Targeted Drug Therapy in Childhood Acute Lymphoblastic Leukemia
Pediatric acute lymphoblastic leukemia (ALL) is one of the most drug-responsive cancers, with approximately 70% of children being cured with chemotherapy alone (Pui and Crist, 1994). Focussing on the collective good responsiveness, however, may obscure the fact that there remain children who are not cured, and there are children who experience excessive toxicity from regimens that are well tolerated by the majority of children. Of the many factors that can affect how an individual responds to a particular ALL treatment regimen, one factor may be variability in the pharmacokinetics of antineoplastic agents. We describe herein our studies of whether overall clinical outcome is related to pharmacokinetic variability.
KeywordsToxicity Leukemia Methotrexate Neutropenia Prednisone
Unable to display preview. Download preview PDF.
- 1.Abromowitch M, Ochs J, Pui C-H, Kalwinsky D, Rivera GK, Fairclough D, Look AT, Hustu O, Murphy SB, Evans WE, Dahl GV, Bowman WP. High-dose methotrexate improves clinical outcome in children with acute lymphoblastic Leukemia: St. Jude Total Therapy Study X. Med Pediatr Oncol 16: 297–303, 1988.PubMedCrossRefGoogle Scholar
- 4.Evans WE, Rodman JR, Relling MV, Crom WR, Rivera GK, Crist WM, Pui C-H. Individualized dosages of chemotherapy as a strategy to improve response for acute lymphocytic leukemia. Semin Hematology 1991a; 28: (suppl 4) 15–21.Google Scholar
- 9.Feickert HJ, Bettoni C, Schrappe M, Reiter A, Ludwig W-D, Bode U, Ebell W, Riehm H. Event-free survival of children with T-cell acute lymphoblastic leukemia after introduction of high dose methotrexate in multicenter trial ALL-BFM 86. ASCO Proc 12: 317, 1993.Google Scholar
- 11.Pui CH, Riberio R, Hancock ML, Rivera GK, Evans WE, Raimondi, S, David R. Head, Fred G. Behm, M. Hazem Mahmoud, John T Sandlund, William Crist: Acute myeloid leukemia in children treated with epipodophyllotoxins for acute lymphocytic leukemia. N. Engl. J. Med. 325: 1682–7, 1991.PubMedCrossRefGoogle Scholar
- 12.Pui C-H, Crist WM. Biology and treatment of acute lymphoblastic leukemia. J Peds (in press) 1994.Google Scholar
- 14.Rodman JH, Abromowich M, Sinkule JA et al. Clinical Pharmacodynamics os Continuous Infusion Teniposide: Systemic Exposure as a Determinant of Response in a Phase I trial. J Clin Oncol. 7: 1007–1014, 1987.Google Scholar