title: Late thyroid complications in survivors of childhood acute leukemia. An L.E.A. study.
abstract: Thyroid complications are known side effects of irradiation. However, the risk of such complications in childhood acute leukemia survivors who received either central nervous system irradiation or hematopoietic stem cell transplantation is less described. We prospectively evaluated the incidence and risk factors for thyroid dysfunction and tumors in survivors of childhood acute myeloid or lymphoid leukemia. A total of 588 patients were evaluated for thyroid function, and 502 individuals were assessed for thyroid tumors (median follow-up duration: 12.6 and 12.5 years, respectively). The cumulative incidence of hypothyroidism was 17.3% (95% CI: 14.1-21.1) and 24.6% (95% CI: 20.4-29.6) at 10 and 20 years from leukemia diagnosis, respectively. Patients who received total body irradiation (with or without prior central nervous system irradiation) were at higher risk of hypothyroidism (adjusted HR: 2.87; P=0.04 and 2.79, P=0.01, respectively) as compared with transplanted patients who never received any irradiation. Patients transplanted without total body irradiation who received central nervous system irradiation were also at higher risk (adjusted HR: 3.39; P=0.02). Patients irradiated or transplanted at older than 10 years of age had a lower risk (adjusted HR: 0.61; P=0.02). Thyroid malignancy was found in 26 patients (5.2%). Among them, two patients had never received any type of irradiation: alkylating agents could also promote thyroid cancer. The cumulative incidence of thyroid malignancy was 9.6% (95% CI: 6.0-15.0) at 20 years. Women were at higher risk than men (adjusted HR: 4.74; P=0.002). In conclusion, thyroid complications are frequent among patients who undergo transplantation after total body irradiation and those who received prior central nervous system irradiation. Close monitoring is thus warranted for these patients. Clinicaltrials.gov identifier: NCT 01756599.
authors.affiliation: Department of Pediatric Hematology and Oncology, Timone Enfants Hospital and Aix-Marseille University, France Research Unit EA 3279 and Department of Public Health, Aix-Marseille University and Timone Hospital Marseille, France claire.oudin@ap-hm.fr.
authors.forename: Claire
authors.initials: C
authors.lastname: Oudin
authors.affiliation: Research Unit EA 3279 and Department of Public Health, Aix-Marseille University and Timone Hospital Marseille, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Auquier
authors.affiliation: Department of Pediatric Hematology and Oncology, University Hospital of Lyon, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Bertrand
authors.affiliation: Department of Pediatric Onco-Haematology, Children's Hospital of Brabois, Vandoeuvre Les Nancy, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Chastagner
authors.affiliation: Department of Pediatric Hematology and Oncology, CIC Inserm 501, University Hospital of Clermont-Ferrand, France.
authors.forename: Justyna
authors.initials: J
authors.lastname: Kanold
authors.affiliation: Pediatric Hematology and Oncology Department, University Hospital L'Archet, Nice, France.
authors.forename: Maryline
authors.initials: M
authors.lastname: Poirée
authors.affiliation: Pediatric Hematology, University Hospital, Saint Etienne, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Thouvenin
authors.affiliation: Department of Pediatric Hematology and Oncology, University Hospital of Bordeaux, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Ducassou
authors.affiliation: Department of Pediatric Hematology-Oncology, University Hospital of Grenoble, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Plantaz
authors.affiliation: Pediatric Hematology Department, Trousseau Hospital, Paris, France.
authors.forename: Marie-Dominique
authors.initials: MD
authors.lastname: Tabone
authors.affiliation: Pediatric Hematology Department, Robert Debré Hospital, Paris, France.
authors.forename: Jean-Hugues
authors.initials: JH
authors.lastname: Dalle
authors.affiliation: Department of Pediatric Hematology and Oncology, University Hospital of Rennes, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Gandemer
authors.affiliation: Department of Pediatric Hematology-Oncology, University Hospital, Strasbourg, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Lutz
authors.affiliation: Pediatric Hematology and Oncology Department, University Hospital, Montpellier, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Sirvent
authors.affiliation: Research Unit EA 3279 and Department of Public Health, Aix-Marseille University and Timone Hospital Marseille, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Villes
authors.affiliation: Department of Pediatric Hematology and Oncology, Timone Enfants Hospital and Aix-Marseille University, France Research Unit EA 3279 and Department of Public Health, Aix-Marseille University and Timone Hospital Marseille, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Barlogis
authors.affiliation: Pediatric Hematology Department, Robert Debré Hospital, Paris, France.
authors.forename: André
authors.initials: A
authors.lastname: Baruchel
authors.affiliation: Pediatric Hematology Department, Trousseau Hospital, Paris, France.
authors.forename: Guy
authors.initials: G
authors.lastname: Leverger
authors.affiliation: Research Unit EA 3279 and Department of Public Health, Aix-Marseille University and Timone Hospital Marseille, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Berbis
authors.affiliation: Department of Pediatric Hematology and Oncology, Timone Enfants Hospital and Aix-Marseille University, France Research Unit EA 3279 and Department of Public Health, Aix-Marseille University and Timone Hospital Marseille, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Michel
mesh_terms: D000208:Acute Disease; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D007938:Leukemia / Q000150:complications* / Q000453:epidemiology* / Q000628:therapy; D008297:Male; D015999:Multivariate Analysis; D015995:Prevalence; D012307:Risk Factors; D017741:Survivors; D013959:Thyroid Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology*