A 47-year-old African American male with stage III cutaneous T-cell lymphoma with large cell transformation presented to the hospital with shortness of breath, fatigue, and failure to thrive. The patient had progressed through multiple lines of chemotherapy including EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin), romidepsin, gemcitabine, brentuximab, and pralatrexate. At inpatient presentation, he had malignant pleural effusions, hypercalcemia, and leukocytosis with eosinophilia. Given the patient’s rapidly worsening clinical course, it was decided to start ifosfamide, carboplatin, and etoposide (ICE) chemotherapy with etoposide 100 mg/m2 on days 1 to 3, ifosfamide 5000 mg/ on day 2 infused over 24 hours, and carboplatin with an area under curve (AUC) of 5 on day 3. He was alert and oriented prior to and during the infusion but became delirious on day 3 of the regimen, 6 hours after the completion of the ifosfamide infusion. Physical examination did not reveal any stereotypical movements or twitching. His mental status worsened from initial agitation and confusion to drowsiness and eventually stupor. Diagnostic evaluation for acute mental status change including complete blood count, comprehensive metabolic panel, ammonia level, and computed tomography scan of the head was negative. Infectious workup including blood cultures, urine culture, and chest X-ray did not reveal any infectious process contributing to the altered mental status. Thus, the patient’s acute altered mental status was attributed to IME. He was started on hydration, and 50 mg of intravenous MB was given every 4 hours. His mental status began to improve 16 hours after start of MB and was back to his baseline after 48 hours of treatment (received 12 total doses). The one cycle of ICE chemotherapy temporarily improved his disease but due to neurotoxicity, he was not rechallenged.
A 39-year-old woman had a surgical resection for a uterine leiomyosarcoma in February 2011. A local relapse was treated by resection in March 2012, and the patient was referred for adjuvant chemotherapy in May 2012. Because of the deterioration of her general condition due to an early local relapse, she received first doxorubicin 75 mg/m2 alone. Improvement of her general condition allowed for a combined treatment with doxorubicin (60 mg/m2) and IFO (9 g/m2) for the next 4 cycles. In the 5th and 6th cycles, IFO alone was used because of the cumulative dose of anthracyclines (adjuvant epirubicin had previously been given for a breast cancer). A partial response was obtained, but the tumor remained unresectable and a therapeutic break was decided. In February 2013, CT scan showed progression, and IFO (5 g/m2/day) was started again. Aprepitant (125 mg on day 1 and 80 mg on days 2 and 3) was given with steroids to prevent nausea. Within a few hours after the 2nd cycle, the patient had obnubilation and awareness troubles without any other symptoms. These troubles did not improve with the evacuation of a vesical globe or the cessation of neurodepressing drugs (oxycodone and chlorpromazine). There was no hydroelectrolytic disorder. Encephalic MRI did not show bleeding or a cerebrovascular event. IFO-induced encephalopathy was suspected, and a treatment with methylene blue was started. Improved awareness was transiently observed, but the patient remained disoriented and died 8 days later, without return to normal consciousness.