Natori, Yoichiro

Abstract Background RSV is a common respiratory infection that causes significant morbidity in SOTR. However, risk factors for complications such as hypoxic respiratory failure, mechanical ventilation, and secondary infections have not been well described. Methods This retrospective, international, multicenter cohort study is actively recruiting SOTR hospitalized with RSV. Here, we analyzed data from Mayo Clinic (Rochester, Florida, Arizona), Miami Transplant Institute, Cleveland Clinic, and Royal Melbourne Hospital between 2016 and 2019. Secondary infection was defined as culture positive infection within 90 days of RSV diagnosis. Whenever appropriate, logistic and Cox regression analysis were conducted to identify risk factors. Survival functions were estimated using the Kaplan-Meier method.Figure 1:Forest plots of multivariable logistic regression models for risk factors for A) hypoxia, B) secondary infections, C) mechanical ventilation. Note: all variables included are the ones statistically significant on univariate analysis. Abbreviations: CI, confidence interval; OR, Odds ratio; LRTI: lower respiratory tract infection. Results 233 SOTRs (58.8% male; median, 61 years), including 77 (49.1%) kidney, 23 (9.9%) liver, 79 (33.9%) lung, and 38 (16.3%) heart transplants (Table). Hypoxic respiratory failure, mechanical ventilation, and secondary infection were seen in 98 (42.1%), 23 (9.9%), and 58 (24.9%) patients, respectively. After multivariate analysis, age >60 years, symptoms and imaging evidence of lower respiratory tract infection (LRTI) were associated with oxygen requirement (Figure 1A); similar results were observed in an analysis of the lung transplant cohort only. Risk factors on multivariate analysis for secondary infection include a history of rejection within six months and mechanical ventilation (Figure 1B). Risk factors for mechanical ventilation included age >60 years and LRTI on imaging (Figure 1C) after multivariate analysis. Seventeen (7.3%) patients died within 90 days of diagnosis. Cox univariate analysis identified age >60 years and LRTI on imaging, secondary infections, mechanical ventilation and hypoxia on admission were associated with higher mortality (Figure 2 and 3).Figure 2:Forest plot with Cox proportional hazards models. Note: only univariate results shown, multivariate not done due to low number of events. Conclusion This multicenter study of SOTR hospitalized with RSV identified older age ( >60 years old) as a risk factor for hypoxic respiratory failure, mechanical ventilation and death. Mechanical ventilation and a history if rejection within six months of RSV were associated with increased risk of secondary infections, identifying them as high-risk that needs close surveillance for this complication.Figure 3:Effects of A) Age older than 60 years old and B) mechanical ventilation on 90 day probability of survival after RSV infection Disclosures Michelle Yong, MBBS, FRACP, MPH, PhD, MSD: Grant/Research Support|MSD: Honoraria|Takeda: Advisor/Consultant Yoichiro Natori, MD, Eurofin/Viracor: Honoraria|Nobel Pharma: Advisor/Consultant

Abstract Cytomegalovirus (CMV) infection and disease are important causes of morbidity and mortality in transplant recipients. For the purpose of developing consistent reporting of CMV outcomes in clinical trials, definitions of CMV infection and disease were developed and most recently published in 2017. Since then, there have been major developments, including registration of new antiviral agents. Therefore, the Transplant Associated Virus Infections Forum, which consists of scientists, clinicians, regulators, and industry representatives, has produced an updated version of these definitions that incorporates recent knowledge with the aim of supporting clinical research and drug development. This also includes an update regarding the definition of resistant and refractory CMV infections previously published in 2019. As the field evolves, the need for updates of these definitions is clear, and collaborative efforts among clinicians, scientists, regulators, and industry representatives can provide a platform for this work.

