Patriarca F, Sacco C, Sperotto A, Geromin A, Damiani D, Fili C, Cerno M, Clochiatti L, Cartei G, Fanin R
Bone Marrow Transplant Unit, Department of Clinical and Morphological Research, Udine University, Italy.
Bone Marrow Transplant. 2003 May;31(9):789-94. doi: 10.1038/sj.bmt.1703929.
The purpose of this study was to evaluate the incidence and extent of tumour cell contamination in bone marrow specimens and stem cell collections from 34 breast cancer patients undergoing high-dose therapy as adjuvant treatment, and to determine the prognostic significance for the clinical outcome. Tumour cell contamination was evaluated by flow cytometry using a double-colour test and an anti- Pan cytokeratin (CK) antibody. Two out of 34 (6%) baseline bone marrow specimens, none of seven marrow harvests and nine out of 32 aphereses (28%) mobilised from seven out of 27 patients (26%) contained CK+ cells. Tumour contamination was more frequent in patients with 10 or more involved lymph nodes and in those who received a shorter course of adjuvant chemotherapy before mobilisation. At a median follow-up of 43 months, 24 patients are in complete remission, whereas 10 patients experienced recurrence. Out of the 10 patients who relapsed, five (50%) had CK+ peripheral blood stem cell (PBSC) collections, whereas disease recurrence was seen in only two out of 24 (8%) patients who received CK- products (P=0.02). Moreover, CK+ PBSC collections were associated with a significantly shorter event-free survival and overall survival. CK+ collection is an unfavourable prognostic factor for patients treated with high-dose therapy. Whether the negative impact on clinical outcome depends on reinfusion of tumour cells or whether it simply indicates a larger disease extension is still unclear.
本研究旨在评估34例接受高剂量治疗作为辅助治疗的乳腺癌患者骨髓标本和干细胞采集中肿瘤细胞污染的发生率及程度,并确定其对临床结局的预后意义。采用双色检测和抗泛细胞角蛋白(CK)抗体,通过流式细胞术评估肿瘤细胞污染情况。34份基线骨髓标本中有2份(6%)、7次骨髓采集标本均未发现、27例患者中有7例动员采集的32份单采干细胞中有9份(28%)含有CK+细胞。肿瘤污染在有10个或更多受累淋巴结的患者以及在动员前接受辅助化疗疗程较短的患者中更为常见。中位随访43个月时,24例患者完全缓解,而10例患者复发。在10例复发患者中,5例(50%)有CK+外周血干细胞(PBSC)采集物,而在接受CK-产品的24例患者中只有2例(8%)出现疾病复发(P=0.02)。此外,CK+PBSC采集物与显著缩短的无事件生存期和总生存期相关。CK+采集物是接受高剂量治疗患者的不良预后因素。对临床结局的负面影响是取决于肿瘤细胞的回输,还是仅仅表明疾病范围更大,目前仍不清楚。