自体外周血CD34+细胞移植治疗小儿重症自身免疫性疾病的初步观察

目的探讨自体外周血CD34^＋细胞移植治疗小儿重症自身免疫性疾病的疗效问题。方法3例重症自身免疫性疾病患儿接受自体外周血CD34^＋细胞移植。首先采用环磷酰胺（CTX）＋粒细胞集落刺激因子（G—CSF）方案动员外周血干细胞，通过CliniMACS细胞分选仪分选CD34^＋细胞后冻存。然后选用BEAM＋抗胸腺细胞球蛋白（ATG）或CTX＋马法兰（Mel）＋ATG两种方案预处理，0d回输CD34^＋细胞。观察造血重建、免疫恢复以及症状体征变化情况。结果动员获得了足够单个核细胞，纯化后CD34^＋细胞纯度高。粒细胞植入时间分别为9、13、11d，血小板植入时间分别为14、18和13d。3例原发病缓解。随访14～16个月，皮肌炎皮损消失、四肢肌力恢复正常，类风湿关节炎疾病活动评分（DAS28）由7.3分降至2.4分，系统性红斑狼疮DAI评分由16分降至4分。结论自体外周血CD34^＋细胞移植是常规治疗无效的小儿重症自身免疫性疾病的可选择治疗措施之一。     

自体外周血干细胞移植治疗难治性系统性红斑狼疮的临床研究

目的探讨自体外周血干细胞移植(APBSCT)治疗难治性系统性红斑狼疮(SLE)的临床疗效。方法对难治性SLE患者进行APBSCT治疗。采用环磷酰胺(CTX) 粒细胞集落刺激因子(G-CSF)方案动员,CS-3000血细胞分离机采集外周血干细胞并保存于-80℃冰箱;用CTX50mg/(kg.d)×3～4d方案预处理后,解冻后回输冻存的干细胞的治疗方法。观察APBSCT前后临床表现及免疫学指标的变化。结果动员后获得单个核细胞数(MNC)(3.383～3.704)×108/kg;CD34 细胞数(4.4～11.12)×106/kg。3例均获得造血重建,中性粒细胞>0.5×109/L、血小板>20×109/L的中位数时间分别是8.3d、10d。移植后患者临床症状消失,1例并肾功能不全、难治性高血压和重度贫血的患者移植后恢复正常。3例患者自身抗体转阴或滴度减低,尿蛋白定性消失,SLE疾病活动指数(SLE-DAI)由移植前的平均15分下降为移植后6个月的平均4分。结论APBSCT治疗难治性SLE安全有效,近期疗效好,远期疗效有待进一步观察。     

长短效粒细胞集落刺激因子联合应用提高自体外周血造血干细胞采集优良率

目的:比较长短效粒细胞集落刺激因子(G-CSF)联合[聚乙二醇化重组人粒细胞集落刺激因子(PEG-rhG-CSF)+G-CSF]、化疗联合短效G-CSF以及单用短效G-CSF动员方案在患者自体外周血造血干细胞动员、采集及移植后造血重建中的差异,以期获得更有效的动员方案。方法:收集2019年2月—2022年2月我院血液科71例恶性血液系统疾病行自体外周血造血干细胞移植患者的临床数据进行前瞻性研究。将长短效G-CSF联合(PEG-rhG-CSF+G-CSF组,12例)、化疗联合短效G-CSF(化疗+G-CSF组,34例)以及单用短效G-CSF(单用G-CSF组,25例)3种动员方案对采集细胞数、成功率、移植后造血重建时间结果进行比较,并对影响动员疗效的因素进行统计分析。结果:3组在采集CD34⁺细胞数、采集优良率、造血重建时间方面比较差异有统计学意义(P<0.05)。PEG-rhG-CSF+G-CSF组采集CD34⁺细胞数[(15.77±5.44)×10⁶/kg vs (4.30±0.59)×10⁶     

