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Title: Hematopoietic stem cell transplantation in 29 patients hemizygous for hypomorphic IKBKG/NEMO mutations
Authors: Miot, Charline
Imai, Kohsuke
Imai, Chihaya
Mancini, Anthony J.
Kucuk, Zeynep Yesim
Kawai, Tokomki
Nishikomori, Ryuta
Ito, Etsuro
Pellier, Isabelle
Girod, Sophie Dupuis
Rosain, Jeremie
Sasaki, Shinya
Chandrakasan, Shanmuganathan
Schmid, Jana Pachlopnik
Okano, Tsubasa
Colin, Estelle
Olaya-Vargas, Alberto
Yamazaki-Nakashimada, Marco
Qasim, Waseem
Espinosa Padilla, Sara
Jones, Andrea
Krol, Alfons
Cole, Nyree
Jolles, Stephen
Bleesing, Jack
Vraetz, Thomas
Gennery, Andrew R.
Abinun, Mario
Gungor, Tayfun
Costa-Carvalho, Beatriz [UNIFESP]
Condino-Neto, Antonio [UNIFESP]
Veys, Paul
Holland, Steven M.
Uzel, Gulbu
Moshous, Despina
Neven, Benedicte
Blanche, Stephane
Ehl, Stephan
Doffinger, Rainer
Patel, Smita Y.
Puel, Anne
Bustamante, Jacinta
Gelfand, Erwin W.
Casanova, Jean-Laurent
Orange, Jordan S.
Picard, Capucine
Issue Date: 2017
Publisher: Amer Soc Hematology
Citation: Blood. Washington, v. 130, n. 12, p. 1456-1467, 2017.
Abstract: X-linked recessive ectodermal dysplasia with immunodeficiency is a rare primary immunodeficiency caused by hypomorphic mutations of the IKBKG gene encoding the nuclear factor kappa B essential modulator (NEMO) protein. This condition displays enormous allelic, immunological, and clinical heterogeneity, and therapeutic decisions are difficult because NEMO operates in both hematopoietic and nonhematopoietic cells. Hematopoietic stem cell transplantation (HSCT) is potentially life-saving, but the small number of case reports available suggests it has been reserved for only the most severe cases. Here, we report the health status before HSCT, transplantation outcome, and clinical follow-up for a series of 29 patients from unrelated kindreds from 11 countries. Between them, these patients carry 23 different hypomorphic IKBKG mutations. HSCT was performed from HLA-identical related donors (n = 7), HLA-matched unrelated donors (n = 12), HLA-mismatched unrelated donors (n = 8), and HLA-haploidentical related donors (n = 2). Engraftmentwas documented in 24 patients, and graft-versus-host disease in 13 patients. Up to 7 patients died 0.2 to 12 months after HSCT. The global survival rate after HSCT among NEMO-deficient children was 74% at a median follow-up after HSCT of 57months (range, 4-108 months). Preexisting mycobacterial infection and colitis were associated with poor HSCT outcome. The underlyingmutation does not appear to have any influence, as patients with the same mutation had different outcomes. Transplantation did not appear to cure colitis, possibly as a result of cell-intrinsic disorders of the epithelial barrier. Overall, HSCT can cure most clinical features of patients with a variety of IKBKG mutations.
ISSN: 0006-4971
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