bluuebunny/crossref_metadata_2025_split huggingface dataset:
1098. Norovirus Infection in Cancer Patients Undergoing Chimeric Antigen Receptor T-cell Immunotherapy (CAR-T)
Authors: Kondapi Divya S , Ramani Sasirekha , Olvera Adilene , Atmar Robert L , Estes Mary K , Okhuysen Pablo C 
Published: January 2021

Abstract

Background
CAR-T is used to treat certain refractory hematological malignancies. B-cell aplasia and immunosuppression used to treat CAR-T side effects increase infection risk. Little data are available describing Norovirus (NoV) infections in CAR-T recipients.

Methods
We reviewed the medical records of 134 patients with NoV diarrhea (identified by nucleic acid amplification test) between 2016-2019. Of these patients, nine received CAR-T prior to developing NoV. Here we describe their demographics, clinical characteristics, treatments, and complications.

Results
The median age was 49 years (Table 1). Patients’ underlying malignancies included Non-Hodgkin’s Lymphoma (4), Acute Lymphoblastic Leukemia (3), Chronic Lymphocytic Leukemia (1) and metastatic Sarcoma (1). Prior to development of NoV, six patients had undergone hematopoietic stem cell transplant, and 1 had received checkpoint inhibitor therapy. Five patients experienced cytokine release syndrome after CAR-T, and 1 experienced CAR-T-related encephalopathy syndrome (Table 2). Two patients received interleukin-6 antagonist therapy, and one received high dose steroids. Time to diarrhea onset post-CAR-T cell infusion was variable(median 256days, IQR 26-523 days).Six had an absolute lymphocyte count&lt; 1000/mm3 at diarrhea onset. Three had diarrhea for &gt;14 days; median diarrhea duration in the other 6 patients was 4 days. Other GI complaints included abdominal pain (3), nausea (4), and vomiting (3). For NoV treatment, three received oral immunoglobulin, and 8 received Nitazoxanide. Complications included development of concomitant GI-GVHD(5), ileus (2), need for TPN (3), renal failure requiring dialysis (2), ICU stay (3), and death (2). Two patients were co-infected with other enteropathogens such as rotavirus, enteropathogenic and enteroaggregative E.Coli and Clostridioides difficile. Three patients with diarrhea lasting &gt;14 days had serial samples collected over time; NoV shedding lasted 81-546 days. NoV was genotyped in 6 patients(Table 3) and included GII.2(2), GII.4(2), GII.6(1) and GII.12(1).
Table 1: Patient characteristics (N=9)

Table 2: CAR-T related factors

Table 3: NoV Genotypes

Conclusion
NoV belonging to various genotypes is an important cause of acute and chronic diarrhea in patients receiving CAR-T cell therapy.

Disclosures
Adilene Olvera, MPH MLS (ASCP), MERK (Grant/Research Support, Scientific Research Study Investigator) Robert L. Atmar, MD, Takeda Vaccines, Inc. (Grant/Research Support) Mary K. Estes, PhD, Takeda Vaccines (Consultant, Grant/Research Support)
1101. Pulmonary Aspergillosis Complicating Non-Influenza Respiratory Virus Infections Among Solid Organ Transplant Recipients
Authors: Apostolopoulou Anna , Clancy Cornelius J , Viehman J Alex , Nguyen Minh Hong T 
Published: January 2021

Abstract

Background
Invasive pulmonary aspergillosis (IPA) complicating influenza (flu) has been increasingly recognized. We have shown that IPA occurred in 22% of solid organ transplant (SOT) patients (pts) with flu. Associations between IPA and non-flu respiratory infections (non-flu-RVI) in SOT are unknown.

Methods
Retrospective review of consecutive pts transplanted from Jan 15, 2010-Dec 19, 2017. Pts who died within 100 days of SOT were excluded. Non-flu-RVI IFI was defined according to revised EORTC/MSG criteria. IFI had to occur within 100 days of non-flu-RVI. Colonization (COL) was defined as recovery of mold from airways in absence of IFI.

