Late effects after allogeneic hematopoietic stem cell transplantation in patients with primary immunodeficiency

Allogeneic hematopoietic stem cell transplantation (HSCT) has markedly improved survival in children with primary immunodeficiencies (PIDs) transforming previously fatal diseases into curable conditions. As survival improves late effects are emerging as major concerns. We performed a systematic review aiming to identify, categorize, and summarize late effects (LEs) following allogeneic HSCT in pediatric patients with PIDs.

Following PRISMA guidelines, PubMed and EBSCOhost databases were searched without date restrictions for studies reporting LEs in patients who underwent allogeneic HSCT for PIDs at the age of 0-17 years and survived at least 2 years after HSCT.

Of 1,142 screened publications, 31 met the inclusion criteria, including 2,293 patients transplanted from 1981 to 2019 and followed for long-term outcomes. The main indications included severe combined immunodeficiency, Wiskott-Aldrich Syndrome (WAS), chronic granulomatous disease, leukocyte adhesion deficiency, and other rare PIDs. At least one LE was reported in 544 out of 2,293 patients (24%) who were followed up from 2 to 38 years. Growth and developmental delay were the most frequently reported LEs, observed in at least 280 patients (12.2%). This was followed by neurological (n=173, 7.5%) and autoimmune or hematologic (n=161, 7.0%) long-term issues. Pulmonary and skin complications were noted in 150 patients each (6.5% each), while dental and skeletal impairments affected 112 patients (4.9%). Endocrine issues were reported in 99 patients (4.3%), and gastrointestinal or liver impairments occurred in 75 patients (3.3%). Secondary malignancies, renal/metabolic, recurrent infections, hearing loss, ocular and vascular late complications were rare and reported in less than 1% of patients.

A substantial proportion of pediatric HSCT survivors with PIDs experience LEs. They affect various organs and systems years after an immune system replacement. These findings highlight the need for lifelong, multidisciplinary follow-up to optimize long-term health, functional outcomes, and quality of life.

https://www.crd.york.ac.uk/PROSPERO/view/CRD42024621972, identifier CRD42024621972.