Recommendations for Surveillance for Children with Leukemia-Predisposing Conditions

Clin Cancer Res. 2017 Jun 1;23(11):e14-e22. doi: 10.1158/1078-0432.CCR-17-0428.

Abstract

Leukemia, the most common childhood cancer, has long been recognized to occasionally run in families. The first clues about the genetic mechanisms underlying familial leukemia emerged in 1990 when Li-Fraumeni syndrome was linked to TP53 mutations. Since this discovery, many other genes associated with hereditary predisposition to leukemia have been identified. Although several of these disorders also predispose individuals to solid tumors, certain conditions exist in which individuals are specifically at increased risk to develop myelodysplastic syndrome (MDS) and/or acute leukemia. The increasing identification of affected individuals and families has raised questions around the efficacy, timing, and optimal methods of surveillance. As part of the AACR Childhood Cancer Predisposition Workshop, an expert panel met to review the spectrum of leukemia-predisposing conditions, with the aim to develop consensus recommendations for surveillance for pediatric patients. The panel recognized that for several conditions, routine monitoring with complete blood counts and bone marrow evaluations is essential to identify disease evolution and enable early intervention with allogeneic hematopoietic stem cell transplantation. However, for others, less intensive surveillance may be considered. Because few reports describing the efficacy of surveillance exist, the recommendations derived by this panel are based on opinion, and local experience and will need to be revised over time. The development of registries and clinical trials is urgently needed to enhance understanding of the natural history of the leukemia-predisposing conditions, such that these surveillance recommendations can be optimized to further enhance long-term outcomes. Clin Cancer Res; 23(11); e14-e22. ©2017 AACRSee all articles in the online-only CCR Pediatric Oncology Series.

Publication types

  • Review

MeSH terms

  • Child
  • Genetic Predisposition to Disease*
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Leukemia, Myeloid, Acute / epidemiology
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / therapy
  • Li-Fraumeni Syndrome / epidemiology
  • Li-Fraumeni Syndrome / genetics*
  • Li-Fraumeni Syndrome / pathology
  • Mutation
  • Myelodysplastic Syndromes / epidemiology
  • Myelodysplastic Syndromes / genetics*
  • Myelodysplastic Syndromes / therapy
  • Tumor Suppressor Protein p53 / genetics

Substances

  • TP53 protein, human
  • Tumor Suppressor Protein p53