French report successful NEMO stem cell transplant

Successful Allogeneic Hemopoietic Stem Cell Transplantation in a Child Who Had Anhidrotic Ectodermal Dysplasia With Immunodeficiency
Sophie Dupuis-Girod, MDa,b, Caterina Cancrini, MD, PhDc, Françoise Le Deist , MD, PhDd,1, Paolo Palma, MDc, Christine Bodemer, MDe, Anne Puel, PhDf, Susanna Livadiotti, MDc, Capucine Picard, MDa, Xavier Bossuyt, MD, PhDg, Paolo Rossi, MD, PhDc, Alain Fischer, MD, PhDa,h and Jean-Laurent Casanova, MD, PhDa,f
a Unité d’Immunologie et d’Hématologie Pédiatriques
d Centre d’études des Déficits Immunitaires
e Service de Dermatologie
h Développement Normal et Pathologique du Système Immunitaire, Institut National de la Santé et de la Recherche Médicale U429, Hôpital Necker-Enfants Malades, Paris, France
b Service de Génétique, Hospices Civils de Lyon, Hôpital de l’Hotel Dieu, Lyon, France
c Division of Immunology and Infectious Disease, Bambino Gesù Children’s Hospital, University of Rome Tor Vergata, Rome, Italy
f Laboratoire de Génétique Humaine des Maladies Infectieuses, Université René Descartes-Institut National de la Santé et de la Recherche Médicale U550, Faculté de Médecine Necker-Enfants Malades, Paris, France
g Laboratory of Experimental Medicine, University Hospital Leuven, Leuven, Belgium
Anhidrotic ectodermal dysplasia with immunodeficiency is associated with multiple infections and a poor clinical outcome. Hypomorphic mutations in nuclear factor {kappa}B essential modulator (NEMO)/I{kappa}B kinase complex and a hypermorphic mutation in inhibitor {alpha} of nuclear factor {kappa}B (I{kappa}B{alpha}) both result in impaired nuclear factor {kappa}B activation and are associated with X-recessive and autosomal-dominant forms of anhidrotic ectodermal dysplasia with immunodeficiency, respectively. Autosomal-dominant anhidrotic ectodermal dysplasia with immunodeficiency is also associated with a severe T-cell phenotype. It is not known whether hematopoietic stem cell transplantation can cure immune deficiency in children with anhidrotic ectodermal dysplasia with immunodeficiency. A boy with autosomal-dominant anhidrotic ectodermal dysplasia with immunodeficiency and a severe T-cell immunodeficiency underwent transplantation at 1 year of age with haploidentical T-cell–depleted bone marrow after myeloablative conditioning. Engraftment occurred, with full hematopoietic chimerism. Seven years after transplantation, clinical outcome is favorable, with normal T-cell development. As expected, the developmental features of the anhidrotic ectodermal dysplasia syndrome have appeared and persisted. This is the first report of successful hematopoietic stem cell transplantation in a child with anhidrotic ectodermal dysplasia with immunodeficiency. Hematopoietic stem cell transplantation is well tolerated and efficiently cures the profound immunodeficiency associated with autosomal-dominant anhidrotic ectodermal dysplasia with immunodeficiency.