Dighiero G, Maloum K, Desablens B, Cazin B, Navarro M, Leblay R, Leporrier M, Jaubert J, Lepeu G, Dreyfus B, Binet J L, Travade P
Unité d'Immuno-Hématologie et d'Immunopathologie, Institut Pasteur, Paris, France.
N Engl J Med. 1998 May 21;338(21):1506-14. doi: 10.1056/NEJM199805213382104.
To determine whether chlorambucil treatment benefits patients with indolent chronic lymphocytic leukemia (CLL), we conducted two randomized trials in 1535 patients with previously untreated stage A CLL.
In the first trial, 609 patients were randomly assigned to receive either daily chlorambucil or no treatment; in the second trial, 926 patients were randomly assigned to receive either intermittent chlorambucil plus prednisone or no treatment. Median follow-up for the first and second trials exceeded 11 and 6 years, respectively. The end points were overall survival, response to treatment, and disease progression.
Treatment of indolent CLL did not increase survival in either trial. In the treated group, as compared with the untreated group, the relative risk of death was 1.14 (95 percent confidence interval, 0.92 to 1.41; P=0.23) in the first trial and 0.96 (95 percent confidence interval, 0.75 to 1.23; P=0.74) in the second trial, with 76 percent and 69 percent of patients, respectively, having a response to therapy. Although chlorambucil slowed disease progression, there was no effect on overall survival. In the untreated group in the first trial, 49 percent of patients did not have progression to more advanced disease and did not need therapy after follow-up of more than 11 years; however, 27 percent of patients with stage A CLL died of causes related to the disease.
Chlorambucil does not prolong survival in patients with stage A CLL. Since deferring therapy until the disease progresses to stage B or C does not compromise survival, treatment of indolent CLL is unnecessary.
为了确定苯丁酸氮芥治疗对惰性慢性淋巴细胞白血病（CLL）患者是否有益，我们对1535例未经治疗的A期CLL患者进行了两项随机试验。
在第一项试验中，609例患者被随机分配接受每日苯丁酸氮芥治疗或不治疗；在第二项试验中，926例患者被随机分配接受间歇苯丁酸氮芥加泼尼松治疗或不治疗。第一项和第二项试验的中位随访时间分别超过11年和6年。终点指标为总生存期、治疗反应和疾病进展。
在两项试验中，惰性CLL的治疗均未提高生存率。在第一项试验中，治疗组与未治疗组相比，死亡相对风险为1.14（95%置信区间为0.92至1.41；P=0.23），在第二项试验中为0.96（95%置信区间为0.75至1.23；P=0.74），分别有76%和69%的患者对治疗有反应。虽然苯丁酸氮芥减缓了疾病进展，但对总生存期没有影响。在第一项试验的未治疗组中，49%的患者在随访超过11年后未进展至更晚期疾病且无需治疗；然而，27%的A期CLL患者死于与疾病相关的原因。
苯丁酸氮芥不能延长A期CLL患者的生存期。由于将治疗推迟至疾病进展至B期或C期不会影响生存，因此无需对惰性CLL进行治疗。