外周血干细胞移植治疗难治性系统性红斑狼疮

目的 观察自体外周血干细胞移植（APBSCT）治疗难治性系统性红斑狼疮（RSLE）的疗效及安全性。方法 RSLE3例，先给予血浆置换，环磷酰胺（CTX）和大剂量丙种球蛋白，然后用环磷酰胺和粒细胞集落刺激因子（G-CSF）动员造血干细胞（HSC），多功能加强型血细胞分离机采集外周血干细胞，-86℃超低温冻存，环磷酰胺预处理，经静脉回输干细胞，最后应用抗胸腺淋巴细胞球蛋白（ATG）行体内去T淋巴细胞。观察移植前后临床症状，体征和免疫学指标的变化。结果 APBSCT后患者的临床症状完全缓解，异常免疫学指标基本恢复正常，抗体全部转阴。结论 APBSCT对难治性系统性红斑狼疮有明显的疗效。尤其适用对各种药物治疗无效的患者，远期疗效还需长期随访。     

-80 ℃低温保存自体外周血干细胞移植治疗多发性骨髓瘤的临床研究

目的探讨-80℃低温保存自体外周血干细胞移植(APBSCT)治疗多发性骨髓瘤(MM)的有效性和安全性。方法对10例MM患者进行APBSCT治疗。采用环磷酰胺(CTX)+粒细胞集落刺激因子(G-CSF)方案动员干细胞,CS-3000血细胞分离机采集外周血干细胞并保存于-80℃冰箱;用马法兰200 mg/m2方案预处理后,解冻回输冻存的干细胞。结果 (1)动员后获得单个核细胞数(MNC)中位数为4.54(2.31~9.80)×108/kg;CD34+细胞数中位数为4.17(2.03~7.76)×106/kg。(2)移植后10例患者均获得造血重建,中性粒细胞计数0.5×109/L、血小板计数20×109/L的中位时间分别是13.3(9~16)d、15(11~19)d。(3)移植后3个月完全缓解(CR)8例,非常好的部分缓解(VGPR)2例。中位随访54.6(3~111)月,生存8例(CR5例,VGPR 3例),其中无进展生存6例。复发4例中再次治疗维持CR 2例,多次复发死亡2例。(4)移植的并发症是感染,无移植相关死亡。结论 -80℃低温保存APBSCT治疗MM安全有效,近期疗效好,移植后需要长期维持治疗。     

急性心肌梗塞患者外周血干细胞动员效率及安全性观察

目的:观察急性心肌梗塞(AMI)患者使用粒细胞集落刺激因子(G-CSF)行自体外周血干细胞动员的效率与安全性。方法:我院2003年11月至2004年8月收治的45例AMI患者,入院后在常规急性心肌梗塞 (AMI)药物与介入治疗的基础上给予包涵体型G-CSF(商品名:惠尔血)或分泌型G-CSF(商品名:金磊赛强),300～600μg／d皮下注射,连续5 d,第6 d经美国Baxter公司生产的CS3000PLUS血细胞分离机,分离外周血干细胞,然后进行经皮经腔冠状动脉内移植,进一步治疗AMI。外周血干细胞动员前及动员后第3、 4、5、6、7 d行外周血白细胞(WBC)计数检查,经流式细胞仪测定CD34 的细胞数量。并在外周血干细胞同时观察其副作用。结果:在外周血干细胞动员前及动员后第3、4、5、6、7 d外周血中WBC数量分别为 (8．42±2．59)×109／L、(31．28±8．34)×109／L、(35．24±9．38)×109／L、(37．03±13．07)×109／L、(35．34 ±14．68)×109／L、(20．35±9．22)×109／L;CD34 量分别为(14．89±11．46)×106、(67．78±50．88)× 106、(124．79±136．13)×106、(208．92±206．97)×106、(206．10±164．57)×106、(66．63±56．56)×106; 在动员前及动员后第3、4、5、6、7 d外周血中WBC,CD34 量与动员时间变化曲线均显示曲线高峰在动员后第5 d;患者外周血中CD34 细胞数量与WBC数量变化呈正相关(r=0．835),外周血干细胞动员时不良反应占37．8%(17／45),其中骨痛发生率为15．6％(7／45),低热约6．7%(3／45),乏力约4．4％(2／45),皮疹约4．4％(2／45),心衰加重约4．4％(2／45),自发性脾栓塞约2．2％(1／45);无死亡等严重并发症发生。结论:AMI患者应用G-CSF行外周血干细胞动员安全可行;外周血中CD34 细胞数量与WBC变化曲线高峰均出现在第5 d,且WBC与CD34 细胞数量之间具有正相关,与体重、年龄、性别、AMI时间,无明显相关性。     

