Mahendran Malena, Upton Julia E M, Ramasubramanian Ramya, Memmott Heidi L, Germain Guillaume, Büsch Katharina, Laliberté François, Harrington Amanda
Groupe d'analyse, Ltée, Montréal, Québec, Canada.
Clinical Immunology and Allergy, Department of Pediatrics, The Hospital For Sick Children, Toronto, ON, Canada.
Orphanet J Rare Dis. 2025 May 3;20(1):212. doi: 10.1186/s13023-025-03734-z.
This study aimed to describe overall survival (OS) of patients with APDS relative to the global population as well as among subsets of patients with concurrent lymphoma or hematopoietic stem cell transplant (HSCT) relative to the overall APDS population.
Patient-level data were extracted from a recent systematic literature review of 351 unique patients with APDS. OS was evaluated using the Kaplan-Meier method up to age 65 years. OS rate and corresponding 95% CI were reported at each decade of age. Global mortality estimates were obtained from World Health Organization life tables for 2019.
Of the 351 patients with APDS (APDS1, 267 [76.1%]; APDS2, 83 [23.6%]; unspecified, 1 [0.3%]), 41 (11.7%) died. The OS rate was 25.0% (95% CI, 1.6-62.7%) by the last death event at 64 years of age. Starting at 12 years of age, the OS rate was numerically lower in patients with APDS relative to the global population (median OS, 64 vs. 75 years, respectively). Relative to the overall APDS population, OS rates were numerically similar in those who underwent HSCT (median OS, 64 years for both; p = 0.569), whereas OS rates were numerically lower in patients with concurrent lymphoma (median OS, 41 vs. 64 years, respectively; p = 0.109). Publication bias in source data was a possible limitation.
Reduced survival in patients with APDS suggests a high disease burden, particularly in those with concurrent lymphoma. These results highlight the unmet need for disease-modifying treatments for APDS.
本研究旨在描述伴有活化PI3Kδ综合征（APDS）患者相对于全球人群的总生存期（OS），以及相对于整个APDS患者群体，并发淋巴瘤或接受造血干细胞移植（HSCT）的患者亚组中的总生存期。
从最近一项对351例独特的APDS患者进行的系统文献综述中提取患者层面的数据。使用Kaplan-Meier方法评估至65岁的总生存期。报告每个十岁年龄段的总生存率及相应的95%置信区间（CI）。全球死亡率估计值来自世界卫生组织2019年的生命表。
在351例APDS患者中（APDS1型，267例[76.1%]；APDS2型，83例[23.6%]；未明确分型，1例[0.3%]），41例（11.7%）死亡。在64岁时最后一例死亡事件发生时，总生存率为25.0%（95%CI，1.6 - 62.7%）。从12岁开始，APDS患者的总生存率在数值上低于全球人群（中位总生存期分别为64岁和75岁）。相对于整个APDS患者群体，接受HSCT的患者总生存率在数值上相似（中位总生存期均为64岁；p = 0.569），而并发淋巴瘤的患者总生存率在数值上较低（中位总生存期分别为41岁和64岁；p = 0.109）。源数据中的发表偏倚可能是一个局限性。
APDS患者生存率降低表明疾病负担较重，尤其是并发淋巴瘤的患者。这些结果凸显了对APDS进行疾病修饰治疗的未满足需求。
