title: Leukemia after therapy with alkylating agents for childhood cancer.
abstract: The risk of leukemia was evaluated in 9,170 2-or-more-year survivors of childhood cancer in the 13 institutions of the Late Effects Study Group. Secondary leukemia occurred in 22 nonreferred individuals compared to 1.52 expected, based on general population rates [relative risk (RR) = 14; 95% confidence interval (CI), 9-22]. The influence of therapy for the first cancer on subsequent leukemia risk was determined by a case-control study conducted on 25 cases and 90 matched controls. Treatment with alkylating agents was associated with a significantly elevated risk of leukemia (RR = 4.8; 95% CI, 1.2-18.9). A strong dose-response relationship was also observed between leukemia risk and total dose of alkylating agents, estimated by an alkylator score. The RR of leukemia reached 23 in the highest dose category. Radiation therapy, however, did not increase risk. Although doxorubicin was also identified as a possible risk factor, the excess risk of leukemia following treatment for childhood cancer appears almost entirely due to alkylating agents.
authors.forename: M A
authors.initials: MA
authors.lastname: Tucker
authors.forename: A T
authors.initials: AT
authors.lastname: Meadows
authors.forename: J D
authors.initials: JD
authors.lastname: Boice
authors.forename: M
authors.initials: M
authors.lastname: Stovall
authors.forename: O
authors.initials: O
authors.lastname: Oberlin
authors.forename: B J
authors.initials: BJ
authors.lastname: Stone
authors.forename: J
authors.initials: J
authors.lastname: Birch
authors.forename: P A
authors.initials: PA
authors.lastname: Voûte
authors.forename: R N
authors.initials: RN
authors.lastname: Hoover
authors.forename: J F
authors.initials: JF
authors.lastname: Fraumeni
mesh_terms: D000477:Alkylating Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006689:Hodgkin Disease / Q000188:drug therapy / Q000532:radiotherapy; D006801:Humans; D007223:Infant; D007938:Leukemia / Q000139:chemically induced*; D007953:Leukemia, Radiation-Induced; D008297:Male; D009369:Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D012306:Risk
chemical_list: D000477:Alkylating Agents; D004317:Doxorubicin