Impact of Influenza Infection Among Adult and Pediatric Populations With Hematologic Malignancy and Hematopoietic Stem Cell Transplant: A Systematic Review and Meta-Analysis

Purpose: Influenza is increasingly recognized as a leading cause of morbidity and mortality in patients with hematologic malignancies and recipients of hematopoietic stem cell transplantation (HSCT). However, the impact of influenza on this population has not been previously evaluated in a systematic review. This study systematically reviewed and summarized the outcomes of influenza infection as to in-hospital influenza-related mortality, development of lower respiratory tract infection and acute respiratory distress syndrome, need for hospitalization, intensive care unit admission, and mechanical ventilation. Methods: We conducted a systematic search of literature using the PubMed and EMBASE databases for articles published from January 1989 through January 19, 2020, reporting laboratory-confirmed influenza in patients of any age with hematologic malignancies and HSCT. Time from transplantation was not included in the search criteria. The impact of antiviral therapy on influenza outcomes was not assessed due to heterogeneity in antiviral treatment provision across the studies. Patients with influenza-like illness, solid-tumor cancers, or nonmalignant hematologic diseases were excluded from the study. A random-effects meta-analysis was performed to estimate the prevalences and 95% CIs of each outcome of interest. A subgroup analysis was carried out to assess possible sources of heterogeneity and to evaluate the potential impact of age on the influenza infection outcomes. Heterogeneity was assessed using the I² statistic. Findings: Data from 52 studies providing data on 1787 patients were included in this analysis. During seasonal epidemics, influenza-related in-hospital mortality was 16.60% (95% CI, 7.49%–27.7%), with a significantly higher death rate in adults compared to pediatric patients (19.55% [95% CI, 10.59%–29.97%] vs 0.96% [95% CI, 0%–6.77%]; P < 0.001). Complications from influenza, such as lower respiratory tract infection, developed in 35.44% of patients with hematologic malignancies and HSCT recipients, with a statistically significant difference between adults and children (46.14% vs 19.92%; P < 0.001). However, infection resulted in a higher hospital admission rate in pediatric patients compared to adults (61.62% vs 22.48%; P < 0.001). For the 2009 H1N1 pandemic, no statistically significant differences were found between adult and pediatric patients when comparing the rates of influenza-related in-hospital mortality, lower respiratory tract infection, and hospital admission. Similarly, no significant differences were noted in any of the outcomes of interest when comparing H1N1 pandemic with seasonal epidemics. Implications: Regardless of influenza season, patients, and especially adults, with underlying hematologic malignancies and HSCT recipients with influenza are at risk for severe outcomes including lower respiratory tract infection and in-hospital mortality.