Hertzberg M S, Crombie C, Benson W, Taper J, Gottlieb D, Bradstock K F
Department of Haematology, Westmead Hospital, Westmead, NSW 2145, Australia.
Ann Oncol. 2006 May;17 Suppl 4:iv25-30. doi: 10.1093/annonc/mdj995.
We have treated 75 transplant-eligible patients with relapsed or refractory lymphoma using an outpatient-based fractionated regimen of ifosfamide, carboplatin and etoposide (ICE) for both salvage and stem cell mobilisation. Patients included DLBC (n = 33), follicular (n = 23), NK/T-cell (n = 3), mantle cell (n = 3) and Hodgkin's lymphoma (n = 13). Cycles of outpatient ICE were given every 21 days and consisted of: ifosfamide 5000 mg/m(2) i.v. fractionated into three equally divided doses and infused over 2-3 h on days 1-3, carboplatin (mg dose = 5 x AUC) i.v. over 1 h on day 1; and etoposide 100 mg/m(2) i.v. daily on days 1-3, plus filgrastim 5 microg/kg/day. Most patients with indolent lymphoma also received rituximab. The median age of patients was 52 years (range 26-69 years). Patients received a mean of 2.8 cycles of ICE. Non-haematological toxicities included grade 1/2 CNS toxicity in four patients, cardiac toxicity in two, reversible renal impairment and haematuria in one each. Haematological toxicity included grades III/IV thrombocytopenia and neutropenia with at least one cycle of ICE in 71% and 72% of patients, respectively. The median time to PBSC harvest was 14 days (range 10-20 days), while the median CD34(+) cell yield was 4.8 x 10(6)/kg (range 2.3-37.8). Five patients (7%) failed to mobilise PBSCs. The overall response rate to ICE was 89%, comprising 29% who achieved a CR and 60% who achieved a PR; for DLBCL, the overall response rate was 85% including 36% who achieved a CR and 49% who exhibited a PR. At a median follow-up of 24 months, the Kaplan-Meier estimates of the overall and event-free survival for all patients were 65% and 42%, respectively. For patients with DLBCL overall and event-free survival figures were 51% and 35%, respectively, at a median follow-up of 14 months. These data confirm the efficacy and tolerability of outpatient fractionated ICE as both a salvage and mobilisation regimen in relapsed/refractory lymphoma.
我们采用门诊分次给药方案，使用异环磷酰胺、卡铂和依托泊苷（ICE）对75例符合移植条件的复发或难治性淋巴瘤患者进行挽救治疗及干细胞动员。患者包括弥漫性大B细胞淋巴瘤（DLBC，n = 33）、滤泡性淋巴瘤（n = 23）、NK/T细胞淋巴瘤（n = 3）、套细胞淋巴瘤（n = 3）和霍奇金淋巴瘤（n = 13）。门诊ICE方案每21天进行一个周期，具体如下：异环磷酰胺5000 mg/m²静脉滴注，分3等份剂量，在第1 - 3天2 - 3小时内输注完毕；卡铂（剂量mg = 5×曲线下面积）在第1天静脉滴注1小时；依托泊苷100 mg/m²静脉滴注，第1 - 3天每日1次，加用非格司亭5 μg/kg/天。大多数惰性淋巴瘤患者还接受了利妥昔单抗治疗。患者的中位年龄为52岁（范围26 - 69岁）。患者平均接受2.8个周期的ICE治疗。非血液学毒性包括4例患者出现1/2级中枢神经系统毒性，2例出现心脏毒性，各1例出现可逆性肾功能损害和血尿。血液学毒性包括71%和72%的患者在至少一个ICE周期后分别出现III/IV级血小板减少和中性粒细胞减少。外周血干细胞（PBSC）采集的中位时间为14天（范围10 - 20天），而CD34⁺细胞产量的中位数为4.8×10⁶/kg（范围2.3 - 37.8）。5例患者（7%）未能成功动员PBSC。ICE的总体缓解率为89%，其中29%达到完全缓解（CR），60%达到部分缓解（PR）；对于弥漫性大B细胞淋巴瘤（DLBCL），总体缓解率为85%，包括36%达到CR和49%出现PR。在中位随访24个月时，所有患者的总生存率和无事件生存率的Kaplan - Meier估计值分别为65%和42%。对于DLBCL患者，在中位随访14个月时，总生存率和无事件生存率分别为51%和35%。这些数据证实了门诊分次给药ICE方案作为复发/难治性淋巴瘤的挽救治疗及动员方案的有效性和耐受性。
