Papadopoulos K P, Ayello J, Tugulea S, Heitjan D F, Williams C, Reiss R F, Vahdat L T, Suciu-Foca N, Antman K H, Hesdorffer C S
Division of Medical Oncology, Columbia University College of Physicians and Surgeons, New York, NY, USA.
J Hematother. 1997 Feb;6(1):61-8. doi: 10.1089/scd.1.1997.6.61.
The use of CFU-GM and CD34+ cell enumeration for assessing harvest quality and factors affecting peripheral blood progenitor cell (PBPC) harvest and engraftment were investigated in 45 women with high-risk and metastatic breast cancer scheduled for dose-intensive cyclophosphamide, thiotepa, and carboplatin (CTCb). PBPC were mobilized with standard breast cancer regimens or cyclophosphamide (1.5 g/m2) and 5 micrograms/kg/day G-CSF and used together with G-CSF for hematopoietic support post-CTCb. There was a significant correlation between peripheral blood CD34+ cells/microliter and harvest CD34+/kg (r = 0.73, p < 0.0001) and between harvest CFU-GM and CD34+ cells/kg (r = 0.5, p < 0.0001). CFU-GM clonogenic assays were of no clinical use beyond that of CD34+ cell enumeration, with the latter allowing for real-time decisions regarding harvesting. Multiple stepwise regression identified the number of prior chemotherapy cycles as the only significant clinical predictor of CD34+ cell yield. For 34 patients proceeding to CTCb with PBPC support, multiple stepwise regression identified as the best predictors for engraftment CFU-GM and CD34+ cells/kg for neutrophils and CFU-GM, CD34+ cells/kg, and the number of prior cycles of chemotherapy for platelets, respectively. A threshold dose of 1 x 10(6) CD34+ cells/kg, obtained in 87% of these heavily pretreated breast cancer patients, was adequate to ensure engraftment within 15 days. There was no significant difference in length of hospital stay or blood product use between patients receiving 1-2.5 x 10(6) CD34+ cells/kg and greater than 2.5 x 10(6) CD34+ cells/kg, although median time to engraftment of neutrophils (9 days versus 8 days, p = 0.007) and platelets (12 days versus 9 days, p = 0.006) was significantly longer. The established threshold of > or = 1 x 10(6) CD34+ cells/kg will allow for more confident consideration of using aliquots of this threshold dose for hematopoietic support in sequential high-dose regimens inclusive of CTCb.
对45例计划接受大剂量环磷酰胺、噻替派和卡铂(CTCb)治疗的高危转移性乳腺癌女性患者,研究了使用集落形成单位 - 粒细胞巨噬细胞(CFU - GM)和CD34⁺细胞计数来评估采集质量以及影响外周血祖细胞(PBPC)采集和植入的因素。PBPC采用标准乳腺癌方案或环磷酰胺(1.5 g/m²)加5微克/千克/天粒细胞集落刺激因子(G - CSF)动员,并与G - CSF一起用于CTCb后的造血支持。外周血CD34⁺细胞/微升与采集的CD34⁺/千克之间存在显著相关性(r = 0.73,p < 0.0001),采集的CFU - GM与CD34⁺细胞/千克之间也存在显著相关性(r = 0.5,p < 0.0001)。CFU - GM克隆形成试验除了CD34⁺细胞计数外没有临床用途,后者可用于关于采集的实时决策。多元逐步回归确定既往化疗周期数是CD34⁺细胞产量的唯一显著临床预测指标。对于34例在PBPC支持下进行CTCb的患者,多元逐步回归分别确定植入的最佳预测指标为中性粒细胞的CFU - GM和CD34⁺细胞/千克,以及血小板的CFU - GM、CD34⁺细胞/千克和既往化疗周期数。在这些经过大量预处理的乳腺癌患者中,87%的患者获得的1×10⁶ CD34⁺细胞/千克的阈值剂量足以确保在15天内植入。接受1 - 2.5×10⁶ CD34⁺细胞/千克和大于2.5×10⁶ CD34⁺细胞/千克患者的住院时间或血液制品使用量没有显著差异,尽管中性粒细胞(9天对8天,p = 0.007)和血小板(12天对9天,p = 0.006)植入的中位时间显著更长。已确定的≥1×10⁶ CD34⁺细胞/千克的阈值将允许更有信心地考虑在包括CTCb的序贯大剂量方案中使用该阈值剂量的等分试样进行造血支持。