细胞株有较强的抑制作用，对小鼠移植性瘤有一定抑制作用。     

激素与细胞毒药物联合治疗晚期乳腺癌

本文报告87例绝经后晚期乳腺癌患者应用己烯雌酚、环磷酰胺和5-氟脲嘧啶(DES+CTX+FU)联合治疗的效果,并与单用DES 或仅用CTX+FU 治疗的疗效进行对比。还分析经用DES 后疗效较高的患者再加用OTX+FU 能否提高疗效,并对联合用药(DES+CTX+FU)与序贯用药(DES→CTX+Fu)孰优孰劣进行了探讨。患者按雌激素受体(ER)情况分为高含量组(ER     

环磷酰胺联合照射后半相合淋巴细胞对小鼠肝癌移植瘤的抑制作用

目的:观察不同剂量环磷酰胺(cyclophosphamide,CTX)预处理联合5 Gy60Co照射的半相合淋巴细胞输注(hap-loidentical lymphocyte infusion,HLI)对小鼠肝癌移植瘤的抑制作用。方法:以皮下接种Hepa1-6肝癌细胞的BABL/c×C57BL杂交F1代雌性小鼠(表型为H-2b/d)为受鼠,以BALB/c×C3H杂交F1代雌性小鼠(表型为H-2d/k)为MHC半相合的供者,分PBS组、CTX 80 mg/kg+5 Gy照射HLI组、CTX 200 mg/kg+5 Gy照射HLI组、CTX 300 mg/kg+5 Gy照射HLI组、5 Gy照射HLI组,每组5只小鼠;观察各组小鼠瘤块生长和大小,检测受鼠体内的嵌合状态及移植物抗宿主病(graft-versus host disease,GVHD)的发病情况。结果:80、200 mg CTX联合HLI组小鼠瘤体积小于PBS组[(1.25±0.24)、(1.38±0.31)vs(2.03±0.24)cm3,P<0.01],小鼠生存时间显著长于PBS组[48 d(39 d,55 d)、40 d(35 d,48 d)vs 35 d(18 d,39 d),P<0.05];80mg CTX联合HLI组的抑瘤作用强于单纯HLI组[(1.25±0.24)vs(1.76±0.40)cm3,P<0.05];300 mg CTX联合HLI组和单纯HLI组无明显抑瘤作用。各治疗组小鼠均未出现GVHD。80、200 mg CTX联合HLI组小鼠嵌合度低于300 mg CTX联合HLI组,且消失时间明显早于后者。结论:低剂量CTX联合输注经照射的半相合供者淋巴细胞可获得较好的抗小鼠肝癌移植瘤的作用,CTX剂量增加后抗肿瘤作用并未增强。     

中药乳宁Ⅱ号对Ca761小鼠移植性乳腺癌的抑制作用

目的 中药乳宁Ⅱ号对Ca761荷瘤小鼠抑瘤作用及对化疗药物抗肿瘤影响的研究。方法 对Ca761荷瘤小鼠进行为期3周的灌胃,腹腔注射环磷酰胺(CTX),通过抑瘤率及胸腺、脾重来判断乳宁Ⅱ号对小鼠移植瘤的抑制作用及对CTX抗肿瘤作用的影响。结果 乳宁Ⅱ号对Ca761荷瘤小鼠肿瘤大小、瘤重抑制率分别为28.29％、26.28％,CTX组为46.5％、47.62％,乳宁Ⅱ号 CTX组为66.77％、68.86％。结论 (1)中药乳宁Ⅱ号有较好的抑瘤作用。(2)中药乳宁Ⅱ号对CTX抑瘤有增效作用。(3)中药乳宁Ⅱ号有缓解CTX对免疫功能的抑制作用。     

五色灵芝提取液与环磷酰胺小鼠灌胃抑瘤作用的观察

目的:探讨五色灵芝提取液与环磷酰胺(CTX)合用对小鼠移植性动物肿瘤的抑制作用。方法:小鼠随机分成四组,每组10只。阴性对照组以生理盐水(NS)20m l/(kg.d)灌胃,阳性对照组以环磷酰胺(CTX)20mg/(kg.d)灌胃。第1实验组:灵芝液组20g/(kg.d)灌胃;第2实验组:灵芝液20g/(kg.d) 环磷酰胺(CTX)20mg/(kg.d)灌胃。各组均于接种后24小时开始灌胃给药,连续10天。均于末次给药后24小时处死,计算抑瘤率。结果:各组抑瘤率分别是:第一实验组为(47.41~60.42)%,第二实验组为(78.02~80.23)%。各实验组的抑瘤作用与阴性对照组相比较,差异均有显著性意义(P<0.001)。灵芝液与环磷酰胺(CTX)联合组与单用灵芝液组或单用环磷酰胺(CTX)组比较,差异均有显著性意义(P<0.05)。结论:五色灵芝提取液与环磷酰胺(CTX)联合使用具有协同抑瘤作用。     

