Burden and Outcomes of Mucosal Barrier Injury-Laboratory Confirmed Bloodstream Infections (MBI-LCBI) in the First 100 Days after Allogeneic Stem Cell Transplant: A CIBMTR Analysis

Background: Patients undergoing stem cell transplant (SCT) are at risk of bloodstream infections (BSI). BSI led to prolonged hospitalization, intensive care admissions, prolonged antibiotic treatment and increased mortality. Recently, the Centers for Disease Control and Prevention developed a modification of the Central line associated bloodstream infection (CLABSI) definition, termed "mucosal barrier injury laboratory-confirmed bloodstream infection" (MBI-LCBI) to differentiate BSI likely related to mucosal barrier injury. BSI are identified as an MBI-LCBI if: (1) it resulted from 1 or more of a group of selected organisms known to be commensals of the oral cavity or gastrointestinal tract and (2) occurred in a patient with signs or symptoms compatible with the presence of mucosal barrier injury such as gastrointestinal graft-versus-host disease and/or neutropenia. We utilized the CIBMTR database to determine the incidence and timing of MBI-LCBI, risk factors for development of MBI-LCBI, and compare transplant outcomes by 1 year after SCT.

Methods: We identified 16,875 pediatric and adult patients receiving first allogeneic transplant from 2009-2016. Patients were classified into 4 categories based on the occurrence of BSI in first 100 days: MBI-LCBI (n=1434; 8.5%), MBI-LCBI +other BSI (n=700; 4.1%), BSI only (n=3016; 17.8%), and control (n=11725; 69.5%) (Figure 1). Demographics and outcomes, including overall survival (OS), chronic GVHD, and transplant-related mortality (TRM, for malignant disease patients only), were compared between groups.

Results: The cumulative incidence of MBI-LCBI was 13% (99% CI: 12-13%) by day 100 whereas the probability for another BSI not meeting MBI-LCBI criteria was 22% (99% CI: 21-23%) by day 100. The median time from transplant to first MBI-LCBI was 8 days (<1-98), MBI-LCBI + other BSI 10 days (<1-99), and other BSI was 38 days (<1-100). Karnofsky/Lansky performance status <90 [RR 1.21 (99% CI: 1.06 - 1.38)], myeloablative conditioning [RR 1.45 (99% CI: 1.27-1.69)], post-transplant cyclophosphamide as GVHD prophylaxis [RR 1.83 (99% CI: 1.40 - 2.39)], and receipt of cord blood [RR 2.89 (99% CI: 2.06 - 4.06)] were associated with a significant increase in the risk of MBI-LCBI (Table 1). The 1 year OS was inferior for patients with MBI-LCBI only [59% (99% CI: 56 - 61%); RR 1.86 (99% CI: 1.65 - 2.09)], Other BSI only [60% (99% CI: 58 - 63%); RR 1.86 (99% CI: 1.70 - 2.04)], and MBI-LCBI + Other BSI [46% (99% CI: 41 - 50%); RR 2.79 (99% CI: 2.42 - 3.23)] compared to controls [72% (71 - 73); p <0.0001] (Table 2). There was no impact of MBI-LCBI only, Other BSI only, or MBI-LCBI + Other BSI compared to controls on development of chronic GVHD. As expected 1 year TRM in patients with malignant disease was increased with any BSI but was similar for patients with MBI-LCBI only [30% (99% CI: 27 - 34%); RR 2.41 (99% CI: 2.05-2.82] or Other BSI [25% (99% CI: 23 - 27%); RR 2.20 (1.94 - 2.51)] and further worsened for patients with both MBI-LCBI + Other BSI [45% (99% CI: 39 - 50%); RR 4.23 (3.53 - 5.07)] compared to controls [16% (99% CI:15 - 17%)]. Finally, infection as a cause of mortality was higher in patients with MBI-LCBI (19%), BSI only (17%), and MBI-LCBI + BSI (21%) then controls (12%).

Discussion: Our data demonstrate approximately 13% of all patients develop at least one MBI-LCBI and an additional 22% of patients develop another BSI in the first 100 days post SCT. Multivariable analysis revealed increased risk of MBI-LCBI with poor performance status, cord blood grafts, myeloablative conditioning, and post-transplant cyclophosphamide GVHD prophylaxis. BSI, whether or not MBI-LCBI, significantly decreases overall survival, primarily related to an increased TRM. The combination of MBI-LCBI and other BSI worsens both TRM and OS, but the respective impact of MBI-LCBI only was similar to Other BSI only. BSI, both MBI-LCBIs and other BSI, lead to significant morbidity and mortality and healthcare resource utilization. Reduction in frequency of BSI should be a major public health and scientific priority.

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