A 38-year-old African American female with refractory stage IV mycosis fungoides with large cell transformation was admitted to the hospital for initiation of ICE chemotherapy. Patient had extensive cutaneous and muscle involvement of the lymphoma and had failed multiple lines of chemotherapy regimens including romidepsin and rituximab, brentuximab, and gemcitabine. Laboratory testing prior to initiation of ICE therapy was normal except for low serum albumin level of 1.7 g/dL. Patient received ICE therapy with etoposide 100 mg/m2 on days 1 to 3, ifosfamide 5000 mg/m2 on day 2 infused over 24 hours, and carboplatin with an AUC of 5 on day 3. She was premedicated with aprepitant for prevention of nausea. She was alert and oriented prior to and during the infusion but became lethargic, somnolent, and confused within 6 to 8 hours of completion of ifosfamide infusion. Physical examination was significant for random jerky movements of both upper and lower extremities, twitching of the right eye, and somnolence. The patient’s evaluation for sudden neurological changes included complete blood count, comprehensive metabolic panel, computed tomography scan of the head, and infectious workup (blood cultures, urine culture, and chest X-ray), all of which were negative. She received naloxone with no reversal of mental status changes. Based on the timing of the infusion and change in mental status, patient was diagnosed with IME and MB was immediately initiated at a dose of 50 mg every 4 hours. An improvement in the patient’s mental status was noticed within 12 hours of initiation of MB, and the patient was back to her baseline in 72 hours (received 18 total doses). Given the neurotoxicity, patient was not rechallenged with ifosfamide and was switched to a different chemotherapeutic regimen.
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.