环磷酰胺或足叶乙甙联合粒细胞集落刺激因子动员自体外周血造血干细胞的对照研究

背景与目的:通过动员采集获得高质量的自体外周血造血干细胞(autologousperipheralbloodstemcell,APBSC)是造血干细胞移植成功的关键,环磷酰胺(cyclophosphamide,CTX)联合重组人粒细胞集落刺激因子(recombinedhumangranulocytecolony-stimulatingfactor,rhG-CSF)是APBSC经典的动员方案,足叶乙甙(etoposide,VP-16)联合rhG-CSF是近年来应用的另一个动员方案。本研究的目的是比较上述两种动员方案对恶性淋巴瘤和生殖细胞肿瘤患者APBSC的动员效果。方法:共有52例恶性实体瘤患者,其中CTX方案组26例,剂量为CTX3.5g/m2加rhG-CSF5μg·kg-1·d-1;VP-16方案组26例,VP-16的剂量随机采用1000mg/m2或1500mg/m2加rhG-CSF5μg·kg-1·d-1。两组均在白细胞(whitebloodcell,WBC)降至最低点时开始皮下注射rhG-CSF,直至采集结束前一天。当CTX组WBC恢复到2.5×109/L、VP-16组WBC恢复到5.0×109/L以上时开始连日采集APBSC,当累计采集的单个核细胞(mononuclearcell,MNC)≥5×108/kg或CD34+细胞≥2×106/kg时停止采集。患者经预处理后回输采集到的APBSC。比较两组动员采集过程中的血液学指标变化、采集细胞数量、造血重建时间、不良反应等。结果:CTX组患者化疗后外周血中WBC和血小板(platelet,PLT)降至最低值的时间明显早于VP-     

足叶乙甙联合重组人粒细胞集落刺激因子动员自体外周血干细胞的临床研究

目的　观察足叶乙甙 (Vp 16 )联合重组人粒细胞集落刺激因子 (rhG CSF)对恶性实体瘤患者自体外周血造血干细胞 (APBSC)的动员效果 ,并寻找Vp 16合适的给药剂量。方法　按照入组的先后顺序 ,将 30例患者随机分成A、B两组 ,每组 15例。A组Vp 16的给药剂量为 10 0 0mg/m2 ,B组为15 0 0mg/m2 。白细胞 (WBC)降至最低点时开始皮下注射rhG CSF 30 0 μg/d ,直至采集结束前一天。WBC恢复到 5 .0× 10 9/L以上时开始连日采集APBSC ,当累计采集的单个核细胞 (MNC)≥ 5× 10 8/kg或CD34 细胞≥ 2× 10 6/kg时停止采集。结果　Vp 16给药后 ,A、B两组患者外周血中WBC和中性粒细胞绝对值 (ANC)的最低值及最低值出现的时间 ,差异均无显著性。两组rhG CSF给药的开始时间和给药次数、APBSC采集的开始时间和采集次数差异均无显著性 ;在APBSC采集时的循环血量、血流速度和采集时间相同的情况下 ,每次APBSC采集的细胞数量和总量差异亦无显著性 ,B组Vp 16引起的某些毒副反应略重于A组 ,但两组间差异无显著性。结论　Vp 16联合rhG CSF是一种安全、高效的APBSC动员方法 ,15 0 0mg/m2 与 10 0 0g/m2 的Vp 16均可获得满意的APBSC动员采集效果。     

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     

Successful mobilization of Ph-negative blood stem cells with intensive chemotherapy + G-CSF in patients with chronic myelogenous leukemia in first chronic phase