Results
3,077 pts were included. 256 cases of non-flu-RVI were identified in lung (28%), multi-organ (16%), heart (6%), liver (1.3%) and kidney (1%) SOT pts. Parainfluenza (PIV) was most common (44%), followed by Respiratory Syncytial Virus (RSV, 60%) and Adenovirus (ADV, 15%). Median time to non-flu-RVI infections was 18.1 mos. 24% of pts with non-flu-RVI had lower tract disease. ADV was associated with longer hospital stay (median 14.5 days) than PIV (6.5 days) or RSV (6 days) (p=0.004). 59% of pts with non-flu-RVI required admission, and 64% received augmented steroids. Aspergillus was recovered from respiratory culture in 17% of non-flu-RVI pts. No other fungi were identified. Median time from non-flu-RVI to + culture was 29 days (Figure). 23% of pts with + culture had proven (7) or probable IPA (3), respectively; 77% had COL. 8% (3/37), 5% (6/114) and 7% (1/15) of pts with ADV, PIV, RSV infections developed IPA, respectively. 36% of pts were treated with a mold-active azole after + culture. Multivariate analysis identified lung transplant (p=0.02), PIV infection (p=0.02) and cumulative steroid dose in preceding 7 days (p=0.015) as independent risk factors for Aspergillus culture positivity. Cumulative steroid dose in preceding 7 days was an independent risk factor for IPA (p=0.03).
Cumulative incidence of Aspergillus infections within 100 days of non-flu RVI

Conclusion
IPA and COL occurred in 4% and 13% of non-flu-RVI in SOT recipients. Routine antifungal prophylaxis is not recommended for SOT pts with non-flu-RVI. The value of prophylaxis at time of PIV infection for lung transplant pts with recent steroid augmentation should be studied.

Disclosures
Cornelius J. Clancy, MD, Astellas (Consultant, Grant/Research Support)Cidara (Consultant, Research Grant or Support)Melinta (Grant/Research Support)Merck (Consultant, Grant/Research Support)Needham Associates (Consultant)Qpex (Consultant)Scynexis (Consultant)Shionogi (Consultant)
1102. Reconstitution of CMV-specific cell-mediated immunity during letermovir prophylaxis in hematopoietic stem cell recipients
Authors: Abidi Maheen , Gutman Jonathan , Weinberg Adriana 
Published: January 2021

Abstract

Background
Patients who are cytomegalovirus (CMV) seropositive (R+) prior to hematopoietic cell transplant (HCT), have 30% incidence of clinically significant CMV reactivation in the absence of prophylaxis. At our institution, letermovir prophylaxis through Day 100 is used in CMV R+ high-risk (HR) (cord blood, haplocord, haploidentical) HCT recipients. We hypothesized that clinically nonsignificant CMV reactivation during letermovir prophylaxis may lead to reconstitution of CMV specific cell mediated immunity (CMV CMI), which may protect the host against CMV disease after letermovir discontinuation.

Methods
Blood samples from CMV R+ HR HCT recipients on letermovir were tested by dual color CMV specific IL2/IFNg FLUOROSpot pre-transplant and on Days 100, 182 and 360 post-transplant. Clinical and virologic information were obtained from medical records.

Results
Among 35 participants enrolled to date, 19 were eligible for this analysis, which included only participants with CMV CMI defined as ≥20 spot-forming cells/106 PBMC pre-transplantation and follow up ≥180 post-transplantation. Median age was 51.5 years (range 22-75), 9 were women, 9 were white non-Hispanic, 8 were Hispanic and the most common underlying malignancy was acute myeloid leukemia (n=10). 14 participants had CMV CMI reconstitution at Day 100; including 5 with and 9 without low level CMV DNAemia, defined as &lt;5000 international units/ml in whole blood quantitative polymerase chain reaction assay, while on letermovir prophylaxis. Among the 14 participants, 11 remained free of clinically significant CMV reactivation for a median (range) of 260 (80; 260) days post-letermovir discontinuation, while 3 developed acute graft vs. host disease (aGvHD) followed by clinically significant CMV reactivation. 5 participants did not reconstitute CMV CMI at Day 100 and none of them had DNAemia while on letermovir. 1 of 5 participants without CMV CMI reconstitution or aGvHD developed CMV disease after letermovir discontinuation.

Conclusion
High-risk patient populations can reconstitute CMV CMI while on letermovir. Ongoing investigation will help establish predictive parameters for CMV CMI that may allow risk stratification for CMV monitoring and letermovir usage.

Disclosures
Maheen Abidi, MD, Merck (Research Grant or Support) Jonathan Gutman, MD, Merck (Research Grant or Support) Adriana Weinberg, MD, GSK (Grant/Research Support)merck (Grant/Research Support)
1105. The Burden of Infections Prior to Chimeric Antigen Receptor (CAR) Modified T-cell Therapy Predicts Post-CAR T-cell Infectious Complications
Authors: Garner Will , Samanta Palash , Dorritie Kathleen , Sehgal Alison , Winfield Denise , Agha Mounzer , Boudreau Robert , Nguyen Minh Hong T , Haidar Ghady 
Published: January 2021

Abstract

Background
CAR T -cell therapy (CTT) is a novel treatment for B-cell cancers. CTT patients (pt) are at risk of infection due to neutropenia, cytokine release syndrome (CRS), and CAR T-cell related encephalopathy syndrome (CRES), which are treated with steroids and tocilizumab (anti-IL-6). This is a single-center study evaluating the risk factors for infection after CTT.

