High Risk Of Reactivation Research Articles

Secretion of IFN-γ by specific T cells in HCMV infection

One major risk for recipients undergoing allogeneic hematopoietic stem cell transplants (allo-HSCTs) is infection with the human cytomegalovirus (HCMV). For HCMV treatment, it is especially crucial to be able to differentiate between recipients who are at high risk of reactivation and those who are not. In this study, HCMV-DNA was collected from 60 HLA-A*02 allo-HSCT recipients before and after transplantation. After transplantation, the release of interferon (IFN)-γ by T cells specific to HCMV was assessed using the enzyme-linked immunospot assay (ELISPOT). The results show that the median viral load (VL) was significantly higher in the HCMV persistent-infection group compared to the non-persistent-infection group (p = 0.002), and that the late-infection rate was considerably higher in the high-VL group compared to the low-VL group (p = 0.014). The uninfected group had a considerably higher median IFN-γ spot‐forming cell (SFC) count than the persistent-infection group (p = 0.001), and IFN-γ SFC counts correlated negatively and linearly with VLs (r = −0.397, p = 0.002). The immune-response groups showed significantly difference in median VL (p = 0.018), and the high immune response group had a reduced late-infection rate than the no/low immune response groups (p = 0.049). Our study showed that allo-HSCT recipients with a high VL at an early transplantation stage were at high risk for late HCMV infection. Further HCMV reactivation can be prevented by HCMV-specific T cells secreting enough IFN-γ.

B-036 Multi-Biomarker Approach to Latent Tuberculosis Diagnosis Using Microring Resonator Sensors

Abstract Background Tuberculosis (TB) is an infectious disease that induces a complex response from the host immune system. Most carriers of the bacteria experience the asymptomatic, non-infectious phase, latent tuberculosis infection (LTBI), but have the potential to reactivate to active, contagious TB infection. Current diagnostics for TB are not sufficient for LTBI and are focused on using one biomarker, interferon-gamma (IFN-g). To build better diagnostics for the complex disease, multi-biomarker approaches to profile the immune system, coupled with machine learning algorithms, are necessary to diagnose LTBI and determine patients' risks of reactivation to active TB. We aim to use a multiplexed silicon photonic microring resonator sensing platform to profile thirteen biomarkers in patients with LTBI infection and use machine learning data analysis to identify biomarkers relevant for diagnosing LTBI and predicting reactivation risk. Methods We employed microring resonators coupled with a sandwich-style detection format to simultaneously detect thirteen cytokines and chemokines in plasma in under 40 minutes. Chip-integrated silicon photonic microrings are small in size and easily multiplexed with up to sixteen different capture agents. Biomolecular binding events are measured by monitoring the resonant wavelength within the sensing cavity, which shifts as binding events occur. Quantitation of each biomarker is possible with calibration curves that correlate standard protein concentrations to wavelength shifts. The multiplexed assay has been optimized for each individual biomarker, tested for cross-reactivity, and calibrated in the plasma matrix of interest. The LODs vary, depending on biomarker and matrix dilution, but range from 4.9 pg/mL to 691 pg/mL. The patient plasma samples are left over from the TB screening IFN-g release assay, QuantiFERON-TB Gold Plus (QFT), putting this method within the current clinical workflow. We use precision normalization approaches from the four QFT stimulations to account for immunologic differences among the subjects. The biomarker concentrations are evaluated using a random forest machine learning model to identify which biomarkers are important for identifying patients with LTBI and predicting their reactivation risk. Results We used this sensor method to profile 42 patients, 24 LTBI negative controls and 18 LTBI positive controls, with 13 being considered at high risk of reactivation. Using a precision normalization approach, a combination of nine normalized conditions using five of the thirteen biomarkers (CCL4, CCL8, IP-10, IL-2, IL-17) discriminated between LTBI positive and negative subjects with a ROC AUC of 0.90. Additionally, eight normalized conditions using four of the same biomarkers discriminated between high and low-risk subjects with an AUC of 0.83. Currently, we have expanded the sample cohort to include an additional 72 subjects, 25 LTBI positive and 47 LTBI negative. Preliminary analysis shows CCL8, IL-2, and IP-10 alone are able to distinguish between LTBI status (P values <0.01) using raw target concentrations prior to precision normalization. Conclusion Overall, we show the importance of multi-biomarker approaches to develop diagnostic and prognostic tools for a complex disease, such as TB. Further work to use the initial machine learning algorithm with the expanded cohort to validate biomarker importance is underway.

Latent Toxoplasmosis among Breast Cancer Patients in Jahrom, South of Iran.