The aim of the study was to investigate the feasibility of mobilizing Philadelphia chromosome negative (Ph-) blood stem cells (BSC) with intensive chemotherapy and lenograstim (G-CSF) in patients with CML in first chronic phase (CP1). During 1994-1999 12 centers included 37 patients <56 years. All patients received 6 months' IFN, stopping at median 36 (1-290) days prior to the mobilization chemotherapy. All received one cycle of daunorubicin 50 mg/m2 and 1 hour infusion on days 1-3, and cytarabine (ara-C) 200 mg/m2 24 hours' i.v. infusion on days 1-7 (DA) followed by G-CSF 526 microg s.c. once daily from day 8 after the start of chemotherapy. Leukaphereses were initiated when the number of CD 34+ cells was >5/microl blood. Patients mobilizing poorly could receive a 4-day cycle of chemotherapy with mitoxantrone 12 mg/m2/day and 1 hour i.v infusion, etoposide 100 mg/m2/day and 1 hour i.v. infusion and ara-C 1 g/m2/twice a day with 2 hours' i.v infusion (MEA) or a second DA, followed by G-CSF 526 microg s.c once daily from day 8 after the start of chemotherapy. Twenty-seven patients received one cycle of chemotherapy and G-CSF, whereas 10 were mobilized twice. Twenty-three patients (62%) were successfully (MNC >3.5 x 10(8)/kg, CFU-GM >1.0 x 10(4)/kg, CD34+ cells >2.0 x 10(6)/kg and no Ph+ cells in the apheresis product) [n = 16] or partially successfully (as defined above but 1-34% Ph+ cells in the apheresis product) [n = 7] mobilized. There was no mortality during the mobilization procedure. Twenty-one/23 patients subsequently underwent auto-SCT. The time with PMN <0.5 x 10(9)/l was 10 (range 7-49) and with platelets <20 x 10(9)/l was also 10 (2-173) days. There was no transplant related mortality. The estimated 5-year overall survival after auto-SCT was 68% (95% CI 47 - 90%), with a median follow-up time of 5.2 years.We conclude that in a significant proportion of patients with CML in CP 1, intensive chemotherapy combined with G-CSF mobilizes Ph- BSC sufficient for use in auto-SCT.     

Sequential Changes in Stem Cell Markers in Peripheral Blood and Leukapheresis Samples after Injections of Recombinant Human Granulocyte Colony-stimulating Factor in Patients with Urogenital Malignant Solid Tumors: A Preliminary Study

In order to evaluate the mobilization effect of recombinanthuman granulocyte colony-stimulating factor (rhG-CSF) on peripheralblood stem, cells (PBSCs), rhG-CSF was given to patients withurogenital malignancy before chemotherapy. Markers for the stemcells, such as colony forming unit-granulocyte/macrophage (CFU-GM)and burst forming unit-erythrocyte (BFU-E), were sequentiallymonitored in peripheral blood and leukapheresis samples. Fivepatients, including a 13-year-old boy, were given 5 µg/kgrhG-CSF subcutaneously: the pediatric case for four consecutivedays and the adult cases for six consecutive days (53–72years of age). None of the patients had received chemotherapywithin the four weeks prior to the start of the rhG-CSF series.PBSC collections were performed on the fifth day in the pediatriccase and on the fifth and seventh days in the adult cases. Progenitorcells were monitored by methylcellulose cell culture techniques.CFU-GM on day 5 of the rhG-CSF series in peripheral blood increased14- to 53-fold compared with samples taken immediately beforethe series. CFU-GM in the leukapheresis products on day 5 wasgreatest (70 x 10³/kg) in the pediatric case and least (14 x10³/kg) in the oldest patient's case. The totals of the CFU-GMcollected by two phereses in the adult cases were 21–73x10³/kg and the totals of CD34 positive cells were 0.6 to 1.4x10⁶/kg.The data suggest rhG-CSF to induce sufficient PBSCs for bonemarrow rescue into the peripheral blood without any precedingchemotherapy. The patient's age may, however, be a contributoryfactor in using this method.     

The use of peripheral-blood hematopoietic progenitors mobilized with standard-dose chemotherapy plus granulocyte-colony-stimulating factor to support multicyclic dose-intensive chemotherapy for advanced breast-cancer

