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.
Bohn
Georg
G
Department of Pediatric Hematology and Oncology, Hannover Medical School, OE 6780, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Hardtke-Wolenski
Matthias
M
Zeidler
Cornelia
C
Maecker
Britta
B
Sauer
Martin
M
Sykora
Karl-Walter
KW
Grigull
Lorenz
L
Welte
Karl
K
Klein
Christoph
C
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