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 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.