Department of Medical Oncology and Hematology, Princess Margaret Hospital, University of Toronto, Toronto, ON, Canada.
J Natl Cancer Inst. 2012 Jan 4;104(1):18-28. doi: 10.1093/jnci/djr450. Epub 2011 Dec 21.
The impact of high-dose therapy and autologous stem cell transplantation (ASCT) vs conventional-dose chemotherapy in the initial management of adults with advanced follicular lymphoma (FL) on overall survival remains uncertain. We performed a systematic review of the randomized clinical trials addressing this question.
We searched MEDLINE, EMBASE, CENTRAL, American Society of Hematology, American Society of Clinical Oncology, BIOSIS, PAPERSFIRST, PROCEEDINGS, clinical trials registries, and bibliographies of relevant studies for randomized clinical trials comparing myeloablative chemotherapy with ASCT to any chemotherapy in adults with untreated advanced FL. We performed a meta-analysis using random effects models to estimate overall survival, event-free survival, and risks of adverse outcomes. Statistical heterogeneity was calculated by using the I(2) statistic.
Seven trials proved eligible, four of which provided data from 941 patients that could be included in a meta-analysis and three of which remain unpublished. In two of the trials, patients in both arms received rituximab during the induction treatment. Moderate quality evidence from the three trials that reported overall survival (n = 701 patients) suggests that ASCT did not result in improved overall survival (hazard ratio of death = 0.99, 95% confidence interval [CI] = 0.73 to 1.33). Low-quality evidence from the four trials of 941 patients suggests improvement in event-free survival in favor of ASCT (hazard ratio of death = 0.54, 95% CI = 0.36 to 0.82) with substantial heterogeneity (I(2) = 80%). Adverse outcomes of treatment-related mortality, myelodysplastic syndrome, acute myeloid leukemia, and solid tumors were not different between the two arms (relative risk [RR] of treatment-related mortality = 1.04, 95% CI = 0.29 to 3.70; RR of myelodysplastic syndrome/acute myeloid leukemia = 2.19, 95% CI = 0.45 to 10.55; I(2) = 48%; and RR of solid tumors = 1.30, 95% CI = 0.33 to 5.08). The absolute risk of death from treatment was 14 per 1000 patients for those who received chemotherapy and 15 per 1000 for those who received ASCT (range = 4-52).
Available evidence suggests that high-dose therapy and ASCT as part of FL initial treatment does not improve overall survival. Future trials of ASCT in the context of current chemoimmunotherapy approaches to FL are needed.
高剂量化疗和自体干细胞移植（ASCT）与常规剂量化疗在初治成人晚期滤泡性淋巴瘤（FL）中的总体生存影响仍不确定。我们对这一问题进行了系统评价。
我们在 MEDLINE、EMBASE、CENTRAL、美国血液学会、美国临床肿瘤学会、BIOSIS、PAPERSFIRST、PROCEEDINGS、临床试验注册处和相关研究的参考文献中搜索了比较清髓性化疗与 ASCT 与任何化疗在未经治疗的成人晚期 FL 中的随机临床试验。我们使用随机效应模型进行荟萃分析，以估计总生存率、无事件生存率和不良结局的风险。通过 I(2)统计量计算统计异质性。
有 7 项试验符合条件，其中 4 项试验提供了可纳入荟萃分析的 941 例患者的数据，3 项试验仍未发表。在两项试验中，两组患者在诱导治疗期间均接受了利妥昔单抗。来自三项报告总生存率（n=701 例患者）的试验的中等质量证据表明，ASCT 并未改善总体生存率（死亡风险比=0.99，95%置信区间[CI]为 0.73 至 1.33）。来自四项 941 例患者的试验的低质量证据表明，ASCT 有利于无事件生存率的改善（死亡风险比=0.54，95%CI 为 0.36 至 0.82），且存在较大异质性（I(2)=80%）。治疗相关死亡率、骨髓增生异常综合征、急性髓系白血病和实体瘤等不良治疗结局在两组之间无差异（治疗相关死亡率的相对风险[RR]=1.04，95%CI 为 0.29 至 3.70；骨髓增生异常综合征/急性髓系白血病的 RR=2.19，95%CI 为 0.45 至 10.55；I(2)=48%；实体瘤的 RR=1.30，95%CI 为 0.33 至 5.08）。接受化疗的患者每 1000 例中有 14 例死于治疗，接受 ASCT 的患者每 1000 例中有 15 例死于治疗（范围=4-52）。
现有证据表明，FL 初始治疗中高剂量化疗和 ASCT 并不能提高总体生存率。需要在当前的化疗免疫治疗方法的背景下进行 ASCT 的临床试验。
