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。     

经冠状动脉移植自体外周血干细胞治疗急性心肌梗死

目的观察经皮经腔冠状动脉内移植外周血干细胞治疗急性心肌梗死(acute myocardial infarction,AMI)的可行性与近期临床疗效。方法入选AMI患45例,随访6个月13例。AMI患入院后在常规治疗(药物与介入治疗)基础上给予粒细胞集落刺激因子(granuloeyte colony-stimulating factor,G—CSF),300～600μg／d皮下注射,连用5日。第6日分离外周血干细胞混悬液57ml,经皮经腔导管技术建立梗死相关动脉(infarct related artery,IRA)通道,利用球囊封闭IRA,并将分离的外周血干细胞悬液经导管中心腔注入IRA。在外周血干细胞动员、分离及回输过程中观察有无不良反应产生。术前和术后6个月应用超声心动图评价全心功能及对局部心肌节段运动评分。结果在外周血干细胞的动员、分离、采集及回输中发生不良反应共30例,其中发生在外周血干细胞动员时占38％(17／45);在外周血干细胞分离和采集时占17％(7／41);在回输过程中占20％(8／41)。术后6个月随访,显示移植前后左心室射血分数分别为0．44、0．56,(P=0．008);移植前后心室壁运动积分指数分别为1．23、1．11,(P=0．100);移植前后左心室舒张末期内径分别为52．4、52．0,(P=0．591)。结论经皮腔内冠状动脉内移植外周血干细胞治疗急性AMI安全可行．能显提高左心室射血分数,但对左心室重构无影响。     

自体外周血干细胞移植治疗急性心肌梗死安全性的观察

目的　观察经皮经腔冠状动脉内移植自体外周血干细胞 (PBSC)治疗急性心肌梗死 (AMI)的可行性与安全性。方法　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 ) 30 0～ 6 0 0 μg/d皮下注射 ,连续 5d ;或分泌型G CSF(商品名金磊赛强 ) ,6 0 0 μg/d皮下注射 ,连用 5d。第 6d经美国Baxter公司生产的CS30 0 0PLUS血细胞分离机 ,分离外周血干细胞悬液 5 0mL ,采集后干细胞未做任何处理 ,常规经皮经腔导管技术建立梗死相关动脉 (IRA)通道 ,利用over the Wire球囊封闭IRA ,并将分离的PBSC经Over the Wire导管中心腔注入IRA。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 ;在外周血干细胞分离及采集过程中观察有无低钙性口周麻木、抽搐 ,迷走神经反应性面色苍白、晕厥 ,低血容量性面色苍白、晕厥 ,心绞痛发作 ,心衰加重等 ;在自体外周血干细胞经冠状动脉内回输过程中可出现心律失常 ,如 :窦性心动过缓 (球囊封堵所致 )、窦性停搏 (窦停 )或三度房室传导阻滞 (AVB) (球囊刺激支架近端引起严重的冠脉痉挛所致 )、室颤     

急性心肌梗死患者外周血干细胞动员的安全性

目的观察急性心肌梗死(AMI)患者在外周血干细胞动员过程中出现的不良反应,探讨其安全性。方法对44例AMI患者在药物治疗与介入治疗的基础上,给予包涵体型粒细胞集落刺激因子(GCSF)300～600μg/d,皮下注射,连续5d;或分泌型GCSF600μg/d,皮下注射,连续5d,观察出现的不良反应。结果在外周血干细胞的动员过程中共发生不良反应16例(36.4%),骨痛6例(13.6%),低热3例(6.8%),皮疹、乏力、心力衰竭或心绞痛加重各2例(4.5%),脾栓塞1例(2.3%)。结论GCSF动员过程中近期最常见的不良反应为骨痛,外周血干细胞移植治疗AMI已成为一种新的治疗途径。     

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。     

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.     

骨髓干细胞动员对急性心肌梗死后左室重构影响的临床研究

目的 :观察骨髓干细胞动员对急性心肌梗死 (AMI)患者左室重构的影响。方法 :4 8例AMI患者随机分为动员组 (2 5例 )和对照组 (2 3例 ) ,动员组连续 3d给予粒细胞集落刺激因子 (G CSF) 30 0 μg/d ,用2 0 1Tl静息—再分布心肌显像比较两组第 6d、 30d的梗死面积 ,超声心动图观察 72h内和 3个月的左室舒张末期容积指数 (LVEDVI)、收缩末期容积指数 (LVESVI)、室壁运动指数 (WMSI)、射血分数(LVEF)。结果 :动员组治疗后心肌梗死面积明显减少 (0 383± 0 0 77vs 0 5 6 1± 0 0 96 ,P <0 0 1) ,LVESVI减少 [(2 7 4 7± 7 86 )ml/m2 vs (34 5 0± 8 0 8)ml/m2 ,P <0 0 5 ],WMSI减少 (1 10± 0 11vs 2 2 6±0 14 ,P <0 0 1) ,LVEF增加 (0 5 9± 0 0 7vs 0 4 8± 0 0 7,P <0 0 1)。结论 :应用G CSF动员AMI患者自身骨髓干细胞可明显缩小心肌梗死面积及有效防治左室重构     

