Girouard C, Dufresne J, Imrie K, Stewart A K, Brandwein J, Prince H M, Pantolony D, Keating A, Crump M
University of Toronto Autologous Blood and Marrow Transplant Program, University of Toronto, Ontario, Canada.
Ann Oncol. 1997 Jul;8(7):675-80. doi: 10.1023/a:1008294725992.
The role of intensive chemotherapy with autologous blood and marrow transplantation (ABMT) for patients with relapsed or refractory intermediate grade non-Hodgkin's lymphoma has recently been established. However, conventional dose salvage chemotherapy is frequently used to determine chemotherapy sensitivity and reduce tumor bulk prior to intensive therapy. Different salvage regimens have been proposed but none appears significantly superior. The purpose of this study was to determine the efficacy of mini-BEAM salvage chemotherapy in patients referred for AMBT and to define prognostic factors of response.
One hundred four patients referred for consideration of AMBT after failure of primary anthracycline-based chemotherapy received BCNU 60 mg/m2 day 1, etoposide 75 mg/m2 day 2-5, ara-C 100 mg/m2 q12 h day 2-5, melphalan 30 mg/m2 day 6 (mini-BEAM) until maximum tumor reduction. Median age was 52 (range 18-65), 57% had failed to achieve a complete response (CR) to doxorubicin-based chemotherapy at diagnosis and only 13% had a previous CR lasting > 12 months. Seventy-six received mini-BEAM as first salvage chemotherapy.
The overall response rate (RR) was 37% (95% confidence interval (CI) 28-46%) with 12 patients achieving CR and 25 achieving PR. The response rate among patients treated as first salvage was 43% compared to 20% for patients who had failed to respond to a previous salvage regimen. Only 15% of patients who failed to respond to mini-BEAM responded to another conventional dose salvage regimen. Thirty-eight of 104 patients ultimately demonstrated sufficient response to proceed to ABMT. Actuarial survival at four years is 22% for all 104 patients, and 36% for those who went on to AMBT. For those who were not transplanted, four-year survival was 18%. B symptoms and tumor burden at relapse were significant predictors of response to mini-BEAM in multivariate analysis, and identified a poor prognosis group of patients unlikely to be cured by the approach.
Mini-BEAM does not appear to be a superior salvage regimen in this high-risk group of relapsed or refractory NHL patients for whom ABMT was the ultimate treatment intention. Only one-third of patients referred for ABMT ultimately proceed to transplant; alternative treatment strategies should be developed for those with a low likelihood of cure by this approach.
强化化疗联合自体血和骨髓移植（ABMT）对复发或难治性中级别非霍奇金淋巴瘤患者的作用最近已得到确立。然而，在强化治疗前，常规剂量的挽救性化疗常被用于确定化疗敏感性并缩小肿瘤体积。已提出了不同的挽救方案，但似乎没有一种明显更优。本研究的目的是确定小剂量BEAM挽救性化疗对转介接受ABMT的患者的疗效，并确定反应的预后因素。
104例在以蒽环类药物为基础的一线化疗失败后转介考虑进行ABMT的患者接受了卡莫司汀（BCNU）60mg/m²第1天、依托泊苷75mg/m²第2 - 5天、阿糖胞苷100mg/m²每12小时1次第2 - 5天、美法仑30mg/m²第6天（小剂量BEAM）治疗，直至肿瘤最大限度缩小。中位年龄为52岁（范围18 - 65岁），57%的患者在诊断时对基于阿霉素的化疗未达到完全缓解（CR），只有13%的患者之前有持续超过12个月的CR。76例患者接受小剂量BEAM作为首次挽救性化疗。
总缓解率（RR）为37%（95%置信区间（CI）为28 - 46%），12例患者达到CR，25例达到PR。作为首次挽救治疗的患者缓解率为43%，而对先前挽救方案无反应的患者为20%。对小剂量BEAM无反应的患者中只有15%对另一种常规剂量挽救方案有反应。104例患者中有38例最终显示出足够的反应从而能够进行ABMT。104例患者4年的精算生存率为22%，进行ABMT的患者为36%。未进行移植的患者4年生存率为18%。在多变量分析中，B症状和复发时的肿瘤负荷是对小剂量BEAM反应的重要预测因素，并确定了一组预后不良、不太可能通过该方法治愈的患者。
对于以ABMT为最终治疗目的的这组复发或难治性非霍奇金淋巴瘤高危患者，小剂量BEAM似乎不是一种更优的挽救方案。转介接受ABMT的患者中只有三分之一最终进行了移植；对于通过该方法治愈可能性低的患者，应制定替代治疗策略。
