J Natl Cancer Inst. 1999 May 19;91(10):861-8. doi: 10.1093/jnci/91.10.861.
The randomized trials that evaluate the timing and intensity of initial chemotherapy for chronic lymphocytic leukemia (CLL) have, in general, been too small to provide separately reliable results. We compared the effects on survival of the following: a) immediate versus deferred chemotherapy for early-stage CLL and b) combination chemotherapy (e.g., cyclophosphamide and vincristine plus prednisone/prednisolone [COP] or COP plus doxorubicin [CHOP]) versus single-agent chlorambucil as first-line treatment for more advanced disease.
All relevant randomized trials, whether published or not, were sought for a collaborative meta-analysis involving centralized review of the data for each patient.
There were 2048 patients with early disease in six trials of immediate versus deferred chemotherapy (chlorambucil or chlorambucil plus prednisone/prednisolone). The 10-year survival was slightly worse (but not statistically significantly so) with immediate chemotherapy (44% versus 47% survival; difference = -3%; 95% confidence interval [CI] = -10% to 4%). There were another 2022 patients in 10 trials of combination chemotherapy versus chlorambucil, with or without prednisone/prednisolone. The 5-year survival was 48 % in both cases (difference = 0%; 95% CI = -6% to 5%). A subgroup of six of these 10 trials involved an anthracycline-containing regimen but again overall survival appeared no better than with chlorambucil (anthracycline-based regimen: 325 deaths among 627 patients; chlorambucil: 306 deaths among 636 patients; death rate ratio = 1.07; 95% CI = 0.91-1.25; not statistically significant).
In terms of survival, these trials support a conservative treatment strategy for CLL, i.e., no chemotherapy for most patients with early-stage disease, and single-agent chlorambucil as the first line of treatment for most patients with advanced disease, with no evidence of benefit from early inclusion of an anthracycline. This strategy will, however, need to be reconsidered as mature results become available from trials of other agents.
评估慢性淋巴细胞白血病（CLL）初始化疗时机和强度的随机试验总体规模较小，无法分别提供可靠结果。我们比较了以下各项对生存的影响：a）早期CLL立即化疗与延迟化疗；b）联合化疗（如环磷酰胺、长春新碱加泼尼松/泼尼松龙[COP]或COP加阿霉素[CHOP]）与单药苯丁酸氮芥作为更晚期疾病的一线治疗。
寻找所有相关随机试验，无论是否发表，以进行协作荟萃分析，包括对每位患者数据的集中审查。
在6项立即化疗与延迟化疗（苯丁酸氮芥或苯丁酸氮芥加泼尼松/泼尼松龙）的试验中，有2048例早期疾病患者。立即化疗的10年生存率略低（但无统计学显著差异）（生存率分别为44%和47%；差异=-3%；95%置信区间[CI]=-10%至4%）。在10项联合化疗与苯丁酸氮芥（有或无泼尼松/泼尼松龙）的试验中，另有2022例患者。两种情况下的5年生存率均为48%（差异=0%；95%CI=-6%至5%）。这10项试验中的6项亚组涉及含蒽环类药物方案，但总体生存率似乎仍不比苯丁酸氮芥更好（基于蒽环类药物的方案：627例患者中有325例死亡；苯丁酸氮芥：636例患者中有306例死亡；死亡率比=1.07；95%CI=0.91-1.25；无统计学显著差异）。
就生存率而言，这些试验支持CLL的保守治疗策略，即大多数早期疾病患者不进行化疗，大多数晚期疾病患者以单药苯丁酸氮芥作为一线治疗，且无证据表明早期加入蒽环类药物有益。然而，随着其他药物试验获得成熟结果，这一策略将需要重新考虑。
