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

A 15-year-old girl with homozygous sickle cell anemia (HbSS) and osteosarco ma is described. Delayed clearance of methotrexate (MTX) after the second c ourse 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 abnormal ities resolved, focal tonic-clonic seizures developed, accompanied by abnor mal brain imaging. Four weeks after this episode, all clinical and biochemi cal abnormalities resolved. Preexistent end-organ damage associated with Hb SS may compromise the ability to deliver high-dose chemotherapy with curati ve intent in patients with malignant disease.