Reticular dysgenesis: International survey on clinical presentation, transplantation, and outcome
Hoenig, Manfred; Lagresle-Peyrou, Chantal; Pannicke, Ulrich; Notarangelo, Luigi D; Porta, Fulvio; Gennery, Andrew R.; Slatter, Mary; Cowan, Morton J.; Stepensky, Polina; Al-Mousa, Hamoud; Al-Zahrani, Daifulah; Pai, Sung-Yun; Al-Herz, Waleed; Gaspar, Hubert B; Veys, Paul; Oshima, Koichi; Imai, Kohsuke; Yabe, Hiromasa; Noroski, Lenora M; Wulffraat, Nico M.; Sykora, Karl-Walter; Soler-Palacin, Pere; Muramatsu, Hideki; Al Hilali, Mariam; Moshous, Despina; Debatin, Klaus-Michael; Schuetz, Catharina; Jacobsen, Eva-Maria; Schulz, Ansgar S; Schwarz, Klaus; Fischer, Alain; Friedrich, Wilhelm; Cavazzana-Calvo, Marina
(2017) Blood, volume 129, issue 21, pp. 2928 - 2938
(Article)
Abstract
Reticular dysgenesis (RD) is a rare congenital disorder defined clinically by the combination of severe combined immunodeficiency (SCID), agranulocytosis, and sensorineural deafness. Mutations in the gene encoding adenylate kinase 2 were identified to cause the disorder. Hematopoietic stem cell transplantation (HSCT) is the only option to cure this otherwise fatal
... read more
disease.Retrospective data on clinical presentation, genetics, and outcome of HSCT were collected from centers in Europe, Asia, and North America for a total of 32 patients born between 1982 and 2011.Age at presentationwas <4 weeks in 30 of 32 patients (94%). Grafts originated frommismatched family donors in 17 patients (55%), frommatched family donors in 6 patients (19%), and from unrelated marrow or umbilical cord blood donors in 8 patients (26%). Thirteen patients received secondary or tertiary transplants. After transplantation, 21 of 31 patients were reported alive at a mean follow-up of 7.9 years (range: 0.6-23.6 years). All patients who died beyond 6 months after HSCT had persistent or recurrent agranulocytosis due to failure of donor myeloid engraftment. In the absence of conditioning, HSCT was ineffective to overcome agranulocytosis, and inclusion of myeloablativecomponents in theconditioningregimenswasrequiredtoachievestable lymphomyeloidengraftment. Incomparisonwith other SCID entities, considerable differences were noted regarding age at presentation, onset, and type of infectious complications, as well as the requirement of conditioning prior toHSCT.Although long-termsurvival is possible in the presence ofmixed chimerism, highlevel donor myeloid engraftment should be targeted to avoid posttransplant neutropenia.
show less
Download/Full Text
The full text of this publication is not available.
Keywords: Biochemistry, Immunology, Hematology, Cell Biology
ISSN: 0006-4971
Publisher: Elsevier
Note: Funding Information: This work was supported by a grant 01GM1517B from the German Federal Ministry of Education and Research (M.H. and K.S.), grants U54 AI 082973 and R13 AI 094943 from the National Institute of Allergy and Infectious Diseases and Office of Rare Diseases, National Center for Advancing Translational Sciences, National Institutes of Health (M.J.C., L.D.N., and S-Y.P.), and by the Great Ormond Street Hospital Children's Charity and the Great Ormond Street Hospital/University College London National Institute for Health Research Biomedical Research Centre (H.B.G.). Publisher Copyright: © 2017 by The American Society of Hematology.
(Peer reviewed)