Somlo G, Sniecinski I, ter Veer A, Longmate J, Knutson G, Vuk-Pavlovic S, Bhatia R, Chow W, Leong L, Morgan R, Margolin K, Raschko J, Shibata S, Tetef M, Yen Y, Forman S, Jones D, Ashby M, Fyfe G, Hellmann S, Doroshow J H
Departments of Medical Oncology and Therapeutics Research, Transfusion Medicine, and Biostatistics, City of Hope National Medical Center, Duarte, CA, USA.
Blood. 1999 May 1;93(9):2798-806.
Lineage-specific growth factors mobilize peripheral blood progenitor cells (PBPC) and accelerate hematopoietic recovery after high-dose chemotherapy. Recombinant human thrombopoietin (rhTPO) may further increase the progenitor-cell content and regenerating potential of PBPC products. We evaluated the safety and activity of rhTPO as a PBPC mobilizer in combination with granulocyte colony-stimulating factor (G-CSF) in 29 breast cancer patients treated with high-dose chemotherapy followed by PBPC reinfusion. Initially, patients received escalating single doses of rhTPO intravenously (IV) at 0.6, 1.2, or 2.4 micrograms/kg, on day 1. Subsequent patients received rhTPO 0.6 or 0.3 micrograms/kg on days -3, -1, and 1, or 0.6 micrograms/kg on days -1 and 1. G-CSF, 5 micrograms/kg IV or subcutaneously (SC) twice daily, was started on day 3 and continued through aphereses. Twenty comparable, concurrently and identically treated patients (who were eligible and would have been treated on protocol but for the lack of study opening) mobilized with G-CSF alone served as comparisons. CD34(+) cell yields were substantially higher with the first apheresis following rhTPO and G-CSF versus G-CSF alone: 4.1 x 10(6)/kg (range, 1.3 to 17.6) versus 0.8 x 10(6)/ kg (range, 0.3 to 4.2), P =.0003. The targeted minimum yield of 3 x 10(6) CD34(+) cells/kg was procured following a single apheresis procedure in 61% of the rhTPO and G-CSF-mobilized group versus 10% of G-CSF-mobilized patients (P =.001). In rhTPO and G-CSF mobilized patients, granulocyte (day 8 v 9, P =.0001) and platelet recovery (day 9 v 10, P =.07) were accelerated, and fewer erythrocyte (3 v 4, P =.02) and platelet (4 v 5, P =.02) transfusions were needed compared with G-CSF-mobilized patients. Peripheral blood platelet counts, following rhTPO and G-CSF, were increased by greater than 100% and the platelet content of PBPC products by 60% to 110% on the first and second days of aphereses (P <.0001) with the greatest effect seen with repeated dosing of rhTPO at 0.6 microgram/kg. rhTPO is safe and well tolerated as a mobilizing agent before PBPC collection. Mobilization with rhTPO and G-CSF, in comparison to a comparable, nonrandomized G-CSF-mobilized group of patients, decreases the number of apheresis procedures required, may accelerate hematopoietic recovery, and may reduce the number of transfusions required following high-dose chemotherapy for breast cancer.
谱系特异性生长因子可动员外周血祖细胞（PBPC），并加速大剂量化疗后的造血恢复。重组人血小板生成素（rhTPO）可能会进一步增加PBPC产品中的祖细胞含量和再生潜力。我们评估了rhTPO作为PBPC动员剂与粒细胞集落刺激因子（G-CSF）联合使用在29例接受大剂量化疗后进行PBPC回输的乳腺癌患者中的安全性和活性。最初，患者在第1天静脉注射（IV）递增单剂量的rhTPO，剂量分别为0.6、1.2或2.4微克/千克。随后的患者在第-3、-1和1天接受0.6或0.3微克/千克的rhTPO，或在第-1和1天接受0.6微克/千克的rhTPO。G-CSF，5微克/千克，静脉注射或皮下注射（SC），每日两次，在第3天开始并持续至采集单采。20例仅用G-CSF动员的可比较、同期且相同治疗的患者（符合条件但因研究未启动而未按方案治疗）作为对照。与仅用G-CSF相比，rhTPO和G-CSF联合后的首次单采中CD34(+)细胞产量显著更高：4.1×10(6)/千克（范围，1.3至17.6）对0.8×10(6)/千克（范围，0.3至4.2），P =.0003。在rhTPO和G-CSF动员组中，61%的患者在单次单采程序后获得了3×10(6) CD34(+)细胞/千克的目标最低产量，而G-CSF动员组患者中这一比例为10%（P =.001）。在rhTPO和G-CSF动员的患者中，粒细胞恢复（第8天对第9天，P =.0001）和血小板恢复（第9天对第10天，P =.07）加速，与G-CSF动员的患者相比，所需的红细胞（3次对4次，P =.02）和血小板（4次对5次，P =.02）输注次数减少。在单采的第一天和第二天，rhTPO和G-CSF联合使用后外周血血小板计数增加超过100%，PBPC产品中的血小板含量增加60%至110%（P <.0001），以0.6微克/千克的rhTPO重复给药效果最佳。rhTPO作为PBPC采集前的动员剂是安全且耐受性良好的。与可比较的、非随机的G-CSF动员患者组相比，rhTPO和G-CSF联合动员可减少所需的单采程序数量，可能加速造血恢复，并可能减少乳腺癌大剂量化疗后所需的输注次数。
