Epstein–Barr virus infection is most commonly asymptomatic in the acute setting, where the end result of infection is the adoption of a viral latency phenotype. The virus can reactivate later in life leading to the abnormal proliferation of the infected B, T, or NK cells. Hereby, we report a 71-year-old female with seronegative rheumatoid arthritis who presented with massive splenomegaly, pancytopenia, and positivization of antibodies against double-stranded deoxyribonucleic acid (dsDNA) after initiation of the anti-tumor necrosis factor (TNF) golimumab. The diagnosis of EBV-associated lymphoproliferative disorder (LPD) was demonstrated by elevation of the plasmatic EBV viral load. Withdrawal of the anti-TNF and treatment with the anti-CD20 antibody rituximab were able to revert the clinical abnormalities. EBV-associated LPDs are described after initiation of other anti-TNF agents, such as infliximab, but no reports of golimumab-associated EBV LPD are found in the literature. The mechanisms for this occurrence are not clear, but these are known to involve expression of a panel of viral proteins specific to the viral latency phenotypes.

The generalized form of UDP-galactose-4′-epimerase (GALE) deficiency causes hypotonia, failure to thrive, cataracts, and liver failure. Individuals with non-generalized forms may remain asymptomatic with uncertain long-term outcomes. We report a 2-year-old child compound heterozygous for GALE p.R51W/p.G237D who never developed symptoms of classic galactosemia but has a history of congenital combined mitral and tricuspid valve malformation and pyloric stenosis, and presented with pancytopenia. Variant pathogenicity was supported by predictive computational tools and decreased GALE activity measured in erythrocytes. GALE function extends to the biosynthesis of glycans by epimerization of UDP-<i>N</i>-acetyl-galactosamine and -glucosamine. Interrogation of the Gene Ontology consortium database revealed several putative proteins involved in normal hematopoiesis and atrioventricular valve morphogenesis, requiring <i>N</i>-glycosylation for adequate functionality. We hypothesize that by limiting substrate supply due to GALE deficiency, alterations in <i>N</i>-linked protein glycosylation can explain the patient’s phenotype.

Background Cytomegalovirus (CMV) infection is a frequent complication after allogeneic hematopoietic cell transplant (allo-HCT) and may increase the risk of other viral infections through its immunomodulatory effects. Donor CMV serology (seropositive [D+] or seronegative donor [D-]) in CMV-seropositive (R+) or seronegative recipients (R-) may impact outcomes post allo-HCT. We analyzed the significance of donor CMV serostatus in a large cohort of alloHCT recipients. Methods This is a single-center, retrospective cohort study of 651 allo-HCT recipients cared for at our institution between March 2016 and December 2018. Data on baseline demographics, transplant characteristics, preventive strategies, CMV infection characteristics, and transplant-related outcomes (development of graft versus host disease (GVHD), all-cause mortality, and non-relapse mortality) were collected. A univariate analysis was performed for outcomes of interest using CMV serostatus D-/R- as a control group. Results Out of the 651 allo-HCT recipients, 77 were D-/R-, 43 D+/R-, 290 D+/R+, and 241 D-/R+ (table 1). Most patients underwent HCT for AML (40%), received myeloablative conditioning (51%), and had a matched unrelated donor (MUD) HCT (46%). In 2018, letermovir was used in 27% of the D+/R+, 18% of the D-/R+ allo-HCT recipients (table 1) for a total of 116 (55%) allo-HCT recipients. Compared to the CMV D-/R- group, D+/R+ and D-/R+ groups (table 2) had a greater incidence of clinically signicant CMV infections (CS-CMVi) (3.9% vs. 40% vs. 50.6%; all p&lt; 0.01, respectively), CMV end organ disease (0% vs. 14.8% vs. 19.1%; all p&lt; 0.001, respectively), and refractory/resistant (R/R) CMV infections (0% vs. 5.5% vs. 12.4%; all p&lt; 0.03, respectively) with 48 weeks of allo-HCT. CS-CMVi and R/R CMV was more common in D-/R+ allo-HCT when compared to D+/R+ group (50.6% vs. 40.0%, p&lt; 0.001). D-/R+ allo-HCT had worse non-relapse mortality at day 100 compared to D-/R- (3.9% vs. 10.8%, p=0.07). Table 1:Baseline characteristicsTable 2:Outcome analysis Conclusion Allo-HCT recipients with CMV seronegative donor and recipient had less CMV related complications and a trend towards better survival when compared to D-/R+ allo-HCT. CMV D-/R+ HCT recipients had greater CMV related complications when compared to CMV D+/R+ HCT recipients, possibly due to the protective affect of donor seropositivity. Disclosures Terri Lynn Shigle, PharmD, BCOP, Takeda: Advisor/Consultant Gabriella Rondon, MD, Omeros: Advisor/Consultant Elizabeth Shpall, MD, Adaptimmune: Advisor/Consultant|Affimed: License agreement|Axio: Advisor/Consultant|Bayer Helathcare Pharmaceuticals: Honoraria|Fibroblasts and FibrioBiologics: Advisor/Consultant|Navan: Advisor/Consultant|NY Blood Center: Advisor/Consultant|Takeda: License agreement Ella Ariza-Heredia, MD, MERCK: Grant/Research Support Roy F. Chemaly, MD/MPH, Karius: Advisor/Consultant|Karius: Grant/Research Support.

