Toh H C, McAfee S L, Sackstein R, Multani P, Cox B F, Garcia-Carbonero R, Colby C, Spitzer T R
Bone Marrow Transplant Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Bone Marrow Transplant. 2000 Jan;25(1):19-24. doi: 10.1038/sj.bmt.1702091.
While high-dose chemotherapy and stem cell transplantation is associated with higher complete response rates than conventional chemotherapy in patients with metastatic breast cancer (MBC), its role in conferring a survival advantage is unproven. We report the results of a prospective phase II trial of 33 patients accrued between 1996 to 1998 with chemosensitive MBC, who received cyclophosphamide (Cy) 2000 mg/m2/day and carboplatin (Cb) 600 mg/m2/day for 3 consecutive days, followed by infusion of peripheral blood stem cells cultured in IL-2 for 24 h on day 0 as adoptive immunotherapy. Low-dose interleukin-2 (IL-2) was administered from day 0 to +4 and/or +7 to +11, +14 to +18, +21 to +25, then 5 days per month for 11 months to augment a graft-versus-tumor effect. The results of this study were compared to those of a historical control group treated with an identical high-dose Cb + Cy regimen with SCT but without IL-2 treatment. Only gastrointestinal (GI) toxicity was more frequent in the IL-2 cohort (P = 0.0031). At a median follow-up of 18.6 months, the median progression-free survival (PFS) is 9 months (2.4-40) and the median OS has not been reached yet. The Kaplan-Meier estimated 2 year PFS is 35%, compared with 17% in the control arm (P = 0.73), and the estimated 2 year OS is 78%, compared with 61% in the control arm (P = 0.22). Multivariate analysis showed that ER status was an independent predictor for OS and PFS, and less chemotherapy prior to HDCSCT predicted for a better PFS. These results show that augmenting HDC with IL-2 activated SCT is well-tolerated. Whether a therapeutic advantage is achievable in patients with MBC remains to be determined. Bone Marrow Transplantation (2000) 25, 19-24.
虽然在转移性乳腺癌（MBC）患者中，高剂量化疗和干细胞移植比传统化疗具有更高的完全缓解率，但其在带来生存优势方面的作用尚未得到证实。我们报告了一项前瞻性II期试验的结果，该试验纳入了1996年至1998年间33例对化疗敏感的MBC患者，他们连续3天接受环磷酰胺（Cy）2000 mg/m²/天和卡铂（Cb）600 mg/m²/天治疗，随后在第0天输注在白细胞介素-2（IL-2）中培养24小时的外周血干细胞作为过继免疫疗法。从第0天至 +4天和/或 +7天至 +11天、+14天至 +18天、+21天至 +25天给予低剂量白细胞介素-2（IL-2），然后每月5天，共11个月，以增强移植物抗肿瘤效应。将本研究结果与接受相同高剂量Cb + Cy方案及自体造血干细胞移植（SCT）但未接受IL-2治疗的历史对照组结果进行比较。仅胃肠道（GI）毒性在IL-2组中更常见（P = 0.0031）。中位随访18.6个月时，中位无进展生存期（PFS）为9个月（2.4 - 40），中位总生存期（OS）尚未达到。根据Kaplan-Meier法估计，2年PFS为35%，而对照组为17%（P = 0.73），估计2年OS为78%，对照组为61%（P = 0.22）。多变量分析显示，雌激素受体（ER）状态是OS和PFS的独立预测因素，高剂量化疗联合自体造血干细胞移植（HDCSCT）前化疗次数较少预示着更好的PFS。这些结果表明，用IL-2激活的自体造血干细胞移植增强高剂量化疗耐受性良好。MBC患者是否能获得治疗优势仍有待确定。《骨髓移植》（2000年）第25卷，第19 - 24页
