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

在儿童期罹患肿瘤的幸存者中，头颅放疗（CRT）是已知的造成神经认知功能受损的危险因素，其可能会增加成年期轻度认知功能缺陷和痴呆的发生风险。为了评估上述问题，来自St.Jude儿童研究医院的Gregory T. Armstrong等设计了相关研究，并将其研究结果发表在JNCI 4月最新的在线期刊上。

本研究为横断面评价研究，本研究的受试者为儿童期罹患急性淋巴母细胞性白血病的幸存者，其中127人在儿童期接受过治疗剂量为18Gy的头颅放疗，另有138人接受过治疗剂量为24Gy的头颅放疗。研究者采用韦氏记忆量表IV（WMS-IV）对受试者记忆受损程度进行评估。另有一个由85名受试者组成的亚组接受了神经影像学结构和功能的评估。

研究者发现，与接受治疗剂量为18Gy的受试者相比，接受治疗剂量为24Gy的受试者更易出现即刻记忆功能缺损和延迟记忆功能缺损，即刻记忆缺损的发生率为33.8%，而延迟记忆功能缺损的发生率为30.2%，两组相比，差异具有显著统计学意义。在接受24Gy的受试者中，长期叙事记忆平均得分与69岁的老年人的平均得分相当。即刻记忆缺损与左右颞叶体积减小程度相关（具有显著统计学意义），延迟记忆与顶叶和额叶的厚薄相关，顶叶和额叶越薄，延迟记忆缺损可能越大。在具有记忆缺损的患者中，研究者观察到了海马体积的缩小和功能磁共振影像激活的增加。在进行过24Gy的头颅放疗之后受试者的认知状态会出现减退（18.5%），而在接受了18Gy的头颅放疗后却不会出现认知状态的减退（8.7%），研究者认为这一结果提示认知功能减退与放疗剂量相关。但是研究者指出两组受试者的就业率相当——18Gy组为63.0%，24Gy组为63.8%。

本研究结果指出，在接受过24Gy头颅放疗的儿童期急性淋巴母细胞性白血病的成人患者中，会出现认知功能和记忆功能的减退，表现为与记忆形成有着至关重要联系的神经解剖部位的整合性减低，这与早期的轻度认知功能缺陷的表现一致。

与白血病相关的拓展阅读：

• 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
• 苏州将建亚洲大规模白血病标本库 更多信息请点击：有关白血病更多资讯

Evaluation of Memory Impairment in Aging Adult Survivors of Childhood Acute Lymphoblastic Leukemia Treated With Cranial Radiotherapy
Background
Cranial radiotherapy (CRT) is a known risk factor for neurocognitive impairment in survivors of childhood cancer and may increase risk for mild cognitive impairment and dementia in adulthood.
Methods
We performed a cross-sectional evaluation of survivors of childhood acute lymphoblastic leukemia (ALL) treated with 18 Gy (n = 127) or 24 Gy (n = 138) CRT. Impairment (age-adjusted score >1 standard deviation below expected mean, two-sided exact binomial test) on the Wechsler Memory Scale IV (WMS-IV) was measured. A subset of survivors (n = 85) completed structural and functional neuroimaging.
Results
Survivors who received 24 Gy, but not 18 Gy, CRT had impairment in immediate (impairment rate = 33.8%, 95% confidence interval [CI] = 25.9% to 42.4%; P < .001) and delayed memory (impairment rate = 30.2%, 95% CI = 22.6% to 38.6%; P < .001). The mean score for long-term narrative memory among survivors who received 24 Gy CRT was equivalent to that for individuals older than 69 years. Impaired immediate memory was associated with smaller right (P = .02) and left (P = .008) temporal lobe volumes, and impaired delayed memory was associated with thinner parietal and frontal cortices. Lower hippocampal volumes and increased functional magnetic resonance imaging activation were observed with memory impairment. Reduced cognitive status (Brief Cognitive Status Exam from the WMS-IV) was identified after 24 Gy (18.5%, 95% CI = 12.4% to 26.1%; P < .001), but not 18 Gy (8.7%, 95% CI = 4.4% to 15.0%; P = .11), CRT, suggesting a dose–response effect. Employment rates were equivalent (63.8% for 24 Gy CRT and 63.0% for 18 Gy CRT).
Conclusions
Adult survivors who received 24 Gy CRT had reduced cognitive status and memory, with reduced integrity in neuroanatomical regions essential in memory formation, consistent with early onset mild cognitive impairment.