Mucosal Barrier Injury-Laboratory Confirmed Bloodstream Infection in Patients Who Receive HSCT

Mucosal barrier injury-laboratory confirmed bloodstream infection (MBI-LCBI), in addition to any bloodstream infections (BSIs), were associated with significant morbidity and mortality after hematopoietic stem cell transplant (HSCT), according to this study published in JAMA Network Open. 

The researchers indicated that further investigation into risk reduction should be a clinical and scientific priority for this patient population.

“Reduction in MBI-LCBI will require a better understanding of its mechanisms and risk factors, and our data contribute to the knowledge needed to make important progress,” the authors wrote.

According to the study, a BSI is defined as an MBI-LCBI if it resulted from 1 or more of a group of selected organisms known to be commensals of the oral cavity or gastrointestinal tract, and it occurred in a patient with specific signs or symptoms compatible with the presence of mucosal barrier injury, like gastrointestinal graft-vs-host disease (GVHD) and/or neutropenia. 

Of this cohort of 16,875 patients, 13,686 underwent HSCT for a malignant neoplasm, and 3,189 (18.9%) underwent HSCT for a nonmalignant condition. The cumulative incidence of MBI-LCBI was 13% (99% CI, 12%-13%) by day 100, and the cumulative incidence of BSI-other was 21% (99% CI, 21%-22%) by day 100. The median time from transplant to first MBI-LCBI was 8 (<1 to 98) days, versus 29 (<1 to 100) days for BSI-other. Most cases of MBI-LCBI met the definition secondary to neutropenia alone (1,915 of 2,179 [87.9%]), with the other 12.1% (264 of 2,179) meeting criteria owing to the presence of gastrointestinal GVHD (166 of 2,179 [7.6%]) or gastrointestinal GVHD with neutropenia (98 of 2,179 [4.5%]). 

Multivariable analysis exposed an increased risk of MBI-LCBI with poor Karnofsky/Lansky performance status (hazard ratio [HR], 1.21 [99% CI, 1.04-1.41]), cord blood grafts (HR, 2.89 [99% CI, 1.97-4.24]), myeloablative conditioning (HR, 1.46 [99% CI, 1.19-1.78]), and posttransplant cyclophosphamide GVHD prophylaxis (HR, 1.85 [99% CI, 1.19-1.78]). These findings support current efforts to use umbilical cord blood graft expansion to shorten the duration of neutropenia. 

One-year mortality was significantly higher for patients with MBI-LCBI (HR, 1.81 [99% CI, 1.56-2.12]), BSI-other (HR, 1.81 [99% CI, 1.60-2.06]), and MBI-LCBI plus BSI-other (HR, 2.65 [99% Ci, 2.17-3.24]) compared with controls. Moreover, one-year TRM (non-relapse mortality) among patients with malignant disease increased for patients with any BMI. There was no association of any BSI with the development of chronic GVHD.

Infection was more often reported as a cause of death for patients with MBI-LCBI (139 of 740 [18.8%]), BSI (251 of 1,537 [16.3%]), and MBI-LCBI plus BSI (94 of 435 [21.6%]) than for controls (566 of 4,740 [11.9%]). Additionally, infection as an associated secondary cause of death was higher in patients with MBI-LCBI (158 of 740 [21.4%]), BSI only (343 of 1,537 [22.3%]), and MBI-LCBI plus BSI (116 of 435 [26.7%]) than in the control group (739 of 4,740 [15.6%]). 

“To our knowledge, this is the first large-scale study to evaluate MBI-LCBI,” the authors wrote. “The inclusion of multiple centers provides a diverse population of all ages, stem cell sources, and transplant types and minimizes overreporting or underreporting biases inherent in single-center studies.” 

Each year, more than 50,000 HSCTs are performed worldwide, according to the researchers. Though transplant strategies and supportive care has evolved, leading to improved overall survival, patients who have undergone HSCT are still at high risk for BSIs and associated morbidity and mortality.

Reference:

Dandoy CE, Kim S, Chen M, et al. Incidence, Risk Factors, and Outcomes of Patients Who Develop Mucosal Barrier Injury-Laboratory Confirmed Bloodstream Infections in the First 100 Days After Allogeneic Hematopoietic Stem Cell Transplant. JAMA Network Open. doi:10.1001/jamanetworkopen.2019.18668.