title: Risk of Subsequent Leukemia After a Solid Tumor in Childhood: Impact of Bone Marrow Radiation Therapy and Chemotherapy.
abstract: OBJECTIVE
  To investigate the roles of radiation therapy and chemotherapy in the occurrence of subsequent leukemia after childhood cancer.
  
  
  METHODS
  We analyzed data from a case-control study with 35 cases and 140 controls. The active bone marrow (ABM) was segmented into 19 compartments, and the radiation dose was estimated in each. The chemotherapy drug doses were also estimated to enable adjustments. Models capable of accounting for radiation dose heterogeneity were implemented for analysis.
  
  
  RESULTS
  Univariate analysis showed a significant trend in the increase of secondary leukemia risk with radiation dose, after accounting for dose heterogeneity (P=.046). This trend became nonsignificant after adjustment for doses of epipodophyllotoxins, alkylating agents, and platinum compounds and the first cancer on multivariate analysis (P=.388). The role of the radiation dose appeared to be dwarfed, mostly by the alkylating agents (odds ratio 6.9, 95% confidence interval 1.9-25.0). Among the patients who have received >16 Gy to the ABM, the radiogenic risk of secondary leukemia was about 4 times greater in the subgroup with no alkylating agents than in the subgroup receiving ≥10 g/m(2).
  
  
  CONCLUSIONS
  Notwithstanding the limitations resulting from the size of our study population and the quite systematic co-treatment with chemotherapy, the use of detailed information on the radiation dose distribution to ABM enabled consideration of the role of radiation therapy in secondary leukemia induction after childhood cancer.
authors.affiliation: Inserm, Radiation Epidemiology Team, CESP-Unit 1018, Villejuif, France; Gustave Roussy, Villejuif, France; Paris Sud University, Orsay, France. Electronic address: rodrigue.allodji@gustaveroussy.fr.
authors.forename: Rodrigue S
authors.initials: RS
authors.lastname: Allodji
authors.affiliation: Inserm, Radiation Epidemiology Team, CESP-Unit 1018, Villejuif, France; Gustave Roussy, Villejuif, France; Paris Sud University, Orsay, France.
authors.forename: Boris
authors.initials: B
authors.lastname: Schwartz
authors.affiliation: Inserm, Radiation Epidemiology Team, CESP-Unit 1018, Villejuif, France; Gustave Roussy, Villejuif, France; Paris Sud University, Orsay, France.
authors.forename: Cristina
authors.initials: C
authors.lastname: Veres
authors.affiliation: Inserm, Radiation Epidemiology Team, CESP-Unit 1018, Villejuif, France; Gustave Roussy, Villejuif, France; Paris Sud University, Orsay, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Haddy
authors.affiliation: Inserm, Radiation Epidemiology Team, CESP-Unit 1018, Villejuif, France; Gustave Roussy, Villejuif, France; Paris Sud University, Orsay, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Rubino
authors.affiliation: Inserm, Radiation Epidemiology Team, CESP-Unit 1018, Villejuif, France; Gustave Roussy, Villejuif, France; Paris Sud University, Orsay, France.
authors.forename: Marie-Cécile
authors.initials: MC
authors.lastname: Le Deley
authors.affiliation: Inserm, Radiation Epidemiology Team, CESP-Unit 1018, Villejuif, France; Gustave Roussy, Villejuif, France; Paris Sud University, Orsay, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Labbé
authors.affiliation: Inserm, Radiation Epidemiology Team, CESP-Unit 1018, Villejuif, France; Gustave Roussy, Villejuif, France; Paris Sud University, Orsay, France.
authors.forename: Fara
authors.initials: F
authors.lastname: Diop
authors.affiliation: Inserm, Radiation Epidemiology Team, CESP-Unit 1018, Villejuif, France; Gustave Roussy, Villejuif, France; Paris Sud University, Orsay, France.
authors.forename: Angela
authors.initials: A
authors.lastname: Jackson
authors.affiliation: Inserm, Radiation Epidemiology Team, CESP-Unit 1018, Villejuif, France; Gustave Roussy, Villejuif, France; Paris Sud University, Orsay, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Dayet
authors.affiliation: Inserm, Radiation Epidemiology Team, CESP-Unit 1018, Villejuif, France; Gustave Roussy, Villejuif, France; Paris Sud University, Orsay, France.
authors.forename: Aymen
authors.initials: A
authors.lastname: Benabdennebi
authors.affiliation: Inserm, Radiation Epidemiology Team, CESP-Unit 1018, Villejuif, France; Gustave Roussy, Villejuif, France; Paris Sud University, Orsay, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Llanas
authors.affiliation: Inserm, Radiation Epidemiology Team, CESP-Unit 1018, Villejuif, France; Gustave Roussy, Villejuif, France; Paris Sud University, Orsay, France.
authors.forename: Jérémi
authors.initials: J
authors.lastname: Vu Bezin
authors.affiliation: Gustave Roussy, Villejuif, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Chavaudra
authors.affiliation: Gustave Roussy, Villejuif, France.
authors.forename: Dimitri
authors.initials: D
authors.lastname: Lefkopoulos
authors.affiliation: Gustave Roussy, Villejuif, France; Inserm, UMR 1030, Villejuif, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Deutsch
authors.affiliation: Gustave Roussy, Villejuif, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Oberlin
authors.affiliation: Inserm, Radiation Epidemiology Team, CESP-Unit 1018, Villejuif, France; Gustave Roussy, Villejuif, France; Paris Sud University, Orsay, France.
authors.forename: Florent
authors.initials: F
authors.lastname: de Vathaire
authors.affiliation: Inserm, Radiation Epidemiology Team, CESP-Unit 1018, Villejuif, France; Gustave Roussy, Villejuif, France; Paris Sud University, Orsay, France.
authors.forename: Ibrahima
authors.initials: I
authors.lastname: Diallo
mesh_terms: D000293:Adolescent; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000009:adverse effects*; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects; D001853:Bone Marrow / Q000187:drug effects* / Q000528:radiation effects*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016001:Confidence Intervals; D005260:Female; D006801:Humans; D007223:Infant; D007938:Leukemia / Q000139:chemically induced*; D007953:Leukemia, Radiation-Induced; D008297:Male; D009369:Neoplasms / Q000628:therapy*; D016609:Neoplasms, Second Primary / Q000209:etiology; D016017:Odds Ratio; D017671:Platinum Compounds / Q000009:adverse effects; D011034:Podophyllotoxin / Q000009:adverse effects; D011829:Radiation Dosage
chemical_list: D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D017671:Platinum Compounds; D011034:Podophyllotoxin