Reactivation of latent toxoplasmosis is the main cause of severe infection among immunocompromised patients, including patients with cancer. Hence, this study is aimed at screening the status of Toxoplasma gondii infection among breast cancer patients by serological and molecular methods and determining their associated risk factors in Jahrom County, Fars Province, south of Iran. One hundred and seven women with breast cancer (aged 34 to 80 years) were screened for anti-T. gondii antibodies (IgG and IgM) during 2019-2020. A questionnaire regarding demographic factors was filled out by participants. Molecular detection was performed by polymerase chain reaction (PCR) using the primer pair targeting the repetitive element (RE) gene of T. gondii. The risk factors and demographic data were analyzed by SPSS software (ver. 20, Chicago, IL, USA) using the Chi-squared test. Anti-T. gondii IgG was detected in 45.8% (49/107) of the patients, which indicates latent infection, but anti-T. gondii IgM and PCR were negative in all samples. Demographic factors revealed a statistically significant increased T. gondii seropositivity among nonmenopause cancer patients (P < 0.0005), patients without previous breast cancer (P = 0.0001), and human epidermal growth factor receptor 2- (HER2-) negative patients (P = 0.00002). As such, patients with a history of previous abortions and who were at stages II, III, and IIII of cancer had higher seropositivity rates than patients without a history of previous abortions or who were at stage I cancer, but the statistical analysis was not significant. We did not find a statistically significant association between T. gondii seropositivity and other risk factors of toxoplasmosis (e.g., education level, type of water source, washing raw fruits and vegetables, consumption of raw or undercooked meat, and contact with soil, cats, and domestic animal). A high seroprevalence rate of latent T. gondii infection was detected among patients with breast cancer; hence, these patients may be at high risk for reactivation of latent infection. Screening of T. gondii infection is recommended to detect active infection among patients with malignancies.

Effectiveness of Screening in Patients with Rheumatic Disease on Biological Therapy and Risk of Active Tuberculosis

Background: Treatment with biologic therapy has been associated with a high risk of reactivation of latent tuberculosis (TB). Aims and Objectives: The study aimed to access the effectiveness of TB screening recommendations before the initiation of biological therapy and identify the incidence of active TB among these patients. Materials and Methods: A hospital-based retrospective cohort study among rheumatic disease patients on biological therapy in two centers between January 2005 to December 2019 was performed. Data was collected through review of medical records. Results: A total of 365 patients were included over a period of 14 years. Majority had Rheumatoid arthritis (RA) (80%). The mean age was 47.54 (±14.2), 311 (85%) were females with a mean duration of disease 8.45 years (± 6.58). Hundred forty-nine (42.3%) were on steroids. Anti TNFs were prescribed in 213 (58.4%) patients, Non-Anti-TNFs 124 (36.6%) patients, and Jak inhibitors 18 (5%) patients. TB screening was done to all patients except 3 patients (data missing) before commencing biologics. Forty-four (12.1%) patients had latent TB at baseline and all received chemoprophylaxis with isoniazid before starting biologics. Four patients with active TB were identified (one with Behcet’s disease and three with RA). One patient had a reactivation of latent TB and 3 patients developed de novo TB. Two were on rituximab and one each on infliximab and adalimumab. Two cases had pulmonary TB and two others had extrapulmonary TB (pericarditis and brain abscess each). All four patients with active TB were treated with standard anti TB medications. Three had complete resolution of their TB and one died. Conculsion: Baseline screening has been effectively carried out in our cohort as per recommendations. Physicians should be vigilant for symptoms and signs of active TB as not only reactivation of latent TB can occur with patients on biologics but in addition de novo TB can occur specially in endemic areas. Funding: None

Craniofacial involvement in Langerhans cell histiocytosis: A review of 44 cases at a single medical center

BackgroundCraniofacial bones are the most commonly involved site of Langerhans cell histiocytosis (LCH). The main purpose of this study was to clarify the relation between subsites of craniofacial bone and clinical presentation, treatment modalities, outcomes, and permanent consequences (PCs) in patients with LCH. MethodsForty-four patients diagnosed with LCH involving the craniofacial region presenting at a single medical center during 2001–2019 were collected and divided into four groups: single system with unifocal bone lesion (SS-LCH, UFB); single system with multifocal bone lesions (SS-LCH, MFB); multisystem without risk organ involvement (MS-LCH, RO-); and multisystem with risk organ involvement (MS-LCH, RO+). Data including demographics, clinical presentation, treatments, outcomes, and the development of PC were retrospectively reviewed. ResultsTemporal bone (66.7% versus 7.7%, p = 0.001), occipital bone (44.4% versus 7.7%, p = 0.022), and sphenoid bone (33.3% versus 3.8%, p = 0.041) involvement were more common in SS-LCH, MFB than they were in SS-LCH, UFB. No difference of reactivation rate was noted among the four groups. The most common PC is diabetes insipidus (DI), reported in 9 of the 16 (56.25%) patients with PC. The single system group was reported with the lowest incidence of DI (7.7%, p = 0.035). The reactivation rate was also higher in patients with PC (33.3% versus 4.0%, p = 0.021) or DI (62.5% versus 3.1%, p < 0.001). ConclusionAn increased risk of multifocal or multisystem lesions was associated with temporal bone, occipital bone, sphenoid bone, maxillary bone, eye, ear, and oral involvement, which may indicate poor outcomes. Longer follow-up may be indicated if there is the presence of PC or DI due to the high risk of reactivation. Therefore, multidisciplinary evaluation and treatment according to risk stratification are vital for patients diagnosed with LCH involving the craniofacial region.