AbstractBackgroundIsavuconazole (ISA) is a newer antifungal used in patients with history of hematologic malignancies and hematopoietic transplant and cellular therapies (HM/TCT). Although it has a more favorable side‐effect profile, breakthrough invasive fungal infections (bIFIs) while on ISA have been reported.MethodsIn this single‐center retrospective study evaluating HM/TCT patients who received prophylactic ISA for ≥7 days, we evaluated the incidence and potential risk factors for bIFIs.ResultsWe evaluated 106 patients who received prophylactic ISA. The patients were predominantly male (60.4%) with median age of 65 (range: 21–91) years. Acute myeloid leukemia (48/106, 45.3%) was the most common HM, with majority having relapsed and/or refractory disease (43/106, 40.6%) or receiving ongoing therapy (38/106, 35.8%).Nineteen patients (17.9%) developed bIFIs–nine proven [Fusarium (3), Candida (2), Mucorales plus Aspergillus (2), Mucorales (1), Colletotrichum (1)], four probable invasive pulmonary Aspergillus, and six possible infections. Twelve patients were neutropenic for a median of 28 (8–253) days prior to bIFI diagnosis. ISA levels checked within 7 days of bIFI diagnosis (median: 3.65 μg/mL) were comparable to industry‐sponsored clinical trials.All‐cause mortality among the bIFI cases was 47.4% (9/19).We also noted clinically significant cytomegalovirus co‐infection in 5.3% (1/19). On univariate analysis, there were no significant differences in baseline comorbidities and potential risk factors between the two groups.ConclusionISA prophylaxis was associated with a significant cumulative incidence of bIFIs. Despite the appealing side‐effect and drug‐interaction profile of ISA, clinicians must be vigilant about the potential risk for bIFIs. image

AbstractBackgroundData on severe acute respiratory distress syndrome coronavirus 2 monoclonal antibody (SARS‐CoV‐2‐specific mAb) use in hematologic malignancy and hematopoietic cell transplantation (HM/HCT) patients are limited. Here, we describe our experience with the use of casirivimab–imdevimab or bamlanivimab for the treatment of coronavirus disease 2019 (COVID‐19) in HM/HCT patients.MethodsThis was a retrospective chart review at the University of Miami Hospital and Sylvester Comprehensive Cancer Center for HM/HCT patients with COVID‐19 who received casirivimab–imdevimab or bamlanivimab from November 21, 2020, to September 30, 2021. Outcomes measured were mortality, hospital admission, and infusion reaction to SARS‐CoV‐2‐specific mAbs.ResultsWe identified 59 HM/HCT patients with mild to moderate COVID‐19 who received casirivimab–imdevimab or bamlanivimab. Median age was 57 years (interquartile range [IQR]: 45–65). Among the 59 patients, 25 (42%) received cellular therapy: 14 (24%) had undergone allogeneic HCT, nine (15%) autologous HCT, and two (3%) received chimeric antigen receptor T‐cell therapy. The median time from COVID‐19 symptom onset to SARS‐CoV‐2‐specific mAb administration was 4 (IQR: 3–6) days. Forty‐six (78%) patients received SARS‐CoV‐2‐specific mAbs as outpatients and 13 (22%) patients received SARS‐CoV‐2‐specific mAbs during hospitalization. Among patients who received SARS‐CoV‐2‐specific mAbs as outpatients, only four (9%) visited the emergency department at days 10, 11, 15, and 35 after SARS‐CoV‐2‐specific mAb administration. None of these four patients required hospital admission. Among the hospitalized patients, five (38%) were admitted to the hospital with neutropenic fever, four (31%) were already hospitalized for transplantation and cellular therapy, three (23%) were admitted for monitoring of COVID‐19 symptoms, and one (8%) was admitted with acute kidney injury. Three hospitalized patients (23%) died at 14, 35, and 59 days after SARS‐CoV‐2‐specific mAb administration; two of these three deaths were attributed to COVID‐19 infection. One patient developed an immediate infusion reaction to bamlanivimab, and no infusion reactions were reported to casirivimab–imdevimab use.ConclusionDuring the alpha and delta variant surges, early administration of bamlanivimab or casirivimab–imdevimab prevented hospitalization and death when given in the outpatient setting. Among patients who received mAbs at or after hospital admission, the risk of COVID‐19 disease progression and death remains significant. Larger studies of the use of mAb therapy to treat COVID‐19 in this population are needed. image