Hempel L, Kremens B, Weirich A, Graf N, Zintl F, Ludwig R
Dept. of Pediatric Hematology and Oncology, University of Jena.
Klin Padiatr. 1996 Jul-Aug;208(4):186-9. doi: 10.1055/s-2008-1046471.
Patients with nephroblastoma have a high risk of relapse if they present with stage IV and anaplastic histology or with extraregional lymph node involvement; at time of relapse, bad prognosis is heralded by recurrence in an irradiated region, second or subsequent relapse, early first relapse (6 months after nephrectomy), relapse with adverse histology, relapse in two or more organ systems and lymph node or bone metastases at relapse. For such patients, an attempt to increase survival by high-dose chemotherapy seems to be justified. In 8 children aged 7.3 years (3.8-14.7) treated within the German Nephroblastoma Study SIOP9/GPOH, high dose chemotherapy with autologous hematopoietic rescue was instituted for the following reasons: stage IV with anaplastic histology and extra-regional lymph nodes (1), second or subsequent pulmonary relapse (3), early relapse with diffuse pleural (1) or skeletal (1) dissemination, recurrence in irradiated area (1) and lung metastases after early local relapse (1). At megatherapy, the patients were in first (1), second (2), third (2) and fourth complete (2) or in partial remission (1). The high dose regimen consisted of carboplatin, etoposide and melphalan. Treatment related toxicity, all non-lethal, included acute but reversible renal failure (1), esophagitis with need of parenteral nutrition for 6 months (1), cardiomyopathy (3; chronic in 1). After a follow-up of 2.1 years (0.5-3.7), 6/8 patients survive in complete remission; for 5 of them who are in remission since > 18 months a recurrence is unlikely. Both children with local relapse died after a further recurrence 3 and 8 months after high dose treatment.
High dose consolidation with ASCR seems to effectively ameliorate the prognosis of patients with high risk nephroblastoma.
肾母细胞瘤患者若处于IV期且组织学为间变或伴有区域外淋巴结受累，则复发风险很高；复发时，照射区域复发、第二次或后续复发、早期首次复发（肾切除术后6个月）、伴有不良组织学的复发、两个或更多器官系统复发以及复发时出现淋巴结或骨转移预示着预后不良。对于此类患者，尝试通过大剂量化疗提高生存率似乎是合理的。在德国肾母细胞瘤研究SIOP9/GPOH中，对8名年龄为7.3岁（3.8 - 14.7岁）的儿童进行了自体造血挽救的大剂量化疗，原因如下：IV期伴间变组织学和区域外淋巴结（1例）、第二次或后续肺部复发（3例）、伴有弥漫性胸膜（1例）或骨骼（1例）播散的早期复发、照射区域复发（1例）以及早期局部复发后出现肺转移（1例）。在大剂量治疗时，患者处于首次（1例）、第二次（2例）、第三次（2例）和第四次完全缓解（2例）或部分缓解（1例）。大剂量方案包括卡铂、依托泊苷和美法仑。与治疗相关的毒性均非致命，包括急性但可逆的肾衰竭（1例）、需要肠外营养6个月的食管炎（1例）、心肌病（3例；1例为慢性）。经过2.1年（0.5 - 3.7年）的随访，8例患者中有6例存活且完全缓解；其中5例缓解超过18个月，复发可能性不大。两名局部复发的儿童在大剂量治疗后3个月和8个月再次复发后死亡。
采用自体造血干细胞救援的大剂量巩固治疗似乎能有效改善高危肾母细胞瘤患者的预后。
