Department of Pediatrics, Division of Pediatric Oncology, Ege University School of Medicine, Izmir, Turkey.
J Oncol Pharm Pract. 2021 Dec;27(8):2018-2022. doi: 10.1177/10781552211005533. Epub 2021 Mar 27.
Ifosfamide is an alkylating agent, mostly used against variety of solid tumors in pediatric oncology practice. Although hemorrhagic cystitis is known as a common adverse effect, encephalopathy is the another one that should be kept in mind. It may occur in 2-5% of the children, and manifested by different clinical spectrums such as somnolence, lethargy, irritability, excitement, disorientation, confusion, weakness, hallucinations, seizures, movement disorders, and coma.
Herein, we present two patients who developed generalized seizure activity and one who developed coma during ifosfamide infusion. In the first two patients, ifosfamide infusion was discontinued and intravenous diazepam was given. Their seizure stopped in a few minutes and neurological examination was back to normal, and no focal deficits were observed. In the third patient, ifosfamide infusion was discontinued, methylene blue and thiamine were given. After the tenth dose of methylene blue, she became neurologically normal, without any mental and motor deficit. Nevertheless, later she developed febrile neutropenia, septic shock and she died.
These cases highlight that pediatric oncologists and hematologists should be aware of possibility of severe neurological toxicity after administration of ifosfamide in adolescent patients. Apart from seizure, clinicians should also be prepared to notice drowsiness during ifosfamide infusions in children. Most of the time cessation of ifosfamide and hydration is enough. However, in severe toxicities there is a risk of irreversible neurological damage, and for these patients methylene blue (MB) and thiamine treatment should be kept in mind.
异环磷酰胺是一种烷化剂，主要用于儿科肿瘤学实践中的各种实体瘤。虽然出血性膀胱炎是一种常见的不良反应，但脑病也是需要注意的另一种不良反应。它可能发生在 2-5%的儿童中，表现为不同的临床谱，如嗜睡、昏睡、烦躁、兴奋、定向障碍、意识混乱、虚弱、幻觉、癫痫发作、运动障碍和昏迷。
本文介绍了两名在异环磷酰胺输注过程中出现全身癫痫发作和一名昏迷的患者。在前两名患者中，停止了异环磷酰胺输注，并给予了静脉注射地西泮。他们的癫痫在几分钟内停止，神经系统检查恢复正常，没有发现局灶性缺损。在第三名患者中，停止了异环磷酰胺输注，给予了亚甲蓝和硫胺素。在使用第十剂亚甲蓝后，她的神经系统恢复正常，没有任何精神和运动缺陷。然而，后来她出现了发热性中性粒细胞减少症、感染性休克，最终死亡。
这些病例强调了儿科肿瘤学家和血液学家应该意识到青少年患者使用异环磷酰胺后可能发生严重的神经毒性。除了癫痫发作外，临床医生还应该在儿童输注异环磷酰胺时注意到嗜睡的可能性。大多数情况下，停止输注异环磷酰胺和补液就足够了。然而，在严重的毒性反应中，存在不可逆的神经损伤风险，对于这些患者，应考虑使用亚甲蓝（MB）和硫胺素治疗。
