Rijmenams Ilona, Moechars Daan, Uyttebroeck Anne, Radwan Ahmed, Blommaert Jeroen, Deprez Sabine, Sunaert Stefan, Segers Heidi, Gillebert Céline R, Lemiere Jurgen, Sleurs Charlotte
Department of Brain and Cognition, KU Leuven, 3000 Leuven, Belgium.
Department of Pediatric Oncology, KU Leuven, 3000 Leuven, Belgium.
Cancers (Basel). 2021 Apr 16;13(8):1939. doi: 10.3390/cancers13081939.
Methotrexate (MTX) is associated with leukoencephalopathy (LE) in children treated for lymphoblastic leukemia/lymphoma (ALL/LBL). However, large-scale studies with systematic MR acquisition and quantitative volumetric lesion information remain limited. Hence, the prevalence of lesion burdens and the potential risk factors of LE in this population are still inconclusive. FLAIR-MRI scans were acquired at the end of treatment in children who were treated for ALL/LBL, which were quantitatively analyzed for LE. Voxels were assigned to the lesion segmentation if indicated by two raters. Logistic and linear regression models were used to test whether lesion presence and size were predicted by risk factors such as age at diagnosis, gender, intrathecal (IT-) or intravenous (IV-)MTX dose, CNS invasion, and acute neurological events. Patients with a pre-existing neurological condition or low-quality MR scan were excluded from the analyses. Of the 129 patients, ten (8%) suffered from CNS invasion. Chemotherapy-associated neurological events were observed in 13 patients (10%) during therapy, and 68 patients (53%) showed LE post-treatment. LE was more frequent in cases of lower age and higher cumulative IV-MTX doses, while the extent of LE and neurological symptoms were associated only with IV-MTX doses. Neurological events were not significantly associated with LE, even though symptomatic patients demonstrated a higher ratio of LE ( = 9/13) than asymptomatic patients ( = 59/116). This study suggests leukoencephalopathy frequently occurs in both symptomatic and asymptomatic leukemia patients. Younger children and patients treated with higher cumulative IV-MTX doses might need more regular screening for early detection and follow-up of associated sequelae.
甲氨蝶呤（MTX）与接受淋巴细胞白血病/淋巴瘤（ALL/LBL）治疗的儿童的白质脑病（LE）有关。然而，采用系统磁共振成像采集和定量体积病变信息的大规模研究仍然有限。因此，该人群中病变负担的患病率以及LE的潜在危险因素仍无定论。对接受ALL/LBL治疗的儿童在治疗结束时进行液体衰减反转恢复序列磁共振成像（FLAIR-MRI）扫描，并对LE进行定量分析。如果两位评估者均指出，则将体素指定为病变分割。使用逻辑回归和线性回归模型来测试病变的存在和大小是否可由诊断时的年龄、性别、鞘内（IT-）或静脉内（IV-）MTX剂量、中枢神经系统侵犯和急性神经事件等危险因素预测。分析排除了已有神经疾病或磁共振扫描质量差的患者。在129例患者中，10例（8%）发生中枢神经系统侵犯。治疗期间13例患者（10%）出现化疗相关神经事件，68例患者（53%）治疗后出现LE。年龄较小和累积IV-MTX剂量较高的病例中LE更常见，而LE的程度和神经症状仅与IV-MTX剂量有关。神经事件与LE无显著相关性，尽管有症状的患者LE发生率（=9/13）高于无症状患者（=59/116）。本研究表明，白质脑病在有症状和无症状白血病患者中均频繁发生。年龄较小的儿童和接受较高累积IV-MTX剂量治疗的患者可能需要更定期的筛查，以便早期发现并随访相关后遗症。