Methods
A retrospective review was conducted of 60 consecutive CTT recipients between 7/17/17 and 9/5/19. Data was collected from 6 months (mo) pre- and at least 6 mo post-CTT. Data was censored for death, additional chemotherapy, or loss to follow up. Cox proportional hazard and Poisson regression were used.

Results
Median age was 66 (23-84) years; 48% (29) were female. The most common cancer was non-Hodgkin lymphoma (89%, 54). 25% (15) had a prior stem cell transplant (SCT). 73% (44) and 45% (27) of pts developed CRS and CRES, respectively. 43% (26) received steroids; 65% (39) received tocilizumab. In the 6 mo pre-CTT, 39 infections occurred in 45% (27) of pts. 103 infections occurred in 66% (40) after CTT; 33 (55%) had an infection within 6 mo. Infections were bacterial (52%; 54/103), viral (30%; 37/103), fungal (10%; 10/103), mycobacterial (1%; 1/103), protozoal (1%; 1/103). Cumulative incidence of infection in the first 6 mo are shown in Fig 1. All-cause and infection-related mortality were 32% (19) and 15% (9), respectively. Mortality among pts with fungal infections was 20% (2/10). Infection density was 1.28 and 0.58 infections per 100 pt-days between days 0-30 and 30-89, respectively. Factors associated with infection post CTT were number (no.) of infections in the 6 mo prior to infusion (HR 1.62, CI [1.1-2.38]; p=0.015), no. of lines of therapy in the 6 mo pre-CTT (HR 1.52, CI [1.01-2.27]; p=0.04), prior allogeneic SCT (HR 5.96, CI [1.34-26.47]; p=0.019), and no. of tocilizumab doses. Grade 1 CRS and grade 2 CRES were risk factors between days 0-30 and 0-180, respectively (HR 4.67, CI [1.02 -21.4], p = 0.047; HR 2.48, CI [1.17-5.23], p = 0.02).
Fig 1: Cumulative Incidence of Infection 6 Months Post CAR T-cell Therapy

Conclusion
Infections after CTT are common. Infection before CTT was associated with risk of infection after CTT. Pt selection may ameliorate this risk. Mortality due to fungal infections was high. Randomized-controlled trials of antifungal prophylaxis in high-risk pts are needed.

Disclosures
All Authors: No reported disclosures
1106. The incidence and risk factors associated with varicella zoster virus infection in kidney transplant recipients after 1-month acyclovir prophylaxis in a CMV preemptive therapy era
Authors: Kim Haein , jung Joo hee , Jung Jiwon , Kim Min Jae , Kim Hyosang , Shin Sung , Chong Yong Pil , Kim Young-Hoon , Lee Sang-Oh , Choi Sang-Ho , Kim Yang Soo , Woo Jun Hee , Park Su-Kil , Han Duck Jong , Kim Sung-Han 
Published: January 2021

Abstract

Background
Varicella zoster virus (VZV) infection is a well-known opportunistic infection in solid organ transplant recipients. Since the various strategies of the use of anti-herpetic drugs including ganciclovir or acyclovir have evolved, the epidemiology of VZV infection is changing. However, there are limited data on the recent incidence and risk factors of post-transplant VZV infection in popular preemptive ganciclovir era for CMV infection. We evaluated the incidence, risk factors and clinical characteristic of patients with development of post-transplant VZV infection in kidney transplant (KT) recipients after 1-month acyclovir prophylaxis in the hospital that adopted preemptive ganciclovir therapy for CMV infection.

Methods
All adult patients with seropositive CMV antibody admitted to a KT unit from January 2014 to December 2017 were retrospectively reviewed in a tertiary-care hospital in South Korea. Our hospital adopted preemptive ganciclovir therapy for CMV infection in all CMV seropositive KT recipients. We administered acyclovir prophylaxis for 1-month to CMV seropositive KT recipients. The primary endpoint was VZV infection development after KT.

