Long-term outcomes of 176 patients with X-linked hyper-IgM syndrome treated with or without hematopoietic cell transplantation - 19/04/17
, David Leonard, PhD a, Troy R. Torgerson, MD, PhD b, Otavio Cabral-Marques, PhD c, Mary Slatter, MD d, Asghar Aghamohammadi, MD e, Sharat Chandra, MD f, Luis Murguia-Favela, MD g, Francisco A. Bonilla, MD, PhD h, Maria Kanariou, MD i, Rongras Damrongwatanasuk, MD j, Caroline Y. Kuo, MD k, Christopher C. Dvorak, MD l, Isabelle Meyts, MD m, Karin Chen, MD n, Lisa Kobrynski, MD, MPH o, Neena Kapoor, MD p, Darko Richter, MD q, Daniela DiGiovanni, MD r, Fatima Dhalla, MD s, Evangelia Farmaki, MD t, Carsten Speckmann, MD u, Teresa Español, MD v, Anna Shcherbina, MD w, Imelda Celine Hanson, MD x, Jiri Litzman, MD y, John M. Routes, MD z, Melanie Wong, MD, PhD aa, Ramsay Fuleihan, MD bb, Suranjith L. Seneviratne, MD cc, Trudy N. Small, MD dd, †, Ales Janda, MD ee, Liliana Bezrodnik, MD r, Reinhard Seger, MD ff, Andrea Gomez Raccio, MD r, J. David M. Edgar, MD gg, Janet Chou, MD hh, Jordan K. Abbott, MD ii, Joris van Montfrans, MD jj, Luis Ignacio González-Granado, MD kk, Nancy Bunin, MD ll, Necil Kutukculer, MD mm, Paul Gray, MD nn, Gisela Seminario, MD r, Srdjan Pasic, MD oo, Victor Aquino, MD a, Christian Wysocki, MD, PhD a, Hassan Abolhassani, MD e, Morna Dorsey, MD pp, Charlotte Cunningham-Rundles, MD, PhD qq, Alan P. Knutsen, MD rr, John Sleasman, MD ss, Beatriz Tavares Costa Carvalho, MD tt, Antonio Condino-Neto, MD uu, Eyal Grunebaum, MD g, Helen Chapel, MD s, Hans D. Ochs, MD, PhD b, Alexandra Filipovich, MD f, Mort Cowan, MD l, Andrew Gennery, MD d, Andrew Cant, MD d, Luigi D. Notarangelo, MD vv, Chaim M. Roifman, MD gAbstract |
Background |
X-linked hyper-IgM syndrome (XHIGM) is a primary immunodeficiency with high morbidity and mortality compared with those seen in healthy subjects. Hematopoietic cell transplantation (HCT) has been considered a curative therapy, but the procedure has inherent complications and might not be available for all patients.
Objectives |
We sought to collect data on the clinical presentation, treatment, and follow-up of a large sample of patients with XHIGM to (1) compare long-term overall survival and general well-being of patients treated with or without HCT along with clinical factors associated with mortality and (2) summarize clinical practice and risk factors in the subgroup of patients treated with HCT.
Methods |
Physicians caring for patients with primary immunodeficiency diseases were identified through the Jeffrey Modell Foundation, United States Immunodeficiency Network, Latin American Society for Immunodeficiency, and Primary Immune Deficiency Treatment Consortium. Data were collected with a Research Electronic Data Capture Web application. Survival from time of diagnosis or transplantation was estimated by using the Kaplan-Meier method compared with log-rank tests and modeled by using proportional hazards regression.
Results |
Twenty-eight clinical sites provided data on 189 patients given a diagnosis of XHIGM between 1964 and 2013; 176 had valid follow-up and vital status information. Sixty-seven (38%) patients received HCT. The average follow-up time was 8.5 ± 7.2 years (range, 0.1-36.2 years). No difference in overall survival was observed between patients treated with or without HCT (P = .671). However, risk associated with HCT decreased for diagnosis years 1987-1995; the hazard ratio was significantly less than 1 for diagnosis years 1995-1999. Liver disease was a significant predictor of overall survival (hazard ratio, 4.9; 95% confidence limits, 2.2-10.8; P < .001). Among survivors, those treated with HCT had higher median Karnofsky/Lansky scores than those treated without HCT (P < .001). Among patients receiving HCT, 27 (40%) had graft-versus-host disease, and most deaths occurred within 1 year of transplantation.
Conclusion |
No difference in survival was observed between patients treated with or without HCT across all diagnosis years (1964-2013). However, survivors treated with HCT experienced somewhat greater well-being, and hazards associated with HCT decreased, reaching levels of significantly less risk in the late 1990s. Among patients treated with HCT, treatment at an early age is associated with improved survival. Optimism remains guarded as additional evidence accumulates.
