Georgios Angelidakis

Background: Patients with cancer are at elevated risk for tuberculosis (TB) reactivation. Diagnosis of latent TB infection and TB disease remains challenging in this patient population despite the advent of interferon‐γ release assays (IGRA). Methods: We retrospectively reviewed medical records of all patients with cancer who had IGRA testing (QuantiFERON–TB [QFT‐TB] or T‐SPOT. TB ) at a major cancer center in the United States from June 2010 to July 2017. The results were analyzed with respect to the likelihood of latent TB infection and TB disease. Results: A total of 1299 patients were included with 1599 tests performed: 586 QFT‐TB and 1013 T‐SPOT. TB . Forty‐nine (4%) patients were diagnosed with latent TB, and four (1%) with TB disease. T‐SPOT. TB was more likely to yield an actionable result (positive or negative) than QFT‐TB (89% vs. 65%, p < 0.001). The rate of indeterminate results for QFT‐TB was higher than the rate of invalid results for T‐SPOT. TB (35% and 10%, respectively, p < 0.001). On multivariate analysis, independent predictors of an invalid T‐SPOT. TB included prior receipt of alemtuzumab, lower hemoglobin, absolute lymphocyte count, or serum albumin ( p < 0.05 each), whereas the independent predictors of an indeterminate QFT‐TB were female gender, prior receipt of systemic corticosteroids, and lower hemoglobin, or serum albumin or higher absolute neutrophil count ( p < 0.05 each). Conclusions: T‐SPOT. TB yielded more actionable results than QFT‐TB in patients with cancer. T‐SPOT. TB might be a better IGRA for screening for latent TB infection in patients with cancer, although a direct comparison would be needed to definitively determine this. image

Patients undergoing immune effector cell therapy (IECT) are at high risk for infections. We assessed seropositivity against pneumococcus, tetanus, and diphtheria in patients before and after IECT and the patients’ response to vaccination. We enrolled patients who underwent IECT from January 2020 to March 2022. Antibody levels for diphtheria, tetanus, and pneumococcus were measured before IECT, at 1 month, and 3–6 months after. Eligible patients were vaccinated after IECT. In non-seroprotected patients, we discontinued testing. Before IECT, most patients had seroprotective antibody levels against tetanus (68/69, 99%) and diphtheria (65/69, 94%), but fewer did against pneumococcus (24/67, 36%). After IECT, all patients had seroprotective antibody levels for tetanus at 1 month (68/68) and 3–6 months (56/56). For diphtheria, 65/65 patients (100%) had seroprotective antibody levels at 1 month, and 48/53 (91%) did at 3–6 months. For pneumococcus, seroprotective antibody levels were identified in 91% (21/23) of patients at 1 month and 79% (15/19) at 3–6 months following IECT. Fifteen patients received a pneumococcal vaccine after IECT, but none achieved seroprotective response. One patient received the tetanus-diphtheria vaccine and had a seroprotective antibody response. Because some patients experience loss of immunity after IECT, studies evaluating vaccination strategies post-IECT are needed.

Vancomycin-resistant enterococci (VRE) commonly colonize the gut of individuals with hematologic malignancies or undergoing hematopoietic cell transplant (HCT) and may cause bacteremia. In 2012, we identified VRE isolates from patients and patients’ rooms and showed transmission networks of highly genetically related daptomycin-resistant (DR)-VRE strains. This is a follow-up study performing whole-genome sequencing (WGS) and phylogenetic analyses on 82 clinical VRE strains isolated from stools and blood cultures of patients with leukemia and HCT between 2015 and 2019. Here, we observed transmission of highly genetically related strains between rooms on the same or on different floors, including a DR-VRE strain identified in 2012. Eleven of twenty-eight patients with DR-VRE were never exposed to daptomycin, suggesting horizontal transmission. Fifteen of the twenty-eight patients with DR-VRE died within 30 days of positive blood cultures. Amongst those, one DR-VRE strain belonging to ST1471 had the virulence gene bopD responsible for biofilm formation. Additionally, to our knowledge, this is the first report of a DR-VRE strain belonging to ST323 in the United States. In summary, our study demonstrated the emergence and persistence of VRE strains, especially DR-VRE, in our hospital. Adding WGS to routine infection control measures may timely identify potential horizontal VRE transmission including multi-drug-resistant isolates.

Testing for antibody against hepatitis C virus (anti-HCV) is a low-cost diagnostic method worldwide; however, an optimal screening test for HCV in patients with cancer has not been established. We sought to identify an appropriate screening test for HCV infection in patients with hematologic malignancies and/or hematopoietic cell transplants (HCT). Patients in our center were simultaneously screened using serological (anti-HCV) and molecular (HCV RNA) assays (February 2019–November 2019). In total, 214 patients were enrolled in this study. Three patients (1.4%) were positive for anti-HCV, and 2 (0.9%) were positive for HCV RNA. The overall percentage agreement was 99.5% (95% CI: 97.4–99.9). There were no cases of seronegative HCV virus infection. The positive percentage agreement was 66.7% (95% CI: 20.8–93.9), and the negative percentage agreement was 100.0% (95% CI: 98.2–100.0). Cohen kappa coefficient was 0.80 (95% CI: 0.41–1.00, P < .0001). The diagnostic yield of screening for chronic HCV infection in patients with cancer is similar for serologic and molecular testing.

