Lethal graft-versus-host disease in congenital neutropenia caused by p14 deficiency after allogeneic bone marrow transplantation from an HLA-identical sibling

Pediatr Blood Cancer. 2008 Sep;51(3):436-8. doi: 10.1002/pbc.21643.

Abstract

The molecular heterogeneity of severe congenital neutropenia (SCN) is increasingly recognized and may influence the risk-benefit assessment of therapeutic strategies. We report on a patient with p14 deficiency who succumbed to severe grade IV graft-versus-host disease (GvHD) after a human leukocyte antigen-identical bone marrow transplantion (BMT) from a sibling donor. Before BMT, in vitro generated p14-deficient dendritic cells showed a markedly elevated tumor necrosis factor (TNF-) alpha production upon toll-like receptor stimulation. We hypothesize that p14 deficiency predisposes to GvHD through increased TNF-alpha production. Adequate genetic testing is needed to prospectively assess potential risk factors for GvHD in defined SCN subgroups.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Marrow Transplantation / adverse effects*
  • Child
  • Fatal Outcome
  • Graft vs Host Disease / etiology*
  • HLA Antigens
  • Histocompatibility
  • Humans
  • Male
  • Neutropenia / congenital
  • Neutropenia / etiology*
  • Siblings
  • Transplantation, Homologous
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • HLA Antigens
  • Tumor Necrosis Factor-alpha