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-     

中剂量环磷酰胺为主的联合化疗加同一剂量G-CSF动员恶性血液病患者自体外周血干细胞

目的:观察中剂量环磷酰胺(CTX)为主的联合化疗加G蛳CSF对恶性血液病患者自体外周血造血干细胞(APBSC)的动员效果。方法:31例患者接受中剂量CTX 2.2 g/m2(1.8 g/m2~3.0 g/m2)联合VP16(600 mg ~ 800 mg)或Ara蛳C(1.0 g/m2 ~ 2.0 g/m2)化疗,WBC降至最低值后开始皮下注射G蛳CSF 300 μg/d直至采集结束。WBC≥(3.0~5.0)×109/L时开始采集,当单个核细胞(MNC)累计≥3.8×108/kg或CD+34细胞≥2.0×106/kg时停止采集。结果:采集次数为(2.9±1.0)次,G蛳CSF持续应用时间为(7.4±2.0)d,采集到的MNC细胞数为(5.53±2.54)×108/kg,CD+34细胞数为(9.46±7.24)×106/kg,CFU蛳GM(46.02±70.58)×104/kg。全部移植患者造血功能均获满意重建。结论:中剂量CTX为主的联合化疗加同一剂量G蛳CSF对血液病患者的APBSC动员是安全、有效的。     

自体外周血造血干细胞的动员和采集及冷冻保存研究

目的 评价自体外周血造血干细胞的动员和采集及冷冻保存效果。方法 20例病人采用大剂量化疗加刺激因子动员自体外周血干细胞(APBSC)后用CS—3000血细胞分离机和程控降温仪进行了65次APBSC采集和冷冻保存。结果 经化疗 rhG-CSF动员后采集的PBSC总数、CD34~ 细胞总数和CFU—GM总数不同病人相差较大,分别为MNC5.56±2.00×10~8/kg,CD34~ 23.25±41.90×10~6/kg,CFU—GM 21.68±15.39×10~4/kg。化疗后平均15.1天,用rhG—CSF7.9天CD34~ 细胞达峰值。经冷冻保存的干细胞回输后均使病人造血重建,采集与回输的PBSC数与造血重建时间相关。结论 本研究APBSC动员和采集及冷冻保存的效果肯定,APBSCT后全部病人造血重建,移植成功。     

预防性应用rhG-CSF的随机自身对照研究

目的 :探讨预防性应用rhG CSF在肿瘤化疗中的临床意义。方法 :采用随机自身交叉对照的方法 ,将化疗患者分成AB和BA两组 ,A(周期 )组为预防组 ,在化疗结束 4 8小时后预防性应用rhG CSF 5 μg/kg ,皮下注射 ,连用 5～ 1 4天 ;B(周期 )组为对照组 ,在WBC总数≤ 4 0× 1 0 9/L时 ,应用rhG CSF ,剂量用法同A组。比较化疗第 2 1、2 8序日时的WBC总数的差异。结果 :预防组WBC(平均值 )在整个化疗期间均在正常值 (4 0× 1 0 9/L)以上 ,波动幅度相对较小 ;对照组则于化疗第1 4序日低于正常 ,持续低于正常的中位时间约 7天左右。但在 2 1、2 8序日两组的WBC总数并无统计学差异 (P >0 0 5 )。两种治疗方法对维持WBC的正常无显著性差异 (P >0 0 5 )。结论 :尚无足够的证据说明预防性应用rhG CSF可以作为化疗患者的常规使用 ,需要临床进一步研究     

化疗后24小时与血液学毒性增至Ⅱ度以上时皮下注射rhG-CSF的疗效对比

目的　分析基因重组人粒细胞集落刺激因子 (rhG -CSF)在化疗后 2 4h与血液学毒性降至Ⅱ度以下时开始给药的临床疗效。方法　采用随机分组法 ,将 160例患者随机分成A组和B组。A组 :化疗后 2 4h即刻皮下注射rhG -CSF、连续 3天 ;B组 :血液学毒性增至Ⅱ度以上时皮下注射rhG -CSF连续 3天。结果　A组与B组比较 ,A组白细胞 (WBC)及中性粒细胞 (ANC)下降程度低 ,持续时间短 ,化疗延迟率较低 ,化疗延迟时间较短 ,2组不良反应相比较无显著性差异 (P >0 .0 5 )。结论　化疗 2 4h后给药可减轻化疗所致WBC及ANC下降的程度及缩短其持续时间 ,保证下 1次化疗的顺利进行     

