Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2017 Apr;139(4):1282-1292.
doi: 10.1016/j.jaci.2016.07.039. Epub 2016 Sep 30.

Long-term Outcomes of 176 Patients With X-linked hyper-IgM Syndrome Treated With or Without Hematopoietic Cell Transplantation

M Teresa de la Morena  1 David Leonard  2 Troy R Torgerson  3 Otavio Cabral-Marques  4 Mary Slatter  5 Asghar Aghamohammadi  6 Sharat Chandra  7 Luis Murguia-Favela  8 Francisco A Bonilla  9 Maria Kanariou  10 Rongras Damrongwatanasuk  11 Caroline Y Kuo  12 Christopher C Dvorak  13 Isabelle Meyts  14 Karin Chen  15 Lisa Kobrynski  16 Neena Kapoor  17 Darko Richter  18 Daniela DiGiovanni  19 Fatima Dhalla  20 Evangelia Farmaki  21 Carsten Speckmann  22 Teresa Español  23 Anna Shcherbina  24 Imelda Celine Hanson  25 Jiri Litzman  26 John M Routes  27 Melanie Wong  28 Ramsay Fuleihan  29 Suranjith L Seneviratne  30 Trudy N Small  31 Ales Janda  32 Liliana Bezrodnik  19 Reinhard Seger  33 Andrea Gomez Raccio  19 J David M Edgar  34 Janet Chou  35 Jordan K Abbott  36 Joris van Montfrans  37 Luis Ignacio González-Granado  38 Nancy Bunin  39 Necil Kutukculer  40 Paul Gray  41 Gisela Seminario  19 Srdjan Pasic  42 Victor Aquino  2 Christian Wysocki  2 Hassan Abolhassani  6 Morna Dorsey  13 Charlotte Cunningham-Rundles  43 Alan P Knutsen  44 John Sleasman  45 Beatriz Tavares Costa Carvalho  46 Antonio Condino-Neto  47 Eyal Grunebaum  8 Helen Chapel  20 Hans D Ochs  3 Alexandra Filipovich  7 Mort Cowan  13 Andrew Gennery  5 Andrew Cant  5 Luigi D Notarangelo  48 Chaim M Roifman  8
Affiliations
Free PMC article
Observational Study

Long-term Outcomes of 176 Patients With X-linked hyper-IgM Syndrome Treated With or Without Hematopoietic Cell Transplantation

M Teresa de la Morena et al. J Allergy Clin Immunol. .
Free PMC article

Abstract

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.

Keywords: CD40 ligand; Karnofsky/Lansky scores; X-linked hyper-IgM syndrome; defects in class-switch recombination; hematopoietic cell transplantation; long-term outcomes; primary immunodeficiency.

Conflict of interest statement

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.

Figures

FIG 1
FIG 1
Geographic distribution of study subjects and HCT practices. Stacked bar graphs indicate the number of patients with XHIGM treated with (dark bars) or without (light bars) HCT.
FIG 2
FIG 2
Kaplan-Meier estimate of postdiagnosis survival of 176 patients with XHIGM for all patients (A) and by HCT group (B). Median survival time was 25 years for all patients, and there was no statistical difference in survival probability between the HCT and non-HCT treatment groups (P = .671).
FIG 3
FIG 3
Estimated hazard ratio and 95% confidence band for treatment with versus without HCT in 176 patients with XHIGM, showing line of unity (dashed) and number of deaths by HCT group for diagnosis years with at least 5 preceding and subsequent deaths.
FIG 4
FIG 4
Karnofsky/Lansky scores (as percentages) of surviving patients with XHIGM.
FIG 5
FIG 5
Kaplan-Meier estimates of postdiagnosis survival of patients with XHIGM by liver disease. Among all patients with XHIGM, liver disease at the time of diagnosis is a significant negative predictor of survival (P < .001).
FIG 6
FIG 6
A, Kaplan-Meier estimate of posttransplantation survival of 67 patients with XHIGM treated with HCT. B, Kaplan-Meier estimates of posttransplantation survival by year of diagnosis: before 1993 (1964–1992) and after 1993 (1993–2013). C–F, Kaplan-Meier estimates of posttransplantation survival by age at transplantation: Fig 6, C, less than 1 year versus greater than 1 year; Fig 6, D, less than 2 years versus greater than 2 years; Fig 6, E, less than 5 years versus greater than 5 years; Fig 6, F, less than 10 years versus greater than 10 years.

Similar articles

See all similar articles

Cited by 25 articles

See all "Cited by" articles

Publication types

Feedback