Lethal graft-versus-host disease in congenital neutropenia caused by p14 deficiency after allogeneic bone marrow transplantation from an HLA-identical sibling.
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.
Department of Pediatric Hematology and Oncology, Hannover Medical School, OE 6780, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Georg
G
Bohn
Matthias
M
Hardtke-Wolenski
Cornelia
C
Zeidler
Britta
B
Maecker
Martin
M
Sauer
Karl-Walter
KW
Sykora
Lorenz
L
Grigull
Karl
K
Welte
Christoph
C
Klein
D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002648:Child; D017809:Fatal Outcome; D006086:Graft vs Host Disease / Q000209:etiology*; D006680:HLA Antigens; D006648:Histocompatibility; D006801:Humans; D008297:Male; D009503:Neutropenia / Q000151:congenital / Q000209:etiology*; D035781:Siblings; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D006680:HLA Antigens; D014409:Tumor Necrosis Factor-alpha