改良CVP联合rhG—CSF动员方案外周血干细胞移植治疗血液肿瘤及实体瘤41例

目的：研究改良CVP联合rhG—CSF方案对血液肿瘤和实体瘤41例患者自体外周血干细胞移植（APBSCT）动员及造血重建效果。方法：2001年3月至2006年3月采用改良CVP联合rhG—CSF动员方案，完成APBSCT41例（血液肿瘤32例，实体瘤9例），平均年龄39．6岁（18岁～67岁）。WBC升至4．0×10^9／L左右采集单个核细胞（MNC）并计数MNC和CD34^＋细胞数；预处理结束48h～72h回输MNC。结果：动员期间患者WBC均降至1．0×10^9／L以下，PLT 40×10^9以下。34例1次采集成功，7例（双次移植5例）作第2次采集。采集MNC数0．9×10^8／kg～8．3×10^8／kg（2．8±2．0×10^8／kg），CD34^＋细胞1．1×10^6／kg～9．4×10^6／kg（3．2±2．6×10^6／kg）。预处理后所有病例均达到骨髓抑制，WBC恢复到1．0×10^9／L时间为＋8～＋16d（平均＋11．3d）；38例PLT恢复到50×10^9／L时间为＋13～＋22d（平均＋16．8d），3例P1月恢复延迟，最长＋35d。随访15～65个月，持续完全缓解19例（46．3％），部分缓解或好转13例（31．7％），总有效率78．0％，无效9例（22．0％），无1例发生移植相关死亡（其中5例带瘤生存，17例死亡）。结论：改良CVP联合rhG—CSF动员方案行APBSCT是一种安全有效的动员自体外周血造血干细胞的方法，临床疗效满意。     

格拉诺赛特与化疗药物联合动员自体外周血干细胞的临床研究

目的:观察格拉诺赛特联合化疗对恶性实体瘤患者自体外周血造血干细胞(APBSC)的动员效果.方法:32例患者进入本研究,其中恶性淋巴瘤18例,乳腺癌11例,生殖细胞肿瘤3例.自化疗后白细胞降至最低点时开始皮下注射格拉诺赛特150～250μg/day1,至APBSC采集结束前一天,白细胞恢复到5.0×109/L以上时开始连日采集APBSC;当累计采集的单核细胞≥5.0×108/kg或CD34 细胞≥2.0×106/kg时停止采集.结果:开始给予格拉诺赛特及开始采集APBSC的中位时间分别为化疗开始后的第12(5～15)天和第15(13～20)天,格拉诺赛特的中位给药次数为5(3～12)次,全组患者平均采集到的单核细胞及CD34 细胞总数分别为5.76±2.05×108/kg和15.58±10.36×106/kg,平均粒-单集落形成单位21.01±20.75×104/kg.动员过程中不良反应轻微,此后30例接受移植者全部获得造血功能重建.结论:格拉诺赛特联合化疗是一种安全、有效的APBSC的动员方法,国人采用150～250μg/day1的剂量即可得到满意的动员效果.     

