Long-term follow up of IPEX syndrome patients after different therapeutic strategies: an international multicenter retrospective study

Publication date: Available online 11 December 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Federica Barzaghi, Laura Cristina Amaya Hernandez, Benedicte Neven, Silvia Ricci, Zeynep Yesim Kucuk, Jack Bleesing, Zohreh Nademi, Mary Anne Slatter, Erlinda Rose Ulloa, Anna Shcherbina, Anna Roppelt, Austen Worth, Juliana Silva, Alessandro Aiuti, Luis Murguia-Favela, Carsten Speckmann, Magda Carneiro-Sampaio, Juliana Folloni Fernandes, Safa Baris, Ahmet Ozen, Elif Karakoc-Aydiner, Ayca Kiykim, Ansgar Schulz, Sandra Steinmann, Lucia Dora Notarangelo, Eleonora Gambineri, Paolo Lionetti, William Thomas Shearer, Lisa Forbes, Caridad Martinez, Despina Moshous, Stephane Blanche, Alain Fisher, Frank M. Ruemmele, Come Tissandier, M. Ouachee-Chardin, Frédéric Rieux-Laucat, Marina Cavazzana, Waseem Qasim, Barbarella Lucarelli, Michael H. Albert, Ichiro Kobayashi, Laura Alonso, Cristina Diaz De Heredia, Hirokazu Kanegane, Anita Lawitschka, Jong Jin Seo, Marta Gonzalez-Vicent, Miguel Angel Diaz, Rakesh Kumar Goyal, Martin G. Sauer, Akif Yesilipek, Minsoo Kim, Yesim Yilmaz-Demirdag, Monica Bhatia, Julie Khlevner, Erick .J. Richmond Padilla, Silvana Martino, Davide Montin, Olaf Neth, Agueda Molinos-Quintana, Justo Valverde-Fernandez, Arnon Broides, Vered Pinsk, Antje Ballauf, Filomeen Haerynck, Victoria Bordon, Catharina Dhooge, Maria Laura Garcia-Lloret, Robbert G. Bredius, Krzysztof Kałwak, Elie Haddad, Markus Gerhard Seidel, Gregor Duckers, Sung-Yun Pai, Christopher C. Dvorak, Stephan Ehl, Franco Locatelli, Frederick Goldman, Andrew Richard Gennery, Mort J. Cowan, Maria Grazia Roncarolo, Rosa Bacchetta
BackgroundImmunedysregulation Polyendocrinopathy Enteropathy X-linked (IPEX) syndrome is a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined.ObjectiveTo evaluate disease onset, progression and long-term outcome of the two main treatments in long-term IPEX survivors.MethodsClinical histories of 96 patients with a genetically proven IPEX syndrome were collected from 38 institutions worldwide and retrospectively analyzed. To investigate possible factors suitable to predict the outcome, an organ involvement (OI) scoring system was developed.ResultsWe confirm neonatal onset with enteropathy, type 1 diabetes (T1D), and eczema. In addition, we found less common manifestations in delayed onset patients or during disease evolution. There is no correlation between the site of mutation and the disease course or outcome, and the same genotype can present with variable phenotypes. HSCT patients (n=58) had a median follow-up of 2.7 years (range: 1 week - 15 years). Patients receiving chronic IS (n=34) had a median follow-up of 4 years (range: 2 months - 25 years). The overall survival (OS) after HSCT was 73.2% (95% confidence interval [CI], 59.4 to 83.0) and after IS was 65.1% (95 % CI, 62.8 to 95.8). The pre-treatment OI score was the only significant predictor of OS after transplant (p=0.035) but not under IS.ConclusionsPatients receiving chronic IS were hampered by disease recurrence or complications, impacting long-term disease-free survival. When performed in patients with a low OI score, HSCT resulted in disease resolution with better quality of life, independent of age, donor source or conditioning regimen.

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Teaser

This international retrospective multicenter study of patients with long-term IPEX syndrome (n=96) provides data on onset, disease progression, and outcomes after different treatments to inform future therapeutic choices.


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