Le texte complet de cet article est disponible en PDF.Key words : X-linked hyper-IgM syndrome, CD40 ligand, hematopoietic cell transplantation, defects in class-switch recombination, long-term outcomes, primary immunodeficiency, Karnofsky/Lansky scores
Abbreviations used : CD40LG, GVHD, HCT, PID, REDCap, XHIGM
Plan
| Supported by a grant from Jeffrey Modell Foundation (to M.d.l.M.). The Primary Immune Deficiency Treatment Consortium (PIDTC) is supported by the National Institutes of Health Office of Rare Diseases, National Center for Advancing Translational Sciences and National,Institute of Allergy and Infectious Disease grants U54 AI 082973 and R13AI094943. |
|
| Disclosure of potential conflict of interest: M. T. de la Morena receives grant support from the Jeffrey Modell Foundation Specific Defects Research Grant Program and travel support from the Jeffrey Modell Foundation Specific Defects Research Grant Program and has served on the board for Atlantic Research Group. D. Leonard receives grant support from the Jeffrey Modell Foundation. T. Torgerson serves as a consultant for Baxalta Biosciences, CSL Behring, and ADMA Biosciences; receives grant support from Baxalta Biosciences, CSL Behring, and the NIH; and received payments for educational presentations from Baxalta Biosciences, CSL Behring, Questor Pharmaceuticals, and RWJF. F. Bonilla serves as a consultant for CSL Behring, Baxalta, the Cowen Group, the Gerson-Lehrman Group, Grand Rounds Health, Grifols, Harvard Pilgrim Health Care, and the Immune Deficiency Foundation; receives grant support from CSL Behring; received payments for lectures from Pediatric Update; received royalties from UpToDate; and receives travel support from the Immune Deficiency Foundation. C. Kuo receives grant support from the K12 CHRCDA. C. C. Dvorak serves as a consultant for Jazz Pharmaceuticals and Chimerix. I. Meyts receives travel support from Gilead and Octapharma. K. Chen receives grant support from Bio Products Laboratory. L. Kobrynski receives grant support from Baxalta and Grifols, receives travel support from Baxalta Jiri Litzman, serves on the board for Octapharma, serves as a consultant for Baxalta and Baxter, and receives payment for lectures from Biotest, Baxter, and CSL Behring. N. Kapoor receives grant support from the NIH. R. Fuleihan receives payment for lectures from Baxter and serves on the Data Safety Monitoring Board for Sigma-Tau. J. D. M. Edgar receives travel support from Shire, CSL Behring, and Baxter. J. Chou is an employee of Boston Children's Hospital and receives grant support from the National Institute of Allergy and Infectious Diseases (NIAID). M. Dorsey receives grants from Sigma-Tau. A. Condino-Neto serves on the board for Baxalta, serves as a consultant for Baxalta, is an employee of the University of Sao Paulo, receives grant funding from FAPESP, receives payments for lectures from GlaxoSmithKline, and receives travel support from Baxalta. H. Chapel serves on the advisory board for Baxalta, serves as a consultant for Biotest, and receives payment for lectures from Octapharma, Biotest, Baxalta, and Grifols. H. Ochs receives grant support from the National Institute of Health (NIH). M. Cowan serves on the board for Exogen, Homology, and Bluebird Bio; receives grant support from the NIH and the CA Institute of Regenerative Medicine; received royalties from UpToDate; and receives stock options from Homology and Exogen Bio. A. Cant serves as a consultant for LFB Biomedicaments. L. Notarangelo serves as a consultant for Novimmune and Sigma-Tau; receives grant support from the NIH and the March of Dimes; and received royalties from UpToDate. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 139 - N° 4
P. 1282-1292 - avril 2017 Retour au numéro
Article précédent
- Physical health conditions and quality of life in adults with primary immunodeficiency diagnosed during childhood: A French Reference Center for PIDs (CEREDIH) study
- Vincent Barlogis, Nizar Mahlaoui, Pascal Auquier, Isabelle Pellier, Fanny Fouyssac, Camille Vercasson, Maya Allouche, Carolina Brito De Azevedo, Felipe Suarez, Despina Moshous, Bénédicte Neven, Marlène Pasquet, Eric Jeziorski, Nathalie Aladjidi, Nicolas Schleinitz, Caroline Thomas, Virginie Gandemer, Françoise Mazingue, Patrick Lutz, Olivier Hermine, Capucine Picard, Stéphane Blanche, Gérard Michel, Alain Fischer
- Heterozygosity for transmembrane activator and calcium modulator ligand interactor A144E causes haploinsufficiency and pneumococcal susceptibility in mice
- Haifa H. Jabara, John J. Lee, Erin Janssen, Sumana Ullas, Kyriaki Liadaki, Lilit Garibyan, Halli Benson, Tatyana Sannikova, Richard Bram, Lennart Hammarstrom, Anthony C. Cruz, Richard Siegel, John Manis, Richard Malley, Raif S. Geha
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?