以国产rHuG-CSF为动员剂作外周血造血干细胞移植治疗恶性血液病的临床观察

为了进一步探讨外周血造血干细胞移植 (PB SCT)的动员方法 ,我们分别采用国产重组人粒细胞集落刺激因子 (rHuG CSF ,商品名特尔津 )和进口rHuG CSF(商品名惠尔血 )动员后作异基因外周血造血干细胞移植 (Allo PBSCT)和自体外周血造血干细胞移植 (APBSCT)治疗恶性血液病患者各2 4例和 2 7例 ,结果特尔津作为动员剂在APBSCT中安全、有效 ,现报告如下。1　资料与方法1 .1 　 分组与动员方法Allo PBSCT分组及动员方法 :特尔津组正常供者 1 3例 ,男 8例 ,女 5例 ,中位年龄 2 8(1 8～ 5 2 )岁 ,中位体重 6 5 (46～ 85 )kg。惠尔血…     

粒细胞集落刺激因子动员自体外周血干细胞移植治疗急性心肌梗死的临床研究

目的观察经皮经腔冠状动脉内移植自体外周血干细胞(PBSC)治疗急性心肌梗死(AMI)的疗效。方法自2003年11月至2005年1月共入选AMI患者70例,随机分为干细胞移植组和对照组,两组均为35例。干细胞治疗组在常规AMI治疗(药物与介入治疗)基础上应用粒细胞集落刺激因子(GCSF)皮下注射动员自体骨髄干细胞,连用5天,第6天分离外周血干细胞悬液,将采集后的干细胞悬液经OVERTHEWIRE球囊导管中心腔注入梗死相关动脉(IRA),进行外周血干细胞移植;对照组经AMI常规方法(药物与介入)治疗。在外周血干细胞动员、采集及经冠状动脉回输过程中观察其不良反应。两组患者在移植前及移植后6个月应用超声心动图评价左室形态及心功能变化,室壁节段性运动积分;比较两组患者生存率及心脏事件发生率。结果6个月时干细胞移植组心脏收缩末容积(ESV)明显减小[(63.8±23.9)ML比(52.6±20.3)ML,P=0.01],舒张末容积(EDV)无显著性变化[(134.2±36.7)ML比(119.2±30.3)ML,P=0.07];左室射血分数(LVEF)显著增高[(50.0±8.2)%比(57.1±7.8)%,P<0.001];左室壁节段性运动积分指数(WMSI)明显减低[(1.219±0.190)比(1.101±0.118),P<0.001]。对照组介入术前及术后6个月随访ESV、EDV、LVEF及WMSI均无统计学差异(P=0.490、0.259、0.117、0.395)。两组术后6个月生存率及心脏事件发生率无统计学差异。不良反应:在PBSC动员、分离、采集及回输中总的不良反应共25例次,其中动员时不良反应占37.1%(13/35),分离和采集中的不良反应占14.3%(5/35),经冠状动脉回输过程中出现的不良反应占20.0%(7/35)。结论经皮经腔冠状动脉内移植自体PBSC治疗AMI可以在近期有效地减少心肌梗死缺血面积,减轻左室重构,改善心功能。     

静脉注射粒细胞集落刺激因子动员自体骨髓干细胞治疗急性心肌梗死的安全性观察

目的观察急性心肌梗死患者静脉注射粒细胞集落刺激因子（G-CSF）动员自体骨髓干细胞的可行性和安全性。方法自2008年1月至2009年6月收治的22例急性心肌梗死患者,入院后在常规急性心肌梗死治疗（药物治疗和介入治疗）的基础上给予静脉注射粒细胞集落刺激因子（G-CSF,商品名：惠尔血）10μg/（kg·day）,连续5天。观察外周血干细胞动员过程中的不良反应。结果急性心肌梗死患者在外周血干细胞动员期间不良反应发生率为45.5%,其中低热为18.2%,骨痛为13.6%,高热为0.09%,1例因支架内血栓形成退出试验。结论急性心肌梗死患者静脉注射GCS-F动员自体骨髓干细胞是安全的。     

