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 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.