JCO：儿童急性淋巴细胞白血病患者脑体积存在减少趋势

在2013年4月15日在线出版的《临床肿瘤学杂志》(Journal of Clinical Oncology)上，挪威奥斯陆大学Bernward Zeller博士等人发表了一项研究结果，该研究针对曾于儿童期患有急性淋巴细胞白血病(ALL)的成年长期幸存者与健康对照人群，旨在对这些人群的局部脑容量进行比较。

该研究考察了130例儿童ALL幸存者，这些患者曾于1970年至2002年期间，经核磁共振成像(MRI)方式得到确诊，在患者确诊后中位时间为22.5年时，研究人员对这些患者进行了神经心理测试。此外，通过一种经过验证过的自动程序，进行了包括全脑分段在内的全脑形态测定分析；该研究对照组为130名健康成人。

研究人员发现，与健康对照人群相比，ALL幸存者在皮层灰质、脑白质、杏仁核、尾状核、海马区、丘脑以及颅内容积估测值等方面均明显较小。相关效应量值为小至中等。研究发现尾状核的效应最强，ALL幸存者尾状核平均减小5.2%。将颅内容积设为对照后，尾状核体积也呈减小趋势，这表明尾状核具有特定效应。此外，确诊时的年龄或治疗变量，如放疗或药物剂量，均不能对神经解剖体积产生重大影响。神经心理评价结果表明，与对照组人群相比，ALL幸存者在处理速度、执行功能以及语言学习/记忆等方面均有所降低，但二者在一般智力估测结果方面并无差异。与对照组人群不同，ALL幸存者的神经心理测试结果与皮层灰质体积、尾状区体积、丘脑体积以及颅内容积间存在关联。

研究人员根据结构MRI结果认为，与健康对照人群相比，儿童期ALL幸存者的多种脑部结构体积均有减小。但鉴于可能存在的筛选偏倚，研究人员建议对该研究结果进行谨慎解读。另外，需通过进一步研究对这些结果以及相关的神经生物学机制的显著性进行阐释。
与白血病相关的拓展阅读：

• Cancer：阿仑单抗联合FMC方案能有效治疗T细胞幼淋巴细胞白血病
• JNCI：头颅放疗剂量影响急性淋巴母细胞性白血病成人患者的认知功能
• Blood:汉黄芩苷或可治疗急性髓系白血病(AML)
• PNAS：人源化CD44单克隆抗体可直接杀死白血病细胞
• PNAS：陈赛娟白血病治疗药物毛萼乙素在自身免疫病领域研究获进展
• J Med Chem：新型Bcr-Abl小分子抑制剂有望用于慢粒性白血病耐药的治疗 更多信息请点击：有关白血病更多资讯

Reduced Neuroanatomic Volumes in Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia.
PURPOSE
To compare regional brain volumes in adult long-term survivors of childhood acute lymphoblastic leukemia (ALL) and healthy controls.
PATIENTS AND METHODS
We investigated 130 survivors of childhood ALL diagnosed between 1970 and 2002 with magnetic resonance imaging (MRI) and neuropsychological testing at a median of 22.5 years after diagnosis. Morphometric analyses including whole-brain segmentation were performed using a validated automated procedure; 130 healthy adults served as controls.
Results
Compared with healthy controls, ALL survivors showed significantly smaller volumes of cortical gray matter, cerebral white matter, amygdala, caudate, hippocampus, thalamus, and estimated intracranial volume. Effect sizes ranged from small to medium. The strongest effect was found for the caudate, which on average was 5.2% smaller in ALL survivors. Caudate volumes were also smaller when controlling for intracranial volume, suggesting a specific effect. Neither age at diagnosis nor treatment variables such as radiation therapy or drug dose had a major impact on neuroanatomic volumes. Neuropsychological assessment revealed reduced processing speed, executive function, and verbal learning/memory in survivors compared with controls but no difference in estimated general intellectual ability. In ALL survivors, but not in controls, neuropsychological test results correlated with volumes of cortical gray matter, caudate, and thalamus as well as intracranial volume.
CONCLUSION
Structural MRI of long-term survivors of childhood ALL demonstrated smaller volumes of multiple brain structures compared with healthy controls. Because of possible selection biases, these results must be interpreted with caution. Future studies are required to clarify the significance of these findings and the neurobiologic mechanisms involved.