Weaver C H, Hazelton B, Birch R, Palmer P, Allen C, Schwartzberg L, West W
Clinical Research Division of Response Technologies, Inc, Memphis, TN, USA.
Blood. 1995 Nov 15;86(10):3961-9.
The CD34 antigen is expressed by committed and uncommitted hematopoietic progenitor cells and is increasingly used to assess stem cell content of peripheral blood progenitor cell (PBPC) collections. Quantitative CD34 expression in PBPC collections has been suggested to correlate with engraftment kinetics of PBPCs infused after myeloablative therapy. We analyzed the engraftment kinetics as a function of CD34 content in 692 patients treated with high-dose chemotherapy (HDC). Patients had PBPCs collected after cyclophosphamide based mobilization chemotherapy with or without recombinant human granulocyte colony-stimulating factor (rhG-CSF) until > or = 2.5 x 10(6) CD34+ cells/kg were harvested. Measurement of the CD34 content of PBPC collections was performed daily by a central reference laboratory using a single technique of CD34 analysis. Forty-five patients required a second mobilization procedure to achieve > or = 2.5 x 10(6) CD34+ cells/kg and 15 patients with less than 2.5 x 10(6) CD34+ cells/kg available for infusion received HDC. A median of 9.94 x 10(6) CD34+ cells/kg (range, 0.5 to 112.6 x 10(6) CD34+ cells/kg) contained in the PBPC collections was subsequently infused into patients after the administration of HDC. Engraftment was rapid with patients requiring a median of 9 days (range, 5 to 38 days) to achieve a neutrophil count of 0.5 x 10(9)/L and a median of 9 days (range, 4 to 53+ days) to achieve a platelet count of > or = 20 x 10(9)/L. A clear dose-response relationship was evident between the number of CD34+ cells per kilogram infused between the number of CD34+ cells per kilogram infused and neutrophil and platelet engraftment kinetics. Factors potentially influencing the engraftment kinetics of neutrophil and platelet recovery were examined using a Cox regression model. The single most powerful mediator of both platelet (P = .0001) and neutrophil (P = .0001) recovery was the CD34 content of the PBPC product. Administration of a post-PBPC infusion myeloid growth factor was also highly correlated with neutrophil recovery (P = .0001). Patients receiving high-dose cyclophosphamide, thiotepa, and carboplatin had more rapid platelet recovery than patients receiving other regimens (P = .006), and patients requiring 2 mobilization procedures versus 1 mobilization procedure to achieve > or = 2.5 x 10(6) CD34+ cells/kg experienced slower platelet recovery (P = .005). Although a minimal threshold CD34 dose could not be defined, > or = 5.0 x 10(6) CD34+ cells/kg appears to be optimal for ensuring rapid neutrophil and platelet recovery.
CD34抗原由定向和未定向造血祖细胞表达，越来越多地用于评估外周血祖细胞（PBPC）采集物中的干细胞含量。有人提出，PBPC采集中CD34的定量表达与清髓性治疗后输注的PBPC的植入动力学相关。我们分析了692例接受大剂量化疗（HDC）患者的植入动力学与CD34含量的关系。患者在接受基于环磷酰胺的动员化疗（联合或不联合重组人粒细胞集落刺激因子（rhG-CSF））后采集PBPC，直至收获≥2.5×10⁶个CD34⁺细胞/kg。PBPC采集物的CD34含量由一个中央参考实验室每天使用单一的CD34分析技术进行测量。45例患者需要进行第二次动员程序才能达到≥2.5×10⁶个CD34⁺细胞/kg，15例可用于输注的CD34⁺细胞/kg少于2.5×10⁶的患者接受了HDC。随后，在给予HDC后，将PBPC采集中中位数为9.94×10⁶个CD34⁺细胞/kg（范围为0.5至112.6×10⁶个CD34⁺细胞/kg）注入患者体内。植入迅速，患者达到中性粒细胞计数0.5×10⁹/L的中位数为9天（范围为5至38天），达到血小板计数≥20×10⁹/L的中位数为9天（范围为4至53⁺天）。每千克输注的CD34⁺细胞数量与中性粒细胞和血小板植入动力学之间存在明显的剂量反应关系。使用Cox回归模型检查了可能影响中性粒细胞和血小板恢复植入动力学的因素。血小板（P = 0.0001）和中性粒细胞（P = 0.0001）恢复的唯一最有力的介导因素是PBPC产品的CD34含量。PBPC输注后给予髓系生长因子也与中性粒细胞恢复高度相关（P = 0.0001）。接受大剂量环磷酰胺、噻替派和卡铂的患者血小板恢复比接受其他方案的患者更快（P = 0.006），需要2次动员程序才能达到≥2.5×10⁶个CD34⁺细胞/kg的患者与需要1次动员程序的患者相比，血小板恢复较慢（P = 0.005）。虽然无法确定最小阈值CD34剂量，但≥5.0×10⁶个CD34⁺细胞/kg似乎最有利于确保中性粒细胞和血小板的快速恢复。
