大剂量多西他塞联合粒细胞集落刺激因子用于恶性实体瘤外周血造血干/祖细胞动员

目的观察大剂量多西他塞联合粒细胞集落刺激因子(G-CSF)在恶性实体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30例恶性实体瘤患者入组,第一天采用多西他塞120mg/m2经静脉持续滴注3小时,在白细胞1.0×109/L左右时每天给予G-CSF5μg/kg,分早晚两次皮下注射,直至采集结束。结果在给予多西他塞后平均第(6.47±1.01)天白细胞降至1.0×109/L,皮下注射G-CSF平均(3.50±1.01)天即多西他塞动员后平均第(9.97±1.03)天开始外周血造血干/组细胞单采,每人每天采集一次,采集两天,共获CD34+细胞中位数3.49×106/kg(1.71×106～16.69×106/kg),其中CD34+细胞>2.0×106/kg的患者25例。不同采集时间获CD34+细胞数差异无统计学意义(P=0.651)。6例发生关节轻度疼痛,3例轻度腹泻,1例口腔粘膜炎。结论多西他塞120mg/m2联合G-CSF5μg/kg是恶性实体瘤患者动员采集自体干/祖细胞的有效安全方案。     

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.     

Comparison of Peripheral Blood Stem Cells Mobilized with Granulocyte Colony-stimulating Factor with or without Prior Standard-dose Chemotherapy in Patients with Malignancy

We studied the effect of granulocyte colony-stimulating factoron the magnitude of peripheral blood stem cell mobilizationin patients with malignancy. The leukapheresis products mobilizedwith granulocyte colony-stimulating factor alone at a steadystate (a period of full hematopoietic recovery) (group 1) werecompared with those obtained after cytotoxic chemotherapy usinggranulocyte colony-stimulating factor (group 2). In group 1,six patients underwent six courses of stem cell collection witha median of 20 l leukapheresis. In group 2, 10 patients underwent12 courses of stem cell collection with a median of 10 l leukapheresis.Median yields of group 1 vs. group 2 were mononuclear cells(x10⁹), 21.9 vs. 11.6; CD34⁺ cells (x10⁶/l), 14.5 vs. 17.1;colony-forming unit for granulocyte-macrophage (/ml), 223 vs.1193; burst-forming unit for erythroid (/ml), 29 vs. 71; colony-formingunit for erythroid (/ml), 42 vs. 29; colony-forming unit formegakaryocyte (/ml), 26 vs. 59. While there were no statisticallysignificant differences in the number of CD34⁺ cells betweenthe two groups, granulocyte-macrophage-committed progenitorcells were more enriched in the apheresis products of group2. The correlation between CD34⁺ cells and colony-forming unitfor granulocyte-macrophage was poor. Our results demonstratethat granulocyte colony-stimulating factor can mobilize a sufficientnumber of progenitor cells into the peripheral blood for stemcell transplantation with or without prior chemotherapy.     

Patient with Extensive Small Cell Lung Cancer Given Moderately Doseintensified Chemotherapy and Peripheral Blood Stem Cell Support

Although recent progress in multi-drug chemotherapy has increasedthe median survival of patients with extensive Small cell lungcancer (SCLC) to 7 months, 2-year survivors are still exceptional.We describe a 40-year-old man with extensive SCLC involvingthe lungs and systemic nodes who was initially treated with6 cycles of an alternating combination regimen consisting ofcyclophosphamide, doxorubicin, vincristine, cisplatin and etoposide.After the second cycle of the regimen, Peripheral blood stemcells (PBSC were harvested and frozen. The patient then receiveda moderately dose-intensified regimen consisting of cisplatin(80 mg/m²)and etoposide (500 mg/m²x3), followed by infusionof the thawed PBSC. Hematopoietic recovery was rapid, and thepatient remained tumor-free for 12 months until multiple tumorrecurrence.     

