title: Trends in treatment-related deaths (TRDs) in childhood cancer and leukemia over time: a follow-up of patients included in the childhood cancer registry of the Rhône-Alpes region in France (ARCERRA).
abstract: BACKGROUND
  We assessed the number and causes of treatment-related deaths (TRDs) in childhood cancer over time and correlated them with adherence to therapeutic guidelines.
  
  
  METHODS
  We compared two cohorts of children of the Childhood Cancer Registry of the Rhône-Alpes Region: Cohort I (1987-1992, 909 patients) and Cohort II (1996-1999, 648 patients).
  
  
  RESULTS
  In all cancers together, 75 TRDs were reported in Cohort I and 24 in Cohort II (P = 0.001). Cumulative incidence at 5 years declined from 7.9% to 4.1%, and overall survival (OS) increased from 71.0% to 77.2%. TRDs declined by nearly 10-fold in patients with solid malignant tumors (P = 0.02) and central nervous system tumors (P = 0.001), but OS improved for patients with solid malignant tumors only (P = 0.01). No difference was observed in treatment- and transplantation-related deaths in patients with acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML), but OS was better in patients with AML (P = 0.02). Between the two cohorts, transplantation-related mortality did not decrease and was higher at 5 years in patients with ALL who received unrelated-matched donor transplants (41.3%) than in those receiving sibling-matched donor transplants (18.7%). OS improved in the respective transplant groups (37.0% and 64.2%). Severe graft-versus-host disease was also observed among patients with ALL (P = 0.036). The decrease in TRDs was correlated with compliance to therapeutic guidelines.
  
  
  CONCLUSIONS
  Although mortality declined, improved adherence to therapeutic guidelines and more restricted indications of allograft are needed to preclude further treatment- and transplantation-related deaths, particularly among those with leukemia.
authors.affiliation: Childhood Cancer Registry of the Rhône-Alpes Region, Saint-Etienne, France.
authors.forename: Fernand
authors.initials: F
authors.lastname: Freycon
authors.forename: Béatrice
authors.initials: B
authors.lastname: Trombert-Paviot
authors.forename: Léonie
authors.initials: L
authors.lastname: Casagranda
authors.forename: Yves
authors.initials: Y
authors.lastname: Bertrand
authors.forename: Dominique
authors.initials: D
authors.lastname: Plantaz
authors.forename: Perrine
authors.initials: P
authors.lastname: Marec-Bérard
mesh_terms: D016543:Central Nervous System Neoplasms / Q000401:mortality / Q000628:therapy; D002648:Child; D015331:Cohort Studies; D005260:Female; D005602:France / Q000453:epidemiology; D019983:Guideline Adherence; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000628:therapy; D008297:Male; D009369:Neoplasms / Q000401:mortality* / Q000628:therapy*; D017410:Practice Guidelines as Topic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality / Q000628:therapy; D012042:Registries