This study was aimed at determining: (a) the degree of mobilization of peripheral blood hematopoietic progenitors (PBSC) induced by a single course of standard-dose chemotherapy (CT) followed by G-CSF and the feasibility and safety of the administration of multiple courses of intensified CT with repeated PBSC reinfusions; (b) the relationship between the number of mononuclear cells (MC) in S-phase of the cell cycle (as evaluated by DNA flow cytometry, FCM), the CRT-GM and the CD34(+) cells in the leukapheresis product. Six patients with metastatic breast cancer received a course of standard FEC (5-FU 600 mg/m(2), epirubicin 75 mg/m(2), cyclophosphamide, CTX, 600 mg/m(2), day 1) followed by G-CSF (5 mu g/kg twice a day, from day 3 until leukapheresis), which served as both initial treatment for their disease as well as the PBSC mobilization technique. Collected PBSC were fractionated and reinfused, without G-CSF, following each of further 5 subsequent intensified FEC (HD-FEC: 5-FU 750 mg/m(2), epirubicin 100 mg/m(2), CTX 1,000 mg/m(2)) courses planned at 21-day intervals. The individual hematopoietic reconstitution curves showed superimposable profiles for all patients, and the leukaphereses were performed between days 7 and 10 after the first CT course. A median of 18.8x10(9) (10.4-35.6) MC, 9.3 (2.6-23.3) CD34(+) cells x 10(6)/kg body weight and 9.8 (1.6-27.3) CFU-GM x 10(4)/kg body weight were collected from each patient (with 1 or 2 phereses). All patients received the planned 5 courses of HD-FEC followed by PBSC reinfusion, without experiencing haematological cumulative toxicity >WHO grade 3 for WBC and >grade 2 for PLT. No >grade 3 non-hematological toxicity was recorded. There were no treatment-related delays in CT administration so that the delivered average relative dose-intensity (ARDI) was 1.65. A good correlation was seen between the percentage of MC in S-phase and the number of CFU-GM (R(2)=0.566, p<0.0065) or the number of CD34(+) cells (R(2)=0.625, p<0.0031) in the leukapheresis product. A single course of standard FEC+G-CSF is effective in mobilizing sufficient amounts of PBSC to support 5 additional courses of HD-FEC, which could represent an alternative to single, myelo-suppressive CT programs. DNA analysis by FCM should be further investigated as a rapid method for PBSC quantification, since proliferating MC and CFU-GM were closely related.     

自体造血干细胞移植支持下BEAC方案治疗晚期复发恶性淋巴瘤

目的：报告 20例恶性淋巴瘤在自体造血干细胞移植支持下接受超大剂量化疗的初步治疗经验 ,评价所用外周血造血干细胞 (peripheral blood progenitors,PBPC )动员方案的动员效果,预处理方案的远期疗效和耐受性,以及回输后造血重建情况。方法： 20例复发、晚期恶性淋巴瘤中, 1例复发霍奇金病 (Hodgkin s disease,HD),19例非霍奇金淋巴瘤 (non- Hodgkin s lymphoma,NHL）。经常规化疗获缓解后, 3例采用自体骨髓移植 (autologous bone marrow transplantation,ABMT), 17例采用自体外周血干细胞移植 (autologous peripheral blood stem cell transplantation,APBSCT);动员方案为环磷酰胺 (CTX)3 500 mg/m2＋ G- CSF 3.5～ 5μ g/kg＋地塞米松 10 mg,预处理方案为 BEAC(CTX 3 600～ 4 000 mg/m2,Vp- 16 1 200 mg/m2,BCNU 300 mg/m2和 Ara- C 1 500～ 2 000 mg/m2),化疗结束后 24～ 48 h回输自体造血干细胞。结果： ABMT病人回输单核细胞 (MNC)1.3(1.0～ 1.7)× 108/kg, APBSCT病人回输 MNC 1.8(1.0～ 4.4)× 108、 CFU- GM 5.1 (1.9～ 9.6 )× 105/kg和 CD34＋细胞 2.9(1.9～ 8.7)× 106/kg。回输造血干细胞后均获快速造血功能重建,中性粒细胞 (ANC)≥ 0.5× 109/L时间为 9(6～ 17)天,血小板≥     

High-versus standard-dose filgrastim (rhG-CSF) for mobilization of peripheral-blood progenitor cells from allogeneic donors and CD34(+) immunoselection.

