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.
Our patient was a 71 year old woman diagnosed with a high-grade right triceps pleomorphic sarcoma in 2017, which was resected with a wide local excision and treated with adjuvant radiation. A surveillance computed tomography (CT) scan of the thorax showed metastases to the lung and mediastinum in September 2018 and she was treated with 6 cycles of doxorubicin. Progression of disease identified in January 2019 necessitated a change of treatment to ifosfamide and mesna, and she was admitted for each cycle. Re-staging CT scan after 2 cycles demonstrated an interval decrease in the size and number of the multiple pulmonary nodules with one nodule reducing in size from 18 mm down to 6 mm, complete resolution of a 15 mm right para-oesophageal node and no new disease identified.\nPast medical history included hypertension, hysterectomy for menorrhagia and appendectomy. Her medications on admission were lercanidipine, losartan, hydrochlorothiazide, potassium supplement, enoxaparin (thrombosis prophylaxis), senna, domperidone, aprepitant, Fortisip Compact Fibre, Procal Shot, multivitamin and evening primrose oil (not administered due to unknown possible drug interactions). She was known to develop a rash with penicillin but had no other allergies.\nExamination on admission for cycle 3 was remarkable for oral candidiasis. Routine blood investigations identified potassium 2.7 mmol/l which was replaced with IV and oral potassium and albumin of 32 g/l. She developed nausea after day 2 and had one episode of vomiting.\nOn day 3, she was noted to be resting during the morning, however was easily rousable and able to stay awake. Chemotherapy was commenced at midday. Within 4 h, it was noted that she was difficult to rouse. Vital signs were within normal ranges. A blood gas confirmed a potassium of 2.7 mmol/l, but no other abnormality was identified and the pH was uncompensated and in the normal range. An ECG was unremarkable. It was hypothesized that she had developed ifosfamide encephalopathy and an EEG was obtained.