title: Preexisting conditions in pediatric ALL patients: Spectrum, frequency and clinical impact.
abstract: BACKGROUND
  The etiology of acute lymphoblastic leukemia remains undisclosed in the majority of cases. A number of rare syndromic conditions are known to predispose to different forms of childhood cancer including ALL. The present study characterized the spectrum and clinical impact of preexisting diseases in a cohort of ALL patients from Germany, Austria and Switzerland with a focus on genetic diseases predisposing to cancer development.
  
  
  METHODS
  Retrospective database and study chart review included all patients from Germany, Austria and Switzerland (n = 4939) enrolled into multicenter clinical trial AIEOP-BFM ALL 2000 between July 1999 and June 2009. Patients enrolled into study AIEOP-BFM ALL 2009 - which was initiated subsequent to AIEP-BFM ALL 2000 - who were reported with a cancer prone syndrome or chromosomal abnormality were additionally included in this study to increase conclusiveness of observations.
  
  
  RESULTS
  A total of 233 patients with at least one reported condition could be identified. The following conditions were reported in more than one patient: Gilbert's disease (n = 13), neurofibromatosis type I (n = 8), ataxia telangiectasia (n = 8), thalassemia (n = 7), Nijmegen Breakage syndrome (n = 6), cystic fibrosis (n = 4), glucose-6-phosphate dehydrogenase deficiency (n = 4), Noonan syndrome (n = 2), Klinefelter syndrome (n = 2), alpha-1-antitrypsin deficiency (n = 2), primary ciliary dyskinesia (n = 2). Especially those syndromes with a known cancer predisposition (NF type I, Ataxia telangiectasia, Nijmegen Breakage syndrome etc.) were associated with certain general and ALL-related characteristics, high therapy-related toxicity and reduced survival.
  
  
  CONCLUSIONS
  The spectrum of underlying diseases within ALL patients is dispersed. A small number of ALL patients are reported with cancer predisposition syndromes at initial diagnosis which are associated with high rates of therapy-related toxicity and a markedly reduced chance of survival. The true prevalence of these conditions within the ALL population remains unknown due to inapparent clinical presentation. A targeted clinical and/or genetic examination for certain diagnoses like NF type I, Ataxia telangiectasia or Nijmegen Breakage syndrome could identify patients who benefit from adjustment of antileukemic therapy or intensification of supportive care.
authors.affiliation: Department of Pediatric Hematology and Oncology, Hanover Medical School, Germany. Electronic address: schuette.peter@mh-hannover.de.
authors.forename: P
authors.initials: P
authors.lastname: Schütte
authors.affiliation: Department of Pediatrics, ALL BFM trial center, University Medical Center Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Möricke
authors.affiliation: Department of Pediatric Hematology and Oncology, Hanover Medical School, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Zimmermann
authors.affiliation: Department of Pediatrics, ALL BFM trial center, University Medical Center Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Bleckmann
authors.affiliation: Department of Pediatric Hematology and Oncology, St. Anna Children's Hospital, Medical University of Vienna, Austria.
authors.forename: B
authors.initials: B
authors.lastname: Reismüller
authors.affiliation: Department of Pediatric Hematology and Oncology, St. Anna Children's Hospital, Medical University of Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Attarbaschi
authors.affiliation: Department of Pediatric Hematology and Oncology, St. Anna Children's Hospital, Medical University of Vienna, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Mann
authors.affiliation: Department of Oncology, University Children's Hospital, Zurich, Switzerland.
authors.forename: N
authors.initials: N
authors.lastname: Bodmer
authors.affiliation: Department of Oncology, University Children's Hospital, Zurich, Switzerland.
authors.forename: F
authors.initials: F
authors.lastname: Niggli
authors.affiliation: Department of Pediatrics, ALL BFM trial center, University Medical Center Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schrappe
authors.affiliation: Department of Pediatric Hematology and Oncology, Hanover Medical School, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Stanulla
authors.affiliation: Department of Pediatric Hematology and Oncology, Hanover Medical School, Germany.
authors.forename: C P
authors.initials: CP
authors.lastname: Kratz
mesh_terms: D000293:Adolescent; D000367:Age Factors; D001317:Austria / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D004198:Disease Susceptibility; D005260:Female; D020022:Genetic Predisposition to Disease; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D015337:Multicenter Studies as Topic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology*; D015995:Prevalence; D012189:Retrospective Studies; D013557:Switzerland / Q000453:epidemiology
keywords: Acute lymphoblastic leukemia; Ataxia telangiectasia; Cancer predisposition syndromes; Neurofibromatosis type I; Nijmegen breakage syndrome; Preexisting conditions