A Registry Study of 240 Patients with X-Linked Agammaglobulinemia Living in the USA

Abstract

Purpose: To understand the natural history and clinical outcomes for patients with X-linked agammaglobulinemia (XLA) in the United States utilizing the United States Immunodeficiency Network (USIDNET) patient registry.

Methods: The USIDNET registry was queried for data from XLA patients collected from 1981 to 2019. Data fields included demographics, clinical features before and after diagnosis of XLA, family history, genetic mutation in Bruton's tyrosine kinase (BTK), laboratory findings, treatment modalities, and mortality.

Results: Data compiled through the USIDNET registry on 240 patients were analyzed. Patient year of birth ranged from 1945 to 2017. Living status was available for 178 patients; 158/178 (88.8%) were alive. Race was reported for 204 patients as follows: White, 148 (72.5%); Black/African American, 23 (11.2%); Hispanic, 20 (9.8%); Asian or Pacific Islander, 6 (2.9%), and other or more than one race, 7 (3.4%). The median age at last entry, age at disease onset, age at diagnosis, and length of time with XLA diagnosis was 15 [range (r) = 1-52 years], 0.8 [r = birth-22.3 years], 2 [r = birth-29 years], and 10 [r = 1-56 years] years respectively. One hundred and forty-one patients (58.7%) were < 18 years of age. Two hundred and twenty-one (92%) patients were receiving IgG replacement (IgGR), 58 (24%) were on prophylactic antibiotics, and 19 (7.9%) were on immunomodulatory drugs. Eighty-six (35.9%) patients had undergone surgical procedures, two had undergone hematopoietic cell transplantation, and two required liver transplantation. The respiratory tract was the most affected organ system (51.2% of patients) followed by gastrointestinal (40%), neurological (35.4%), and musculoskeletal (28.3%). Infections were common both before and after diagnosis, despite IgGR therapy. Bacteremia/sepsis and meningitis were reported more frequently before XLA diagnosis while encephalitis was more commonly reported after diagnosis. Twenty patients had died (11.2%). The median age of death was 21 years (range = 3-56.7 years). Neurologic condition was the most common underlying co-morbidity for those XLA patients who died.

Conclusions: Current therapies for XLA patients reduce early mortality, but patients continue to experience complications that impact organ function. With improved life expectancy, more efforts will be required to improve post-diagnosis organ dysfunction and quality of life. Neurologic manifestations are an important co-morbidity associated with mortality and not yet clearly fully understood.

Keywords: X-linked agammaglobulinemia; XLA Registry.

Fig. 1

A Prevalence of different types of infections before and after diagnosis, sorted by post-diagnosis prevalence. B Post- vs. pre-differences in prevalence for each type of infection. For example, bacteremia/sepsis and meningitis infections had the largest reduction after diagnosis, as shown at the bottom of the graph. OM = otitis media

Fig. 2

A The prevalence of body system involvement before and after XLA diagnosis. B Post- vs. pre-differences. The three body systems with the largest increases after diagnosis are gastrointestinal, respiratory, and neurological. MSK = musculoskeletal

Fig. 3

KM survival analysis of US XLA patients. A Overall survival (N = 191); B probability of survival for 117 XLA patients comparing IgG therapy starting before (N = 62) or after (N = 55) 2 years of age; C probability of survival for 191 XLA patients comparing patients with (N = 180) or without (N = 11) IgGR therapy