PEG －rhG －CSF 预处理对 BUCY 方案致小鼠骨髓抑制模型骨髓造血恢复的影响

目的：研究聚乙二醇化粒细胞集落刺激因子（PEG －rhG －CSF）预处理后不同时间间隔对 BUCY 方案致小鼠骨髓抑制模型骨髓及外周血象恢复情况的影响，为进一步扩展 PEG －rhG －CSF 的临床应用范围提供理论依据。方法：BLAB／c 雌性小鼠50只，随机分为5组（n ＝10）。实验组（Group6、Group10、Group13、Group16）皮下注射 PEG －rhG －CSF 70mg·kg －1，给药后的第6、10、13及16天给予白消安（BU）35mg·kg －1· d －1连续4天，之后给予环磷酰胺（CY）50mg·kg －1·d －1连续2天。粒细胞缺乏组（Model）给予 BU 35mg· kg －1·d －1连续4天，之后给予 CY 50mg·kg －1·d －1连续2天。结果：经 BUCY 方案处理后，除 Group6组白细胞于第5天开始下降外，其余各组白细胞均于第3天开始下降；各组的（Model、Group6、Group10、Group13、Group16）白细胞最低值分别出现在第11、9、9、11及11天，白细胞恢复正常的时间分别为第19、23、23、21及19天。第19天时 Model 和 Group16组的骨髓病理结果均已趋于正常，其他组骨髓组织还存在不同程度的空泡结构，表现为低增生骨髓状态。结论：使用 PEG －rhG －CSF 后16天对于 BUCY 方案引起的小鼠骨髓抑制模型的骨髓恢复已无影响，临床5天用药的3周化疗方案可以尝试性使用 PEG －rhG －CSF 预防粒细胞降低。     

MA或MOED方案联合造血生长因子动员自体外周血干细胞效果观察

目的：探讨米托蒽醌(MIT)为主的MA或MOED化疗方案联合造血生长因子对自体外周血干细胞(APBSC)的动员效果。方法：12例患者用MA联合造血生长因子动员方案(Ⅰ组)，8例患者用MOED联合造血生长因子动员方案(Ⅱ组)，两组均在白细胞(WBC)降至最低点开始回升时。皮下注射G-CSF或G-CSF+GM-CSF至采集结束。wBC恢复至＞2.5×109／L，CD34)+细胞比例＞1.0％时，用血细胞分离机连续2天采集APBSC。当累计采集的单个核细胞(MNC)达到4×108／kg以上时停止采集。以文献报道的环磷酰胺联合造血生长因子动员方案为对照(Ⅲ组)。结果：Ⅰ组动员方案在两次采集的CD34)+细胞数量优于Ⅱ组动员方案。Ⅰ组和Ⅱ组两种动员方案在第1次采集的CD34)+细胞数、采集次数、骨髓抑制强度方面优于Ⅱ组动员方案，但是第2次采集CD34)+细胞较少。20例患者连续采集APBSC 2次，共采集到MNC(4.36±2.08)×108／kg，CD34)+细胞(9.87±7.30)×106／kg，CFU-GM(2.86±2.10)×104／kg。18例接受自体外周血干细胞移植(APBSCT)者造血功能均获得满意重建。结论：以MIT为主的化疗联合造血生长因子是一种安全、高效的APBSC动员方法。     

rhG-CSF预防化疗后粒细胞减少的Ⅱ期临床试验

[目的]评价InstitutoSidusS.A.生物公司生产的若美斯(rhG CSF)对防治化疗后粒细胞减少症的作用及不良反应。[方法]采用随机分组的方法 ,将34例患者分为AB组和BA组。AB组第一周期(A周期)化疗48h后加用G CSF ,第二周期为空白对照周期(B周期) ,仅单独使用化疗 ;BA组与上相反。rhG CSF在化疗药物末次给药后48h起 ,5μg/kg,皮下注射 ,每日1次。同时观察患者血中白细胞(WBC)值及中性粒细胞(ANC)值变化。[结果]运用rhG CSF支持后的研究组和对照组相比 ,化疗后WBC值<1×109/L,2×109/L,3×109/L ,4×109/L的持续平均天数明显减少(P<0.05,P<0.01)。ANC值<0.5×109/L,1.0×109/L,1.5×109/L ,2.0×109/L的持续平均天数也明显减少(P<0.05,P<0.01) ,并能减少感染和运用其他抗生素的几率 ,用药后白细胞值及中性粒细胞值在d2 出现第1个高峰、d8 出现第2个高峰。rhG CSF对血小板无明显影响。不良反应表现为 :30%的病人出现轻中度的骨骼肌疼痛 ,6%出现轻度乏力 ,6%出现轻度局部注射痛 ,一般不需特殊处理 ,易于耐受。[结论]rhG CSF可以促进化疗病人WBC和ANC的恢复 ,安全性好 ,可作为化疗提高剂量的辅助用药。     

