A 25-year-old male patient diagnosed as a case of Philadelphia chromosome-negative B-cell acute lymphoblastic lymphoma (ALL) and who had relapsed after receiving the Berlin-Frankfurt-Münster 90 acute lymphoblastic leukemia protocol (BFM ALL protocol) was started on MINE protocol (injection ifosfamide 4 g/m2 was divided over 3 days [day 1–3] and administered IV over a 1 h period, injection mitoxantrone 8 mg/m2 [day 1] administered as a short IV infusion, injection etoposide 65 mg/m2/day [day 1–3] was infused over 1 h, and injection mesna 1330 mg/m2 [days 1–3]) after the patient had progressed on DHAP regimen (injection cisplatin 100 mg/m2 [day 1], high-dose cytarabine 2 g/m2 twice a day [day 2], and tablet prednisolone 40 mg/day [day 2–4]). After 24 h of the 1st day of chemotherapy, the patient started developing headache, vomiting which was followed in couple of hours by disoriented behavior, and one episode of seizure. In view of above complaints, patient chemotherapy was withheld as the patient developed headache and vomiting. For the above complaints, patient's all routine investigations such as complete blood count, renal function, and liver function test were performed along with albumin and electrolytes. All the investigations were within normal limits. Electrocardiogram was done which was within normal limits. Magnetic resonance imaging of brain was obtained which did not show any abnormality. Considering the above case scenario and ruling out the possible causes of acute delirious state such as electrolyte abnormalities and intracranial bleed, we entertained the possibility of IIE. The patient was started on hydration therapy with IV fluids and dextrose normal saline infusion at the rate of 100 ml/m2 followed by which injection methylene blue was procured and started at the dose of 50 mg (1% aqueous solution) IV over 5 min, six times daily, and antiemetics such as ondansetron 4 mg by needle were administered twice a day for initial 3 days and then whenever needed. Within a period of 24 h, the patient started improving in the form of decrease in vomiting and response to oral commands. Later complete recovery occurred within 48–72 h. Till then injection methylene blue and hydration were continued. Furthermore, the patient was given IV 5% albumin.\nHence, the patient who had presented with above-mentioned complaints with normal imaging and blood investigations and who had responded to methylene blue confirmed our diagnosis of the IIE. Furthermore, retrospectively, we looked over the factors that precipitated the IIE. Albumin, renal and liver function, and electrolytes were well within normal limits at the start of infusion of ifosfamide. However, the patient had received injection fosaprepitant before the start of injection ifosfamide.\nWe then reviewed the literature, and it confirmed that the precipitating factor for IIE was none other than aprepitant.
A 46-year-old, gravida 2, para 2, married woman with recurrent epithelial ovarian cancer (serous adenocarcinoma) was referred to our institution for further management. She had no specific medical history.\nAt initial diagnosis of epithelial ovarian cancer, she underwent bilateral salpingo-oophorectomy, partial omentectomy and incidental appendectomy at another hospital, and cytoreductive surgery was suboptimal. She received 12 cycles of adjuvant chemotherapy with paclitaxel and carboplatin. However, an abdomino-pelvic CT scan showed residual peritoneal carcinomatosis and her serum CA-125 concentration was elevated, from 517 to 1,020 U/mL. After referral to our center, she underwent optimal cytoreductive surgery, including total abdominal hysterectomy, pelvic and paraaortic lymph node dissection, low anterior resection, and right diaphragmatic stripping. After surgery, she received 3 cycles of adjuvant chemotherapy with topotecan and cisplatin. Due to disease progression, her regimen was switched to 3 cycles of docetaxel and carboplatin. Due to the disease progression on this regimen, we changed her chemotherapy regimen to a combination of ifosfamide and etoposide. She received the first cycle of etoposide (75 mg/m2/day in 3-hour infusions on days 1-5) and ifosfamide (1,200 mg/m2/day in 3-hour infusions on days 1-5), along with 300 mg/m2/day mesna, without any complications. On day 6, her speech became unintelligible but her orientation was intact. On day 7, she developed delirium, disorientation, visual and auditory hallucinations, stereotyped movements, and emotional instability. At that time, her estimated glomerular filtration rate, serum creatinine and blood urea nitrogen were 27 mL/min (normal, >60 mL/min), 2.3 mg/dL (normal, 0.7 to 1.4 mg/dL) and 33 mg/dL (normal, 10 to 26 mg/dL), respectively, and her renal function decreased gradually. Brain MRI was normal. After referral to a nephrologist, her electrolyte imbalance was corrected and her uremia was improved by hemodialysis. However, her mental impairments showed no improvement. She was diagnosed as having severe ifosfamide-induced encephalopathy. She never recovered and was discharged in a hopeless condition on day 10 and died within 1 month.