Kadan-Lottick Nina S, Brouwers Pim, Breiger David, Kaleita Thomas, Dziura James, Liu Haibei, Chen Lu, Nicoletti Megan, Stork Linda, Bostrom Bruce, Neglia Joseph P
Yale University School of Medicine and Yale Cancer Center, New Haven, CT, USA.
Blood. 2009 Aug 27;114(9):1746-52. doi: 10.1182/blood-2008-12-186502. Epub 2009 Jun 22.
In previous clinical trials of childhood acute lymphoblastic leukemia (ALL), dexamethasone resulted in higher event-free survival rates than prednisone, presumably due to greater central nervous system penetration. Dexamethasone's association with long-term neurocognitive toxicity is unknown. In this multisite study, we measured neurocognitive functioning in 92 children with standard-risk ALL, 1 to 9.99 years at diagnosis, at a mean of 9.8 years after randomization to prednisone (n = 41) or dexamethasone (n = 51) on Children's Cancer Group (CCG) 1922. No significant overall differences in mean neurocognitive and academic performance scores were found between the prednisone and dexamethasone groups after adjusting for age, sex, and time since diagnosis. The exception was that patients receiving dexamethasone scored one-third of a standard deviation worse on word reading (98.8 +/- 1.7 vs 104.9 +/- 1.8; P = .02). There were no group differences in the distribution of test scores or the parents' report of neurologic complications, psychotropic drug use, and special education. Further analyses suggested for the dexamethasone group, older age of diagnosis was associated with worse neurocognitive functioning; for the prednisone group, younger age at diagnosis was associated with worse functioning. In conclusion, our study did not demonstrate any meaningful differences in long-term cognitive functioning of childhood ALL patients based on corticosteroid randomization. This study is registered with http://www.clinicaltrials.gov under NCT00085176.
在先前针对儿童急性淋巴细胞白血病(ALL)的临床试验中,地塞米松带来的无事件生存率高于泼尼松,这可能是由于其对中枢神经系统的穿透性更强。地塞米松与长期神经认知毒性之间的关联尚不清楚。在这项多中心研究中,我们对92名诊断时年龄在1至9.99岁的低危ALL儿童进行了神经认知功能测量,这些儿童在儿童癌症组(CCG)1922试验中被随机分配接受泼尼松(n = 41)或地塞米松(n = 51)治疗,平均随访时间为随机分组后9.8年。在对年龄、性别和诊断后的时间进行校正后,泼尼松组和地塞米松组在平均神经认知和学业成绩得分上没有显著的总体差异。唯一的例外是,接受地塞米松治疗的患者在单词阅读方面的得分比标准差低三分之一(98.8 +/- 1.7对104.9 +/- 1.8;P = .02)。在测试分数分布或家长报告的神经系统并发症、精神药物使用及特殊教育方面,两组之间没有差异。进一步分析表明,对于地塞米松组,诊断时年龄较大与神经认知功能较差有关;对于泼尼松组,诊断时年龄较小与功能较差有关。总之,我们的研究没有显示出基于皮质类固醇随机分组的儿童ALL患者在长期认知功能上有任何有意义的差异。本研究已在http://www.clinicaltrials.gov上注册,注册号为NCT00085176。