联合化疗加重组人粒细胞集落刺激因子动员自体外周血干细胞

目的观察环磷酰胺(CTX)为主的联合化疗加重组人粒细胞集落刺激因子(rhG-CSF)对自体外周血干细胞(APBSC)的动员效果。方法CTX（2.5±1.0）g/m     

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     

中剂量依托泊苷联合粒细胞集落刺激因子动员恶性淋巴瘤的外周血造血干/祖细胞

 目的　观察中剂量依托泊苷（VP16）和粒细胞集落刺激因子（G-CSF）在恶性淋巴瘤患者动员采集自体外周血造血干／祖细胞的有效性和安全性。方法　31例恶性淋巴瘤患者（非霍奇金淋巴瘤30例,霍奇金淋巴瘤1例）,VP16 1.2 g／m2分3 d静脉滴注,外周血白细胞降至最低点时给予G-CSF每天5 μg／kg,分2次,皮下注射,直至采集结束。结果　VP16应用后12 d（10～15 d）开始采集外周血造血干／祖细胞,获得单个核细胞（MNC）7.8×108／kg[（5.2～11.3）×108／kg],CD+34细胞7.2×106／kg [（5.3～13.1）×106／kg]。18例患者采集1次,13例采集2次。所有患者移植后均恢复造血,外周血粒细胞>0.5×109／L的中位时间为12 d（9～18 d）,血小板>20×109／L的中位时间为14 d（10～21 d）。患者无严重不良反应。结论　中剂量VP16和G-CSF 动员恶性淋巴瘤患者外周血干／祖细胞有效、安全,可获得满意的动员采集效果。     

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.     

重组人粒细胞集落刺激因子促进自体造血干细胞移植后造血功能恢复的临床研究

背景与目的:高剂量化放疗联合自体造血干细胞移植(autologoushematopoieticstemcellstransplantation,AHSCT)能够提高某些实体瘤的疗效,该疗法的成功得益于重组人粒细胞集落刺激因子(recombinanthumangranulocytecolony-stimulatingfactor,rhG-CSF)的运用。本研究的目的是观察rhG-CSF对实体瘤患者自体造血干细胞移植后造血功能重建的影响。方法:将接受AHSCT的130例实体瘤患者分为rhG-CSF组和对照组,rhG-CSF组在造血干细胞回输后第6天开始连日给予rhG-CSF250～300μg/d,皮下注射,直至白细胞(whitebloodcell,WBC)≥5.0×109/L为止;对照组在造血干细胞回输后不给予rhG-CSF。结果:130例患者共完成移植132次,其中2例为2次移植。研究早期的24例患者采取自体骨髓移植,其中12例移植后给予rhG-CSF;此后的106例均采用自体外周血造血干细胞移植(2例为2次移植),其中47例移植后给予rhG-CSF。(1)rhG-CSF组和对照组自体骨髓移植患者住无菌病房的中位时间为33天和41天,WBC恢复到1.5×109/L以上的中位时间为14天和24天,两组之间的差异有显著性(P<0.05);两组血小板(platelet,PLT)恢复到20×109/L及50×109/L以上的中位时间均无显著性差异。(2)rhG-CSF组和对照组自体外周血干细胞移植患者住无菌病房的中位时间为17天和20天,     

