AN ANALYSIS OF ENGRAFTMENT KINETICS AS A FUNCTION OF THE CD34 CONTENT OF PERIPHERAL-BLOOD PROGENITOR-CELL COLLECTIONS IN 692 PATIENTS AFTER THE ADMINISTRATION OF MYELOABLATIVE CHEMOTHERAPY

AN ANALYSIS OF ENGRAFTMENT KINETICS AS A FUNCTION OF THE CD34 CONTENT OF PERIPHERAL-BLOOD PROGENITOR-CELL COLLECTIONS IN 692 PATIENTS AFTER THE ADMINISTRATION OF MYELOABLATIVE CHEMOTHERAPY
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DOI:
10.1182/blood.v86.10.3961.bloodjournal86103961
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发表时间:
1995-11-15
期刊:
影响因子:
20.3
通讯作者:
WEST, W
WEST, W
中科院分区:
医学1区
文献类型:
--
作者:
WEAVER, CH;HAZELTON, B;WEST, W

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CD34抗原由定型和未定型造血祖细胞表达,并且越来越多地用于评估外周血祖细胞(PBPC)集合的干细胞含量。已经表明PBPC集合中的定量CD34表达与清髓治疗后输注的PBPC的植入动力学相关。我们分析了692例接受大剂量化疗(HDC)的患者的植入动力学,作为CD 34含量的函数。患者在使用或不使用重组人粒细胞集落刺激因子(rhG-CSF)的环磷酰胺动员化疗后采集PBPC,直至收获大于或等于2.5 x 10(6)个CD34(+)细胞/kg,由中心参考实验室使用单一CD34分析技术每天测量PBPC采集物的CD34含量,45例患者需要第二次动员程序以达到大于或等于2.5 x 10(6)CD34(+)细胞/kg,15例可用于输注的CD34(+)细胞低于2.5 x 10(6)细胞/kg的患者接受了HDC。随后,在给予HDC后,将PBPC采集物中含有的中位9.94 x 106个CD34(+)细胞/kg(范围:0.5 - 112.6 x 106个CD34(+)细胞/kg)输注给患者。植入迅速,患者需要中位9天(范围:5 - 38天)达到中性粒细胞计数0.5 x 10(9)/L,中位9天(范围:4 - 53+天)达到血小板计数大于或等于20 x 10(9)/L。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。使用考克斯回归模型检查了可能影响中性粒细胞植入动力学和血小板恢复的因素。血小板(P = 0.0001)和中性粒细胞(P = 0.0001)恢复的单一最强大的介质是PBPC产品的CD34含量。PBPC输注后给予髓样生长因子也与中性粒细胞恢复高度相关(P =.0001)。接受高剂量环磷酰胺、塞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次动员程序与1次动员程序以达到大于或等于2.5 × 106 CD34(+)细胞/kg的患者血小板恢复较慢(P = 0.005)。尽管无法确定最小阈值CD34剂量,但大于或等于5.0 × 10(6)CD34(+)细胞/kg似乎是确保中性粒细胞和血小板快速恢复的最佳剂量。(C)1995年,美国血液学会。
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 greater than or equal to 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 greater than or equal to 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 106 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 greater than or equal to 20 x 10(9)/L. A clear dose-response relationship was evident 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 greater than or equal to 2.5 x 10(6) CD34(+) cells/kg experienced slower platelet recovery (P = .005). Although a minimal threshold CD34 dose could not be defined, greater than or equal to 5.0 x 10(6) CD34(+) cells/kg appears to be optimal for ensuring rapid neutrophil and platelet recovery. (C) 1995 by The American Society of Hematology.