title: Risk of secondary leukemia after a solid tumor in childhood according to the dose of epipodophyllotoxins and anthracyclines: a case-control study by the Société Française d'Oncologie Pédiatrique.
abstract: OBJECTIVE
  To estimate the risk of secondary leukemia as a function of the dose of epipodophyllotoxins and anthracyclines.
  
  
  METHODS
  We conducted a case-control study of the risk of secondary leukemia or myelodysplasia after a solid tumor in childhood within the Société Française d'Oncologie Pédiatrique, including 61 patients with leukemia matched with 196 controls. The characteristics of the first cancer, the patient's family history of cancer, and the treatment (type, cumulative dose of chemotherapy, schedule of etoposide administration, and radiation dose delivered to active bone marrow) were compared in the two groups.
  
  
  RESULTS
  Only two factors were found to increase the risk of leukemia in multivariate analysis, namely, the type of the first tumor, with an excess risk in patients with Hodgkin's disease (relative risk 6.4; 95% confidence interval [CI], 1.6 to 24) or osteosarcoma (relative risk 5; 95% CI, 1.3 to 19), and exposure to epipodophyllotoxins and anthracyclines. The risk of leukemia increased regularly with the cumulative dose of etoposide. In summary, patients who received between 1.2 and 6 g/m(2) of epipodophyllotoxins or more than 170 mg/m(2) of anthracyclines had a seven-fold higher risk (95% CI, 2.6 to 19) compared with patients who received lower doses or none of these drugs. The risk of leukemia in patients who received more than 6 g/m(2) of epipodophyllotoxins was multiplied by 197 (95% CI, 19 to 2,058). The risk of leukemia was not increased by exposure to alkylating agents or radiotherapy.
  
  
  CONCLUSIONS
  Both epipodophyllotoxins and anthracyclines increase the risk of secondary leukemia. The current challenge is to minimize the mutagenic effects of these drugs by diminishing cumulative doses without losing the therapeutic benefits.
authors.affiliation: Biostatistics and Epidemiology Unit, the Radiophysics Unit, the Department of Pediatric Oncology, the Cytogenetics Laboratory, Institut Gustave-Roussy, Villejuif, France. le_deley@igr.fr
authors.forename: Marie-Cécile
authors.initials: MC
authors.lastname: Le Deley
authors.forename: Thierry
authors.initials: T
authors.lastname: Leblanc
authors.forename: Akthar
authors.initials: A
authors.lastname: Shamsaldin
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Raquin
authors.forename: Brigitte
authors.initials: B
authors.lastname: Lacour
authors.forename: Danièle
authors.initials: D
authors.lastname: Sommelet
authors.forename: Agnès
authors.initials: A
authors.lastname: Chompret
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Cayuela
authors.forename: Chantal
authors.initials: C
authors.lastname: Bayle
authors.forename: Alain
authors.initials: A
authors.lastname: Bernheim
authors.forename: Florent
authors.initials: F
authors.lastname: de Vathaire
authors.forename: Gilles
authors.initials: G
authors.lastname: Vassal
authors.forename: Catherine
authors.initials: C
authors.lastname: Hill
mesh_terms: D000293:Adolescent; D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects*; D001853:Bone Marrow / Q000528:radiation effects*; D016022:Case-Control Studies; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005602:France; D006801:Humans; D007938:Leukemia / Q000139:chemically induced / Q000209:etiology*; D008297:Male; D015999:Multivariate Analysis; D009369:Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D016609:Neoplasms, Second Primary / Q000139:chemically induced / Q000209:etiology*; D018714:Radiotherapy, Adjuvant; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide