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接受高剂量化疗联合自体造血祖细胞移植的晚期乳腺癌患者早期淋巴细胞恢复情况的预后分析

Prognostic analysis of early lymphocyte recovery in patients with advanced breast cancer receiving high-dose chemotherapy with an autologous hematopoietic progenitor cell transplant.

作者信息

Nieto Yago, Shpall Elizabeth J, McNiece Ian K, Nawaz Samia, Beaudet Julie, Rosinski Steve, Pellom Julie, Slat-Vasquez Victoria, McSweeney Peter A, Bearman Scott I, Murphy James, Jones Roy B

机构信息

Bone Marrow Transplant Program and Departments of Pathology and Biostatistics, University of Colorado, Denver, Colorado 80262, USA.

出版信息

Clin Cancer Res. 2004 Aug 1;10(15):5076-86. doi: 10.1158/1078-0432.CCR-04-0117.

Abstract

PURPOSE

The purpose of this study was to evaluate the prognostic effect of early posttransplant lymphocyte recovery in patients with advanced breast cancer receiving high-dose chemotherapy with autologous hematopoietic progenitor cell transplantation.

EXPERIMENTAL DESIGN

We analyzed the effect of the absolute lymphocyte count on day +15 posttransplant on freedom from relapse and overall survival in patients with high-risk primary breast cancer or metastatic breast cancer, enrolled between 1990 and 2001 in prospective high-dose chemotherapy trials, using a uniform regimen of cyclophosphamide, cisplatin, and 1,3-bis(2-chloroethyl)-1-nitrosourea.

RESULTS

Four hundred and seventy-six patients (264 high-risk primary breast cancer and 212 metastatic breast cancer patients) were evaluated at median follow-up of 8 years (range, 1.5-11 years). The disease-free survival and overall survival rates in the high-risk primary breast cancer group were 67% and 70%, respectively. Patients with metastatic breast cancer patients had 21.8% disease-free survival and 31.5% overall survival rates. Day +15 absolute lymphocyte count correlated with freedom from relapse (P = 0.007) and overall survival (P = 0.04) in the metastatic breast cancer group, but not in the high-risk primary breast cancer group (P = 0.5 and 0.8, respectively). The prognostic effect of absolute lymphocyte count in metastatic breast cancer was restricted to those patients receiving unmanipulated peripheral blood progenitor cells (P = 0.04). In contrast, absolute lymphocyte count had no significant effect in those metastatic breast cancer patients receiving bone marrow or a CD34-selected product. In multivariate analyses, the prognostic effect of day +15 absolute lymphocyte count in metastatic breast cancer was independent of other predictors, such as disease status, pre-high-dose chemotherapy treatment, number of tumor sites, or HER2.

CONCLUSIONS

Early lymphocyte recovery is an independent outcome predictor in metastatic breast cancer patients receiving high-dose chemotherapy and an autologous peripheral blood progenitor cell transplant. These observations suggest that immune strategies targeting minimal posttransplant residual disease may prove worthwhile.

摘要

目的

本研究旨在评估接受大剂量化疗联合自体造血祖细胞移植的晚期乳腺癌患者移植后早期淋巴细胞恢复的预后效果。

实验设计

我们分析了移植后第15天的绝对淋巴细胞计数对1990年至2001年期间参加前瞻性大剂量化疗试验的高危原发性乳腺癌或转移性乳腺癌患者无复发生存期和总生存期的影响,采用环磷酰胺、顺铂和1,3 - 双(2 - 氯乙基)-1 - 亚硝基脲的统一方案。

结果

476例患者(264例高危原发性乳腺癌患者和212例转移性乳腺癌患者)接受评估,中位随访时间为8年(范围1.5 - 11年)。高危原发性乳腺癌组的无病生存率和总生存率分别为67%和70%。转移性乳腺癌患者的无病生存率为21.8%,总生存率为31.5%。在转移性乳腺癌组中,移植后第15天的绝对淋巴细胞计数与无复发生存期(P = 0.007)和总生存期(P = 0.04)相关,但在高危原发性乳腺癌组中无相关性(分别为P = 0.5和0.8)。转移性乳腺癌中绝对淋巴细胞计数的预后效果仅限于接受未处理外周血祖细胞的患者(P = 0.04)。相比之下,绝对淋巴细胞计数对接受骨髓或CD34选择产品的转移性乳腺癌患者无显著影响。在多变量分析中,转移性乳腺癌患者移植后第15天绝对淋巴细胞计数的预后效果独立于其他预测因素,如疾病状态、大剂量化疗前治疗、肿瘤部位数量或HER2。

结论

早期淋巴细胞恢复是接受大剂量化疗和自体外周血祖细胞移植的转移性乳腺癌患者的独立预后预测指标。这些观察结果表明,针对移植后微小残留疾病的免疫策略可能是值得的。

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