Prevalence and Impact of BK Polyomavirus in the Ureters of Kidney Donors: Research Letter.

More than 75% of the population is seropositive for BK polyomavirus (BKV), which remains quiescent in the urothelium in immunocompetent hosts. However, it can reactivate in kidney transplant recipients (KTRs), and up to 30% of them will develop BKV viremia in the 2 years following transplant, with a risk of developing BKV-associated nephropathy (BKVAN). Viral reactivation is associated with the level of immunosuppression, but there is currently no way to predict which patients are at high risk for reactivation. As BKV originates from kidney donors, our primary objective was to determine the prevalence of detectable BKV in donor ureters. Our secondary objective was to see if there is a correlation between the presence of BKV in donor urothelium and the development of BKV viremia and BKVAN in KTR. Prospective cohort study. Single-center academic kidney transplant program. Prospective sequential KTRs that received a kidney transplant between March 2016 and March 2017. The presence of BKV in donor ureters was determined by TaqMan-based quantitative polymerase chain reaction (PCR; qPCR). We performed a prospective study which was done on 35 out of the 100 donors initially foreseen to take part in the study. During surgery, the distal part of donor ureter was kept and analyzed by qPCR (to establish the presence of BKV in the urothelium). The primary outcome was the development of BKV viremia in KTR over a period of 2 years after transplant. Secondary outcome was the development of BKVAN. Out of 35 ureters analyzed, only one had a positive qPCR for BKV (2.86%, 95% confidence interval [CI]: [0.07-14.92]). Considering the primary objective would not be met, the study was interrupted after 35 specimens. After surgery, 9 recipients had a slow graft function and 4 had delayed graft function, one of which never recovered graft function. Over the 2-year follow-up, 13 patients developed BKV viremia, while 5 patients developed BKVAN. The patient who received a graft from a positive qPCR donor eventually developed BKV viremia and nephropathy. The specimen analyzed was a distal rather than a proximal portion of the ureter. However, BKV replication is known to concentrate in the corticomedullary junction. BK polyomavirus prevalence in the distal part of donor ureters is lower than previously reported. It cannot be used as a predictor for the development of BKV reactivation and/or nephropathy.

405: A CASE OF CMV POLYRADICULOMYELITIS IN AN IMMUNOCOMPETENT PATIENT

Introduction: Cytomegalovirus (CMV) is a common virus. It can reside latent after primary infection and be reactivated at any time. Reactivation is most common in immunocompromised patients, though it can still occur in immunocompetent patients, often in the ICU in the setting of critical illness and typically limited to pneumonia or viremia. Neurologic infections are less common and primarily in immunocompromised patients. The following case is a unique presentation of polyradiculomyelitis in an immunocompetent patient, caused by CMV reactivation. Description: A 77-year-old male with hypertension was admitted for dyspnea and encephalopathy and treated for pneumonia. Lumbar puncture and head MRI were unremarkable. After 17 days, he was transferred to our institution and required mechanical ventilation for respiratory failure due to mucus plugging. After extubation two days later, he was noted to have new bilateral lower extremity flaccid paralysis and bowel incontinence. MRI revealed transverse myelitis from T6 through the conus medullaris, neuritis of all lumbar nerve roots, and significant cord edema. Repeat lumbar puncture was remarkable for CSF pleocytosis and positive CMV. Serum IgG was also positive for CMV. Findings were felt to be inconsistent with alternative diagnoses, such as multiple sclerosis, neuromyelitis optica, acute inflammatory demyelinating polyneuropathy, or Guillain-Barre. Ganciclovir, foscarnet, and dexamethasone were initiated. Patient ultimately required re-intubation and tracheostomy for inability to clear secretions. There was no improvement in his neurologic status by time of discharge to a long-term acute care facility. Discussion: Neurologic manifestations (meningitis, encephalitis, etc.) from CMV are usually only seen in immunocompromised patients. CMV causing a polyradiculomyelitis (besides the ascending paralysis associated with Guillain-Barre) is rare, especially so in this patient with a normal immune status. This case is uniquely relevant to the intensivist. The patient developed symptoms weeks after admission, indicating that it was likely his critical illness that put him at high risk for reactivation of a latent infection. Additionally, diffuse transverse myelitis placed him at high risk for respiratory compromise and irreversible respiratory failure.

