Leukoencephalopathy and long-term neurobehavioural, neurocognitive, and brain imaging outcomes in survivors of childhood acute lymphoblastic leukaemia treated with chemotherapy: a longitudinal analysis.
Leukoencephalopathy and long-term neurobehavioural, neurocognitive, and brain imaging outcomes in survivors of childhood acute lymphoblastic leukaemia treated with chemotherapy: a longitudinal analysis.
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DOI：
10.1016/s2352-3026(16)30110-7
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发表时间：
2016-10
期刊：
影响因子：
--
通讯作者：
Krull KR
中科院分区：
文献类型：
--
作者：
Cheung YT;Sabin ND;Reddick WE;Bhojwani D;Liu W;Brinkman TM;Glass JO;Hwang SN;Srivastava D;Pui CH;Robison LL;Hudson MM;Krull KR
在一些接受急性淋巴细胞白血病(ALL)化疗的儿童中观察到白质脑病，尽管它对长期结果的影响尚不清楚。这项研究考察了急性白质脑病与神经行为、神经认知和脑白质成像结果之间的关系，这些患者长期接受非颅脑放射治疗的化疗。在积极治疗期间，190名幸存者(平均年龄13·7[4·4]岁，确诊后7·7[1·7]岁)接受了脑磁共振成像(MRI‘s)，并使用不良事件v4的通用术语标准对脑白质脑病进行了系统编码。在诊断后5年的≥，幸存者完成了神经认知测试，另一项大脑核磁共振，他们的父母完成了神经行为评级。随诊MRI包括扩散张量成像，以额叶和顶叶的分数各向异性(FA)、轴向扩散率(AD)和径向扩散率(RD)以及额纹状体内与执行功能相关的轴突纤维束的指数来评估白质的完整性。与人群常模相比，幸存者被报告在工作记忆、组织、启动和计划方面表现出更多的问题(所有P<；0·001)。有急性脑白质病史的幸存者中有51人(27%)在组织和起始方面比没有白质脑病病史的幸存者表现出更多的问题。急性白质脑病的幸存者在随访时额纹状体内白质完整性也降低：FA降低(p=0.069)，AD增加(p=0.020)，RD增加(p=0.0077)。RD指数每改变一个单位，初始记忆、计划记忆和工作记忆的原始分数分别增加15.0、30.3和28.0分(P均为0.050)。在没有接受头颅放射治疗的儿童接受化疗期间，急性白质脑病都预示着长期神经行为问题的风险更高，额叶脑区脑白质完整性降低。ALL的幸存者可以从预防性的认知和/或行为干预中受益，特别是那些发展为急性白质脑病的人。
Leukoencephalopathy is observed in some children undergoing chemotherapy for acute lymphoblastic leukemia (ALL), though its impact on long-term outcomes is unknown. This study examines associations between acute leukoencephalopathy, and neurobehavioral, neurocognitive and brain white matter imaging outcomes in long-term survivors of ALL treated with chemotherapy without cranial radiation. During active therapy, 190 survivors (mean[SD] age 13·7[4·4] years, 7·7[1·7] years post-diagnosis) had brain magnetic resonance imaging (MRI’s), which were systematically coded for leukoencephalopathy using Common Terminology Criteria for Adverse Event v4. At ≥5 years post-diagnosis, survivors completed neurocognitive testing, another brain MRI, and their parents completed neurobehavioral ratings. Follow-up MRI included diffusion tensor imaging to assess white matter integrity, with indices of fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD) from frontal and parietal lobes, and within the frontostriatal tract, an axonal fiber bundle associated with executive function. Compared to population norms, survivors were reported to demonstrate more problems with Working Memory, Organization, Initiation and Planning (all p’s<0·001). The 51/190 survivors (27%) with a history of acute leukoencephalopathy displayed more problems than survivors with no history of leukoencephalopathy on Organization and Initiation. Survivors with acute leukoencephalopathy also had reduced white matter integrity within the frontostriatal tract at follow-up: lower FA (p=0·069), higher AD (p=0·020) and higher RD (p=0·0077). A one-unit change in the RD index corresponded to a 15·0, 30·3 and 28·0 increase in raw score points on Initiation, Planning and Working Memory, respectively (all p’s<0·050). Acute leukoencephalopathy during chemotherapy treatment without cranial radiation for childhood ALL predicted higher risk for long-term neurobehavioral problems and reduced white matter integrity in frontal brain regions. Survivors of ALL may benefit from preventative cognitive and/or behavioral interventions, particularly those who develop acute leukoencephalopathy.