Reticular dysgenesis: international survey on clinical presentation, transplantation, and outcome
Year: 2017
Type: article
Study design: Observational Study
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 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 presentation was <4 weeks in 30 of 32 patients (94%). Grafts originated from mismatched family donors in 17 patients (55%), from matched 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 myeloablative components in the conditioning regimens was required to achieve stable lymphomyeloid engraftment. In comparison with 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 to HSCT. Although long-term survival is possible in the presence of mixed chimerism, high-level donor myeloid engraftment should be targeted to avoid posttransplant neutropenia.
Source: Blood
Authors: Manfred Hoenig, Chantal Lagresle-Peyrou, Ulrich Pannicke, Luigi D. Notarangelo, Fulvio Porta, Andrew R. Gennery, Mary Slatter, Morton J. Cowan, Polina Stepensky, Hamoud Al-Mousa, Daifulah Al-Zahrani, Sung-Yun Pai, Waleed Al Herz, Hubert B. Gaspar, Paul Veys, Koichi Oshima, Kohsuke Imai, Hiromasa Yabe, Lenora M. Noroski, Nico M. Wulffraat, Karl-Walter Sykora, Pere Soler-Palacin, Hideki Muramatsu, Mariam Al Hilali, Despina Moshous, Klaus-Michael Debatin, Catharina Schuetz, Eva-Maria Jacobsen, Ansgar S. Schulz, Klaus Schwarz, Alain Fischer, Wilhelm Friedrich, Marina Cavazzana
Institutions: University Hospital Ulm, Hôpital Necker-Enfants Malades, Universität Ulm, German Red Cross, Boston Children's Hospital, University of Brescia, Great North Children's Hospital, Newcastle University, University of California, San Francisco, UCSF Benioff Children's Hospital, Hadassah Medical Center, King Faisal Specialist Hospital & Research Centre, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Dana-Farber Cancer Institute, Kuwait University, Great Ormond Street Hospital, Great Ormond Street Hospital for Children NHS Foundation Trust, University College London, Kyoto University, Center for iPS Cell Research and Application, Kyoto University, Tokyo Medical and Dental University, Tokai University, Tokai University Hospital, Baylor College of Medicine, Texas Children's Hospital, University Medical Center Utrecht, Medizinische Hochschule Hannover, Vall d'Hebron Hospital Universitari, Nagoya University, Riyadh Armed Forces Hospital, Assistance Publique – Hôpitaux de Paris
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2598867633