Danova M, Rosti V, Mazzini G, De Renzis M R, Locatelli F, Cazzola M, Riccardi A, Ascari E
Department of Internal Medicine and Medical Oncology, University and IRCCS San Matteo, Pavia, Italy.
Int J Cancer. 1995 Nov 27;63(5):646-51. doi: 10.1002/ijc.2910630508.
Bone-marrow (BM) hematopoietic precursors are recruited into proliferative activity when colony-stimulating factors (CSF) are sequenced with chemotherapy (CT). Previous studies suggested that further CT can be safely administered only when the increased proliferative activity of these cells has subsided, because most cytostatic drugs selectively damage cycling cells. The safest interval between CSF discontinuation and the start of the next CT course needs to be ascertained in vivo. Thirty patients with advanced breast cancer were treated with an intensified FEC regimen, planned at 21-day intervals, sequenced with granulocyte-macrophage (GM)-CSF (15 patients) or granulocyte (G)-CSF (15 patients). Using flow cytometry (FCM) we evaluated the proliferation kinetics of CD34+ BM hematopoietic progenitors before CT+CSF and at different times after CSF administration was stopped. FEC+GM- and FEC+G-CSF sequences both induced a rapid and sustained increase in the percentage of BM myeloid precursors (BMMP%) and in the cycling status of CD34+BM cells. However, while the BMMP% remained elevated in both cases after CSF were stopped, the enhanced proliferative activity of CD34+ cells decreased more rapidly after GM- than after G-CSF. Using FCM, CD34+ BM-derived hematopoietic presursor cell kinetics is readily evaluated in the clinical setting. The administration of CSF following CT increases both the proliferative activity of CD34+ BM cells and the BMMP%. After CSF were discontinued a kinetic refractoriness of hematopoietic progenitors was more evident after GM-CSF than after G-CSF. These data may be of value in designing clinical trials to avoid cytostatic damage to the BM hematopoietic stem-cell compartment.
当集落刺激因子（CSF）与化疗（CT）联合使用时，骨髓（BM）造血前体细胞会被募集进入增殖活动。先前的研究表明，只有当这些细胞的增殖活动增强消退后，才能安全地进行进一步的CT，因为大多数细胞毒性药物会选择性地损伤处于细胞周期的细胞。需要在体内确定停用CSF与开始下一个CT疗程之间最安全的间隔时间。30例晚期乳腺癌患者接受了强化FEC方案治疗，计划每21天进行一次，分别联合粒细胞-巨噬细胞（GM）-CSF（15例患者）或粒细胞（G）-CSF（15例患者）。我们使用流式细胞术（FCM）评估了CT+CSF之前以及停用CSF后不同时间点CD34+ BM造血祖细胞的增殖动力学。FEC+GM-CSF和FEC+G-CSF联合方案均诱导BM髓系前体细胞百分比（BMMP%）以及CD34+BM细胞的细胞周期状态迅速且持续增加。然而，虽然停用CSF后两种情况下BMMP%均保持升高，但GM-CSF组CD34+细胞增强的增殖活性比G-CSF组下降得更快。使用FCM，可以在临床环境中轻松评估CD34+ BM来源的造血前体细胞动力学。CT后给予CSF可增加CD34+ BM细胞的增殖活性以及BMMP%。停用CSF后，GM-CSF组造血祖细胞的动力学不应性比G-CSF组更明显。这些数据对于设计临床试验以避免细胞毒性药物对BM造血干细胞区室的损伤可能具有价值。
