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.     

Phase I/II study of cisplatin, ifosfamide and irinotecan with rhG-CSF support in patients with stage IIIB and IV non-small-cell lung cancer

Purpose: We conducted a phase I/II study in previously untreated patients with stage IIIB or IV non-small-cell lung cancer (NSCLC) to: (1) determine the maximum tolerated dose (MTD) of cisplatin combined with a fixed schedule of ifosfamide and irinotecan with rhG-CSF support; and (2) to determine the overall response rate and median survival of patients entered on this study. Methods: Ifosfamide (1.5 g/m²) and irinotecan (60 mg/m²) were administered at fixed doses on days 1–4 and on days 1, 8 and 15, respectively. Cisplatin was given on day 1 at 60 mg/m² and was increased in 10-mg/m² increments. This regimen was repeated every 4 weeks. rhG-CSF (nartograstim) was administered subcutaneously at a dose of 1 μg/kg on days 5–18 except on the day of irinotecan treatment. Results: Between June 1995 and April 1998, 46 patients were registered onto this phase I/II study. The MTD of cisplatin was defined according to toxicity and the dose during three courses was increased. Since at the 80 mg/m² dose level more than one-third of the patients were treated with dose modification, the dose of 70 mg/m² was recommended for phase II study. The dose-limiting toxicity was leukopenia. The overall response rate was 62.2% (95% CI 48.0–76.4%), the median response duration was 144 days, and the median survival time was 393 days. Conclusion: For phase II study, we recommend doses of cisplatin 70 mg/m² on day 1 combined with ifosfamide and irinotecan with rhG-CSF support. Both the response rate and preliminary survival data in this study suggest a high degree of activity of this combination in previously untreated NSCLC. Received: 29 April 1999 / Accepted: 15 September 1999     

高低剂量Granocyte(rhG－CSF)治疗消化道癌化疗后白细胞减少症

目的 :化疗后白细胞减少时先给高剂量Granocyte,待白细胞正常用量减半并设对照组观察效果。 方法 :5 0例消化道癌患者化疗后白细胞降至 <3 0× 10 9/L。A组 ,每日皮下注射Granocyte 10 0 μg ,共 10日。B组 ,每日皮下注射高剂量Granocyte 2 5 0 μg ,3～ 5日后 ,当白细胞升至 >4 0× 10 9/L ,剂量减半 ,再用 5～ 7日 ,总用药 10日。结果 :观察 5 0例 ,男性 37例 ,女性 13例。计食管癌 9例 ,胃癌 35例 ,肠癌 6例。A组 37例 ,B组 13例 ,共 5 0例 ,总有效率 96 0 % (显效 73 0 % ,有效 2 1 6 % )。B组 10 0 0 % (显效 6 9 2 % ,有效 30 8% ) ,全组 3例 (6 % )有发热副反应。结论 :使用高低剂量Granocyte升白疗效好 ,效果稳定。     

基因重组人粒细胞集落刺激因子在急性白血病化疗后的临床应用

目的：急性白血病,大剂量化疗后,白细胞平均降至１ ．０３３ ×１０９／Ｌ 时,应用重组人粒细胞集落刺激因子（ｒｈＧ－ ＣＳＦ） , 使白细胞恢复。方法： 每天２５０μｇ 皮下注射, 直至连续两次复查中性粒细胞绝对计数（ＡＮＣ） 超过１ ．５ ×１０９／Ｌ 后停药,平均用药时间５ ．９ 天。结果：与未采用ｒｈＧ－ ＣＳＦ 治疗的对照组１３ ．２ 天ＡＮＣ 超过１ ．５ ×１０９／Ｌ 相比,粒细胞缺乏的恢复时间明显缩短。ｒｈＧ－ ＣＳＦ 能够明显增加白血病患者化疗后白细胞的恢复,缩短白细胞减少症的恢复时间。结论：ｒｈＧ－ ＣＳＦ 能够保证白血病患者接受并完成强烈化疗,从而提高患者生存率。     

