Alqahtani Shaikha, Bitar Sabrina D, Mireles Maria Estela, Corrales-Medina Fernando F, Herzog Cynthia E, Slopis John, Daw Najat C
Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Department of Neurology, University of Texas Health Science Center, Houston, TX 77030, USA.
Cancers (Basel). 2025 Jun 29;17(13):2192. doi: 10.3390/cancers17132192.
: Ifosfamide, an alkylating agent used for treating various cancers, can cause encephalopathy in 10-30% of adults and 8% of children. Methylene blue has been used to treat ifosfamide-induced encephalopathy (IIE). This study aimed to describe our institutional experience with IIE in children and young adults with cancer, including its clinical manifestations, treatment, and outcomes. : We reviewed the clinical records of patients with cancer aged up to 30 years who developed IIE over 10 years. : Twenty-four patients (median age: 17.6 years, range: 4-30 years) were included; 54% were male, and 71% had bone/soft tissue sarcomas. Ifosfamide was administered alone or with other drugs (dose range: 1.5-3.3 g/m/day). Twelve patients developed IIE after short intermittent infusions (1-3 h), and twelve developed it after continuous infusions (12-24 h). IIE occurred at a median cumulative ifosfamide dose of 18 g/m. Symptoms appeared within hours to five days and resolved within 24-120 h. An altered mental status was present in all except one patient. Twelve patients had grade 3 IIE (severe somnolence, agitation, and confusion), and five had grade 4 IIE (coma and seizures). Twenty patients (83%) received methylene blue, with symptom resolution in nineteen patients (83%). Imaging studies showed nonspecific findings. Ten patients were re-challenged with ifosfamide; five received prophylactic methylene blue treatment, of whom three had recurrence. : IIE can occur with both short intermittent and continuous ifosfamide infusions and presents as an altered mental status, seizures, and, rarely, hemiparesis. Symptoms are transient, and methylene blue may help alleviate this neurotoxicity, but it does not completely prevent its recurrence.
异环磷酰胺是一种用于治疗多种癌症的烷化剂，可导致10% - 30%的成人和8%的儿童发生脑病。亚甲蓝已被用于治疗异环磷酰胺诱导的脑病（IIE）。本研究旨在描述我们机构对癌症儿童和青年IIE的治疗经验，包括其临床表现、治疗方法及结果。：我们回顾了10年间发生IIE的30岁及以下癌症患者的临床记录。：纳入24例患者（中位年龄：17.6岁，范围：4 - 30岁）；54%为男性，71%患有骨/软组织肉瘤。异环磷酰胺单独或与其他药物联合使用（剂量范围：1.5 - 3.3 g/m²/天）。12例患者在短时间间歇输注（1 - 3小时）后发生IIE，12例在持续输注（12 - 24小时）后发生。IIE发生时异环磷酰胺的中位累积剂量为18 g/m²。症状在数小时至5天内出现，并在24 - 120小时内缓解。除1例患者外，所有患者均出现精神状态改变。12例患者为3级IIE（严重嗜睡、激动和意识模糊），5例为4级IIE（昏迷和癫痫发作）。20例患者（83%）接受了亚甲蓝治疗，19例患者（83%）症状缓解。影像学检查显示非特异性结果。10例患者再次接受异环磷酰胺治疗；5例接受预防性亚甲蓝治疗，其中3例复发。：短时间间歇输注和持续输注异环磷酰胺均可发生IIE，表现为精神状态改变、癫痫发作，很少出现偏瘫。症状是短暂的，亚甲蓝可能有助于减轻这种神经毒性，但不能完全预防其复发。