Prevention and management of human cytomegalovirus in pediatric HSCT recipients: A review.

Cytomegalovirus (CMV), like other herpesviruses, has the unique ability to establish latent infection with subsequent reactivation during periods of stress and immunosuppression. Herpesviruses cause potentially devastating disease, particularly in hematopoietic stem cell transplant (HSCT) recipients. CMV is especially of concern in HSCT recipients given the high community seroprevalence, high risk of reactivation and high risk of transmission from HSCT donors to recipients causing primary infection after transplantation. The risk of CMV infection and severity of CMV disease varies depending on the underlying disease of the HSCT recipient, donor and recipient CMV status prior to HSCT, type of conditioning therapy in preparation for HSCT, allogeneic versus autologous HSCT, donor graft source, timing of infection in relation to HSCT, and other patient comorbidities. Different strategies exist for prevention (e.g., preemptive therapy vs. universal prophylaxis) as well as management of CMV disease (e.g., antiviral therapy, augmenting immune reconstitution, cytotoxic T-cell therapy). The purpose of this narrative review is to discuss diagnosis, prevention, and management of CMV infection and disease at different stages of HSCT, including key points illustrated through presentations of complex cases and difficult clinical scenarios. Traditional and novel strategies for CMV management will be discussed in the context of these unique clinical cases.

REACTIVATION MILIARY TB IN THE SETTING OF POSTINFECTIOUS COVID-19 LUNGS

REACTIVATION MILIARY TB IN THE SETTING OF POSTINFECTIOUS COVID-19 LUNGS

A feasibility study evaluating the uptake, effectiveness and acceptability of routine screening of pregnant migrants for latent tuberculosis infection in antenatal care: a research protocol

IntroductionGlobally, tuberculosis (TB) is a leading cause of death in women of reproductive age and there is high risk of reactivation of latent tuberculosis infection (LTBI) in pregnancy. The uptake...

BIOTHERAPY DURING CHRONIC INFLAMMATORY BOWEL DISEASE: AN OVER-RISK OF TUBERCULOSIS REACTIVATION?

Anti-TNFα have revolutionized the management of chronic inflammatory rheumatic and intestinal diseases however, they are at high risk of reactivation of latent tuberculosis. These are most often extra-pulmonary tuberculosis and disseminated forms which occur during the first year and which can be avoided by screening and prophylactic treatment. The aim of this publication is to describe the epidemiological, clinical, biological, radiological and evolving data of patients having triggered tuberculosis under anti TNFα treatment followed at the Hassan II hospital center (CHU) in Fez during the period between January 2012 and January 2021. During this period, we collected 130 patients under anti TNF alpha of which 84.5% of patients are on Infliximab 15.5% on Adalimumab. Active tuberculosis occurred in 4.6% of patients whose mean age is 35.5 years and the sex ration is 5H / 1F. The duration of onset is on average after 5 sessions of anti TNF alpha. A phtysio assessment was carried out in all our patients before starting the anti TNF α, 2 of which were IDR positive completed by quantifying it which came back positive in a single patient.

Comparison of Interferon Gamma Release Assay and Tuberculin Skin Test for Diagnosis of Latent Tuberculosis in Psoriasis Patients Planned for Systemic Therapy.