PURPOSE: The efficacy of a high- versus a standard-dose filgrastim (recombinant human granulocyte colony-stimulating factor, or rhG-CSF) regimen to mobilize peripheral-blood progenitor cells (PBPCs) for allogeneic transplantation was investigated in 75 healthy donors. PATIENTS AND METHODS: From December 1994 to December 1997, 75 consecutive donors (median age, 38 years; range, 17 to 67 years) were assigned to two different schedules of rhG-CSF for PBPC mobilization. Fifty donors received 24 microg rhG-CSF/kg body weight (BW) divided into two daily subcutaneous injections (two doses of 12 microg, group A), whereas 25 were treated with 10 microg rhG-CSF once daily (group B). Apheresis was started on day 4 in group A and on day 5 in group B. Target CD34(+) cell numbers in apheresis products were >/= 4 x 10(6)/kg recipient BW. RESULTS: Cytokine priming and collection of PBPCs were equally well tolerated in both groups. Significantly higher CD34(+) cell numbers in group A with 3. 7 x 10(6)/kg recipient BW/apheresis (0.47 x 10(6)/L apheresis) compared with 2 x 10(6)/kg recipient BW/apheresis (0.25 x 10(6)/L apharesis) in group B were obtained (P <.05). Using standard aphereses (median, 9 L), two doses of 12 microg rhG-CSF/kg allowed collection of >/= 4 x 10(6)/kg CD34(+) cells with two aphereses (range, one to three) in group A versus three aphereses (range, one to six) in group B (P <.015). Donor age, sex, and BW influenced the collection of CD34(+) cell numbers: in particular, significantly higher apheresis results were obtained in donors younger than 40 years compared with donors older than 40 years of age (P <.05). In 65 CD34(+) selection procedures using avidin-biotin immunoabsorption columns (Ceprate SC System, CellPro, Bothell, WA), a median CD34(+) purity of 53%, CD34(+) recovery of 40%, and the collection of 2 x 10(6)/kg CD34(+) cells/selection were achieved. In group A with higher CD34(+) cells/kg/apheresis, CD34(+) purity, recovery, and cell yields were 60%, 45%, and 2.3 x 10(6)/kg/selection, respectively, as compared with 48%, 31%, and 0.7 x 10(6)/kg in group B (P <.05). CONCLUSION: Our results demonstrate that twice daily rhG-CSF (two doses of 12 microg/kg BM) compared with once daily rhG-CSF (10 microg/kg BW), in addition to being well tolerated, significantly improves PBPC mobilization, allows the collection of higher numbers of CD34(+) cells with one or two standard aphereses, and facilitates subsequent selection procedures in healthy allogeneic donors.     

聚乙二醇化重组人粒细胞集落刺激因子用于多发性骨髓瘤自体造血干细胞动员的研究

目的探讨聚乙二醇化重组人粒细胞集落刺激因子(PEG-rhG-CSF)用于多发性骨髓瘤(MM)患者外周血造血干细胞动员(PBSCM)的效果及药物经济学价值。方法回顾性分析2015年1月至2017年10月在吉林大学第一医院和中国医学科学院血液病医院住院治疗的91例初治MM患者资料。根据患者意愿,采用大剂量化疗结合皮下注射PEG-rhG-CSF或重组人粒细胞集落刺激因子(rhG-CSF)进行干细胞动员,分别为42、49例。分析两组动员后采集单个核细胞(MNC)数、采集物CD34+细胞数、动员中最高中性粒细胞(mANC)数、动员的费用以及移植后白细胞和血小板植入时间。结果PEG-rhG-CSF组和rhG-CSF组的中位采集MNC数分别为5.86×10⁸/kg[(1.08~24.54)×10⁸/kg]和6.61×10⁸/kg[(0.83~33.80)×10⁸/kg],差异无统计学意义(U=883.00,P=0.245);PEG-rhG-CSF组的中位采集物CD34+细胞数高于rhG-CSF组,分别为5.56×10⁶/kg[(0.94~19.90)×10⁶/kg]和4.82×10⁶/kg[(1.12~14.61)×10⁶/kg],差异有统计学意义(U=732.00,P=0.038)。PEG-rhG-CSF组动员期间中位mANC数较rhG-CSF组低,分别为20.50×109/L[(7.26~61.30)×109/L]和32.08×109/L[(6.92~69.99)×109/L],差异有统计学意义(U=490.00,P=0.001)。自体干细胞移植(ASCT)后,PEG-rhG-CSF组白细胞计数(WBC)恢复至1.0×109/L的时间较rhG-CSF组短[(11.59±1.98)d比(12.93±2.83)d],差异有统计学意义(t=-2.395,P=0.019);PEG-rhG-CSF组血小板计数(Plt)恢复至20.0×109/L的时间也较rhG-CSF组有缩短趋势[(12.86±2.62)d比(14.80±5.47)d],但差异无统计学意义(t=-1.749,P=0.085)。PEG-rhG-CSF组的动员总费用与rhG-CSF组差异无统计学意义[(21405.47±7365.98)元比(22976.83±10264.34)元,t=-0.721,P=0.474]。结论PEG-rhG-CSF联合大剂量化疗是MM患者PBSCM的有效方案,其动员费用与rhG-CSF相当。PEG-rhG-CSF可能是MM患者PBSCM的更好选择。     

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。