Central Line-Associated Blood Stream Infections Following Hematopoietic Cell Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome: Incidence, Risk Factors, and Impact On Survival
Authors: Lukenbill Joshua , Rybicki Lisa , Sekeres Mikkael A. , Copelan Alexander , Zaman Omer , Haddad Housam , Duong Hien K. , Hill Brian T. , Kalaycio Matt , Sobecks Ronald , Hanna Rabi , Fraser Thomas , DiGiorgio Megan , Bolwell Brian J. , Copelan Edward A. 
Published: October 2019

Abstract
Abstract 4481
Patients undergoing hematopoietic cell transplantation (HCT) require central venous access during treatment, predisposing this inherently susceptible population to infection. Central line-associated blood stream infection (CLABSI) is defined by the National Healthcare Safety Network as a primary bloodstream infection (BSI) in a patient with a central line within the 48-hour period before the development of the BSI. CLABSI surveillance is being increasingly used as an objective measure of quality of care delivered at individual hospitals. The Centers for Disease Control and Prevention have developed guidelines for the insertion, surveillance, and timely removal of these lines to prevent CLABSI, of which approximately 10% are fatal, and the Centers for Medicare & Medicaid will adjust reimbursement for CLABSI. The incidence, risk factors, and impact on survival of CLABSI in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) patients undergoing HCT has not been reported.
AML or MDS patients undergoing HCT between August 2009 and December 2011 were identified from the Cleveland Clinic Unified Transplant Database, and occurrence of CLABSI was determined from the infection control database. Variables analyzed included occurrence of CLABSI, as well as patient demographics, disease type, prior treatment, HCT comorbidity index, transplant type/HLA-match, CD34+ count, and time to neutrophil recovery (absolute neutrophil count >500). CLABSI incidence was estimated using Kaplan-Meier method, and univariable and multivariable risk factors were identified by Cox proportional hazards analyses. Of the 73 patients identified, 48 were male; 68 were Caucasian; 44 had AML, and 29 MDS. The median age at transplant was 52 (range 16–70), and 39 had a low to intermediate HCT comorbidity index (0–2), while 34 had a high index (≥3). Patients received a median of 2 prior chemotherapy regimens (range 0–6), 3 had prior radiation, and 6 had prior transplant. Preparative regimen was myeloablative (n=54) or reduced-intensity (n=19); 34 received bone marrow (BM), 24 peripheral stem cells (PSC), and 15 cord blood cells (CBC). The median CD34+ count was 2.42 × 106/kg and median time to neutrophil recovery was 14 days (range 6–24) with BM/PSC compared to 28 days with CBC (range 19–77).
Among these 73 patients, 23 (31.5%) developed CLABSI, of whom 16 (69.6%) died. The majority (16/23) of CLABSI occurred within 14 days (median 9 days, range 2–211 days) from HCT (Figure 1), but timing of CLABSI was highly associated with cell source: median of 5 days (range 2–12 days) for CBC and 78 days (range 7–211 days) for BM/PSC (p<.001). Etiologies of CLABSI included 11 enteric Gram-negative bacilli, 7 Streptococcus viridans group, 6 enterococcus (3 vancomycin resistant), 5 Staphylococcus (3 methicillin resistant), 2 fungal species, 2 Gram-positive bacilli, 1 Pseudomonas, 1 other Streptococcus species, and 1 Stenotrophomonas. 4 patients had polymicrobial infections, and 5 (all of whom died) had more than one separately documented CLABSI. Univariable risk factors for CLABSI included cord blood transplant (p<.001), HLA-mismatch (p=.005), low CD34+ count (p=.007), and non-Caucasian race (p=.017). Risk factors for CLABSI in multivariable analysis were CBC (p<.001) and high comorbidity index (p=.002); 4 distinct populations of patients were created based on this data, ranging from a high comorbidity index/cord blood cohort to a low to intermediate co-morbidity index/marrow cohort (Figure 2). When CLABSI was analyzed as a time-varying covariate in univariable analyses, it was associated with an increased risk of mortality (HR 3.17, 95% CI 1.61–6.22, p<.001). Multivariable risk factors for mortality included CLABSI (HR 7.14, CI 3.31 – 15.37, p<.001), MDS diagnosis (HR 5.21, CI 2.40–11.33, p<.001), and age (HR 1.81, CI 1.21–2.71, p=.004).
CLABSI is a common complication in AML and MDS patients undergoing HCT, and is associated with remarkably decreased survival. Cord blood, perhaps related to the extent and duration of severe immune deficiency, and high HCT comorbidity index place patients at higher risk of CLABSI. Efforts to identify patients at high risk of CLABSI, careful adherence to preventative infectious control measures, and design of methods to enhance immune reconstitution post-transplant in the high risk population could improve outcome in a substantial portion of patients.

Disclosures:
No relevant conflicts of interest to declare.