Ara c

On the day of administration, methotrexate (MTX, Intas Pharmaceuticals), paclitaxel (PTX, Athenex), vincristine (VCR, Hospira), and cytarabine (ARA-C, Hospira) were diluted with sterile PBS to appropriate concentrations, while bendamustine (BEN, TEVA Pharmaceutical Industries) was reconstituted using sterile water to 5 mg/ml per the manufacturer’s instructions and then further diluted to the appropriate concentrations with sterile PBS. Cyclophosphamide (CY, Baxter Oncology) was prepared as previously described (5 (link)) and diluted to a 1 mg/ml concentration with sterile PBS on the day of administration for injection. All drugs were diluted to concentrations allowing for administration of 300-500 µl per mouse and administered via intraperitoneal injection. Doses were based on the weight on the day of injection. Vehicle-treated mice received similar volumes of sterile PBS intraperitoneally.

Induction of profound persistent neutropenia and immunosuppression was initiated 6 days before intracisternal inoculation and maintained using cytarabine (Ara-C) (Cytarabine injection; Hospira, Inc., Lake Forest, IL) at a dosage of 440 mg/m² for 5 consecutive days (days 1-5) with subsequent administration on days 8-9 and 13-14, as previously described.²⁰ Methylprednisolone (Solu-Medrol^®, Pfizer Inc., NY, NY) was administered at 5 mg/kg of body weight for immunosuppression from day 1 to the end of experiment. Ceftazidime (75 mg/kg i.v. twice daily; Glaxo Pharmaceuticals, Division of Glaxo Inc., Research Triangle Park, NC), gentamicin (5 mg/kg i.v. every other day; Elkins-Sinn, Inc., Cherry Hill, NJ), and vancomycin (15 mg/kg i.v. daily; Abbott Laboratories, North Chicago, IL) were administered intravenously beginning on day 4 of the study to prevent bacterial infections. Vancomycin (50 mg/L) was added to the drinking water to prevent antibiotic-associated diarrhea due to Clostridium spiroforme from the beginning of induction of neutropenia.