Results
A total of 1295 KT recipients was followed up for 4295.8 person-years. The median follow-up period was 46.6 months (interquartile range (IQR) 34.3-59.5). Of the 1295 recipients, 100 (7.7%, 2.33 per 100 person-years, 95% confidence interval (CI) 1.89-2.83) patients developed VZV infection after KT. The median time for VZV infection development was 9.5 months (IQR 4.7-22.1). All patients had VZV-associated skin lesion, 9 postherpetic neuralgia, 2 visceral involvement and 3 disseminated infection. Of 100 patients, 16 patients need hospitalization due to VZV infection. In multivariate analysis, deceased donor KT (Hazard ratio (HR) 1.6; 95% CI 1.0-2.39, p = 0.05), mycophenolate maintenance immunosuppressive therapy (HR 0.3; 95% CI 0.14-0.75, p = 0.01) and rejection episode (HR 0.31; 95% CI 0.14-0.71, p = 0.01) were independently associated with VZV infection development after KT.

Conclusion
About one tenth of CMV seropositive KT recipients developed zoster after 1-month ACV prophylaxis during CMV preemptive strategy, especially in those who received deceased donor KT, mycophenolate therapy, and rejection episodes.

Disclosures
All Authors: No reported disclosures
1108. Transplantation and Immigration: Comparing Infectious Complications Between Foreign-born vs. U.S.-born Kidney Transplant Recipients in Minnesota
Authors: Espinoza Eloy E Ordaya , Shaughnessy Megan , Walker Patricia F , Husmann Rachel , Hale Gabriel , Stauffer Jacob , Stauffer William 
Published: January 2021

Abstract

Background
Immigrant patients face barriers to kidney transplantation due to language, cultural, and economic issues. Unprepared health systems and providers further contribute to health disparities in transplantation. Foreign-born patients are also at risk for reactivation of latent infections which differ from U.S.-born population. Stratifying transplant recipients according to country of birth could guide clinicians in the prevention, anticipation, diagnostics, and treatment of post-transplant infections.

Methods
A retrospective, observational, multicenter study of patients that underwent kidney transplantation from 1/2014-12/2018 at the University of Minnesota Medical Center and Hennepin Healthcare is being conducted. Sociodemographic, clinical, and laboratory data are collected, including infectious episodes during the first year post-transplant.

Results
One-hundred patients are included in this preliminary analysis (recruitment goal is 800 patients). Sixty-five patients were males (65%), with median age 56 years (range 20 – 77). The majority were Caucasians (64%), followed by Asians (12%) and Africans (9%). Living donation was 59%. Seventy-eight patients developed infectious complications during the first year after transplantation, for a total of 175 infectious episodes: viral etiology (51%), followed by bacterial (42%) and fungal (7%). No tropical diseases were found. Comparing foreign-born (30%) vs. U.S.-born (70%), foreign-born recipients had a higher frequency of latent tuberculosis infection (LTBI) (37% vs 1%, p&lt; 0.001), hepatitis B core antibody positive (20% vs 0, p&lt; 0.001), and deceased donor transplant (67% vs 30%, p= 0.001). CMV mismatch (3% vs 36%, p= 0.002) was more frequent in U.S.-born recipients; CMV reactivation was similar in both groups. While not statistically significant, more foreign-born recipients had an infection in the first year post-transplant (90% vs 73%, p= 0.1), and higher median infectious episodes (2 vs 1, p= 0.6).
Comparison of foreign-born vs U.S.-born kidney transplant recipients (n=100, preliminary data)

Conclusion
Per this preliminary data, foreign-born transplant recipients had a higher frequency of LTBI, hepatitis B core antibody and infectious complications, but lower frequency of CMV mismatch. No cases of tuberculosis, hepatitis B reactivation or tropical diseases were observed.

Disclosures
Patricia F. Walker, MD, DTM&H, FASTMH, UpToDate (Other Financial or Material Support, Royalties from UpToDate for chapter on refugee screening)
1109. Valgancyclovir Dosing for Cytomegalovirus Prophylaxis in Heart Transplant Recipients
Authors: Huang Glen , Davis Matthew R , Beaird Omer E , Carlson Margrit , Gaynor Pryce , Multani Ashrit , Deng Mario , Nsair Ali , Schaenman Joanna M 
Published: January 2021

Abstract

Background
Cytomegalovirus (CMV) is one of the most common infections after transplantation and continues to cause significant morbidity and mortality. Current guidelines recommend 3-6 months of post-transplant prophylaxis with 900mg daily of valganciclovir in heart transplant recipients. At our institution, however, the protocol is to use 450mg daily of valganciclovir for 6-12 months for intermediate risk (R+) patients and 900 mg daily for high risk (D+/R-) patients. In this study we aimed to identify underlying patient characteristics associated with detectable viral load above the quantifiable threshold.
Table 1. Comparison of patients with a CMV viral above and below 137.