大剂量化疗并自体外周血干细胞移植治疗重症原发性干燥综合征

目的探讨大剂量化疗（HDC）并自体外周血干细胞移植（PBSCT）对于常规治疗反应不佳的重症原发性干燥综合征（pSS）的可行性、疗效及安全性。方法选择1999年起3例长期激素和免疫抑制剂治疗病情不能缓解的重症pSS患者作为治疗对象，给予大剂量免疫抑制剂治疗及自体外周血干细胞移植。自体干细胞动员采用环磷酰胺（CTX）2—3g／m^2和粒细胞集落刺激因子（G—CSF），并行CD34^＋细胞分选。干细胞回输前用CTX200mg／kg、抗胸腺细胞免疫球蛋白（ATG）90mg／kg或CTX200mg／kg、全身照射（TBI）4gy进行预处理。结果1例患者完成2次CTX2g／m^2动员，尚未行干预处理和细胞回输，2例重症pSS顺利完成治疗全过程，3例患者随诊时间分别达48、60和18个月。治疗后3例患者的B淋巴细胞功能亢进均得以抑制，2例患者抗SSB抗体转阴，1例患者重复唇腺活检示灶性淋巴细胞浸润消失：2例患者的肺功能改善，间质性肺炎得以逆转。结论自体外周血干细胞移植可控制重症pSS患者的病情，具有可行性和安全性，疗效较为肯定。     

粒细胞集落刺激因子对老年急性心肌梗死患者骨髓干细胞动员效率的临床观察

目的观察急性心肌梗死(AMI)患者应用G-CSF行自体外周血干细胞动员的效率与安全性.方法我院2003年11月至2004年8月收治的45例AMI患者,入院后在常规急性心肌梗死治疗(药物与介入治疗)基础上给予包涵体型G-CSF(商品名惠尔血),300～600μg/day皮下注射,连续5天,第6日经美国Baxter公司生产的CS3000PLUS血细胞分离机,分离外周血干细胞,然后进行经皮经腔冠状动脉内移植自体外周血干细胞进一步治疗急性心肌梗死.动员前及动员后第3、4、5、6、7天行外周血WBC计数检查,经流式细胞仪测定CD34+的细胞数量.并在外周血干细胞动员时观察有无骨痛,乏力,皮疹,发热,胃肠道反应(恶心、呕吐、便秘),心绞痛或心衰加重等并发症发生,及一些少见的并发症自发性脾破裂、严重化脓性感染、高凝状态、自身免疫性疾病等发生.结果在动员前及动员后第3、4、5、6、7天外周血中WBC量分别为(8.42±2.59)×109/L、(31.28±8.34)×109/L、(35.24±9.38)×109/L、(37.03±13.07)×109/L、(35.34±14.68)×109/L、(20.35±9.22)×109/L;CD34+量分别为(14.89±11.46)×106、(67.78±50.88)×106、(124.79±136.13)×106、(208.92±206.97)×106、(206.10±184.57)×106、(66.63±56.56)×106;在动员前及动员后第3、4、5、6、7天外周血中WBC、CD34+量与动员时间变化曲线均显示曲线高峰在动员后第五天;患者外周血中CD34+细胞数量与WBC数量变化呈正相关(r=0.940),与年龄变化呈负相关(r=-0.398).外周血干细胞动员时不良反应占37.8%(17/45),其中骨痛发生率为15.6%(7/45),低热约6.7%(3/45),乏力约4.4%(2/45),皮疹约4.4%(2/45),心衰加重约4.4%(2/45)自发性脾栓赛约2.2%(1/45);无死亡等严重并发症发生.结论急性心肌梗死患者应用G-CSF行外周血干细胞动员安全可行,且外周血中CD34+细胞数量与WBC变化曲线高峰均出现在第五天,且WBC与CD34+细胞数量之间具有正相关,与体重、性别、AMI时间无明显相关性.     

