Seo, Susan K.

There is an increased risk of infection in patients with cancer that results in higher morbidity and mortality. Several risk factors can predispose these patients to infectious complications. Some such factors include immunocompromised states like neutropenia, allogeneic hematopoietic cell transplantation, and graft-versus-host disease, while others include immunosuppressive agents like corticosteroids, purine analogs, monoclonal antibodies, and other emerging cancer therapeutics like CAR T-cell therapy. The NCCN Guidelines for the Prevention and Treatment of Cancer-Related Infections address infection concerns that may be observed in these immunocompromised populations and characterize the major pathogens to which patients with cancer are susceptible, with a focus on the prevention, diagnosis, and treatment of major common and opportunistic infections. This paper highlights 2 recently updated sections of the guidelines, namely, infection concerns related to CAR T-cell therapy and antimicrobial prophylaxis recommendations, including vaccination, in patients at high-risk for infections.

Abstract Background Contemporary information regarding fever and neutropenia (FN) management, including approaches to antibacterial prophylaxis, empiric therapy, and de-escalation across US cancer centers, is lacking. Methods This was a self-administered, electronic, cross-sectional survey of antimicrobial stewardship physicians and pharmacists at US cancer centers. The survey ascertained institutional practices and individual attitudes on FN management in high-risk cancer patients. A 5-point Likert scale assessed individual attitudes. Results Providers from 31 of 86 hospitals (36%) responded, and FN management guidelines existed in most (29/31, 94%) hospitals. Antibacterial prophylaxis was recommended in 27/31 (87%) hospitals, with levofloxacin as the preferred agent (23/27, 85%). Cefepime was the most recommended agent for empiric FN treatment (26/29, 90%). Most institutional guidelines (26/29, 90%) recommended against routine addition of empiric gram-positive agents except for specific scenarios. Eighteen of 29 (62%) hospitals explicitly provided guidance on de-escalation of empiric, systemic antibacterial therapy; however, timing of de-escalation was variable according to clinical scenario. Among 34 individual respondents, a majority agreed with use of antibiotic prophylaxis in high-risk patients (25, 74%). Interestingly, only 10 (29%) respondents indicated agreement with the statement that benefits of antibiotic prophylaxis outweigh potential harms. Conclusion Most US cancer centers surveyed had institutional FN management guidelines. Antibiotic de-escalation guidance was lacking in nearly 40% of centers, with heterogeneity in approaches when recommendations existed. Further research is needed to inform FN guidelines on antibacterial prophylaxis and therapy de-escalation.

5017 Background: HDCT/ASCT represents a curative salvage treatment for patients with GCT but is rarely used for other solid tumors. Patients undergoing HDCT/ASCT for hematologic neoplasms require revaccination for their childhood immunizations. Whether this is necessary in patients with GCT is unknown. Methods: In this prospective longitudinal study, patients with GCT undergoing HDCT-ASCT from 11/2010 to 5/2018 had serologies for Measles, Mumps, Rubella, Diphtheria, Tetanus, Polio, and Varicella Zoster measured before HDCT and at 3, 6, and in a subset, 12+ months after the last HDCT with results at these timepoints compared using descriptive statistics. In addition, titer levels at ≥6 months post-transplant were matched 1:1 for age and gender with HL patients who underwent HDCT/ASCT during the same time period. Immunity was compared between cohorts using the Cochran-Mantel-Haenszel test. Results: Of 80 patients with GCT (median age 30, 84% nonseminoma), 91% received 3 sequential transplants and 68 had repeat titers at ≥6 months. Immunity at baseline was >95% for Diphtheria, Tetanus and Polio and 89% for Varicella Zoster but lower for Measles (74%), Mumps (85%), and Rubella (83%) (Table). Compared to baseline, proportional immunity for all infections was similar at 3, 6, and 12 months post-transplant in the GCT population (≥6 months shown in Table). Matching resulted in 58 GCT-HL pairs. One-year immunity was numerically lower for most infections in the HL vs. GCT patients and significantly decreased for Measles and Rubella (Table). Conclusions: To our knowledge, this is the first study to assess vaccine titers following HDCT/ASCT for GCT. We demonstrate that HDCT/ASCT does not result in loss of immunity to childhood vaccines and that GCT patients retain protective titers more frequently than those with HL. However, 15-31% of GCT patients lack MMR immunity at baseline and at 1-year post-ASCT. Therefore, we recommend checking MMR titers at 1-year post-ASCT with revaccination of those lacking immunity. Titer evaluation and revaccination is not necessary for other childhood immunizations.[Table: see text]

Abstract Background Fever and neutropenia (FN) is common in cancer patients after chemotherapy, and there are national guideline recommendations for FN prevention and treatment. We conducted a survey of practices across multiple US cancer centers to determine the extent to which these guidelines have been adapted. Methods US cancer centers performing 20 allogeneic hematopoietic stem cell transplantations annually were identified from the National Marrow Donor Program’s “Be the Match” directory. Antimicrobial stewardship physicians and pharmacists at each institution were identified using institutional websites, residency or fellowship program directories, and personal contacts. A survey assessing institutional practices and individual attitudes on FN management in high-risk patients was distributed via email. Duplicate responses at the hospital level were removed. Complete surveys regarding individual attitudes were assessed using a 5-point Likert scale ranging from “Strongly Agree” to “Strongly Disagree.” Results Thirty-four (23%) responses from 148 individuals were received, representing 31 of 86 hospitals (36%). 29 (94%) hospitals reported having guidelines for the management of FN. Of these, cefepime was the most commonly recommended agent for empiric treatment (26, 90%) and 16 (55%) provide guidance based on presumed site of infection. Eighteen (62%) hospitals recommend de-escalation of Gram negative therapy in certain situations, most often after being afebrile 48 – 72 hours or after neutrophil recovery (7 each, 39%). Twenty-seven (93%) hospitals recommended antibiotic prophylaxis, most often with levofloxacin (21, 78%). Of 34 respondents, attitudes were split regarding the statement “The benefit of antibiotic prophylaxis outweighs the harms in high-risk patients” (10 strongly agree or agree, 10 strongly disagree or disagree; 29% each); most agreed with the statement “I would use antibiotic prophylaxis in high-risk patients” (25, 78%). Conclusion Most cancer centers across the US have guidelines for the management of FN. While most recommend antibacterial prophylaxis, there were differences in individual perceptions regarding the risk / benefit. Significant variation exists in the approach to antibiotic de-escalation. Disclosures All Authors: No reported disclosures