Methods
We retrospectively reviewed medical records of adult (≥ 18 years) heart transplant recipients with detectable CMV viremia from 2016-2018 resulted during routine clinical screening.

Results
Ninety-seven heart transplant recipients with a detectable CMV viral load were identified. Of those, 38 (37.2%) had a quantifiable viral load above the 137 IU/mL threshold. When compared to the individuals with a detectable viral load below the threshold (&lt; 137 IU/mL), they had similar age at time of transplant, increased likelihood of donor/recipient CMV IgG mismatch, and were more frequently on 900mg daily of prophylaxis at time of viremia. Of the individuals with CMV DNAemia above the threshold, the median time to viremia was 271.4 days and the median peak viral load was 701 IU/mL. When limiting analysis to only recipients who were CMV IgG positive, patients with viremia had similar age and more likely to be on 900mg daily of valganciclovir as prophylaxis when compared to individuals with CMV viremia &lt; 137 IU/mL. When comparing CMV D+/R- patients, age and rates of 900mg valganciclovir as prophylaxis were similar (Table 1).

Conclusion
We found that despite receipt of CMV prophylaxis, an appreciable number of both R+ and D-/R+ heart transplant recipients developed breakthrough DNAemia despite being on prophylaxis of valganciclovir as recommended by guidelines. Despite receipt of the higher 900 mg daily dose, high risk patients had higher rates of breakthrough DNAemia at our institution compared with R+ intermediate risk patients. More research is needed to evaluate the optimal dose and duration for prophylaxis in heart transplant patients against CMV.

Disclosures
All Authors: No reported disclosures
1110. Very Late Onset Infections Amongst Long Term Survivors of Kidney Transplantation
Authors: Cheung Harry , Azar Marwan M , Gan Geliang , Deng Yanhong , Cohen Elizabeth A , Kulkarni Sanjay , Malinis Maricar F 
Published: January 2021

Abstract

Background
Kidney transplant recipients (KTR) are at increased risk for infections immediately post-transplant due to intense immunosuppression. However, this risk decreases over time as immunosuppression is tapered. The incidence of infection in KTR many years after transplant is not well characterized. The aim of this study was to describe these “very-late onset infections” (VLIs) ≥ 10 years after KT.

Methods
We performed a retrospective chart review of patients age ≥ 18 years who underwent KT between 2003 and 2009 and who survived ≥ 10 years post-KT. VLIs included opportunistic infections (OIs) and non-OIs. Demographics, comorbidities, immunosuppression, and clinical data for VLIs ≥ 10 years from KT were collected. Simple logistic regression was performed to determine characteristics associated with risk for VLIs.

Results
Of 332 KTR that met the inclusion criteria, the majority were male (62.0%), white (59.6%), and the largest proportion was transplanted between the ages of 50-59 (28.3%); 220 (67.9%) were on mycophenolate-based regimens. The mean Charlson Comorbidity Index (CCI) was 4.7 (S.D. 2.0). Of 332, 103 (31.0%) KTR experienced ≥ 1 VLI amounting to 187 episodes. Compared to those without VLI, KTR with VLI were more likely to have diabetes (p=0.005), cardiovascular disease (p=0.004), low ALC (p &lt; 0.001) and require dialysis (p=0.002). Of 103 KTR with VLI, 16 (15.5%) had OIs, while 87 KTR (84.5%) had non-OIs, most commonly urinary tract infection (n=85, 45.5%), pneumonia (n=35, 18.7%) and gastrointestinal infection (n=18, 9.6%). The most commonly isolated pathogens were E. coli (n=30, 16%), K. pneumoniae (n=16, 8.6%), MSSA (n=7, 3.7%), and P. aeruginosa (n=7, 3.7%). Higher CCI, diabetes, dialysis, cerebrovascular, cardiovascular disease and lower ALC were associated with increased risk for VLI (p &lt; 0.05), while living donor KTR was protective (p=0.04). Additionally, every 1 year after transplant was associated with an increased risk of VLI (OR=1.31, p &lt; 0.001).
Table 1: Demographics, comorbidities, immunosuppression, and clinical data for all patients

Conclusion
VLIs were common in long-term survivors of KT and included both conventional and opportunistic pathogens. Every additional year from transplant incurred additional risk for VLI, particularly for those with multiple co-morbidities and lower ALC.

Disclosures
All Authors: No reported disclosures