Background:Latent tuberculosis infection (LTBI) is a common yet difficult problem to diagnose in tuberculosis endemic countries. Both tuberculin skin test (TST) and interferon-gamma release assay (IGRA) are used for the diagnosis of LTBI.Aims:The aim of the study is to compare TST and IGRA in patients planned for systemic treatment of psoriasis.Methods:It was a diagnostic study conducted in a tertiary care centre during the study period from January 20 to December 20. Patients more than 18 years of age with chronic plaque psoriasis planned for systemic therapy were included. Psoriasis area severity index (PASI), history of tuberculosis in past or family and BCG vaccination were recorded. Complete blood count, radiograph of the chest, tuberculin skin test and interferon-gamma release assay were performed in all patients. Statistical analysis was performed using statistical package for social sciences (SPSS version 20, Chicago).Results:A total of 75 patients, including 48 males and 27 females, were included in the study. The mean age and mean duration of disease were 46.08 (±12.16) and 4.59 (±3.8) years, respectively. Seventy-one (94.6%) patients had BCG scar, and two (2.6%) had a history of tuberculosis in a family member. The TST and IGRA were positive (>10 mm) in 23 (30.6%) and 16 (21.3%) patients, respectively. Either TST or IGRA was positive in 28 (37.3%) patients. Out of these 28 patients, concordance was seen in 11 (39.2%) and discordance in 17 (60.7%). Discordance was TST+/IGRA − in 12 (42.8%) and TST−/IGRA + in five (17.8%) patients. Abnormality in radiograph of the chest and computed tomography (CT) scan of the chest were seen in five (6.6%) and nine (12%) patients, respectively. The patients with either TST or IGRA + were more likely to have abnormal chest radiographs than those who were TST−/IGRA− (OR: 11.3, 95% CI: 1.24–102.3, P = 0.03). The TST and IGRA showed fair agreement ( = 0.364, P = 0.003). ROC curve was plotted for the absolute value of TST in mm considering IGRA as the gold standard. The area under the curve was 0.805 (95%CI: 0.655–0.954). For the TST positivity cut-off of 10 and 15 mm, specificity was 77.3% and 95.5%, respectively; the sensitivity was 68.8% irrespective of the cut-off value.Limitation:Small sample size and lack of follow-up are the biggest limitations of the study. The lack of a gold standard in the diagnosis of LTBI is an inherent yet unavoidable flaw in the study.Conclusion:Reactivation of LTBI is a concern in a patient planned for immunosuppressive therapy. We suggest the use of both TST and IGRA rather than two-step testing (TST followed by IGRA) or IGRA alone for the diagnosis of LTBI, especially in patients with a high risk of reactivation. The positivity on either test should prompt further evaluation and treatment decisions should be taken considering the risk-benefit ratio of treatment rather than test results alone.

Posoleucel (ALVR105), an Off-the-Shelf, Multivirus-Specific T-Cell Therapy, for the Prevention of Viral Infections Post-HCT: Results from an Open-Label Cohort of a Phase 2 Trial

Posoleucel (ALVR105), an Off-the-Shelf, Multivirus-Specific T-Cell Therapy, for the Prevention of Viral Infections Post-HCT: Results from an Open-Label Cohort of a Phase 2 Trial

Impact of Anti-Hepatitis B Core Following Allogeneic Bone Marrow Transplantation; Single Center Study of 489 Patients

▪Introduction:Hepatitis B core antibodies (Anti-HBC+) are virtually detected in all patients who have been exposed to Hepatitis B Virus (HBV), which make it a reliable serology marker for the previous infection. Anti-HBC+ patients undergoing hematopoietic stem cell transplant (HSCT) are at high risk of reactivation and may change the outcome especially during immunosuppression therapy (IST) phase which believed to enhance viral replications, as with withdrawal of IST which lead to the restoration of immune function making infected hepatocyte easier to destruction. The exact risk of (Anti-HBC+) post HSCT is not very well studied. In this study, we attempted to demonstrate the effect of (Anti-HBC+) positivity in the outcome post HSCT.Methods:Patients who were at least 14 years old receiving HSCT between year 2004 and 2010 at our center were reviewed. Patients with acutely infected hepatitis B (+ve hepatitis S antigen and IgM anti-HBC) were excluded from HSCT. A total of 489 patients were identified and included in the study. Patients were stratified into two groups: anti-hepatitis B core serology positive (Anti-HBC+) versus anti-hepatitis B core serology negative (anti-HBC -ve). After transplant, hepatitis B serology and PCR testing were performed at physician discretion at the time of unexplained elevation of liver enzymes. Prophylaxis use of antiviral medications was routinely given to all patients who are anti-HBC positive. Interpretation of hepatitis B serological test was based on Center for Disease Control and Prevention (CDC).Results:Median age for all patients is 22 years (range, 14 -62), 62% (n=304) were males. Matched related donor was used for majority of patients, 94.3% (n=461), while 18 patients (3.7%) underwent mismatched HSCT and 7 patients (1.4%) had umbilical cord transplantation. Diagnoses were ALL in 158 patients (32%), AML in 142 (29%) and CML in 58 patients (12%).GVHD prophylaxis was CSA/MTX for 83% (n=405), CSA/MMF for 4% and others for 13% (n=63). Conditioning regimen was Cyclophosphamide/TBI in 201 (41%), Busulfan/Cyclophosphamide in 181 patients (37%), Fludarabine/cyclophosphamide in 52 patients (11%) and others in 54 patients (11%). Bone marrow was the source of stem cells for 288 patients (59%).Anti-HBC serology at the time of HSCT was positive in 76 patients (15.5%) versus negative in 413 patients (84.5%). Donors' anti-HBC status was positive in 14% versus negative in (86%).A median follow-up of 5.4 years for anti-HBC+ survivors (range, 3 -5) showed 31 patients (41%) remain positive, 39 patients (51%) sero-converted to negative and six patients (8%) developed re-activation of hepatitis B. A median follow-up unreached for anti-HBC -ve survivors showed 396 patients (95.9%) remain negative, 6 patients (1.9%) became positive for anti-HBC and 3 patients (1%) developed acute hepatitis B after HSCT.Outcomes of HSCT showed overall survival (OS) rate at 5 years of 50% in anti-HBC+ group versus 58% in anti-HBC -ve group (p=0.30), suggesting a trend of lower rate of OS in anti-HBC+ group. The NRM and cumulative incidence of relapse at 5 years was 19% and 42% in anti-HBC+ group versus 17% (p=0.9) and 35% in anti-HBC -ve group (p=0.20), respectively.The cumulative incidence of overall acute GVHD at day 120 and overall chronic GVHD at 2 years were 42% and 47% in anti-HBC+ group versus 33% (p=0.1) and 46% (p=0.9) in anti-HBC -ve group, respectively, suggesting a trend of higher incidence of overall acute GVHD in anti-HBC+ group however it was statistically insignificant.Univariate analysis of risk factors for OS showed anti-HBC+ pre HSCT is an important factor however this was not confirmed in multivariate analysis.Conclusion:The present study suggested very low incidence of hepatitis B re-activation following HSCT for anti-HBC+ group (8%) if given proper anti HBV prophylaxis. Anti-HBC+ group does have a trend of lower overall survival and higher association with overall acute GVHD however this was not confirmed in multivariate analysis. Further studies are strongly warranted to confirm the prognostic role of anti-HBC in HSCT. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Low Risk for Viral Reactivation during Induction for Acute Myeloid Leukemia in Hepatitis B Silent Carriers Who Are Negativefor Hepatitis B Surface Antigen