自体外周血造血干细胞移植治疗难治性系统性红斑狼疮

目的:探讨自体外周血造血干细胞移植(APBSCT)治疗难治性系统性红斑狼疮(SLE)的临床疗效。方法:用APBSCT治疗4例难治性SLE。干细胞动员应用环磷酰胺(CTX)4g/m2,分两天应用和粒细胞集落刺激因子(G-CSF)5~10μg/kg·d-1;预处理方案包括CTX(50mg/kg·d-1,-6、-5、-4、-3d),抗胸腺细胞球蛋白(ATG15~20mg/kg·d-1,-2、-1、 1、 2d)。结果:4例患者均获得造血重建,中性粒细胞>0.5×109/L,血小板>20×109/L的中位数时间分别是9d,10d;SLE的临床表现明显减轻,尿蛋白减少或消失,自身抗体转阴或滴度减低,泼尼松用量<10mg/d;无移植相关死亡。结论:APBSCT治疗难治性SLE近期疗效显著,造血重建恢复迅速,安全有效,远期疗效尚需进一步观察。     

分泌型与包涵体型粒细胞集落刺激因子对骨髓干细胞动员效率的比较

目的观察两种不同粒细胞集落刺激因子(G CSF)动员剂(分泌型与包涵体型)对急性心肌梗死(AMI)患者骨髓血干细胞动员效率。方法一组予以包涵体型G CSF(商品名惠尔血)300μg(包涵体型G CSF组),每日2次,皮下注射,连续5天;另一组予以分泌型G CSF(商品名金磊赛强)300μg(分泌型G CSF组),每日2次,皮下注射,连续5天。第6日经美国Baxter公司生产的CS3000PLUS血细胞分离机,分离外周血干细胞,采集外周血干细胞悬液经流式细胞仪测定CD34+的细胞数量。结果给G CSF前及给G CSF后第3、4、5、6天两组间外周血中细胞表面标记蛋白CD34+细胞数量和白细胞计数无明显统计学差异;在应用两组不同的动员剂后,外周血中白细胞计数与动员时间变化曲线显示曲线高峰在动员后第5天;在包涵体型G CSF组,CD34+细胞数量与时间变化曲线高峰为第5天,但在分泌型G CSF组,CD34+细胞数量与时间变化曲线显示CD34+细胞数量在3～4天内呈急剧升高趋势,但在第5天后升幅明显减缓;显示分泌型G CSF组动员后外周血中干细胞下降较慢;患者外周血中CD34+细胞数量与白细胞计数变化呈正相关(r=0.835),与性别、体重、年龄及AMI发生时间无显著性相关。结论在AMI患者中应用两种不同G CSF动员剂,两组在外周血干细胞动员效率方面无明显统计学差异。     

Efficacy and safety of hematopoietic stem cell remobilization with plerixafor+G-CSF in adult patients with germ cell tumors

Autologous hematopoietic SCT (auto-HSCT) can be curative for patients with germ cell tumors. Poor stem cell mobilization jeopardizes the ability to deliver this therapy. Herein, we describe a retrospective study examining safety and efficacy of plerixafor in combination with G-CSF for patients with germ cell tumors who had previously failed stem cell collection. Overall, 21 patients with germ cell tumors and previous mobilization failure were remobilized with G-CSF (10?μg/kg SC) and plerixafor (0.24?mg/kg SC) beginning the evening of day 4 of G-CSF treatment. Dosing of G-CSF and plerixafor was repeated until collection of 2 × 10(6) CD34+ cells/kg. Remobilization resulted in a median yield of 3.2 × 10(6) CD34+ cells/kg. A total of 17 (81%) patients collected 2 × 10(6) and 9 (43%) patients collected 4 × 10(6) CD34+ cells/kg in a median of 2 (range 1-3) and 3 (range 1-4) days, respectively. In all, 16 (76%) patients proceeded to transplant; 8 (38%) received tandem transplants. There were no serious adverse events. In summary, the majority of patients with germ cell tumors who failed prior mobilization with growth factors ± chemotherapy were remobilized with plerixafor plus G-CSF facilitating at least one auto-HSCT. Use of plerixafor plus G-CSF can increase access of this potentially life-saving procedure to patients with high-risk germ cell tumors.     

