Clinical case of successful desensitization to high-dose methotrexate in a pediatric patient with osteosarcoma

Abstract

Background: Methotrexate (MTX) is a folic acid antagonist which is widely used in chemotherapy treatment in pediatric oncology. High-dose MTX therapy plays a significant role in curing osteosarcoma (OS). OS is a rare cancer, but the most common type of primary malignant bone tumors, usually occurs in the second decade of life during the adolescent growth spurt. A limited number of hypersensitivity reactions (HRs) caused by MTX have been reported in pediatric patients. It was suspected that immediate HSRs to MTX are IgE-mediated, though other mechanisms may also be involved. We present a case of successful desensitization to high-dose MTX which induced an acute urticaria and angioedema in a pediatric patient with OS. Methods: A 17-year-old male with OS in the lower limb (femur) experienced an acute urticaria and angioedema during the course of high-dose MTX. The infusion of MTX was stopped, corticosteroids (methylprednisolone 20 mg) and antihistamines (loratadine 10 mg) were administrated with a relapse of the symptoms after 30 minutes. Later, skin prick and intradermal tests with MTX were per-formed: intradermal test (1 mg/ml) was positive. Immediate HSRs to MTX was confirmed. Results: The desensitization was initiated with premedication using antihistamine (clemastine 1 mg), corticosteroid (methylprednisolone 32 mg) 12 and 2 hours before procedure. Antiemetic therapy with serotonin 5-HT3 receptor antagonist (ondansetron) and H2 antagonist (famotidine 20 mg) was also administered 2 hours before procedure. After premedication, the dose of MTX was gradually increased in 13-steps using intravenous infusions of three serially diluted solutions (table 1). The patient was successfully desensitized without any toxity or HSRs. He received 4 infusions of high-dose MTX (22 g/1000 ml) prior surgery treatment and 8 infusions after success-fully using the same protocol. The patient achieved a complete re-mission and was continuously monitored for a possible relapse. Conclusion: Methotrexate is one of the main medications for pediatric osteosarcoma treatment which may induce HSRs. Individualized desensitization to high-dose methotrexate can be effective and allow to continue essential treatment for the pediatric patient with osteosarcoma despite a proven allergy to methotrexate. Table. 1 […].