@article{discovery1561315,
            note = {This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.},
          volume = {129},
           pages = {2928--2938},
           month = {May},
          number = {21},
         journal = {Blood},
       publisher = {AMER SOC HEMATOLOGY},
           title = {Reticular dysgenesis: international survey on clinical presentation, transplantation, and outcome},
            year = {2017},
             url = {http://doi.org/10.1182/blood-2016-11-745638},
            issn = {1528-0020},
          author = {Hoenig, M and Lagresle-Peyrou, C and Pannicke, U and Notarangelo, LD and Porta, F and Gennery, AR and Slatter, M and Cowan, MJ and Stepensky, P and Al-Mousa, H and Al-Zahrani, D and Pai, S-Y and Al Herz, W and Gaspar, HB and Veys, P and Oshima, K and Imai, K and Yabe, H and Noroski, LM and Wulffraat, NM and Sykora, K-W and Soler-Palacin, P and Muramatsu, H and Al Hilali, M and Moshous, D and Debatin, K-M and Schuetz, C and Jacobsen, E-M and Schulz, AS and Schwarz, K and Fischer, A and Friedrich, W and Cavazzana, M},
        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 {\ensuremath{<}}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.},
        keywords = {Science \& Technology, Life Sciences \& Biomedicine, Hematology, SEVERE COMBINED IMMUNODEFICIENCY, ADENYLATE KINASE 2, SENSORINEURAL DEAFNESS, HEMATOPOIETIC STEM, ALEUKOCYTOSIS, HEALTH}
}