Haematopoietic stem cell mobilization with plerixafor and G-CSF in patients with multiple myeloma transplanted with autologous stem cells

A proportion of patients with multiple myeloma (MM) who have already undergone autologous stem cell transplantation (autoSCT) might benefit from a further transplantation. For this, they might need to undergo another round of stem cell mobilization. We analyzed retrospectively the outcomes of stem cell mobilization with plerixafor and granulocyte colony-stimulating factor (G-CSF) in a group of 30 patients who had undergone autoSCT previously, and in 46 other patients. The previously transplanted patients were significantly different from the remaining patients with respect to the intensity and number of previous therapies. We observed that the median peripheral blood concentration of CD34+ cells after the first administration of plerixafor was lower in previously transplanted (19 cells/μL) than in other patients (30 cells/μL, P < 0.05). Despite a comparable number of apheresis sessions being performed, the median total yield of CD34+ cells was significantly lower in the previously transplanted than in the remaining patients (2.8 × 10(6) cells/kg vs. 4.2 × 10(6) cells/kg, P < 0.05). However, successful collection of at least 2.0 × 10(6) CD34+ cells/kg was achieved finally in a similar proportion of previously transplanted and other patients (70% vs. 82.6%). Our data suggest that stem cell mobilization with plerixafor and G-CSF might overcome the negative effect of prognostic factors for poor stem cell mobilization in patients with MM who have undergone autoSCT previously.     

Difficult stem cell mobilization despite adequate CD34+ cell dose predicts shortened progression free and overall survival after autologous HSCT for lymphoma

Hematopoietic growth factors alone or in combination with myelosuppressive chemotherapy are used to mobilize peripheral blood stem cells for autologous transplantation. To identify characteristics of successful mobilization with granulocyte colony-stimulating factor (G-CSF) alone and to study the impact of immediate chemotherapy mobilization following G-CSF mobilization, we treated 175 chemotherapy sensitive lymphoma patients with G-CSF (G) mobilization and leukapheresis followed by chemotherapy plus G-CSF (CG) mobilization and leukapheresis and then autologous transplantation. Patients with stage I/II disease at diagnosis and < or =5 years from diagnosis were more likely to mobilize successfully with G-CSF alone (G). CG mobilization led to superior stem cell yields compared to the preceding mobilization with G (median 2.37 vs 1.37 ( x 10(6)CD34+ cells/kg); P<0.0001). Patients (n=58, 33%) with successful G-CSF mobilization (> or =2 x 10(6) CD34+ cells/kg) had quicker platelet recovery and improved progression free and overall survival compared to patients who had adequate collection only after chemotherapy mobilization or to those who failed to collect an adequate graft with either type of mobilization. The poor clinical outcome of patients with difficult mobilization using either method identifies them as a high-risk group who might benefit from alternative therapies.     

Etoposide plus G-CSF priming compared with G-CSF alone in patients with lymphoma improves mobilization without an increased risk of secondary myelodysplasia and leukemia

The use of etoposide (VP-16) for stem cell mobilization has been reported as a significant risk factor for the development of therapy-related myelodysplasia/therapy-related AML (tMDS/tAML) after transplantation. We compared the safety and effectiveness of VP-16+G-CSF (VP+G) to G-CSF alone for PBPC mobilization in patients with non-Hodgkin's lymphoma and Hodgkin's lymphoma who underwent autologous transplantation at the Cleveland Clinic and Ohio State University. In the VP+G group, median total CD34+ cells collected were 9.34 × 10(6) per kg (range 0.97-180.89), with 42% of all patients having adequate (2 × 10(6) cells per kg) CD 34+ collection after 2 days of apheresis compared with a median in the G-CSF group of 3.83 × 10(6) per kg (range, 0.72-50.38), with only 16% patients having adequate collection after 2 days (P<0.001). tMDS/tAML occurred in 15 patients (2.3%) in the VP+G and in 12 patients (3.8%) receiving G-CSF alone. (P=0.62). Increased number of days of apheresis was associated with the risk of tMDS/tAML (hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.08-1.30, P<0.001). Priming regimen was not a significant variable for relapse-free survival or OS. The addition of etoposide significantly improves the effectiveness of mobilization at the cost of an increased incidence of neutropenic fever though with no mortalities. There is no evidence of increased incidence of tMDS/tAML in patients receiving VP+G compared with those mobilized with G-CSF alone.     

