Fenaux P
Service des Maladies du Sang, C.H.U. Lille, France.
Leukemia. 1994;8 Suppl 3:S70-2.
Initial results of ATRA in newly diagnosed APL showed that this drug was associated with a high complete remission (CR) rate but also (i) to a risk of hyperleukocytosis and of ATRA syndrome, (ii) to rapid relapse unless ATRA was followed by intensive chemotherapy. These findings prompted our group to design an approach combining ATRA and intensive chemotherapy in newly diagnosed APL, where chemotherapy could prevent relapses and also, in cases with increasing leukocyte counts, could prevent the ATRA syndrome. In a pilot study, this approach gave a high CR rate (96%) and (with now prolonged follow-up) a significant reduction in the incidence of relapse, as compared to a historical control treated with chemotherapy alone. The superiority of the combination of ATRA and chemotherapy over chemotherapy alone (especially for the incidence of relapse) was subsequently confirmed in a randomized European trial (APL 91 trial). We are now testing in a new European trial (APL 93 trial) whether chemotherapy should be administered with ATRA, or should follow ATRA during induction treatment, and whether maintenance therapy with intermittent ATRA, low-dose chemotherapy, or both can further reduce the risk of relapse.
全反式维甲酸（ATRA）用于新诊断的急性早幼粒细胞白血病（APL）的初步结果显示，这种药物与高完全缓解（CR）率相关，但也存在以下情况：（i）有白细胞增多症和ATRA综合征的风险；（ii）除非在ATRA之后进行强化化疗，否则会迅速复发。这些发现促使我们团队设计一种在新诊断的APL中联合使用ATRA和强化化疗的方法，其中化疗可以预防复发，而且在白细胞计数增加的情况下，还可以预防ATRA综合征。在一项试点研究中，与仅接受化疗的历史对照组相比，这种方法取得了较高的CR率（96%），并且（随着随访时间的延长）复发率显著降低。随后在一项欧洲随机试验（APL 91试验）中证实了ATRA与化疗联合使用相对于单纯化疗的优越性（尤其是在复发率方面）。我们现在正在一项新的欧洲试验（APL 93试验）中测试，在诱导治疗期间化疗是应与ATRA同时使用，还是应在ATRA之后使用，以及间歇性ATRA、低剂量化疗或两者联合进行维持治疗是否可以进一步降低复发风险。
