Population Of Immunosuppressed Patients Research Articles

Solid Organ Transplant Recipients Exhibit More TET2-Mutant Clonal Hematopoiesis of Indeterminate Potential Not Driven by Increased Transplantation Risk.

Solid organ transplant recipients comprise a unique population of immunosuppressed patients with increased risk of malignancy, including hematologic neoplasms. Clonal hematopoiesis of indeterminate potential (CHIP) represents a known risk factor for hematologic malignancy and this study describes the prevalence and patterns of CHIP mutations across several types of solid organ transplants. We use two national biobank cohorts comprised of >650,000 participants with linked genomic and longitudinal phenotypic data to describe the features of CHIP across 2,610 individuals who received kidney, liver, heart, or lung allografts. We find individuals with an allograft before their biobank enrollment had an increased prevalence of TET2 mutations (OR, 1.90; P = 4.0e-4), but individuals who received transplants post-enrollment had a CHIP mutation spectrum similar to that of the general population, without enrichment of TET2. In addition, we do not observe an association between CHIP and risk of incident transplantation among the overall population (HR, 1.02; P = 0.91). And in an exploratory analysis, we do not find evidence for a strong association between CHIP and rates of transplant complications such as rejection or graft failure. These results demonstrate that recipients of solid organ transplants display a unique pattern of clonal hematopoiesis with enrichment of TET2 driver mutations, the causes of which remain unclear and are deserving of further study.

2475. Admissions Screening for Influenza and RSV Among a Highly Immunosuppressed Patient Population

Abstract Background During the Fall/Winter 2022-23, the U.S. experienced an early surge of Influenza and RSV cases, while SARS-CoV-2 cases persisted. With concerns of a potential “tripledemic” on the horizon, the NIH Clinical Center, a clinical research hospital with a heavily immunosuppressed patient population, implemented Influenza and RSV testing, in addition to SARS-CoV-2, for all patients on admission to facilitate early detection and prompt isolation of infected patients. Methods Nasopharyngeal (NP) swabs (n=1213) were collected on admission from 11/2022 to 4/2023 and tested for Influenza and RSV by PCR. 1213 NP swabs from 985 unique patients were tested (some patients had multiple admissions); 1100 were tested on the Panther Fusion® SARS-CoV-2 Assay (Hologic, Inc.) and 113 using the SARS-CoV-2 RT-PCR Xpert® Xpress test. Medical chart reviews and discussions with patient care providers elucidated whether cases identified on admission were asymptomatic. Results Of 1213 NP swabs collected from patients admitted to our hospital, 5 (0.41%) were identified with Influenza A infection, 4 (0.33%) RSV infection and no patients were identified with Influenza B. Two (0.16%) had a known history of RSV infection, 3 (0.25%) screened negative for symptoms but subsequently disclosed symptoms, 1 (0.08%) was asymptomatic on admission but disclosed a recent history of an upper respiratory infection, and 3 were asymptomatic. All infections were detected between late November 2022 to mid-January 2023, when community transmission was high, yielding a 2-month positivity rate of 2.3% during this time of peak community spread. Conclusion Admission surveillance for Influenza and RSV during a respiratory virus surge in our community allowed us to isolate nine patients on admission who would likely not have been appropriately isolated, as symptom screening alone is not reliable. Surveillance is important to be able to identify infected patients promptly when respiratory infections are rampant in the community, and especially for institutions serving immunosuppressed patients. Disclosures All Authors: No reported disclosures

Abstract PO-074: The evolution of the tumor immune microenvironment in immunosuppressed patients with cutaneous squamous cell carcinoma

