Ultrahigh-dose chemoherapy with peripheral blood stem cell autotransplantation for patients with chemotherapy-resistant and/or poor prognostic testicular cancer

本文报告了5例化疗耐药和/或预后不良的睾丸癌患者接受超大剂量化疗联合外周血干细胞自体移植（PBSCT）的疗效。3例患者有巨大的腹部转移，1例有多发性肺转移，1例有巨大的腹部和肺转移。年龄范围为31 - 50岁（平均36.8岁）。采用大剂量足叶乙甙（500 mg/m^2 × 4天）治疗，收集外周血干细胞。服用大剂量足叶乙甙后。从最低点状态给予rG-CSF（250 μ g/体）。在骨髓恢复期间，使用Fenwall CS-3000血细胞分离器收集血液单核细胞。采用Percoll不连续梯度离心法获得干细胞富集组分，用患者血清和DMSO将其保存在液氮中，单次采集的外周血粒细胞-巨噬细胞集落形成单位（CFU-GM）平均数为25.8 × 10^5/kg体重。此外，根据我们以前的研究，每次单采可收集到超过2.0 × 10^5/kg体重的CFU-GM，这足以安全地进行PBSCT。顺铂20 mg/m^2 × 5天，足叶乙甙100 mg/m^2 × 5天，博莱霉素15 mg × 3天。3例患者经BEP治疗后获得CR，另2例患者未能获得CR，后经卡铂（200 mg/m^2 × 4天）、足叶乙甙（250 mg/m^2 × 4天）、环磷酰胺（50 mg/kg × 2天）等超大剂量化疗后行PBSCT治疗，分别获得CR 15个月、3个月。结果表明，该方法是有希望的化疗耐药和/或预后不良的睾丸癌患者。

A combination of ultrahigh-dose chemotherapy and peripheral blood stem cell autotransplantation (PBSCT) for 5 patients with chemotherapy-resistant and/or poor prognostic testicular cancer was evaluated. Three patients had bulky abdominal metastases, 1 had multiple pulmonary metastases and 1 had bulky abdominal and pulmonary metastases. Ages ranged from 31 to 50 (ave.36.8 yrs). They were treated with high-dose etoposide (500mg/m^2X4 days) in order to collect peripheral blood stem cells. After the administration of high-dose etoposide. rG-CSF(250 mug/body) was administered from nadir state. Blood mononuclear cells were collected using a Fenwall CS-3000 blood cell separator during bone marrow recovery. Fractions enriched for stem cells were obtained by discontinuous Percoll gradient centrifugation and were stored in liquid nitrogen using patient's sera and DMSO.The mean number of peripheral blood granulocyte-macrophage-colony-forming units (CFU-GM) collected by one apheresis was 25.8X10^5/kg body weight. In addition, CFU-GM more than 2.0X10^5/kg body weight could be collected in each apheresis, which was though to be sufficient dosis to perform PBSCT in safe, based upon our previous studies. All the patients were treated by a combination of cisplatin (20mg/m^2X5 days), etoposide (100mg/m^2X5 days) and bleomycin (15mgX3 days). Three patients responded to BEP therapy and obtained a CR, however, remaining 2 patients failed to achieve CR, who was later treated by ultrahigh-dose chemotherapy including carboplatin (200mg/m^2X4 days), etoposide (250mg/m^2X4 days) and cyclophosphamide (50mg/kgX2 days) followed by PBSCT.They responded to this therapy and obtained a CR for 15, 3 months, respectively. The results suggested the method was promising for patients with chemotherapy-resistant and/or poor prognostic testicular cancer.