Phages are naturally occurring viruses that selectively kill bacterial species without disturbing the individual’s normal flora, averting the collateral damage of antimicrobial usage. The safety and the effectiveness of phages have been mainly confirmed in the food industry as well as in animal models. In this study, we report on the successful isolation of phages specific to Vancomycin-resistant Enterococci, including Enterococcus faecium (VREfm) and Enterococcus faecalis from sewage samples, and demonstrate their efficacy and safety for VREfm infection in the greater wax moth Galleria mellonella model. No virulence-associated genes, antibiotic resistance genes or integrases were detected in the phages’ genomes, rendering them safe to be used in an in vivo model. Phages may be considered as potential agents for therapy for bacterial infections secondary to multidrug-resistant organisms such as VREfm.

Infectious complications in cancer patients (pts) who have received T-cell therapies are similar to those in autologous hematopoietic stem cell transplant (HCT) recipients, who - because they lose prior acquired immunity after undergoing conditioning regimens and transplantation- may be at an increased risk for vaccine-preventable infections. We sought to determine seroprotection rates against pneumococcus and tetanus-diphtheria before and after cellular therapies. In this ongoing prospective observational cohort study, we enrolled pts with any type of cancer who received cellular therapy with chimeric antigen receptor modified T cell (CAR-T), natural killer CAR-T, or T-cell receptor- directed immunotherapies at MD Anderson Cancer Center from January 2020 through May 2021. We performed antibody assays for diphtheria, tetanus, and pneumococcus before, at 1 month, and between 3-6 months after T-cell therapy for each pt regardless of vaccination history. Of 38 pts enrolled, 27 (71%) were men and 25 (66%) had non-Hodgkin lymphoma (Table 1); 38 (100%) and 17 (45%) had a history of previous diphtheria-tetanus-acellular pertussis (Tdap) and pneumococcal vaccination, respectively (Table 2). Tetanus serologies were positive for all pts tested before, at 1 month and 3-6 months after T cell therapy (37/37 [100%], 22/22 [100%], and 13/13 [100%], respectively). Diphtheria serologies were positive for most pts tested before, at 1 month and 3-6 months after therapy (35/37 [95%], 20/22 [91%], and 11/13 [85%], respectively]. Pneumococcal serologies were positive for 8 out of 37 [22%] pts before therapy, among these 8 pts, 4 had positive serologies 1 month after therapy, and 2 of 3 tested 3-6 months after therapy had positive serologies. One pt received a pneumococcal vaccine 10 months after therapy but had negative serologies post-vaccination. Most pts who received T-cell therapy retained their immunity for diphtheria and tetanus, but most also lost their immunity for pneumococcus. This suggests that the standard of care for pts receiving T-cell therapy should include more robust strategy for pneumococcal vaccination, but its timing, need for booster dosing, and antibody response needs to be determined in future trials. Roy F. Chemaly, MD, MPH, FACP, FIDSA, AiCuris (Grant/Research Support)Ansun Biopharma (Consultant, Grant/Research Support)Chimerix (Consultant, Grant/Research Support)Clinigen (Consultant)Genentech (Consultant, Grant/Research Support)Janssen (Consultant, Grant/Research Support)Karius (Grant/Research Support)Merck (Consultant, Grant/Research Support)Molecular Partners (Consultant, Advisor or Review Panel member)Novartis (Grant/Research Support)Oxford Immunotec (Consultant, Grant/Research Support)Partner Therapeutics (Consultant)Pulmotec (Consultant, Grant/Research Support)Shire/Takeda (Consultant, Grant/Research Support)Viracor (Grant/Research Support)Xenex (Grant/Research Support) Fareed Khawaja, MBBS, Eurofins Viracor (Research Grant or Support) Ella Ariza Heredia, MD, Merck (Grant/Research Support)

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Hepatitis B virus (HBV) reactivation had been reported following radiotherapy in patients with hepatocellular carcinoma (HCC) along with limited data focused on patients infected with hepatitis C virus (HCV). Herein, we aimed to examine the virologic impact of radiotherapy in HCV-infected patients with HCC. In this case-control study, we identified all patients with unresectable HCC who received radiotherapy directed to the liver at MD Anderson from March 2009 through November 2018. Cases were defined as patients with HCV infection; controls were defined as patients without HCV infection. The case to control ratio was 1:3, and the subjects were matched by age, radiation dose, and fractionation or biologically effective dose of the radiation to the normal liver (α/β=2.5) and tumor (α/β=10). Thirty-two patients were studied, including 8 cases and 24 controls. No HCV reactivation was observed among the cases. Hepatitis flare was observed in 2 (25%) of 8 cases and 2 (8%) of 24 controls (p=0.25). The peak alanine aminotransferase level within 6 months after radiotherapy did not differ significantly between the cases and controls. Radiotherapy completion rates were similar in the two groups. This is the first report analyzing changes in HCV RNA levels after radiation for HCV-associated HCC. Our results suggest that the effects of radiotherapy on the liver function of HCV-infected patients with HCC do not differ from the HCV-uninfected patients. Therefore, it may not be necessary to monitor for HCV replication in HCV-infected patients receiving radiotherapy for HCC or to incorporate a biological variable based on HCV infection status in mathematical models of liver dose-volume constraints that predict radiation-induced liver disease.