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。     

多西他赛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分析

 目的研究多西他赛联合重组人粒细胞集落刺激因子（rhG-CSF）在乳腺癌患者动员外周血干细胞 （peripheral blood stem cell,PBSC）的效果及影响因素。方法2006年2月—2009年6月我科收治的55例 行多西他赛（商品名多帕菲,TXT,120 mg/m2 持续静脉滴注3 h）动员的乳腺癌患者,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、内脏、骨转移情况及化、放疗情况对采集单个核细胞（mononuclear cell,MNC）和CD34+细胞的影响。结果多西他赛化疗动员后中位7d白细胞降至1.0×109/L 左右,皮下注 射rhG-CSF中位3d,采集总MNC平均(5.51±1.24)×108/kg,采集总CD34+细胞平均(2.90±1.38)×106/kg 。年龄、化疗后白细胞最低数与采集CD34+细胞均显著相关（P<0.05）。化疗的周期数≤6的患者采集平均 CD34+细胞数较周期数≥6患者显著增高（P<0.05）。无1例患者出现严重不良反应。结论TXT（120 mg/m2 持续静脉滴注3 h）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、既往化疗周期数显 著影响患者CD34+细胞的采集数量。患者化疗后白细胞最低数可作为采集CD34+细胞数量的预测指标。     

Dose-dense Vinorelbine and Paclitaxel with Granulocyte Colony-stimulating Factor in Metastatic Breast Cancer Patients: Anti-tumor Activity and Peripheral Blood Progenitor Cell Mobilization Capability

We studied the safety, activity and peripheral blood progenitor cell mobilizing capability of a dose-dense combination of vinorelbine (VNB) and paclitaxel (PTX) as first-line chemotherapy for patients with metastatic breast cancer (MBC). Forty-three MBC patients were submitted to four cycles of VNB 30 mg/m2 and PTX 175 mg/m2 intravenously, every 2 weeks, as the first induction step of a tandem high-dose chemotherapy program. Granulocyte colony-stimulating factor (G-CSF) 5 microg/kg was administered daily from day +5 to +10 in order to accelerate hematopoietic recovery, or 48h after the last VNB-PTX when a leukapheresis was planned (after the third or fourth cycle). A total of 172 cycles were administered. The mean delivered dose-intensity of VNB and PTX was 14.7 and 86 mg/m2/week, respectively (98% of the planned dose-intensity). The main per-patient toxicities were: peripheral neurotoxicity (G1/2 60%, G3 5%), constipation (G1/2 10%), oral mucositis (G1/2 20%), and asthenia (G1/2 35%). Hematological toxicity was unremarkable, except for anemia with hemoglobin (Hb) values < 10 g/dl (28%), and lymphopenia with lymphocyte counts < 1000/mm3 (28%). Two complete (5.1%) and 24 partial (61.5%) responses were observed in 39 assessable patients, for an overall response rate of 66.6% (95% CI 51.6-80.9). A median of one apheretic procedure (range 1-3) was required to achieve the target number of 6 x 10(6)/kg CD34+ cells. The median number of CD34+ harvested per patient was 15 x 10(6)/kg (range 6.4-36.5). Four cycles of dose dense VNB and PTX showed a favorable toxicity profile, a relevant anti-tumor activity and a high peripheral blood progenitor cell mobilizing activity.     

High Dose Chemotherapy with Autologous Stem Cell Rescue in Adults with Malignant Primary Brain Tumors

High dose chemotherapy (HDCT) with autologous (bone marrow or peripheral blood) stem cell rescue (ASCR) has had success in the treatment of some malignant pediatric brain tumors. We report a series of adults enrolled in one of three HDCT and ASCR protocols for malignant primary brain tumors.Overall toxic mortality was 18%; chemotherapy regimen, tumor type, and prior treatment did not predict transplant-related mortality. Patients over the age of 30 had a higher rate of toxic mortality. Patients with recurrent medulloblastoma had a significant improvement in long-term survival (median: 34 months) as compared with historical reports; two patients with glioblastoma survive beyond four years without progression, but overall, a significant improvement in long-term survival could not be demonstrated for malignant gliomas.     

聚乙二醇化重组人粒细胞集落刺激因子预防化疗后中性粒细胞减少症临床疗效观察中性粒细胞减少症临床疗效观察

比较聚乙二醇化重组人粒细胞集落刺激因子（PEG-rhG-CSF）和重组人粒细胞集落刺激因子（rhG-CSF）预防化疗后中性粒细胞减少症的有效性和安全性。方法：采用随机自身交叉对照,选择初治恶性肿瘤患者接受2个周期相同方案的化疗,其中试验周期给予PEG-rhG-CSF 100 μg/kg皮下注射一次,对照周期每日一次皮下注射rhG-CSF 5 μg/kg,直至外周血中性粒细胞绝对值（ANC）在低谷后连续两次检查≥5.0×109/L。结果：入组78例患者,在76个试验周期和74个对照周期中,ANC<1.5×109/L的发生率分别为30.26%和21.16%,持续时间分别为2.34 d和2.31 d;ANC<0.5×109/L的发生率分别为3.8%和3.0%;抗生素使用率分别为11.59%和9.60%（P均<0.05）。试验药和对照药的不良反应均为骨骼肌肉疼痛、乏力、发热、头晕等,发生率与严重程度相似。结论：PEG-rhG-CSF一次给药的疗效和不良反应与rhG-CSF多次给药相似。     

