A 25-year-old male patient diagnosed as a case of Philadelphia chromosome-negative B-cell acute lymphoblastic lymphoma (ALL) and who had relapsed after receiving the Berlin-Frankfurt-Münster 90 acute lymphoblastic leukemia protocol (BFM ALL protocol) was started on MINE protocol (injection ifosfamide 4 g/m2 was divided over 3 days [day 1–3] and administered IV over a 1 h period, injection mitoxantrone 8 mg/m2 [day 1] administered as a short IV infusion, injection etoposide 65 mg/m2/day [day 1–3] was infused over 1 h, and injection mesna 1330 mg/m2 [days 1–3]) after the patient had progressed on DHAP regimen (injection cisplatin 100 mg/m2 [day 1], high-dose cytarabine 2 g/m2 twice a day [day 2], and tablet prednisolone 40 mg/day [day 2–4]). After 24 h of the 1st day of chemotherapy, the patient started developing headache, vomiting which was followed in couple of hours by disoriented behavior, and one episode of seizure. In view of above complaints, patient chemotherapy was withheld as the patient developed headache and vomiting. For the above complaints, patient's all routine investigations such as complete blood count, renal function, and liver function test were performed along with albumin and electrolytes. All the investigations were within normal limits. Electrocardiogram was done which was within normal limits. Magnetic resonance imaging of brain was obtained which did not show any abnormality. Considering the above case scenario and ruling out the possible causes of acute delirious state such as electrolyte abnormalities and intracranial bleed, we entertained the possibility of IIE. The patient was started on hydration therapy with IV fluids and dextrose normal saline infusion at the rate of 100 ml/m2 followed by which injection methylene blue was procured and started at the dose of 50 mg (1% aqueous solution) IV over 5 min, six times daily, and antiemetics such as ondansetron 4 mg by needle were administered twice a day for initial 3 days and then whenever needed. Within a period of 24 h, the patient started improving in the form of decrease in vomiting and response to oral commands. Later complete recovery occurred within 48–72 h. Till then injection methylene blue and hydration were continued. Furthermore, the patient was given IV 5% albumin.\nHence, the patient who had presented with above-mentioned complaints with normal imaging and blood investigations and who had responded to methylene blue confirmed our diagnosis of the IIE. Furthermore, retrospectively, we looked over the factors that precipitated the IIE. Albumin, renal and liver function, and electrolytes were well within normal limits at the start of infusion of ifosfamide. However, the patient had received injection fosaprepitant before the start of injection ifosfamide.\nWe then reviewed the literature, and it confirmed that the precipitating factor for IIE was none other than aprepitant.
A 54-year-old, gravida 2, para 2, married woman presented with recurrent epithelial ovarian cancer (endometrioid adenocarcinoma). She had noninsulin dependent diabetes mellitus, diabetic retinopathy, and hypertension. Seven years earlier, she underwent coronary artery bypass grafting due to coronary artery disease.\nThree years ago, she was transferred to our center after laparoscopic bilateral salpingo-oophorectomy which led to a diagnosis of epithelial ovarian cancer. She underwent a debulking operation, including total abdominal hysterectomy and pelvic and paraaortic lymph node dissection, total omentectomy, appendectomy, peritoneal mass excision, and left ureter resection and anastomosis. The tumor was categorized as International Federation of Obstetrics and Gynecology (FIGO) stage IIIc and cytoreductive surgery was suboptimal. Following the surgery, she received 6 cycles of adjuvant chemotherapy with paclitaxel/carboplatin. However, because there was disease progression in this patient, she was further treated with 3 cycles of topotecan, followed by 3 cycles of docetaxel. An abdomino-pelvic computed tomography (CT) scan showed aggravation of disease and her serum carbohydrate antigen 125 (CA-125) concentration was elevated from 534 to 1,270 U/mL. We decided to change her chemotherapy regimen to ifosfamide monotherapy.\nShe was started on ifosfamide 1,200 mg/m2/day, administered via continuous infusion on days 1-3 of each 4 week cycle, along with mesna 300 mg/m2/day. On the third day she received ifosfamide, her mental status worsened, with a change from drowsiness to stupor, followed by disorientation, stereotyped movements, and emotional instability. She had no lateralizing neurologic signs. Her blood test results, including measurements of serum glucose, brain natriuretic peptide, and electrolytes, were normal, and her cerebrospinal fluid was negative for malignant cells. In addition, brain magnetic resonance imaging (MRI) findings were normal. An electroencephalogram showed frequent 1-1.5 Hz periodic or single triphasic waves on both hemispheres (). She was diagnosed with ifosfamide-induced encephalopathy, and her chemotherapy was discontinued immediately. Her neurologic symptoms and signs did not improve. Despite the supportive care, her encephalopathy became aggravated, and she developed ifosfamide-induced acute tubular necrosis. She was discharged without any hope for recovery and died within 1 month.