Hänel M, Kröger N, Sonnenberg S, Bornhäuser M, Krüger W, Kroschinsky F, Hänel A, Metzner B, Birkmann J, Schmid B, Hoffknecht M M, Fiedler F, Ehninger G, Zander A R
Medical Clinic and Policlinic I, University Hospital Carl Gustav Carus, Dresden, Germany.
Ann Hematol. 2002 Feb;81(2):96-102. doi: 10.1007/s00277-001-0413-8. Epub 2002 Jan 10.
We investigated the efficacy and toxicity of the combination of busulfan, cyclophosphamide, and etoposide (Bu/Cy/VP-16) as a preparative regimen prior to autologous hematopoietic stem cell transplantation (ASCT) in patients with Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL). Fifty-three patients with recurrent ( n=30), refractory ( n=20), or high-risk ( n=3) lymphoma were enrolled. The 10 patients with HD and 43 with NHL (median age: 46 years, range: 18-64) received busulfan (16 mg/kg), cyclophosphamide (120 mg/kg), and etoposide (30 or 45 mg/kg) followed by ASCT. A total of 50 patients (94%) were consolidated in complete ( n=25) or partial ( n=25) remission, whereas 3 patients had chemoresistant disease before Bu/Cy/VP-16. Thirty-five patients (66%) had received prior radiotherapy (RT) excluding total body irradiation (TBI) as part of the conditioning regimen. The main nonhematological toxicities (grade II-IV according to the Bearman score) in 52 evaluable patients were mucositis (79%) and hepatic toxicity (15%). Severe veno-occlusive disease (VOD) occurred in three patients (5.8%) including one treatment-related death caused by VOD. Overall, treatment-related mortality was 3.8%. After a median follow-up for surviving patients of 21 months (range: 6-118), 20 patients (38%) are in continuous complete remission, 8 patients (15%) are alive in relapse, and 25 patients (47%) died. Probabilities of relapse, event-free survival, and overall survival at 3 years were 63% [95% confidence interval (CI): 48-79%], 31% (95% CI: 17-46%), and 43% (95% CI: 27-59%), respectively. In conclusion, Bu/Cy/VP-16 is an effective and well-tolerated conditioning regimen in patients with HD and NHL. Both toxicity and outcome were not significantly different in patients treated with 30 mg/kg and 45 mg/kg etoposide, respectively. The observed long-term results are even comparable to those published for other established high-dose protocols, including TBI-based regimens. However, further investigations are necessary to evaluate the value of Bu/Cy/VP-16 as a high-dose protocol for malignant lymphoma, especially in patients who have already received extensive RT.
我们研究了白消安、环磷酰胺和依托泊苷（Bu/Cy/VP - 16）联合方案作为霍奇金病（HD）或非霍奇金淋巴瘤（NHL）患者自体造血干细胞移植（ASCT）前预处理方案的疗效和毒性。纳入了53例复发（n = 30）、难治（n = 20）或高危（n = 3）淋巴瘤患者。10例HD患者和43例NHL患者（中位年龄：46岁，范围：18 - 64岁）接受了白消安（16 mg/kg）、环磷酰胺（120 mg/kg）和依托泊苷（30或45 mg/kg）治疗，随后进行ASCT。共有50例患者（94%）达到完全（n = 25）或部分（n = 25）缓解巩固，而3例患者在接受Bu/Cy/VP - 16治疗前疾病对化疗耐药。35例患者（66%）在预处理方案中接受过除全身照射（TBI）外的既往放疗（RT）。52例可评估患者的主要非血液学毒性（根据Bearman评分标准为II - IV级）为黏膜炎（79%）和肝毒性（15%）。3例患者（5.8%）发生了严重的静脉闭塞性疾病（VOD），其中1例因VOD导致与治疗相关的死亡。总体而言，与治疗相关的死亡率为3.8%。存活患者的中位随访时间为21个月（范围：6 - 118个月），20例患者（38%）持续完全缓解，8例患者（15%）复发存活，25例患者（47%）死亡。3年时的复发概率、无事件生存率和总生存率分别为63%[95%置信区间（CI）：48 - 79%]、31%（95% CI：17 - 46%）和43%（95% CI：27 - 59%）。总之，Bu/Cy/VP - 16是HD和NHL患者一种有效且耐受性良好的预处理方案。分别接受30 mg/kg和45 mg/kg依托泊苷治疗的患者，其毒性和疗效无显著差异。观察到的长期结果甚至与其他已确立的高剂量方案（包括基于TBI的方案）所发表的结果相当。然而，有必要进一步研究以评估Bu/Cy/VP - 16作为恶性淋巴瘤高剂量方案的价值，尤其是在已经接受过广泛RT的患者中。