The Role of Stem Cell Factor in Mobilization of Peripheral Blood Progenitor Cells

Stem cell factor (SCF) is a hematopoietic growth factor which acts on both primitive and mature progenitors cells. In animals, high doses of SCF alone stimulate increases in cells of multiple lineages and mobilize peripheral blood progenitor cells (PBPC). Phase I studies of rhSCF have demonstrated dose related side effects which are consistent with mast cell activation. Based upon in vitro synergy between SCF and G-CSF we have demonstrated the potential of low doses of SCF to synergize with G-CSF to give enhanced mobilization of PBPC. These PBPC have increased potential for both short and long term engraftment in lethally irradiated mice and lead to more rapid recovery of platelets. On going Phase I/II studies with rhSCF plus rhG-CSF for mobilization of PBPC, demonstrated similar increases in PBPC compared to rhG-CSF alone. These data suggest a clinical role of rhSCF in combination with rhG-CSF for optimal mobilization of PBPC.     

恶性肿瘤患者外周血细胞凋亡检测的意义

为了探讨恶性肿瘤患者外周血细胞的生物学特性变化的临床意义，作者用流式细胞术对８４例恶性肿瘤患者血细胞凋亡水平进行了检测分析。结果表明，肿瘤患者细胞凋亡水平显著高于健康人（分别为５．５１％±８．５２％和０．２５％±０．２８％，Ｐ＜０．０１）；患者细胞凋亡水平虽然随Ｓ期细胞增高有逐渐减低的趋势，但无明显的线性关系。ＤＮＡ异倍体患者凋亡水平虽然低于二倍体患者，但无统计学意义（Ｐ＞０．０５）。这表明，恶性肿瘤患者外周血细胞凋亡水平变化不仅代表恶性肿瘤一种生物学特性，而且还可以作为恶性肿瘤诊断的良好指标。最后对患者外周血细胞中出现凋亡的原因作了分析。     

Analysis of a Chronic Myelogenous Leukemia Patient Vaccinated with Leukemic Dendritic Cells Following Autologous Peripheral Blood Stem Cell Transplantation

Dendritic cells (DCs) are believed to be the most potent antigen-presenting cells and may be important in the induction of anti-leukemia specific T cell responses. In this preliminary clinical study, a patient with chronic phase chronic myelogenous leukemia (CML) was vaccinated with autologous leukemic DCs following autologous peripheral blood stem cell transplantation (PBSCT). In an in vitro study, leukemic DCs were generated using granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-α, and interleukin-4 from granulocyte colony-stimulating factor (G-CSF)-mobilized PBSC fraction of this patient, and were found to be Phl⁺, and to possess the morphologic and phenotypic characteristics of mature DCs. These cells could also elicit antigen-specific immune responses, including a vigorous cytotoxicity specific to CML cells. In the clinical experiment, we obtained evidence that infused leukemic DCs could induce T cell clones expressing the same T cell receptor usage as a cytotoxic T cell line, suggesting that the immune repertoire includes tumor-reactive T cells. These cytotoxic T lymphocytes are activated in vivo . The vaccination of leukemic DC caused a decrease in the number of Phl⁺ cells in the peripheral blood and bone marrow. These results indicate that the activity is an immunologically mediated phenomenon and vaccination therapy with leukemic DC following autologous PBSCT may be effective in treating CML.     

