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. 2024 Jan 27;24(1):17.
doi: 10.1007/s10238-023-01259-y.

Systematic review of mortality and survival rates for APDS

Jennifer Hanson  1 , Penelope E Bonnen  2
Affiliations

Systematic review of mortality and survival rates for APDS

Jennifer Hanson et al. Clin Exp Med. .

Abstract

Activated phosphoinositide 3-kinase delta syndrome (APDS) is a rare genetic disorder that presents clinically as a primary immunodeficiency. Clinical presentation of APDS includes severe, recurrent infections, lymphoproliferation, lymphoma, and other cancers, autoimmunity and enteropathy. Autosomal dominant variants in two independent genes have been demonstrated to cause APDS. Pathogenic variants in PIK3CD and PIK3R1, both of which encode components of the PI3-kinase, have been identified in subjects with APDS. APDS1 is caused by gain of function variants in the PIK3CD gene, while loss of function variants in PIK3R1 have been reported to cause APDS2. We conducted a review of the medical literature and identified 256 individuals who had a molecular diagnosis for APDS as well as age at last report; 193 individuals with APDS1 and 63 with APDS2. Despite available treatments, survival for individuals with APDS appears to be shortened from the average lifespan. A Kaplan-Meier survival analysis for APDS showed the conditional survival rate at the age of 20 years was 87%, age of 30 years was 74%, and ages of 40 and 50 years were 68%. Review of causes of death showed that the most common cause of death was lymphoma, followed by complications from HSCT. The overall mortality rate for HSCT in APDS1 and APDS2 cases was 15.6%, while the mortality rate for lymphoma was 47.6%. This survival and mortality data illustrate that new treatments are needed to mitigate the risk of death from lymphoma and other cancers as well as infection. These analyses based on real-world evidence gathered from the medical literature comprise the largest study of survival and mortality for APDS to date.

Keywords: APDS; Activated PI3K delta syndrome; CVID; Common variable immune deficiency; PI3-kinase; PID; PIK3CD; PIK3R1; Primary immune deficiency.

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Conflict of interest statement

The authors have no financial or proprietary interests in any material discussed in this article.

Figures

Fig. 1
Fig. 1
Age at last report in a cohort of 256 individuals with APDS. The age at last report was plotted in 5-year age bins for individuals with a molecular diagnosis of pathogenic PIK3CD variant resulting in APDS1 (orange), and for those with a molecular diagnosis of pathogenic PIK3R1 variant (blue). The moving average of the age at last report was plotted for individuals with APDS1/PIK3CD in blue and for individuals with APDS2/PIK3R1 in orange
Fig. 2
Fig. 2
Age and cause of death for APDS. A Causes of death in individuals with APDS1 are shown and the size of the pie slice reflects the number of individuals with that cause of death. All individuals with APDS2 had the same cause of death, lymphoma, so it was not plotted. B Cause of death in individuals with APDS1 and APDS2 was plotted with age of death on the x-axis and number of individuals plotted on the y-axis. C The causes of death for both APDS1 and APDS2 grouped by age at death. The number of individuals with the cause of death is shown in the left panel and the percentage of individuals with the cause of death is shown in the right panel. The color scheme in A, B, and C are the same, with each color indicating a different cause of death. The key for color to cause of death is shown in the figure in panel A
Fig. 3
Fig. 3
Kaplan–Meier survival analysis of all-cause mortality in 256 individuals with APDS. A The probability of survival over time plus the 95% confidence interval was plotted for individuals with APDS1, N = 193, and separately for B. APDS2, N = 63. The survival rate conditional on having either APDS1 or APDS2, N = 256, was estimated by Kaplan–Meier analysis and plotted in panel C
See this image and copyright information in PMC

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