Vescio R, Schiller G, Stewart A K, Ballester O, Noga S, Rugo H, Freytes C, Stadtmauer E, Tarantolo S, Sahebi F, Stiff P, Meharchard J, Schlossman R, Brown R, Tully H, Benyunes M, Jacobs C, Berenson R, DiPersio J, Anderson K, Berenson J
West LA VAMC/University of California, Los Angeles, Los Angeles, CA; The Toronto Hospital, Toronto, Ontario, Canada.
Blood. 1999 Mar 15;93(6):1858-68.
High-dose chemotherapy followed by autologous transplantation has been shown to improve response rates and survival in multiple myeloma and other malignancies. However, autografts frequently contain detectable tumor cells. Enrichment for stem cells using anti-CD34 antibodies has been shown to reduce autograft tumor contamination in phase I/II studies. To more definitively assess the safety and efficacy of CD34 selection, a phase III study was completed in 131 multiple myeloma patients randomized to receive an autologous transplant with either CD34-selected or unselected peripheral blood progenitor cells after myeloablative therapy. Tumor contamination in the autografts was assessed by a quantitative polymerase chain reaction detection assay using patient-specific, complementarity-determining region (CDR) Ig gene primers before and after CD34 selection. A median 3.1 log reduction in contaminating tumor cells was achieved in the CD34 selected product using the CEPRATE SC System (CellPro, Inc, Bothell, WA). Successful neutrophil engraftment was achieved in all patients by day 15 and no significant between-arm difference for time to platelet engraftment occurred in patients who received an infused dose of at least 2.0 x 10(6) CD34(+) cells/kg. In conclusion, this phase III trial demonstrates that CD34-selection of peripheral blood progenitor cells significantly reduces tumor cell contamination yet provides safe and rapid hematologic recovery for patients receiving myeloablative therapy.
大剂量化疗后进行自体移植已被证明可提高多发性骨髓瘤和其他恶性肿瘤的缓解率及生存率。然而，自体移植物中常常含有可检测到的肿瘤细胞。在I/II期研究中，使用抗CD34抗体富集干细胞已被证明可减少自体移植物中的肿瘤污染。为了更明确地评估CD34选择的安全性和有效性，对131例多发性骨髓瘤患者完成了一项III期研究，这些患者在清髓治疗后被随机分配接受用CD34选择或未选择的外周血祖细胞进行的自体移植。在CD34选择前后，使用患者特异性互补决定区（CDR）Ig基因引物通过定量聚合酶链反应检测法评估自体移植物中的肿瘤污染情况。使用CEPRATE SC系统（CellPro公司，华盛顿州博塞尔）对CD34选择的产物中污染的肿瘤细胞实现了中位数3.1对数级的减少。所有患者在第15天均成功实现中性粒细胞植入，对于接受至少2.×10(6) CD34(+)细胞/kg输注剂量的患者，血小板植入时间在组间无显著差异。总之，这项III期试验表明，对外周血祖细胞进行CD34选择可显著减少肿瘤细胞污染，同时为接受清髓治疗的患者提供安全且快速的血液学恢复。