2周期大剂量化疗联合自体外周血干细胞移植治疗转移性乳腺癌的临床疗效观察

目的观察2周期大剂量化疗方案联合自体外周血干细胞移植(D—HDC)治疗转移性乳腺癌的疗效及其安全性。方法将28例转移性乳腺癌患者分为2个组。D—HDC组预处理方案：多西紫杉醇(DXL)110～130mg／m^2 噻替哌(THPA)300～400mg／m^2十卡铂(CBP)650～750mg／m^2，预处理后第2天回输外周血干细胞，间隔3～5周重复，共治疗2个周期；S—HDC组预处理方案：DXL110-130mg／m^2 THPA350-450mg／m^2 CBP750-950mg／m^2，预处理后第2天回输外周血干细胞，治疗1个周期。分别评价2组肿瘤客观缓解率和治疗相关的不良反应。结果D-HDC组和S-HDC组的客观缓解率分别为66．7％(10／15)，54．5％(6／11)；2组白细胞毒性相近，但D-HDC组血小板毒性较低，Ⅲ～Ⅳ度发热，恶心呕吐，腹泻和黏膜炎的发生例数较少。结论D-HDC治疗转移性乳腺癌客观缓解率较高，血小板毒性较轻，Ⅲ～Ⅳ度非血液学毒性发生例数较少，患者耐受性良好。     

非小细胞肺癌患者外周血淋巴细胞中CD44表达的临床研究

目的 探讨非小细胞肺癌患者外周血淋巴细胞中CD44表达与其临床病理特征的关系。方法 应用流式细胞术对50例肺癌患者外周血淋巴细胞中CD44表达进行荧光免疫检测,通过自身对照分析治疗前后的变化,并与正常对照组（n=20）及肺部良性病变组（n=25）进行对比研究。结果 CD44在3组中均有不同程度的表达。50例肺癌患者外周血淋巴细胞中CD44表达明显高于正常对照组及良性病变组（P＜0.01）。良性病变组和正常对照组CD44的表达无显著性差异（P＞0.05）。手术前外周血淋巴细胞中CD44表达显著高于手术后（P＜0.01）;肺癌淋巴结转移者CD44表达高于不伴淋巴结转移者（P＜0.01）;Ⅲ、Ⅳ期和Ⅰ-Ⅱ期之间CD44的表达有非常显著性差异（P＜0.01）;肺癌组织学分级与CD44表达有明显相关性（P＜0.05或0.01）;肺癌患者外周血中CD44的表达与组织学类型无相关性。结论 应用流式细胞仪检测CD44的表达水平可作为判断肺癌负荷状况、转移及预后的指标。     

急性白血病异基因外周血造血干细胞移植血缘供者安全性分析

目的：探讨急性白血病异基因外周血造血干细胞移植血缘供者近期的不良事件及远期的安全性。方法185例急性白血病异基因外周血造血干细胞移植血缘供者,干细胞动员后,用COBE Spectra血细胞分离机采集外周血干细胞。检测供者动员时血常规及形态学分类、CD34＋细胞百分比、干细胞混悬液中单个核细胞（ MNC）数量及CD34＋细胞计数,同时记录供者动员和采集过程中的不良事件、采集后第1、3、7天血常规变化及长期随访。结果血缘供者干细胞动员前白细胞计数为（6.16±1.58）x 109·L-1,采集时白细胞计数为（41.55±9.77）x109·L-1,是动员前6.75（4.18-10.87）倍。干细胞混悬液MNC为（247.61±105.99）x 108,CD34＋细胞为（3.54±3.42）x 108。动员时血缘供者的常见不良事件有头痛、腰背困痛、四肢痛、全身痛,合计占94.6%;外周血干细胞采集过程中,静脉持续输注葡萄糖酸钙,供者口周和指尖麻木等低钙症状发生率为3.2%;所有供者的不良事件均可耐受,无一例供者因不良事件终止干细胞动员或采集。供者干细胞采集后1周血象基本恢复正常;随访11 a血缘供者健康状况良好,无与动员及采集相关的远期并发症发生。结论急性白血病异基因外周血造血干细胞移植血缘供者动员采集无明显的近期不良事件及远期并发症,安全性非常高,为非血缘移植供者提供可靠的安全保障依据,减少恐惧感,降低反悔率。     

Effects of the in vivo Administration of Recombinant Human Granulocyte Colony-stimulating Factor Following Cytotoxic Chemotherapy on Granulocytic Precursors in Patients with Malignant Lymphoma1

We examined the effects of the in vivo administration of recombinant granulocytc colony-stimulating factor (rhG-CSF) on granulocytic precursors in the bone marrow of 4 patients with malignant lymphoma who received chemotherapy. Patients were treated with rhG-CSF at doses of 100–800 μg/ m²/day intravenously for 14 days only in the first course of chemotherapy (G-CSF course) followed by the second course of chemotherapy without rhG-CSF which was used as a control course. In the G-CSF course, white blood cell counts (WBCs) demonstrated a biphasic response consisting of a first peak observed within a few days after the initiation of rhG-CSF administration, and a second peak observed on the last day of rhG-CSF injection or the day after. In the second peak, the incidence of granulocyte-macrophage colony-forming units (CFU-GM) in mononucleated bone marrow cells did not change significantly after treatment with rhG-CSF as compared with a control. However, since the number of nucleated cells in the bone marrow increased, the absolute number of CFU-GM in the bone marrow increased. The number of mature and immature granulocytes in the bone marrow increased. These findings suggest that G-CSF stimulates the proliferation and differentiation of granulocytic precursors in the bone marrow in granulocytopenic patients who received cytotoxic drugs and causes mature granulocytes to be released from the bone marrow.     

