Malignancy in common variable immunodeficiency: a systematic review and meta-analysis

ABSTRACT

Background: Common variable immunodeficiency (CVID) is the most common clinically significant primary immunodeficiency (PID) disorder characterized by variable clinical manifestations including recurrent infections, autoimmune disorders, enteropathy, lymphoproliferative disorders, and malignancy. The aim of this study is to estimate the overall prevalence of malignancy in patients with CVID.

Methods: PubMed, Web of Science and Scopus were searched systemically to find eligible studies from the earliest available date to March 2019 with standard keywords. Pooled estimates of the malignancy prevalence and the corresponding 95% confidence intervals (CI) were calculated using random effects models.

Results: Forty-eight studies with a total of 8123 CVID patients met the inclusion criteria and were finally included in the meta-analysis. Overall prevalence of malignancy was 8.6% (95% CI: 7.1–10.0; I² = 79.2%). The prevalence of lymphoma, gastric cancer, and breast cancer in CVID patients were 4.1% (95% CI: 3.3–4.9; I² = 62.6%), 1.5% (95% CI: 0.78–2.2; I² = 68.9%), and 1.3% (95% CI: 0.64–1.9; I² = 54.9%), respectively. Moreover, autoimmunity and malabsorption were more frequent in patients with malignancy than those without malignancy.

Conclusion: The prevalence of malignancy has increased in CVID patients due to recent improvement in survival rate and the lymphoma is the most common type. This research highlighted the significance of malignancy screening and management in CVID patients.

KEYWORDS:

• Malignancy
• lymphoma
• primary immunodeficiency
• common variable immunodeficiency

Article Highlights

• The most frequent malignancies in CVID patients are lymphoma, gastric cancer, and breast cancer.

• The pooled prevalence of malignancy in CVID patients is 8.5% and from this prevalence of lymphoma is estimated to be 4.3%.

• Malignancy in CVID patients may be concurrent with autoimmune disorder due to dual effects of these phenotypes on uncontrolled inflammation and auto-antigen load after tissue destruction.

• CVID patients with malignancy have higher immunoglobulin serum levels and CD8+ T cells than those without malignancy.

Acknowledgments

The authors would like to thank the Clinical Research Development Center of Imam Ali-Karaj Hospital.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was supported by vice chancellor for research, Alborz University of Medical Sciences, under [Grant No. 1397-03-00-2014].