Association between helicobacter pylori infection and immune thrombocytopenia in chronic lymphocytic leukemia: A retrospective cohort study Free

Background Immune thrombocytopenia (ITP) is a known autoimmune complication in chronic lymphocytic leukemia (CLL), likely driven by immune dysregulation. Helicobacter pylori infection has been linked to ITP in the general population, with evidence that eradication can improve platelet counts. However, its role in CLL-associated ITP remains unclear. This study aimed to evaluate whether H. pylori infection is associated with an increased risk of developing ITP in patients with CLL using a large real-world dataset.

Methods We conducted a retrospective cohort study utilizing the TriNetX U.S. Collaborative Network, a large, federated research platform aggregating real-time electronic health record (EHR) data from 68 healthcare organizations across the country. Adult patients (≥18 years old) with a confirmed diagnosis of chronic lymphocytic leukemia were identified and categorized based on the presence or absence of a documented H. pylori infection prior to or at the time of their CLL diagnosis. To minimize potential confounding, propensity score matching was performed on a 1:1 basis, balancing groups by age, sex, race, and relevant comorbid conditions including autoimmune disorders, peptic ulcer disease, and prior infections. After matching, 764 patients were included in each group (CLL with H. pylori infection and CLL without H. pylori infection). The primary outcome was a new diagnosis of immune thrombocytopenia occurring within five years of the index date (defined as the date of H. pylori diagnosis or a matched time point in the uninfected

cohort). Kaplan-Meier survival curves were generated to compare ITP-free survival over time between the two groups. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Risk ratios were also computed for incidence comparisons.

Results After 1:1 propensity score matching, each cohort (CLL with H. pylori and CLL without H. pylori) included 764 patients. Over a five-year follow-up period, immune thrombocytopenia (ITP) was diagnosed in 2.7% (n=21) of patients in the H. pylori-positive CLL group compared to 1.7% (n=13) in the CLL-only group. Although this reflects a numerically higher incidence in the co-infected group, the difference did not reach statistical significance (Risk Ratio 1.62; 95% CI 0.82–3.20; p=0.165).

Kaplan-Meier survival analysis showed a slightly lower ITP-free survival rate in the CLL + H. pylori group (96.7%) versus the CLL-only group (97.8%) at five years. However, this difference was also not statistically significant (Hazard Ratio 1.54; 95% CI 0.77–3.08; Log-rank p=0.215). The hazard ratio proportionality test confirmed the assumptions of the Cox model (χ² = 0.017, p = 0.896).

Subgroup analyses adjusting for potential confounders—including sex, age, comorbidities (e.g., diabetes, autoimmune disorders), and prior infections—showed consistent results, suggesting that these variables did not significantly modify the relationship between H. pylori infection and ITP risk in CLL patients. Moreover, additional sensitivity analyses accounting for immunosuppressive treatment and CLL stage continued to show a similar non-significant trend.

Conclusion In this large, matched, real-world cohort of patients with chronic lymphocytic leukemia, H. pylori infection was associated with a numerically increased- but not statistically significant—risk of developing immune thrombocytopenia within five years. Although the absolute risk difference was small, the trend observed may reflect an underlying immunologic interaction between H. pylori and the CLL disease process that predisposes certain patients to autoimmune complications such as ITP.

While these results do not support a definitive causal relationship, they highlight the need for further research. Larger studies with longer follow-up and detailed immunologic profiling may help clarify whether H. pylori contributes to the development of ITP in CLL, or whether it merely represents a coincidental finding in a population already prone to immune dysregulation. Mechanistic studies exploring molecular mimicry, antigenic stimulation, or microbiome-immune interactions could also shed light on this potential association.