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 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.