Delayed methotrexate clearance in a patient with sickle cell anemia and osteosarcoma.

A 15-year-old girl with homozygous sickle cell anemia (HbSS) and osteosarcoma is described. Delayed clearance of methotrexate (MTX) after the second course of high-dose MTX (HDMTX) led to the development of renal and hepatic toxicities. Rescue was accomplished with high-dose leucovorin, intravenous carboxypeptidase G2, and thymidine. Although the renal and hepatic abnormalities resolved, focal tonic-clonic seizures developed, accompanied by abnormal brain imaging. Four weeks after this episode, all clinical and biochemical abnormalities resolved. Preexistent end-organ damage associated with HbSS may compromise the ability to deliver high-dose chemotherapy with curative intent in patients with malignant disease.