Preexisting conditions in pediatric ALL patients: Spectrum, frequency and clinical impact.

Abstract

INTRODUCTION:

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.

CONCLUSION:

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: P Schütte, A Möricke, M Zimmermann, K Bleckmann, B Reismüller, A Attarbaschi, G Mann, N Bodmer, F Niggli, M Schrappe, M Stanulla, C P Kratz
• Journal: European journal of medical genetics (Eur J Med Genet) Vol. 59 Issue 3 Pg. 143-51 (Mar 2016) ISSN: 1878-0849 [Electronic] Netherlands
• PMID: 26732628 (Publication Type: Journal Article, Meta-Analysis, Review)
• Copyright: Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Topics

• Adolescent
• Age Factors
• Austria (epidemiology)
• Child
• Child, Preschool
• Clinical Trials as Topic
• Disease Susceptibility
• Female
• Genetic Predisposition to Disease
• Germany (epidemiology)
• Humans
• Infant
• Infant, Newborn
• Male
• Multicenter Studies as Topic
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (diagnosis, epidemiology, etiology)
• Prevalence
• Retrospective Studies
• Switzerland (epidemiology)