Outcomes of Pneumococcal Disease in Patients With B-Cell and Hematological Neoplasms: A Retrospective Cohort Study

Background: Streptococcus pneumoniae remains a major cause of pneumonia, sepsis, and meningitis, posing particular risk to immunocompromised adults. Patients with hematologic malignancies especially B-cell neoplasms experience profound humoral immune dysfunction and treatment-related B-cell depletion, predisposing them to invasive pneumococcal disease (IPD). Despite this, current vaccination guidelines do not differentiate between hematologic malignancy subtypes, leaving uncertainty regarding optimal prevention strategies. We aimed to characterize the burden and outcomes of pneumococcal disease among adults with hematologic malignancies, focusing on B-cell neoplasms, and to generate evidence supporting refinement of pneumococcal vaccination strategies for this high-risk group. Methods: We conducted a retrospective, nationally representative analysis of U.S. hospitalizations for pneumococcal disease from 2018–2021 using the National Inpatient Sample. Weighted multivariable logistic and linear regression models were used to assess associations between hematologic malignancy, particularly B-cell neoplasms, and outcomes including in-hospital mortality, need for invasive mechanical ventilation, length of stay, and hospital charges. Results: Among an estimated 186,860 adult pneumococcal hospitalizations, hematologic malignancy was independently associated with increased odds of mechanical ventilation (adjusted OR 1.87, 95% CI 1.73–2.02, p  < 0.001) and greater healthcare utilization, but not with higher in-hospital mortality (OR 0.95, 95% CI 0.86–1.05). Sensitivity analyses limited to B-cell malignancies yielded consistent results. Acute sepsis physiology, comorbidity burden, and socioeconomic disadvantage were the dominant predictors of adverse outcomes. Conclusions: Hematologic and B-cell malignancies significantly amplify the clinical and economic burden of pneumococcal disease, highlighting an urgent need to strengthen pneumococcal vaccination efforts in these populations. Despite comparable in-hospital mortality, the elevated risk of severe respiratory failure and prolonged hospitalization underscores the importance of optimized prevention. Expanding vaccine uptake through routine screening, inpatient vaccination initiatives, and adherence to updated PCV/PPV guidelines should be a public health priority to mitigate preventable morbidity, mortality, and healthcare costs. Trial registration Not applicable. This study was a retrospective observational analysis of a deidentified administrative database and did not involve prospective enrollment or intervention.