吉粒芬在肿瘤化疗中的临床应用研究

为观察吉粒芬（国产基因重组人粒细胞集落刺激因子，ｒｈＧＣＳＦ）防治肿瘤化疗所致白细胞和中性粒细胞减少的临床效果，应用吉粒芬预防和治疗４１个化疗周期中的白细胞和中性粒细胞减少，按吉粒芬剂量分为每天１次７５μｇ和１５０μｇ两组，每组连续用药５～１４ｄ。全组包括吉粒芬７５μｇ组预防用药２３周期，治疗用药６周期；１５０μｇ组预防用药７周期，治疗用药５周期。结果表明，吉粒芬能有效预防和治疗肿瘤化疗所致白细胞和中性粒细胞下降，降低其下降幅度和缩短其持续时间，为按期化疗提供了条件。１５０μｇ的预防和治疗效果优于７５μｇ，结果显示，吉粒芬提升白细胞和中性粒细胞的效果确切，不良反应轻微     

rhG-CSF与rhGM-CSF的临床应用及安全性

应用rhGM-CSF或rhG-CSF治疗由药物或KOSTAMAN综合征等引起的粒细胞减少症疗效较明确,可明显降低死亡率,两者之间无明显差异;白细胞缺乏合并真菌感染,rhGM-CSF可加速中性粒细胞恢复,缩短真菌清除时间,与抗感染药合用可提高疗效;两者单独使用治疗再障可提高粒细胞数,降低感染率;与EPO、ALG/ATG联合治疗再障或重型再障,实验组与对照组有显著性差异,生存率明显提高;在强化免疫抑制的基础上联用治疗重型再障,实验组优于对照组,在提高缓解率、降低死亡率方面具有重要的临床意义。有学者指出rhGM-CSF在体内外对肺鳞状细胞癌的侵袭有促进作用。临床常见不良反应有发热、骨痛、过敏反应,罕见的不良反应有Sweet综合征、类白血病反应、血压下降、癫痫发作等。     

rhG-CSF基因工程菌发酵中pH值对表达率的影响

本文对重组人粒细胞集落刺激因子(rhG-CSF)基因工程菌的摇瓶发酵和发酵工艺进行了研究。结果表明，在摇瓶发酵中梯度调低培养基pH值可以提高产物的表达率；在发酵罐发酵工艺中适当调高培养基pH值可以提高产物的表达率。     

化疗后早期应用粒生素的疗效观察

目的　探讨化疗后早期应用重组人粒细胞集落刺激因子 (rhG -CSF ,粒生素 )对白细胞和粒细胞减少的防治作用。方法　治疗组化疗后 2 4～ 48小时内给予粒生素应用 ;对照组则在白细胞低于正常值时开始给予粒生素应用。结果　治疗组白细胞低于正常值的持续时间明显短于对照组 (P <0 0 5 ) ,且治疗组化疗后感染率明显降低 (P <0 0 5 )。结论　粒生素预防应用可以明显缩短白细胞低于正常值的持续时间 ,减少化疗过程中感染的发生率     

Phase-II trial of idarubicin, fludarabine, cytosine arabinoside, and filgrastim (Ida-FLAG) for treatment of refractory, relapsed, and secondary AML

 The current phase-II trial was initiated to assess the efficacy and toxicity of the Ida-FLAG regimen in patients with poor-risk acute myeloid leukemia (AML). Three subgroups of patients with AML were eligible for the study: (a) refractory, (b) first relapse, or (c) secondary AML (i.e., signs of trilineage myelodysplasia at diagnosis or the history of a myelodysplasia or myeloproliferative disorder). Fifty-seven fully evaluable patients were included in the study. Twenty patients received a second course of Ida-FLAG. Complete remission was achieved by 1/14 patients with refractory AML, 12/15 patients with relapsed AML, and 17/28 patients with secondary AML. The median duration of ANC <1000/μl was 17 days (10–36); of platelets <30,000/μl 23 days (9–65); of days with fever >38.0  °C 6 days (1–33). Thirteen patients (22.8%) died within 42 days of severe infection or hemorrhage. Overall survival at 20 weeks in the subgroups was 24% for patients with refractory, 78% for patients with relapsed, and 55% for patients with secondary AML. The toxicity of the first cycle of Ida-FLAG is moderate. The feasibility and subjective tolerance of the Ida-FLAG regimen are acceptable. There is no evidence for an increase of atypical infections. The efficacy for patients with secondary AML and especially those with first relapse of AML is good, with a high rate of complete remissions. Remission duration seems to be short. Therefore, an intensified post-remission therapy seems necessary. Received: August 28, 1998 / Accepted: April 9, 1999