CTX、G-CSF 动员造血干细胞过程中NK 细胞检测

 目的　探讨环磷酰胺 ( CTX)、粒细胞集落刺激因子 ( G- CSF)动员癌症患者造血干细胞过程中 NK细胞数量和活性的变化。方法　 2 1例诊断明确的癌症患者 ,经 CTX4.0 g/m2和 G- CSF(惠尔血 ) 1 5 0 μg/d动员。动员前 (前期 )、WBC降至最低点时 (极期 )、WBC开始恢复后 3天 (恢复早期 )、WBC开始恢复后 6天 (恢复期 )用流式细胞仪计数 CD34 +细胞和 NK细胞 ,用乳酸脱氢酶释放法测量 NK细胞活性。结果　动员过程中 ,NK细胞极期显著低于前期 ,恢复期则显著高于前期 ,P<0 .0 1 ;其变化与 WBC、MNC、血小板 ( BPC)、CD34 + 细胞呈显著正相关 ,P<0 .0 5。 NK细胞活性无显著差别 ,P>0 .0 5。结论　动员过程中 NK细胞数量增加 ,活性无改变。     

Characterization and outcome of "hard to mobilize"' lymphoma patients undergoing autologous stem cell transplantation

A "hard to mobilize" patient was defined as one in whom >or= 1x10(6) CD 34+ cells/kg cannot be obtained after two consecutive large volume aphereses. Forty-four consecutive Hodgkin's and non-Hodgkin's lymphoma patients who underwent autologous peripheral blood stem cell (PBSC) transplant treatment between June 1996 and June 1998 were included in this study. Twenty-one patients (48%) met the definition of "hard to mobilize" (Group I). All the rest of the patients (n=23) were the good mobilizers (Group II). The initial mobilization protocol for most patients was 10 microg/kg of G-CSF alone for both groups. For Group I, 7/21 (33%) patients were unable to achieve a minimal dose of >or= 1x10(6) CD34+ cells/kg even after a second mobilization attempt and/or bone marrow (BM) harvest (n=5). Overall, 11/21 (52%) required an additional mobilization and/or BM harvest. Only 3/21 (14%) patients were able to meet the target cell dose of >or= 2.5x10(6) CD34+ cells/kg (median of 4 apheresis). In contrast, 87% of Group II achieved the target dose with a median of 2 aphereses. Predictors of poor mobilization were greater than two prior treatment regimens (p=0.038) and the WBC count (<25,000/microL) on the first day of apheresis (p=0.053). Nineteen patients in Group I and all Group II completed treatment with a median time to engraftment of ANC>500/microl of 12 and 11 days, and platelet >20x10(3)/microl of 31 and 13 days, respectively. Outcome analysis revealed that 6/19 patients in Group I died of relapse within one year from transplant compared with only 2/23 of Group II who died of relapse (p=0.005, log rank test). There were no treatment related deaths in either group. Independent predictive features for "hard to mobilize" patients are a lack of significant increase in WBC count on the first day of apheresis and the number of prior treatment regimens. Poor mobilization appears to predict a worse outcome after autografting for lymphoma patients.     

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.     

Efficacy and toxicity of lenograstim (glycosylated recombinant human granulocyte-colony stimulating factor) on peripheral blood stem cell harvest in healthy donors

Peripheral blood stem cell harvest with lenograstim (glycosylated rhG-CSF) was performed 12 times from 10 normal donors. Five micrograms/kg of lenograstim was administered subcutaneously twice a day (10 micrograms/kg/day) for 4 to 6 days, and apheresis was performed on day 5 to 7 depending on the collected CD 34+ cell counts. We collected a sufficient number of CD 34+ cells in 9 mobilizations from 7 donors less than 50 years of age, with a total number of collected CD 34+ cells in each mobilization of 22.1 +/- 6.5 x 10(7). In contrast, we could not obtain a sufficient number of CD 34+ cells in 2 mobilizations from 3 donors above 50 years of age, with a total number of collected CD 34+ cells of 9.8 +/- 3.3 x 10(7). Although all donors had adverse events in response to lenograstim administration, all of them were grade 2 or less toxicity. These results indicate that peripheral blood stem cell mobilization and apheresis by lenograstim is safe and well tolerated, but the risk of poor mobilization may become higher in donors more than 50 years of age.