Cameron D A, Craig J, Gabra H, Lee L, MacKay J, Parker A C, Leonard R C, Anderson E, Anderson T, Chetty U, Dixon M, Hawkins A, Jack W, Kunkler I, Leonard R, Matheson L, Miller W
Western General Hospital, Edinburgh, UK.
Br J Cancer. 1996 Dec;74(12):2013-7. doi: 10.1038/bjc.1996.669.
Current treatments for metastatic breast cancer are not associated with significant survival benefits despite response rates of over 50%. High-dose therapy with autologous bone marrow transplantation (ABMT) has been investigated, particularly in North America, and prolonged survival in up to 25% of women has been reported, but with a significant treatment-related mortality. However, in patients with haematological malignancies undergoing autologous transplantation, haematopoietic reconstruction is significantly quicker and mortality lower than with ABMT, when peripheral blood progenitor cells (PBPCs) are used. In 32 women with metastatic breast cancer, we investigated the feasibility of PBPC mobilisation with high-dose cyclophosphamide and granulocyte colony-stimulating factor (G-CSF) after 12 weeks' infusional induction chemotherapy and the subsequent efficacy of the haematopoietic reconstitution after conditioning with melphalan and either etoposide or thiotepa. PBPC mobilisation was successful in 28/32 (88%) patients, and there was a rapid post-transplantation haematopoietic recovery: median time to neutrophils > 0.5 x 10(9) l-1 was 14 days and to platelets > 20 x 10(9) l-1 was 10 days. There was no procedure-related mortality, and the major morbidity was mucositis (WHO grade 3-4) in 18/32 patients (56%). In a patient group of which the majority had very poor prognostic features, the median survival from start of induction chemotherapy was 15 months. Thus, PBPC mobilisation and support of high-dose chemotherapy is feasible after infusional induction chemotherapy for patients with metastatic breast cancer, although the optimum drug combination has not yet been determined.
尽管转移性乳腺癌的当前治疗有效率超过50%，但并未带来显著的生存获益。自体骨髓移植（ABMT）的高剂量疗法已得到研究，尤其是在北美，据报道高达25%的女性患者生存期得以延长，但治疗相关死亡率较高。然而，对于接受自体移植的血液系统恶性肿瘤患者，使用外周血祖细胞（PBPC）时，造血重建明显更快，死亡率低于ABMT。在32例转移性乳腺癌女性患者中，我们研究了在12周的输注诱导化疗后，使用高剂量环磷酰胺和粒细胞集落刺激因子（G-CSF）动员PBPC的可行性，以及在使用美法仑和依托泊苷或噻替派进行预处理后造血重建的后续疗效。28/32（88%）例患者PBPC动员成功，移植后造血迅速恢复：中性粒细胞>0.5×10⁹/L⁻¹的中位时间为14天，血小板>20×10⁹/L⁻¹的中位时间为10天。无手术相关死亡，主要并发症为18/32（56%）例患者出现黏膜炎（WHO 3-4级）。在一个大多数患者预后特征极差的患者组中，从诱导化疗开始的中位生存期为15个月。因此，对于转移性乳腺癌患者，在输注诱导化疗后进行PBPC动员和高剂量化疗支持是可行的，尽管最佳药物组合尚未确定。