Endogenous G-CSF and CD34+ cell mobilization after acute myocardial infarction

BACKGROUND: Several reports showed an increase of CD34(+) stem/progenitor cell count early after an acute myocardial infarction (AMI), suggesting a contribution of bone marrow cells in myocardial regeneration after the acute event. Nevertheless, at present plasma mediators of CD34(+) cell mobilization from bone marrow to peripheral blood in patients with AMI are poorly understood. Aim of our study was to establish the impact of different well-known mobilizing cytokines on spontaneous stem cell mobilization in patients with different ischemic heart syndromes, such as the AMI and the chronic stable angina (CSA), compared to healthy controls. METHODS: In 16 patients with AMI, 18 with CSA and 22 healthy blood donors the concentration of CD34(+) cells, and mobilizing cyokines (G-CSF, SCF, VEGF, SDF1-alpha) were assessed. RESULTS: The peak number of circulating CD34(+) cells in AMI patients (8.58+/-2.08 cells/microl) was higher than that observed in patients with CSA (3.41+/-0.56 cells/microl, p=0.0061) or in healthy controls (2.18+/-0.35 cells/microl, p<0.001). However endogenous G-CSF was significantly higher in the serum of patients with AMI compared to CSA patients and to controls and in CSA patients compared to controls. Interestingly, as regards VEGF, while this cytokine was increased in AMI with respect to control and CSA group, the latter showed a significantly lower concentration with respect to controls. Finally SDF-1 alpha was higher in AMI patients with respect to controls. CD34(+) cells were significantly correlated to G-CSF (directly) and to SCF (inversely) in patients with AMI. CONCLUSION: In the present study, we have demonstrated for the first time that the spontaneous mobilization of CD34(+) cells into the peripheral blood of patients with AMI is significantly correlated to endogenous G-CSF. Considering recent data suggesting a potential favourable effect of circulating CD34(+) cells on left ventricular function, the present evidence of a correlation between endogenous G-CSF and CD34(+) cell levels supports the pharmacological administration of G-CSF as a non-invasive option for regeneration of myocardial tissue after AMI.     

Peripheral blood stem cell mobilization by granulocyte colony-stimulating factor alone and engraftment kinetics following autologous transplantation in children and adolescents with solid tumor

In 56 pediatric and adolescent patients (median age 7 years, range 1-21) with various solid tumors, peripheral blood stem cells (PBSC) were mobilized with granulocyte colony-stimulating factor (G-CSF) alone, and the yields of PBSC and engraftment kinetics following autologous peripheral blood stem cell transplantation (PBSCT) were evaluated retrospectively. Granulocyte colony-stimulating factor (10 microg/kg) was injected subcutaneously for mobilization when patients showed no influence of previous chemotherapy, and administration was continued for 5 days. The peaks of CD34+ cells and colony-forming units-granulocyte/macrophage in the blood were observed on days 4 through 6 of G-CSF administration in all patients. Peripheral blood stem cell harvest was commenced on day 5 of G-CSF treatment. Compared to the results in patients mobilized by chemotherapy plus G-CSF (N=18), the progenitor cell yields were lower in patients mobilized with G-CSF alone. However, there were no significant differences in WBC and ANC engraftment compared to the chemotherapy plus G-CSF mobilization group. Platelet recovery following autologous PBSCT was delayed in patients mobilized with G-CSF alone. The median time taken for ANC and platelet counts to reach 0.5 x 10(9) and 20 x 10(9)/l was 12 days (range: 9-28) and 15 days (8-55), respectively, in all patients who received PBSC mobilized by G-CSF alone. In summary, mobilization with G-CSF alone can mobilize sufficient CD34+ cells for successful autografting and sustained hematological reconstitution in pediatric and adolescent patients with solid tumors, and even in heavily pre-treated patients.     

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。     

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.     

Comparison between granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in the mobilization of peripheral blood stem cells

Peripheral blood stem cells (PBSC) have become the preferred source of stem cells for autologous transplantation because of the technical advantage and the shorter time to engraftment. Mobilization of CD34+ into the peripheral blood can be achieved by the administration of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), or both, either alone or in combination with chemotherapy. G-CSF and GM-CSF differ somewhat in the number and composition of PBSCs and effector cells mobilized to the peripheral blood. The purpose of this review is to give a recent update on the type and immunologic properties of CD34+ cells and CD34+ cell subsets mobilized by G-CSF or GM-CSF with emphasis on (1) relative efficacy of CD34+ cell mobilization; (2) relative toxicities of G-CSF and GM-CSF as mobilizing agents; (3) mobilization of dendritic cells and their subsets; (4) delineation of the role of adhesion molecules, CXC receptor 4, and stromal cell-derived factor-1 signaling pathway in the release of CD34+ cell to the peripheral blood after treatment with G-CSF or GM-CSF.     

