Long term outcomes of 176 patients with X-linked hyper IgM syndrome treated with or without hematopoietic cell transplantation

Publication date: Available online 30 September 2016
Source:Journal of Allergy and Clinical Immunology
Author(s): M Teresa de la Morena, David Leonard, Troy R. Torgerson, Otavio Cabral-Marques, Mary Slatter, Asghar Aghamohammadi, Sharat Chandra, Luis Murguia-Favela, Francisco Bonilla, Maria Kanariou, Rongras Damrongwatanasuk, Caroline Y. Kuo, Christopher C. Dvorak, Isabelle Meyts, Karin Chen, Lisa Kobrynski, Neena Kapoor, Darko Richter, Daniela DiGiovanni, Fatima Dhalla, Evangelia Farmaki, Carsten Speckmann, Teresa Espanol, Anna Shcherbina, Celine Hanson, Jiri Litzman, John Routes, Melanie Wong, Ramsay Fuleihan, Suranjith L. Seneviratne, Trudy N. Small, Ales Janda, Liliana Bezrodnik, Reinhard Seger, Andrea Gomez Raccio, J.David M. Edgar, Janet Chou, Jordan K. Abbott, Joris van Montfrans, Luis Ignacio Gonzalez-Granado, Nancy Bunin, Necil Kutukculer, Paul Gray, Gisela Seminario, Srdjan Pasic, Victor Aquino, Christian Wysocki, Hassan Abolhassani, Eyal Grunebaum, Morna Dorsey, Beatriz Tavares Costa Carvalho, Antonio Condino-Neto, Charlotte Cunningham-Rundles, Alan P. Knutsen, John Sleasman, Helen Chapel, Hans D. Ochs, Alexandra Filipovich, Mort Cowan, Andrew Gennery, Andrew Cant, Luigi D. Notarangelo, Chaim Roifman
BackgroundX-linked hyper IgM syndrome (XHIGM) is a primary immunodeficiency with high morbidity and mortality compared to normal individuals. Hematopoietic cell transplant (HCT) has been considered a curative therapy, but the procedure has inherent complications, and may not be available for all patients.ObjectivesWe sought to collect data on the clinical presentation, treatment, and follow-up of a large sample of patients with XHIGM in order 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.MethodsPhysicians caring for patients with primary immunodeficiency diseases were identified through the Jeffrey Modell Foundation, United States Immunodeficiency Network, Latin American Society for Immunodeficiency, and the Primary Immune Deficiency Treatment Consortium. Data was collected using a REDCap web application. Survival from time of diagnosis or transplant was estimated using the Kaplan-Meier method, compared using log-rank tests, and modeled using proportional hazards regression.ResultsTwenty-eight clinical sites provided data on 189 patients diagnosed with XHIGM between 1964 and 2013; 176 had valid follow-up and vital status information. Sixty-seven patients (38%) 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=0.671). However, risk associated with HCT decreased for diagnosis years 1987-1995; the hazard ratio was significantly < 1 for diagnosis years 1995-1999. Liver disease was a significant predictor of overall survival [HR (95% CL): 4.9 (2.2, 10.8), p<0.001]. Among survivors, those treated with HCT had higher median Lansky and Karnofsky scores than those treated without HCT (p<0.001). Among patients receiving HCT, 27 (40%) developed graft versus host disease, and most deaths occurred within 1 year of transplant.ConclusionNo 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.

Teaser

A survey of 176 patients with the XHIGM syndrome diagnosed between 1964 and 2013 finds similar overall survival whether treated with or without HCT, although recent experience may favor HCT, especially for those treated at a young age. Given the improvements in care, prospective study of contemporary cohorts is warranted.


from #ENT via xlomafota13 on Inoreader http://ift.tt/2dfSmyX
via IFTTT