Introduction: Latent hepatitis B virus (HBV) infection is a well-recognized risk factor for viral reactivation and life-threatening hepatitis during chemotherapy. Chronic HBV carriers, identified by the presence of hepatitis B antigen (HBsAg) in their serum, have a well-established high risk for reactivation. Patients, exposed to HBV, who have not become true carriers [HBsAg-negative, but anti-hepatitis B core antigen (HBc)-positive] are usually considered to have a “resolved” HBV infection. Current recommendations state that during chemotherapy all patients exposed to HBV in the past are to receive anti-HBV prophylaxis. However, these recommendations are based on data mainly driven from unselected series of cancer patients previously exposed to HBV. It has been clearly demonstrated that HBV reactivation is common in cases where immune suppressive therapy is applied (e.g., patients treated with corticosteroids and/or rituximab or those undergoing stem cell transplantation). Information regarding the incidence and risk factors of HBV reactivation in patients treated for acute myeloid leukemia (AML) is scarce. While some data support prophylaxis for chronic HBV carriers (HbSAg-positive) during chemotherapy for AML, it remains debatable whether this approach is required in AML patients with “resolved” HBV infection undergoing intensive chemotherapy.Methods: The current study reviewed medical files of 1200 patients who were diagnosed with AML between the years 2000-2017 and treated in three large hematology departments in Israel - at the Rambam Health Care Campus, Tel Aviv Sourasky Medical Center and Shaare Zedek Medical Center. Clinical characteristics and laboratory data were retrospectively analyzed. Each patient, diagnosed with AML, was tested for HbSAg, HbSAb, anti-HBc, anti-hepatitis C virus (HCV). Only patients who had not received prophylaxis with anti-HBV agents were included in the analysis.Results: A total of 38 patients with “resolved” HBV infection at the time of leukemia diagnosis were identified, including 15 females (39.5%) and 23 males (60.5%), with a median age of 59.5 years (range 35-80). Six (15.7%) patients were diagnosed with AML secondary to myelodysplastic syndromes (MDS). The following induction regimens were used: daunorubicin + cytarabine (“7+3”) in 34 patients (89.5%), clofarabine in two patients, and high-dose cytarabine (HIDAC) in two patients. Nine patients received re-induction with “7+3”. Twenty seven patients (71%) received consolidation - 26 with HIDAC and one with clofarabine (Table 1). Within 90 days following induction + consolidation therapy, no HBV reactivation was documented in any of the 38 patients. There was a mild and asymptomatic elevation in the levels of hepatocellular liver enzymes (up to 2.5 times the upper limit of normal) in some patients, which could also be attributed to other causes, such as drugs, sepsis, etc. In our cohort of patients, overall survival (OS) was identical to that observed in historical AML patients from our medical centers who were not HBV carriers (Fig. 1).Conclusions: AML patients with previous HBV infection (HBsAg-negative and anti-HBc-positive) undergoing intensive chemotherapy are not at an increased risk for virus reactivation. In the current study, none of the 38 patients had HBV reactivation, suggesting that omission of anti-HBV prophylaxis during induction and consolidation chemotherapy could be considered in select AML patients. Notably, two groups of AML patients with a higher risk of HBV reactivation, i.e., recipients of allogeneic stem cell transplantation and HbSAg-positive patients, were not included in the present study and the conclusions drawn are not applicable to these patient subsets. Larger studies are warranted to explore the role of HBV prophylaxis in “silent” carriers. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Management of Hepatitis‐B Virus Infection in Immunocompromised Children

