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 75-year-old woman was diagnosed with a pleiomorphic rhabdomyosarcoma (FNCLCC grade III) of the left thigh. She underwent a tumor resection in April 2010 followed by local irradiation. Bilateral pulmonary metastases were evidenced on CT scan in July 2011. Six cycles of doxorubicin (60 mg/m2 every 3 weeks) were given before the resection of the left metastasis in December 2011 and of the right one in February 2012. Because of tumor invasion of the left pleura, the patient received 3 cycles of IFO (2 g/m2/day for 5 days every 3 weeks) with aprepitant (80 mg/day × 5 days) and steroids. Eight days after the 3rd cycle of IFO, the patient was admitted for sepsis, lung infection, pancytopenia (1,400 leukocytes, 1,200 neutrophils, hemoglobin 8.2 g/dl, and 13,000 platelets) and renal insufficiency (620 µM creatinine). She presented vigilance disorders and confusion (Glasgow score 13). No abnormality or hemorrhage was detected on cerebral CT. MRI was judged nonfeasible. Lumbar puncture showed neither signs of infection nor presence of tumor cells. Methylene blue was ineffective. Despite restoration of normal blood count and normal renal function after one session of hemodialysis, the coma worsened leading to death.