大剂量环磷酰胺联合粒细胞集落刺激因子动员多发性骨髓瘤造血干细胞的价值研究

目的研究大剂量环磷酰胺(HD-CTX)联合粒细胞集落刺激因子(G-CSF)在多发性骨髓瘤(MM)造血干细胞动员中的临床疗效和安全性。方法选择2006年6月至2010年9月中山大学附属第一医院血液科36例MM患者,全部患者接受HD-CTX联合G-CSF动员,CTX 3~5 g/m2,第1天,G-CSF300μg/d第2天起直到干细胞采集结束。结果 35例(97.2%)动员成功,其中31例第一次动员即成功,4例第二次动员成功。干细胞采集的中位时间为第11(9~13)天,22例(62.9%)患者采集1次,13例(37.1%)患者采集2次。采集的单个核细胞(MNC)数为(4.49±1.71)×108/kg,CD34+细胞数为(3.21±1.87)×106/kg。7例疗效在动员后得到进一步提高。动员的非血液系统副反应包括恶心、呕吐11例(26.8%)、腹痛腹泻5例(12.2%)、发热7例(17.1%)、骨痛4例(9.8%)等。只有1例因感染影响干细胞采集。结论 HD-CTX联合G-CSF是MM造血干细胞动员的安全有效的方法。     

Mobilization, harvesting and selection of peripheral blood stem cells in patients with autoimmune diseases undergoing autologous hematopoietic stem cell transplantation

Peripheral blood stem cells (PBSC) were mobilized in 130 patients with autoimmune diseases undergoing autologous hematopoietic stem cell transplantation using cyclophosphamide 2 g/m(2) and either granulocyte colony-stimulating factor (G-CSF) 5 mcg/kg/day (for systemic lupus erythematosus (SLE) and secondary progressive multiple sclerosis, SPMS) or G-CSF 10 mcg/kg/day (for relapsing remitting multiple sclerosis (RRMS), Crohn's disease (CD), systemic sclerosis (SSc), and other immune-mediated disorders). Mobilization-related mortality was 0.8% (one of 130) secondary to infection. Circulating peripheral blood (PB) CD34(+) cells/microl differed significantly by disease. Collected CD34(+) cells/kg/apheresis and overall collection efficiency was significantly better using Spectra apheresis device compared to the Fenwall CS3000 instrument. Patients with SLE and RRMS achieved the lowest and the highest CD34(+) cell yields, respectively. Ex vivo CD34(+) cell selection employing Isolex 300iv2.5 apparatus was significantly more efficient compared to CEPRATE CS device. Circulating PB CD34(+) cells/microl correlated positively with initial CD34(+) cells/kg/apheresis and enriched product CD34(+) cells/kg. Mean WBC and platelet engraftment (ANC>0.5 x 10(9)/l and platelet count >20 x 10(9)/l) occurred on days 9 and 11, respectively. Infused CD34(+) cell/kg dose showed significant direct correlation with faster white blood cell (WBC) and platelet engraftment. When adjusted for CD34(+) cell/kg dose, patients treated with a myeloablative regimen had significantly slower WBC and platelet recovery compared to non-myeloablative regimens.     

Preemptive dosing of plerixafor given to poor stem cell mobilizers on day 5 of G-CSF administration

Plerixafor, given on day 4 of G-CSF treatment is more effective than G-CSF alone in mobilizing hematopoietic progenitor cells. We tested a strategy of preemptive plerixafor use following assessment of the peak mobilization response to 5 days of G-CSF. Patients were eligible for plerixafor if, on day 5 of G-CSF, there were <7 circulating CD34+ cells/μL or if <1.3 × 10(6) CD34+ cells/kg were collected on the first day of apheresis. Plerixafor (0.24?mg/kg s.c.) was given on day 5 of G-CSF followed by apheresis on day 6. This was repeated for up to two additional doses of plerixafor. The primary end point of the study was the percentage of patients who collected at least 2 × 10(6) CD34+ cells/kg. Twenty candidates for auto-SCT enrolled on the trial. The circulating CD34+ cell level increased a median of 3.1 fold (range 1-8 fold) after the first dose of plerixafor and a median of 1.2 fold (range 0.3-6.5 fold) after the second dose of plerixafor. In all, 15 out of 20 (75%) patients achieved the primary end point. In conclusion, the decision to administer plerixafor can be delayed until after the peak mobilization response to G-CSF has been fully assessed.     

