The impact on outcome of the addition of all-trans retinoic acid to intensive chemotherapy in younger patients with nonacute promyelocytic acute myeloid leukemia: overall results and results in genotypic subgroups defined by mutations in NPM1, FLT3, and CEBPA
The impact on outcome of the addition of all-trans retinoic acid to intensive chemotherapy in younger patients with nonacute promyelocytic acute myeloid leukemia: overall results and results in genotypic subgroups defined by mutations in NPM1, FLT3, and CEBPA
复制标题
DOI：
10.1182/blood-2009-08-236588
复制
发表时间：
2010-02-04
期刊：
影响因子：
20.3
通讯作者：
Gale, Rosemary E.
中科院分区：
文献类型：
--
作者：
Burnett, Alan K.;Hills, Robert K.;Gale, Rosemary E.
我们研究了在非急性早幼粒细胞急性髓细胞白血病和高危骨髓增生异常综合征的年轻患者化疗中加入全反式维甲酸（ATRA）的益处，并考虑了治疗和分子标志物之间的相互作用。总体而言，1075例年龄小于60岁的患者随机接受或不接受ATRA，除了柔红霉素/Ara-C/硫鸟嘌呤化疗与Ara-C在标准或两倍标准剂量。有关于FLT 3内部串联重复和NPM 1突变（n = 592）、CEBPA突变（n = 423）和MN 1表达（n = 195）的数据。完全缓解率为68%，另外16%的患者完全缓解，计数不完全恢复; 8年总生存率为32%。任何结局均无显著治疗效应，治疗与人口统计学或阿糖胞苷随机化之间无显著相互作用。重要的是，FLT 3/内部串联重复、NPM 1或CEBPA突变没有相互作用。有一个建议，全反式维甲酸减少复发的患者（与较低的MN 1水平，但没有显着影响的总生存率。当仅限于正常核型的患者时，结果一致。ATRA对这组患者的治疗结果没有总体影响。该研究没有发现任何亚组的患者可能从ATRA加化疗中获得显着的生存益处。本研究注册于http://www.controlled-trials。comunderISRCTN17833622.（血。2010;115：948-956）
We investigated the benefit of adding all-trans retinoic acid (ATRA) to chemotherapy for younger patients with nonacute promyelocytic acute myeloid leukemia and high-risk myelodysplastic syndrome, and considered interactions between treatment and molecular markers. Overall, 1075 patients less than 60 years of age were randomized to receive or not receive ATRA in addition to daunorubicin/Ara-C/thioguanine chemotherapy with Ara-C at standard or double standard dose. There were data on FLT3 internal tandem duplications and NPM1 mutations (n = 592), CEBPA mutations (n = 423), and MN1 expression (n = 195). The complete remission rate was 68% with complete remission with incomplete count recovery in an additional 16%; 8-year overall survival was 32%. There was no significant treatment effect for any outcome, with no significant interactions between treatment and demographics, or cytarabine randomization. Importantly, there were no interactions by FLT3/ internal tandem duplications, NPM1, or CEBPA mutation. There was a suggestion that ATRA reduced relapse in patients (with lower MN1 levels, but no significant effect on overall survival. Results were consistent when restricted to patients with normal karyotype. ATRA has no overall effect on treatment outcomes in this group of patients. The study did not identify any subgroup of patients likely to derive a significant survival benefit from the addition of ATRA to chemotherapy. This study is registered at http://www.controlled-trials. comunderISRCTN17833622. (Blood. 2010;115:948-956)