Kinetics of circulating haematopoietic progenitors during chemotherapy-induced mobilization with or without granulocyte colony-stimulating factor

Summary. Kinetics of circulating haematopoietic progenitors was analysed during chemotherapy- or chemotherapy plus granulocyte colony-stimulating factor (G-CSF)-induced mobilization of peripheral blood stem cells. Circulating progenitors including colony-forming unit granulocyte/macrophage (CFU-GM), burst forming-unit erythroid (BFU-E) and multilineage colony forming unit (CFU-Mix) were studied serially on alternate days during a recovery phase from chemotherapy for consolidation of complete remission. In 18 patients with acute leukaemia, 27 courses of consolidation chemotherapy were performed with a combination of an intermediate-dose cytosine arabinoside with etoposide (Ara-C/Etop) or mitoxantron (Ara-C/Mit). G-CSF (5 μg/kg) was administered during the recovery phase in 6/14 courses with Ara-C/Etop and in 4/13 courses with Ara-C/Mit. G-CSF induced a significant and synchronized increase of circulating CFU-GM, BFU-E and CFU-Mix by more than 4-fold at their peaks. The peak of CFU-GM was significantly correlated with that of both BFU-E and CFU-Mix, irrespective of additional G-CSF mobilization. G-CSF also produced a significant increase of monocytes in a synchronized fashion with an increase of circulating CFU-GM. Interestingly, peripheral blood monocytes spontaneously produced high concentrations of IL-6; a significant correlation was observed between absolute monocyte counts and plasma levels of IL-6 or peak levels of CFU-GM.
These observations indicate that the addition of G-CSF to chemotherapy-induced mobilization can facilitate further expansion of a blood progenitor pool during the haematopoietic recovery, probably through the stimulation of monocytes to proliferate and to induce their monokine production such as IL-6. The data also suggest that absolute monocyte counts may be a useful indicator to predict the peak of circulating progenitors for collecting autologous blood stem cells.     

Effect of granulocyte colony-stimulating factor treatment at a low dose but for a long duration in patients with coronary heart disease.

BACKGROUND: In animal models, granulocyte colony-stimulating factor (G-CSF) improves post-infarct cardiac function. However, in pilot studies involving patients with angina and acute myocardial infarction (AMI), G-CSF at a high dose frequently induced coronary occlusion or restenosis, but those at a low dose showed no significant beneficial effect. We hypothesized that a low dose but long duration of G-CSF will have a beneficial effect without serious complications to patients with coronary heart disease. METHODS AND RESULTS: Forty-six patients with angina or AMI were randomly assigned into G-CSF and non-G-CSF control groups, respectively. Recombinant G-CSF was subcutaneously injected once a day for 10 days. The leukocyte counts in the peripheral blood were controlled at approximately 30,000/microl. One month later, a Thallium-201 single photon emission computed tomography revealed the increased percentage uptake and the reduced extent and severity scores in the G-CSF angina group. In the G-CSF AMI group, the curve between the ejection fraction and peak creatine kinase shifted significantly upward, compared with that of the non-G-CSF AMI group. Serious complications were not observed during the 6 months of observation. CONCLUSIONS: A low dose but long duration of G-CSF treatment may have a beneficial effect without any serious complications in patients with coronary heart disease.     

Secondary acute myeloid leukemia and myelodysplasia after autologous peripheral blood progenitor cell transplantation

Secondary myelodysplastic syndrome (MDS) and acute leukemia (AL) are well-known complications of antineoplastic therapy. The incidence of these serious complications after autologous hematopoietic transplantation ranges from 1.1% to 24%. Prior chemotherapy is its most likely cause, but other variables related to these long-term complications are seriously discussed. There is evidence that priming of progenitor cells isolated from peripheral blood with chemotherapy is also related to a higher risk of secondary MDS/AL. Whether progenitor cells isolated from bone marrow or peripheral blood after mobilization only with cytokines are related to higher risk is a controversial issue. In this paper, we analyze the incidence and variables related to these complications in a series of 99 patients diagnosed with lymphoma or multiple myeloma who underwent autologous transplantation using hematopoietic progenitors isolated from peripheral blood mobilized with granulocyte colony-stimulating factor (G-CSF). The probability of MDS/AL in patients alive 5 years after transplant in our series is 8.58%, similar to that reported in other series using bone marrow grafts. The total dose of cyclophosphamide ( p=0.099), the number of chemotherapy cycles ( p=0.04) received before transplant, and the total dose of mononuclear cells infused at the time of transplant were the only variables associated with secondary MDS/AL. Autologous transplantation with progenitor cells isolated from peripheral blood after mobilization with cytokines has probability and risk factors for secondary MDS/AL development similar to bone marrow grafts when compared with other published series.