Hourly monitoring of circulating CD34+ cells to optimize timing of autologous apheresis in pediatric patients

In order to increase the CD34+ cell yield in children undergoing autologous stem cell transplantation, the optimum time of apheresis after G-CSF administration has still to be found. We prospectively studied the mobilization of CD34+ cells and white blood cells in the peripheral blood (PB) of 20 pediatric patients before leukapheresis. The monitoring schedule covered 12 h, with blood samples taken before and at 2, 4, 5, 6, 7, 8, 10 and 12 h after G-CSF administration when 10 CD34+ cells/mul were reached. CD34+ cells were measured by flow cytometric analysis both in the single- and dual-platform setting. Two different patterns of mobilization (POM) emerged: 12 patients showed an increase in CD34+ cells in PB during the first 4 h after G-CSF (POM I), while eight patients had an initial decrease of CD34+ cells. However, all patients together showed a significant increase of CD34+ cells about 10 h after G-CSF administration. Further studies with more patients, using an enhanced monitoring schedule will be required to refine the results.     

Reduced dose of lenograstim is as efficacious as standard dose of filgrastim for peripheral blood stem cell mobilization and transplantation: a randomized study in patients undergoing autologous peripheral stem cell transplantation

In vitro studies have demonstrated a 27% increased efficacy of lenograstim over filgrastim. However, equal doses of 10 microg/kg/day of filgrastim and lenograstim have been recommended for mobilization of CD34+ cells without associated chemotherapy. In this study, we investigated whether a 25% reduced dose of lenograstim at 7.5 microg/kg/day is equavalent to 10 microg/kg/day filgrastim for autologous peripheral blood stem cell (PBSC) mobilization and transplantation. A total of 40 consecutive patients were randomized to either filgrastim (n = 20) or lenograstim (n = 20). The two cohorts were similar in regard to disease, sex, body weight, body surface area, conditioning regimens, previous chemotherapy cycles and radiotherapy. Each growth factor was administered for 4 consecutive days. The first PBSC apheresis was done on the 5th day. In the posttransplant period, the same G-CSF was given at 5 microg/kg/day until leukocyte engraftment. Successful mobilization was achieved in 95% of patients. Successful mobilization with the first apheresis, was achieved in 10/20 (50%) patients in the filgrastim group versus 9/20 (46%) patients in the lenograstim group. No significant difference was seen in the median number of CD34+cells mobilized, as well as the median number of apheresis, median volume of apheresis, percentage of CD34+ cells, and CD34+ cell number. Leukocyte and platelet engraftments, the number of days requiring G-CSF and parenteral antibiotics, the number of transfusions were similar in both groups in the posttransplant period. Lenograstim 7.5 microg/kg/day is as efficious as filgrastim 10 microg/kg/day for autologous PBSC mobilization and transplantation.     

Efficacy of further attempts to mobilize CD34+ peripheral stem cells with alternative procedures after primary failure

19 patients who failed the target collection of at least 2.5 x 10(6) CD34+ cells/kg underwent further mobilization procedures either with granulocyte-colony-stimulating factor (G-CSF) alone after failure to chemotherapy plus G-CSF (group 1), or with chemotherapy plus G-CSF (group 2), or with high-dose G-CSF (24 microg/kg) alone (group 3) after failure to respond to standard dose of G-CSF (10 microg/kg) alone. In all groups, an increase in median CD34+ cell yield could be observed following alternative procedures (1.1- to 1.9 x 10(6) kg; p = 0.02). The highest increase in CD34+ cell harvest was achieved in group 1 (0.85 to 2.2 x 10(6) kg), followed by group 2 (1. 2 to 1.7) and group 3 (1.0 to 1.4), but without statistically significant difference between the mobilization technologies. All patients with more than 1.0 x 10(6) CD34+ cells/kg in the first apheresis procedure reached the overall target of 2.5 x 10(6) CD34+ cells/kg after a second or subsequent mobilization procedure. In contrast, only 3 of 8 patients (37%) with less than 1.0 x 10(6) CD34+ cells in the first harvest could reach the target of 2.5 x 10(6) CD34+ cells after further mobilization attempts.