非小细胞肺癌患者外周血CEA mRNA表达及临床意义

 目的：检测非小细胞肺癌(NSCLC)患者外周血CEA表达情况,探讨其作为分子标志物检测 NSCLC微转移的可行性。方法：应用RT-PCR技术检测48例NSCLC患者,15例肺良性疾病(BLD)患者 和10例健康人外周血CEA mRNA的表达。结果：NSCLC患者CEA mRNA的阳性表达率明显高于BLD患 者和健康对照组(P<0.01)。Ⅰ~Ⅳ期NSCLC患者外周血中CEA mRNA阳性表达率分别为27.8%、 83.3%、61.5%和100%。NSCLC患者外周血CEA阳性表达与临床分期及淋巴结转移密切相关 (P<0.05),而与病理类型及分化程度无关(P>0.05)。结论：检测外周血CEA mRNA表达可作为诊 断NSCLC患者微转移的一个有价值的参考指标。     

基因重组人粒细胞集落刺激因子防治CHOP和CAF方案化疗所致白细胞减少症的临床研究

作者采用随机分组、自身交叉对比的方法，观察了基因重组人粒细胞集落刺激因子（ＲｅｃｏｍｂｉｎａｎｔＨｕｍａｎＧｒａｎｕｌｏｃｙｔｅＣｏｌｏｎｙ－ＳｔｉｍｕｌａｔｉｎｇＦａｃｔｏｒ，ｒｈＧ－ＣＳＦ，以下简称ｒｈＧ－ＣＳＦ）对２３例肿瘤患者ＣＨＯＰ和ＣＡＦ方案化疗所致白细胞和中性粒细胞减少的防治作用及毒副反应。结果表明，ｒｈＧ－ＣＳＦ可以减轻化疗过程中白细胞和中性粒细胞下降的程度，缩短白细胞和中性粒细胞降至正常值以下的持续时间，促进其早日恢复，使化疗可以如期进行。ｒｈＧ－ＣＳＦ副反应轻微，安全可靠。     

异基因外周血干细胞移植后巨细胞病毒感染的早期检测及临床意义

目的:选择有效的巨细胞病毒(CMV)早期检测方法用于异基因外周血干细胞移植(allo-PBSCT).方法:采用微粒子酶免疫分析法(MEIA)、间接免疫荧光法(IFA)及实时荧光定量PCR法(Real-time FQ-PCR)对42例allo-PBSCT患者移植后不同时间进行多点动态检测外周血 CMV IgM 抗体、CMV pp65 抗原及 CMV DNA 负荷量.结果:1)移植患者CMV pp65抗原及DNA负荷量的阳性检出率(38.24%,33.82%)明显比IgM抗体阳性检出率(21.50%)高(P＜0.05).2)CMV pp65抗原及DNA负荷量的阳性检出时间(75±64天,60±50天)明显早于IgM(127±73天)(P＜0.05).3)CMV活动性感染的发生与患者移植后急性移植物抗宿主病(aGVHD)的发生密切相关(P＜0.05).结论:pp65抗原和DNA负荷量的检测方法适合用于allo-PBSCT术后患者的CMV感染的早期诊断.aGVHD的发生是allo-PBSCT患者CMV活动性感染的危险因素.     

多周期大剂量化疗辅以外周血干细胞支持对难治性卵巢癌的治疗探索

卵巢癌的复发和耐药是治疗的重点和难点。目前 ,仍没有较为可靠的治疗手段 ,多周期、大剂量化疗辅以外周血干细胞回输支持 ,作为复发或难治性卵巢癌的巩固或一线治疗方案 ,则能够明显减少大剂量化疗引起的毒副反应 ,缩短化疗周期 ,国外已进行了多中心、多周期、多方案的临床探索 ,有望成为治疗此类卵巢癌的有效方案。