Background Letermovir (LTV) primary prophylaxis (PP) has reduced the incidence of clinically significant cytomegalovirus infection (CS-CMVi) in allogeneic hematopoietic cell transplant (allo-HCT) recipients. However, it is not clear if these are similar to low-risk recipients (seronegative donor [D-] and recipient [R-]). Prior studies have reported that D-/R- allo-HCT recipients have reduced relapse rates, graft versus host disease (GVHD), and overall mortality. We compared the clinical outcomes of R+ allo-HCT recipients with and without LTV PP to D-/R- allo-HCT recipients. Methods This is a single-center study of allo-HCT recipients who underwent transplantation between March 2016 and December 2018. Data on baseline and transplant characteristics were collected. Outcomes included incidence of CS-CMVi, GVHD, all-cause mortality, relapse and NRM. Univariate analysis was performed to compare outcomes in R+ with and without LTV PP cohorts to D-/R- cohort. Categorical and continuous variables were compared using Fisher’s exact test and Wilcoxon rank sum respectively. Survival curves were compared with the log-rank test. Patients who relapsed after transplant were excluded from NRM analysis. Results A total of 616 patients underwent an allo-HCT; 124 R+ were on LTV PP, 415 were R+ on no LTV PP as well as the 77 who were CMV D-/R-. When compared to D-/R- group, R+ group who received or not LTV PP were more likely to have AML and ALL, and underwent myeloablative conditioning. The incidence of CS-CMVi was the lowest in the D-/R- group (4%), followed by the R+ on LTV PP (17%), and the highest in the R+ group on no LTV PP (53%) (table 2). Kaplan-Meier survival analysis for NRM 1 year after transplant showed trends towards lower survival in R+ allo-HCT recipients who did not receive LTV PP when compared to the D-/R- group at day 200 and day 360 (p=0.07 vs. p=0.08, respectively). In addition, R+ allo-HCT on LTV PP had similar NRM at day 360 compared to D-/R- (p=0.77) and lower NRM at day 360 compared to R+ allo-HCT on no LTV PP (p=0.0192). Conclusion Our study showed a reduction in the rate of CS-CMVi within 48 weeks post HCT in high risk allo-HCT recipients on LTV. NRM was lower in R+ allo-HCT recipients on LTV PP when compared to those without LTV. No difference in NRM was seen between D-/R- allo-HCT and R+ allo-HCT on LTV PP. Disclosures Terri Lynn Shigle, PharmD, BCOP, Takeda: Advisor/Consultant Gabriella Rondon, MD, Omeros: Advisor/Consultant Elizabeth Shpall, MD, Adaptimmune: Advisor/Consultant|Affimed: License agreement|Axio: Advisor/Consultant|Bayer Helathcare Pharmaceuticals: Honoraria|Fibroblasts and FibrioBiologics: Advisor/Consultant|Navan: Advisor/Consultant|NY Blood Center: Advisor/Consultant|Takeda: License agreement Ella J. Ariza Heredia, MD, Merck & Co. Inc: Grant/Research Support Roy F. Chemaly, MD/MPH, Karius: Advisor/Consultant|Karius: Grant/Research Support.

Background: Rapid diagnostic tests designed to provide bacterial identification and detection of resistance genes directly from positive blood cultures can significantly reduce the time to definitive results, ensuring appropriate and timely antibiotic administration while simultaneously decreasing antibiotic overuse and development of antimicrobial resistance. However, their impact on in-hospital mortality and length of stay (LOS) is yet to be fully assessed. Methods: We retrospectively reviewed bacteremia cases in patients hospitalized over a 6-month period before (n = 78) and after (n = 93) the implementation of Verigene bacterial nanoparticle testing. Exclusion criteria included age >90 years, bacteremia thought to be a contaminant, polymicrobial bacteremia, or hospice admission. Verigene was performed at a central laboratory from 6 a.m. to 11 p.m. Pharmacists notified physicians of results and assisted with antibiotic modifications. Patient demographics, time to organism identification, time to effective antimicrobial therapy, and other key clinical parameters were compared. The primary outcomes were in-hospital LOS, 14-day mortality, and 30-day mortality. Secondary outcomes included time to effective antibiotic therapy and intensive care unit (ICU) LOS. Results: Organism identification was achieved more quickly (4.9 hours vs 44.5 hours; P < .001) and effective antibiotic therapy was started earlier after Verigene implementation. The mean in-hospital LOS decreased from 13.15 days to 10.02 days (P = .0071) after the Verigene intervention, despite a higher mean Charlson comorbidity index among the cases. Mortality was similar between groups. Conclusions: Rapid identification of gram-positive and gram-negative bacteremia with an antimicrobial stewardship intervention can decrease time to effective antibiotic therapy and total LOS.Funding: NoneDisclosures: None