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.
Mantadakis
E
E
Department of Pediatrics, UT Southwestern Medical Center at Dallas and Children's Medical Center of Dallas, Texas 75235-9063, USA.
Rogers
Z R
ZR
Smith
A K
AK
Quigley
R
R
Ratliff
A F
AF
Kamen
B A
BA
D000293:Adolescent; D000671:Amputation, Surgical; D000755:Anemia, Sickle Cell / Q000150:complications / Q000378:metabolism*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003937:Diagnosis, Differential; D004317:Doxorubicin / Q000008:administration & dosage; D004830:Epilepsy, Tonic-Clonic / Q000139:chemically induced*; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism; D002955:Leucovorin / Q000627:therapeutic use; D008657:Metabolic Clearance Rate; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D012516:Osteosarcoma / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D010146:Pain / Q000209:etiology; D013936:Thymidine / Q000627:therapeutic use; D013977:Tibia / Q000601:surgery; D011623:gamma-Glutamyl Hydrolase / Q000627:therapeutic use
D004317:Doxorubicin; D011623:gamma-Glutamyl Hydrolase; D002945:Cisplatin; D002955:Leucovorin; D013936:Thymidine; D008727:Methotrexate