UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia
UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia
复制标题
DOI：
10.1182/blood-2013-09-529008
复制
发表时间：
2014-02-06
期刊：
影响因子：
20.3
通讯作者：
Goldstone, Anthony H.
中科院分区：
文献类型：
--
作者：
Fielding, Adele K.;Rowe, Jacob M.;Goldstone, Anthony H.
UKALLXII/ECOG2993成人急性淋巴细胞性白血病(ALL)研究的费城染色体阳性臂在1993至2003年间招募了266名患者(preimatinib队列)。2003年，伊马替尼作为诱导后的单药疗程被引入(N=86，晚期伊马替尼)。2005年，伊马替尼加入第二阶段诱导(N=89，早期伊马替尼)。完全缓解(CR)率在伊马替尼队列中为92%，而在普瑞马替尼队列中为82%(P=0.004)。4年后，伊马替尼组所有患者的总存活率(OS)为38%，而普瑞马替尼组为22%(P=0.003)。在单因素分析中，在无事件生存率(EFS)、无复发生存率(OS)和无复发生存率(RFS)方面，在多因素分析中，普瑞马替尼和伊马替尼队列之间的差异幅度更大。在普瑞马替尼队列中，31%的开始治疗的患者实现了造血干细胞移植(AllHSCT)，而在伊马替尼队列中，这一比例为46%。考虑到allHSCT的Cox多变量分析显示，伊马替尼有适度的额外益处(EFS的风险比=0.64，95%可信区间0.44-0.93，P=0.02)，但对OS和RFS没有显著益处。在标准治疗的基础上加用伊马替尼可提高成人急性淋巴细胞白血病的缓解率和长期OS。OS受益的一部分来自伊马替尼促进异基因造血干细胞移植的事实。这项试验在Clinicaltrials.gov上注册为NCT00002514。
The Philadelphia chromosome positive arm of the UKALLXII/ECOG2993 study for adult acute lymphoblastic leukemia (ALL) enrolled 266 patients between 1993 and 2003 (preimatinib cohort). In 2003 imatinib was introduced as a single-agent course following induction (N = 86, late imatinib). In 2005 imatinib was added to the second phase of induction (N = 89, early imatinib). The complete remission (CR) rate was 92% in the imatinib cohort vs 82% in the preimatinib cohort (P = .004). At 4 years, the overall survival (OS) of all patients in the imatinib cohort was 38% vs 22% in the preimatinib cohort (P = .003). The magnitude of the difference between the preimatinib and imatinib cohorts in event-free survival (EFS), OS, and relapse-free survival (RFS) seen in univariate analysis was even greater in the multivariate analysis. In the preimatinib cohort, 31% of those starting treatment achieved hematopoietic stem cell transplant (alloHSCT) compared with 46% in the imatinib cohort. A Cox multivariate analysis taking alloHSCT into account showed a modest additional benefit to imatinib (hazard ratio for EFS = 0.64, 95% confidence interval 0.44-0.93, P = .02), but no significant benefit for OS and RFS. Adding imatinib to standard therapy improves CR rate and long-term OS for adults with ALL. A proportion of the OS benefit derives from the fact that imatinib facilitates alloHSCT. This trial was registered at clinicaltrials.gov as NCT00002514.