The aims of the study was to expand the pediatric experience on hepatitis-B virus (HBV) reactivation, a known complication in patients with hematologic malignancies or on immunosuppression. Retrospective appraisal of HBV therapy/prophylaxis in immunocompromised children, studied from April 2006 to March 2020. Eighteen HBV-positive patients, 5 girls, median age 11.1 (4.1--17.9) years were included. Seventeen of 18 were immunosuppressed at HBV-infection diagnosis. Seventeen were at high risk of reactivation, 1 at moderate risk. Five of 18 had acute hepatitis B as first infection or reactivation, 6 had HBeAg-positive infection, 1 an HBeAg-negative infection and 6 HBsAg-negative infection. Median follow-up was 2.7 (0.7--12.5) years. No HBV-related mortality was observed. Prophylaxis had to be repeated in 1. Lamivudine was used in 6/12 viremic patients and HBV-DNA negativization obtained in 2/6 (33%). Tenofovir-DF was used in 2/12 and entecavir in 4/12: 100% attained HBV-DNA negativization. Therapy had to be switched from tenofovir-DF to entecavir in 1 patient because of renal impairment. Virological breakthroughs were observed in 1 lamivudine-treated patient, leading to a hepatitis flare; 1 patient on entecavir had a hepatitis flare at immunoreconstitution. Mortality was 33% in the HBsAg-positive group. Seven prophylactic treatments were administered to 6 patients with HBsAg-negative infection: tenofovir-DF in 2 HBV-DNA-positive, lamivudine in 5 HBV-DNA-negative, without reverse HBsAg seroconversion, morbidity or mortality. There is a residual risk of acute hepatitis B in immunocompromised children, mortality rate was substantial, potentially related to the delays in commencing chemotherapy caused by liver dysfunction. Tenofovir-DF or entecavir are the drugs of choice for HBV treatment in immunocompromised children.

Efficacy assessment of modern regimens of preventive antituberculosis therapy in patients basically treated with TNF-α inhibitors

Background. Biological agents, especially anti-tumor necrosis factor blocking agents, frequently are used to treat autoimmune inflammatory rheumatic diseases. Due to their negative impact on immune system and high risk of reactivation of latent tuberculosis infection all the patients must be well examined before initiation of an anti-tumor necrosis factor therapy (ATNFT).&#x0D; Purposes and tasks. An estimation of efficiency of preventive anti-tuberculosis therapy (PATT) with patients undergoing ATNFT.&#x0D; Methods and materials. In the research took part 128 patients, suffering from different inflammatory rheumatic diseases, whom was planned anti-tumor necrosis factor therapy. In 62 cases were found the indications for prescription PATT for 4 weeks before initiation of biological therapy and from 8 to 20 weeks after.&#x0D; Results. An active tuberculosis has been developed in 8 cases, the process was similar to tuberculosis and human immunodeficiency virus. The factors of risk were the prescription adalimumab and infliximab, impaired glucose tolerance, diabetes type 2 and drunkenness abuse.&#x0D; Conclusion. The existing preventive anti-tuberculosis therapy is not able to preclude the development of tuberculosis in all cases and needs to be optimized.

