Gazitt Y, Tian E, Barlogie B, Reading C L, Vesole D H, Jagannath S, Schnell J, Hoffman R, Tricot G
Division of Hematology-Oncology, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
Blood. 1996 Jan 15;87(2):805-11.
Peripheral blood stem cells (PBSCs) mobilized with high-dose chemotherapy and hematopoietic growth factors are now widely used to support myeloablative therapy of multiple myeloma and effect complete remissions in up to 50% of patients with apparent extension of event-free and overall survival. Because tumor cells are present not only in bone marrow, but also in virtually all PBSC harvests, it is conceivable that autografted myeloma cells contribute to relapse after autotransplants. In this study, the kinetics of mobilization of normal hematopoietic stem cells were compared with those of myeloma cells present in PBSC harvests of 12 patients after high-dose cyclophosphamide and granulocyte-macrophage colony-stimulating factor administration. CD34+ and CD34+Lin-Thy+ stem cell contents were measured by multiparameter flow cytometry, and myeloma cells were quantitated by immunostaining for the relevant Ig light chain and by a quantitative polymerase chain reaction for the myeloma-specific CDRIII sequence. Results indicated marked heterogeneity in the percentages of mobilized stem cells among different patients (0.1% to 22.2% for CD34+ cells and 0.1% to 7.5% for CD34+Lin-Thy+ cells, respectively). The highest proportions of hematopoietic progenitor cells were observed early during apheresis, with 9 of 12 patients mobilizing adequate amounts of CD34+ cells for 2 autotransplants (> 4 x 10(6)/kg) within the first 2 days, whereas peak levels (percent and absolute numbers) of myeloma cells were present on days 5 and 6 (0.5% to 22.0%). During the last days of collection, mobilized tumor cells exhibited more frequently high labeling index values (1% to 10%; median, 4.4%) and an immature phenotype (CD19+). The differential mobilization observed between normal hematopoietic stem cells and myeloma cells can be exploited to reduce tumor cell contamination in PBSC harvests.
用大剂量化疗和造血生长因子动员的外周血干细胞（PBSCs）目前被广泛用于支持多发性骨髓瘤的清髓治疗，并使高达50%的患者实现完全缓解，明显延长无事件生存期和总生存期。由于肿瘤细胞不仅存在于骨髓中，而且几乎存在于所有的PBSC采集中，因此可以想象，自体移植的骨髓瘤细胞会导致自体移植后复发。在本研究中，对12例患者在给予大剂量环磷酰胺和粒细胞-巨噬细胞集落刺激因子后，PBSC采集中正常造血干细胞与骨髓瘤细胞的动员动力学进行了比较。通过多参数流式细胞术测量CD34+和CD34+Lin-Thy+干细胞含量，通过相关Ig轻链免疫染色和骨髓瘤特异性CDRIII序列定量聚合酶链反应对骨髓瘤细胞进行定量。结果表明，不同患者动员的干细胞百分比存在明显异质性（CD34+细胞分别为0.1%至22.2%，CD34+Lin-Thy+细胞为0.1%至7.5%）。在单采早期观察到造血祖细胞比例最高，12例患者中有9例在头2天内动员了足够数量的CD34+细胞用于2次自体移植（>4×10(6)/kg），而骨髓瘤细胞的峰值水平（百分比和绝对数量）出现在第5天和第6天（0.5%至22.0%）。在采集的最后几天，动员的肿瘤细胞更频繁地表现出高标记指数值（1%至10%；中位数，4.4%）和未成熟表型（CD19+）。正常造血干细胞和骨髓瘤细胞之间观察到的差异动员可用于减少PBSC采集中的肿瘤细胞污染。
