Joris Van Montfrans, Netherlands
UMC Utrecht Pediatric ImmunologyPresenter of 1 Presentation
DOCK8 DEFICIENCY AND MALIGNANCIES: CASE REPORT IN TWO SIBLINGS AND REVIEW OF THE LITERATURE.
Abstract
Background and Aims
DOCK8 deficiency is a combined primary immunodeficiency with clinical hallmarks including atopic dermatitis, allergies, respiratory tract infections, viral skin infections and early onset malignancy. The prognosis of DOCK8 deficient patients is poor with a median survival of 20 years in historic patient cohorts without hematopoietic stem cell transplantation (HSCT). Mortality usually results from infections, malignancies, or both. This paper describes the clinical course of two siblings with a compound heterozygous mutation causing DOCK8 deficiency. We also systematically reviewed the literature on DOCK8 deficiency and malignancies.
Methods
In Januari 2019 a literature search focused on DOCK8 deficiency and malignancies was performed in Pubmed that yielded 26 articles and an additional 32 papers were included through snowballing.
Results
The increased malignancy risk of DOCK8 deficient patients can likely be explained by multiple factors, being chronic viral infections with oncogenic viruses, impaired immune surveillance and a possible tumor suppressor function of DOCK8. Previous studies reported that 8 to 19% of the DOCK8 deficient patients develop malignancy, with an associated mortality of 7 to 10%. HPV associated squamous cell carcinoma and EBV related lymphomas are the most prevalent malignancies in DOCK8 deficiency.Currently, HSCT is considered standard of care for DOCK8 deficient patients, but it is unclear whether HSCT protects against future malignancies.
Conclusions
There is no long-term data on malignancy risk post HSCT in DOCK8 deficiency. Furthermore, it is unclear whether a subpopulation of DOCK8 deficient patients exists that do not require HSCT. This underscores the need of prospective cohort studies to anlyse HSCT effectifness and individual malignancy risk.