S2719 A Rare Case of Disseminated Varicella Zoster in a Young Patient With Cirrhosis

INTRODUCTION: Herpes zoster, otherwise known as shingles, occurs after reactivation of the dormant, neurotropic, varicella zoster virus (VZV) that lies in the dorsal root ganglia. The typical manifestation consists of self-limiting, painful, vesicular skin lesions that follow a dermatomal pattern. Herpes zoster can present as a disseminated infection in immunocompromised patients (e.g., HIV, malignancy, chronic immunosuppressive drugs) and, very rarely, in immunocompetent individuals. Patients with cirrhosis are deemed to be at high risk for infections as a result of immune dysfunction although a nationwide, population-based study from Taiwan has shown that cirrhosis is not associated with an increased risk for herpes zoster. Furthermore, although there are case reports of post-vaccine primary varicella infection and subsequent dissemination, there appear to be none detailing a dissemination of reactivated varicella zoster in a cirrhotic patient. CASE DESCRIPTION/METHODS: We present a case of a 34 yr old male on no medications, with a twelve year history of heavy alcohol use and decompensated cirrhosis, who was admitted for higher level of care and liver transplant evaluation. Ten days into his admission, vesicular lesions were noted on his left flank. VZV PCR testing showed 438,342 copies/mL. Workup for other infections such as Hepatitis A, B, C and HIV were negative. The patient was initially started on 350 mg IV acyclovir every twelve hours which was subsequently increased to 700 mg IV due to presence of VZV in the ascitic fluid that was concerning for dissemination. Unfortunately, the patient developed multi-organ system failure and passed away. DISCUSSION: This case highlights a rare instance of VZV dissemination in a young patient with cirrhosis who only displayed a cluster of vesicles on his left flank. While VZV dissemination has been known to occur in immunocompromised patients, cirrhotic patients have not usually been considered to be at higher risk for reactivation or dissemination. Our case highlights the importance of early diagnosis and prompt, aggressive management of shingles in patients with cirrhosis to reduce the risk of disseminated VZV and mortality.

Determination of tuberculin skin test for isoniazid prophylaxis in BCG vaccinated children who are using anti-TNF agents for rheumatologic diseases.

The use of tumor necrosis factor inhibitors (anti-TNF) has a risk of activating latent tuberculosis infection (LTBI). This study was performed to investigate LTBI according to tuberculin skin test (TST) size and to determine the frequency of tuberculosis (TB) in bacillus Calmette-Guerin (BCG)-vaccinated children receiving anti-TNF treatment for rheumatological disease. The study consisted of 559 children. Information on demographics, anti-TNF agents, TST size, and isoniazid (INH) prophylaxis was recorded. Patients (n = 254) with TST size ≥5 mm were divided into three groups according to TST size and INH prophylaxis: group 1, TST size 5 to 9 mm and no INH prophylaxis; group 2, TST size 5 to 9 mm with INH prophylaxis; and group 3, TST size ≥10 mm with INH prophylaxis. The 559 patients comprised 314 (56.3%) females and 245 (43.6%) males; they had a mean age of 13.1 ± 4.1 years. The mean TST size in all patients was 4.2 ± 4.7 mm. Group 1 consisted of 76 (29.9%) patients, group 2 consisted of 88 (34.6%) patients, and group 3 consisted of 90 (35.4%) patients. The mean TST sizes for the three groups were 6.8 ± 3.1 mm, 7.2 ± 3.2 mm, and 13.9 ± 2.8 mm, respectively. New TB was diagnosed in only two (0.35%) patients. Both of them were in group 3. A TST size of ≥10 mm in BCG-vaccinated children receiving anti-TNF treatment may distinguish children at high risk for reactivation of LTBI.

Cytomegalovirus: A Troll in the ICU? Overview of the Literature and Perspectives for the Future.

Cytomegalovirus (CMV) is one of the most pathogenic viruses in human. After a primary infection, CMV resides in the host for life as a latent infection. When immunity is reduced, CMV can escape the suppressive effects of the immune system and lead to viremia and antigenemia. This reactivation, first seen in transplant patients, has also been documented in non-immunocompromised CMV-seropositive critically ill patients and is associated with higher morbidity and mortality. In the latter, it is not clear whether CMV reactivation is an innocent bystander or the cause of this observed worse outcome. Two studies showed no difference in the outcome of CMV-seropositive and seronegative patients. In addition, proof-of-concept studies investigating prophylactic antiviral treatment to prevent CMV reactivation during critical illness, failed to show a beneficial effect on interleukin levels or clinical outcome. Further research is necessary to resolve the question whether CMV replication impairs the prognosis in non-immunocompromised critically ill patients. We here give a concise overview on the available data and propose strategies to further unravel this question. First, post-mortem investigation may be useful to evaluate the effect of viral replication on organ inflammation and function. Second, further research should focus on the question whether the level of viremia needs to exceed a threshold to be associated with worse outcome. Third, clinical and biochemical assessments may help to identify patients at high risk for reactivation. Fourth, preemptive treatment based upon early detection of the virus is currently under investigation. Finally, immune-stimulating biologicals may be beneficial in high-risk groups.