Pharmacogenetic determinants of outcome in acute lymphoblastic leukaemia.
Present day paediatric co-operative group acute lymphoblastic leukaemia (ALL) protocols cure approximately 80% of patients, a result achieved largely through the use of risk-stratified therapies that employ multiple chemotherapy agents. These risk-based therapies utilize host and leukaemia traits to select the most appropriate therapy. However, these risk-stratified approaches predict therapy response imperfectly and an important fraction of patients experience relapse or therapy-related toxicity. Pharmacogenetics, the study of genetic variations in drug-processing genes and individual responses to drugs, may enable the improved identification of patients at higher risk for either disease relapse or chemotherapy-associated side effects. While the impact of genetic variation in the thiopurine-S-methyltransferase gene on ALL treatment outcome and toxicity has been extensively studied, the role of other polymorphisms remains less well known. This review summarizes current research on the impact of genetic variation in drug-processing genes in paediatric ALL and reviews important methodological and statistical issues presently challenging the field of pharmacogenetics.
Aplenc
Richard
R
Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. raplenc@cceb.med.upenn.edu
Lange
Beverly
B
D000477:Alkylating Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D018432:Drug Resistance, Multiple / Q000235:genetics; D014644:Genetic Variation; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015122:Mercaptopurine / Q000627:therapeutic use; D008727:Methotrexate / Q000627:therapeutic use; D010597:Pharmacogenetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D013866:Thioguanine / Q000627:therapeutic use; D016896:Treatment Outcome
D000477:Alkylating Agents; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D013866:Thioguanine; D008727:Methotrexate