Danova M, Rosti V, Mora O, Perotti C, Cazzola M, Riccardi A, Ascari E
IRCCS SAN MATTEO,CNR STUDY CTR HISTOCHEM,I-27100 PAVIA,ITALY. IRCCS SAN MATTEO,CTR TRANSFUS,I-27100 PAVIA,ITALY.
Oncol Rep. 1995 Nov;2(6):1075-8. doi: 10.3892/or.2.6.1075.
This study was aimed at determining: (a) the degree of mobilization of peripheral blood hematopoietic progenitors (PBSC) induced by a single course of standard-dose chemotherapy (CT) followed by G-CSF and the feasibility and safety of the administration of multiple courses of intensified CT with repeated PBSC reinfusions; (b) the relationship between the number of mononuclear cells (MC) in S-phase of the cell cycle (as evaluated by DNA flow cytometry, FCM), the CRT-GM and the CD34(+) cells in the leukapheresis product. Six patients with metastatic breast cancer received a course of standard FEC (5-FU 600 mg/m(2), epirubicin 75 mg/m(2), cyclophosphamide, CTX, 600 mg/m(2), day 1) followed by G-CSF (5 mu g/kg twice a day, from day 3 until leukapheresis), which served as both initial treatment for their disease as well as the PBSC mobilization technique. Collected PBSC were fractionated and reinfused, without G-CSF, following each of further 5 subsequent intensified FEC (HD-FEC: 5-FU 750 mg/m(2), epirubicin 100 mg/m(2), CTX 1,000 mg/m(2)) courses planned at 21-day intervals. The individual hematopoietic reconstitution curves showed superimposable profiles for all patients, and the leukaphereses were performed between days 7 and 10 after the first CT course. A median of 18.8x10(9) (10.4-35.6) MC, 9.3 (2.6-23.3) CD34(+) cells x 10(6)/kg body weight and 9.8 (1.6-27.3) CFU-GM x 10(4)/kg body weight were collected from each patient (with 1 or 2 phereses). All patients received the planned 5 courses of HD-FEC followed by PBSC reinfusion, without experiencing haematological cumulative toxicity >WHO grade 3 for WBC and >grade 2 for PLT. No >grade 3 non-hematological toxicity was recorded. There were no treatment-related delays in CT administration so that the delivered average relative dose-intensity (ARDI) was 1.65. A good correlation was seen between the percentage of MC in S-phase and the number of CFU-GM (R(2)=0.566, p<0.0065) or the number of CD34(+) cells (R(2)=0.625, p<0.0031) in the leukapheresis product. A single course of standard FEC+G-CSF is effective in mobilizing sufficient amounts of PBSC to support 5 additional courses of HD-FEC, which could represent an alternative to single, myelo-suppressive CT programs. DNA analysis by FCM should be further investigated as a rapid method for PBSC quantification, since proliferating MC and CFU-GM were closely related.
(a) 单疗程标准剂量化疗（CT）联合粒细胞集落刺激因子（G-CSF）诱导的外周血造血祖细胞（PBSC）动员程度，以及多次强化CT联合重复PBSC回输的可行性和安全性；(b) 细胞周期S期单核细胞（MC）数量（通过DNA流式细胞术，FCM评估）、集落形成单位 - 粒 - 巨噬细胞（CRT-GM）与白细胞分离产物中CD34(+)细胞之间的关系。6例转移性乳腺癌患者接受了一个疗程的标准FEC方案（5-氟尿嘧啶600 mg/m²、表柔比星75 mg/m²、环磷酰胺，CTX，600 mg/m²，第1天），随后给予G-CSF（5 μg/kg，每日两次，从第3天至白细胞分离），这既是其疾病的初始治疗，也是PBSC动员技术。采集的PBSC进行分离并回输，在无G-CSF的情况下，按照计划每21天间隔进行另外5个疗程的强化FEC（HD-FEC：5-氟尿嘧啶750 mg/m²、表柔比星100 mg/m²、CTX 1000 mg/m²）。所有患者的个体造血重建曲线显示出相似的特征，白细胞分离在第一个CT疗程后的第7至10天进行。每位患者（进行1或2次采集）平均采集到18.8×10⁹（10.4 - 35.6）个MC、9.3（2.6 - 23.3）×10⁶/kg体重的CD34(+)细胞和9.8（1.6 - 27.3）×10⁴/kg体重的CFU-GM。所有患者均接受了计划的5个疗程HD-FEC并随后进行PBSC回输，未出现白细胞＞WHO 3级、血小板＞2级的血液学累积毒性。未记录到＞3级的非血液学毒性。CT给药未出现与治疗相关的延迟，因此所给予的平均相对剂量强度（ARDI）为1.65。白细胞分离产物中S期MC百分比与CFU-GM数量（R² = 0.566，p＜0.0065）或CD34(+)细胞数量（R² = 0.625，p＜0.0031）之间存在良好的相关性。单疗程标准FEC + G-CSF能够有效动员足够数量的PBSC以支持另外5个疗程的HD-FEC，这可能是单一骨髓抑制性CT方案的一种替代方案。由于增殖的MC和CFU-GM密切相关，通过FCM进行DNA分析作为PBSC定量的快速方法应进一步研究。
