van der Wall E, Horn T, Bright E, Passos-Coehlo J L, Bond S, Clarke B, Altomonte V, McIntyre K, Vogelsang G, Noga S J, Davis J M, Thomassen J, Ohly K V, Lee S M, Fetting J, Armstrong D K, Davidson N E, Hess A D, Kennedy M J
Bunting-Blaustein Cancer Research Building, Baltimore, MD 21231, USA.
Br J Cancer. 2000 Dec;83(11):1405-11. doi: 10.1054/bjoc.2000.1499.
The purpose of the present study was to investigate the impact of the use of peripheral blood progenitor cells (PBPCs) on the induction of autologous graft-versus-host disease (GVHD) in patients with advanced breast cancer. 14 women with stage IIIB and 36 women with stage IV breast cancer received cyclosporine (CsA) 2.5 mg kg-1 i.v. daily, d 0-28, and interferon-gamma (IFNg) 0.025 mg/m2 s.c. qod, d7-28, following PBPC-T +/- bone marrow transplantation (BMT). Preceding high-dose chemotherapy consisted of cyclophosphamide 6 g/m2 and thiotepa 800 mg/m2. Histologically proven > or = grade II cutaneous GVHD was induced in18/50 (36%) of patients and was independent of the source of haematopoietic support. In vitro studies showed that post-transplant, 76% of patients had developed auto-cytotoxicity against their own pre-transplant PHA-lymphoblasts. A significant correlation between the occurrence of GVHD > or = grade II and cytolysis was observed in the NK cell-line K562 and the T47D breast cancer cell-line. With a median follow-up of 2(1/2) years, the overall survival (OS) is 58%, the disease-free survival (DFS) 26%, both independent of the development of GVHD and similar to what has been observed in other studies on high-dose chemotherapy in advanced breast cancer. It therefore remains unclear whether the induction of autologous GVHD with the occurrence of auto-cytotoxic lymphocytes can result in an anti-tumour effect in this group of patients.
本研究的目的是调查使用外周血祖细胞(PBPCs)对晚期乳腺癌患者自体移植物抗宿主病(GVHD)诱导的影响。14例IIIB期和36例IV期乳腺癌女性患者在接受PBPC-T±骨髓移植(BMT)后,于第0 - 28天每天静脉注射2.5 mg/kg环孢素(CsA),并于第7 - 28天每隔一日皮下注射0.025 mg/m²干扰素-γ(IFNg)。大剂量化疗前包括6 g/m²环磷酰胺和800 mg/m²噻替派。组织学证实≥II级皮肤GVHD在18/50(36%)的患者中诱发,且与造血支持来源无关。体外研究显示,移植后76%的患者对其移植前的PHA淋巴细胞产生了自身细胞毒性。在NK细胞系K562和T47D乳腺癌细胞系中,观察到≥II级GVHD的发生与细胞溶解之间存在显著相关性。中位随访2(1/2)年,总生存率(OS)为58%,无病生存率(DFS)为26%,两者均与GVHD的发生无关,且与其他晚期乳腺癌大剂量化疗研究中观察到的情况相似。因此,尚不清楚自体GVHD的诱导以及自身细胞毒性淋巴细胞的出现是否能在该组患者中产生抗肿瘤作用。