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对转移性乳腺癌患者给予表柔比星、紫杉醇和粒细胞集落刺激因子化疗后外周血造血祖细胞的动员、采集及特性分析

Mobilization, collection, and characterization of peripheral blood hemopoietic progenitors after chemotherapy with epirubicin, paclitaxel, and granulocyte-colony stimulating factor administered to patients with metastatic breast carcinoma.

作者信息

Bengala C, Pazzagli I, Tibaldi C, Favre C, Vanacore R, Greco F, Mazzoni A, Menconi M C, Macchia P, Conte P F

机构信息

Division of Medical Oncology, University of Pisa, Italy.

出版信息

Cancer. 1998 Mar 1;82(5):867-73.

PMID:9486575
Abstract

BACKGROUND

As single agents, both paclitaxel and epirubicin in combination with cytokines can mobilize peripheral blood progenitor cells (PBPCs). The authors have demonstrated previously that the combination of epirubicin and paclitaxel is very active against metastatic breast carcinoma and tolerated by patients.

METHODS

Twenty-one patients with metastatic breast carcinoma received epirubicin 90 mg/m2 in combination with paclitaxel 200 mg/m2 given as a 3-hour infusion, and granulocyte-colony stimulating factor (G-CSF) starting 24 hours after chemotherapy to mobilize PBPCs. An immunophenotypic analysis for CD3, CD4, CD8, CD 19, CD33, CD34, and CD38 antigen expression was performed on apheresis products. Eighteen patients underwent high dose chemotherapy and were engrafted with PBPCs primed with paclitaxel, epirubicin, and G-CSF.

RESULTS

The median number of circulating CD34+ cells at peak was 70/microL; in the patients less heavily pretreated, it was 106.7/microL. The mean number of CD34+, CD34+/CD33-, and CD34+/CD38- cells/kg collected per apheresis was 6.3 x 10(6), 2.0 x 10(6), and 0.18 x 10(6), respectively. The mean number of CD34+ cells/kg per apheresis was 7.8 x 10(6) when the preleukapheresis CD34+ cell count was more than 50/microL and 0.9 x 10(6) when the CD34+ cell count was less than 50/microL. The mean number of CD3+, CD4+, and CD8+ cells/kg collected per apheresis was 90 x 10(6), 50 x 10(6), and 30 x 10(6), respectively.

CONCLUSIONS

Epirubicin plus paclitaxel in combination with G-CSF mobilizes PBPCs, including more primitive progenitors capable of supporting myeloablative treatment. Moreover, the mononuclear cells collected in this study contained high levels of cytotoxic effector cells suitable for ex vivo manipulation to augment the antitumor effect.

摘要

背景

作为单一药物,紫杉醇和表柔比星与细胞因子联合使用均可动员外周血祖细胞(PBPCs)。作者之前已证明,表柔比星和紫杉醇联合用药对转移性乳腺癌具有很高的活性,且患者能够耐受。

方法

21例转移性乳腺癌患者接受表柔比星90mg/m²与紫杉醇200mg/m²联合治疗,紫杉醇静脉输注3小时,化疗后24小时开始给予粒细胞集落刺激因子(G-CSF)以动员PBPCs。对单采产物进行CD3、CD4、CD8、CD19、CD33、CD34和CD38抗原表达的免疫表型分析。18例患者接受了大剂量化疗,并接受了用紫杉醇、表柔比星和G-CSF预处理的PBPCs移植。

结果

峰值时循环CD34+细胞的中位数为70/μL;预处理程度较轻的患者中,该数值为106.7/μL。每次单采收集的CD34+、CD34+/CD33-和CD34+/CD38-细胞/kg的平均数分别为6.3×10⁶、2.0×10⁶和0.18×10⁶。白细胞单采前CD34+细胞计数超过50/μL时,每次单采收集的CD34+细胞/kg平均数为7.8×10⁶;CD34+细胞计数低于50/μL时,该数值为0.9×10⁶。每次单采收集的CD3+、CD4+和CD8+细胞/kg的平均数分别为90×10⁶、50×10⁶和30×10⁶。

结论

表柔比星加紫杉醇联合G-CSF可动员PBPCs,包括更多能够支持清髓性治疗的原始祖细胞。此外,本研究中收集的单核细胞含有高水平的细胞毒性效应细胞,适合进行体外操作以增强抗肿瘤效果。

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