Abstract Immunosuppression is a major risk and prognostic factor for cutaneous squamous cell carcinoma (cSCC). Immune checkpoint inhibition is approved for the treatment of cSCC, yet most immunosuppressed patients are ineligible for immunotherapy. Better understanding on the tumor microenvironment of cSCC in the context of immunosuppression (i.e., organ transplant recipients, patients with hematological malignancies or autoimmune diseases or acquired immunodeficiencies such as HIV) is of utmost importance for proper implementation of immunotherapy as a therapeutic alternative for these patients. In this study, we characterized the immune cell phenotype of cSCC from immunocompetent (IC) and immunosuppressed (IS) patients treated at two Cancer Centers. We also compared the immune phenotype changes through the steps of skin carcinogenesis between IC and IS patients, and among individuals with distinct causes for immunosuppression. To evaluate the TME dynamics during tumorigenesis, we analyzed specimen of normal epithelium, keratinocytic intraepidermal neoplasia (including carcinoma in situ and actinic keratosis), or invasive cSCC. The analysis of cSCC tumor microenvironment was performed by multiplex immunofluorescence (Opal 12-Color), CyTOF and single-cell RNA sequencing. Our analysis revealed that densities of CD68+ and effector T-cells are diminished in IS patients compared with IC. An analysis of precursor lesions revealed that the density of tumoral CD8+LAG3+ T-cells in patients with hematological malignancies was significantly lower than in patients with other types of immunosuppression. Compared with patients with other types of immunosuppression, patients with hematological malignancies had a higher density of stromal CD4+ T cells in precursor lesions but a lower density of CD20+ B cells. Overall, IS patients had worse outcomes than IC patients, and the densities of CD68+ and CD8+LAG3+ cells were prognostic in this cohort. CD8+LAG3+ was significantly associated with DSS of IS patients indicating the impact of dysfunctional cytotoxic T cells on these patients’ survival. Our findings provide a detailed insight into the underlying immune alterations from tumor inception through growth and invasion, in patients with different types of immunosuppression. This dataset will serve as a benchmark data to guide clinical trials aiming to treat this patient population and provide a potential rationale for designing safer immunotherapy clinical trials for the population of IS patients with cSCC or other head and neck cancers. Citation Format: Mica D. E. Glaun, Frederico O. Gleber-Netto, Priyadharsini Nagarajan, Tongxin Xie, Shamima Akhter, Yu Han Chen, Erez Baruch N. Baruch, Michael K. Wong, Emily Y. Chu, Kenneth Y. Tsai, Elsa R. Flores, Deborah A. Silverman, Ryan P. Goepfert, Murat Cobanoglu, Jared Burks, Padmanee Sharma, James P. Allison, Jeffrey N. Myers, Neil D. Gross, Moran Amit. The evolution of the tumor immune microenvironment in immunosuppressed patients with cutaneous squamous cell carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-074.

Revisiting JC virus and progressive multifocal leukoencephalopathy.

Since its definition 65years ago, progressive multifocal leukoencephalopathy (PML) has continued to devastate a growing population of immunosuppressed patients despite major advances in our understanding of the causative JC virus (JCV). Unless contained by the immune system, JCV lyses host oligodendrocytes collateral to its life cycle, leading to demyelination, neurodegeneration, and death. Novel treatments have stagnated in the absence of an animal model while current antiviral agents fail to address the now ubiquitous polyomavirus. In this review, we highlight the established pathogenesis by which JCV infection progresses to PML, highlighting major challenges that must be overcome to eliminate the underlying virus and, therefore, the debilitating disease.

The Medical Relevance of Toxoplasma Infections in Terms of the Safety of Blood Recipients under Immunosuppression-A Meta-Analysis.

Laboratory diagnosis of Toxoplasma gondii infection plays a crucial role in ensuring the safety of blood recipients, especially in the case of immunosuppressed people, such as organ transplant patients. Toxoplasmosis, caused by the parasite Toxoplasma gondii, is a potential threat to people with weakened immune systems, and blood transfusions from infected donors can lead to severe complications. In this publication, we analyze the medical relevance of Toxoplasma infection in the context of the safety of blood recipients, focusing on the immunosuppressed patient population. We present various diagnostic methods, such as serological, molecular, and microscopic tests, which can detect the presence of Toxoplasma gondii in donors' blood. We also discuss the importance of adequately interpreting diagnostic results, considering risk factors, and detectability of the infection. We pay special attention to high-sensitivity and -specificity diagnostic techniques, which allow us to minimize the risk of Toxoplasma gondii transmission to blood recipients. Our findings have important implications for clinical practice and organ transplantation guidelines, emphasizing the need to diagnose and monitor Toxoplasma infections in blood donors and recipients.

The Role of Excision for Treatment of Chromoblastomycosis: A Cutaneous Fungal Infection Frequently Mistaken for Squamous Cell Carcinoma.

Chromoblastomycosis is an uncommon fungal infection of the skin caused by a variety of dematiaceous fungal species that is typically contracted through direct inoculation into the skin. To collect and examine data pertaining to the clinical presentation and management of patients with chromoblastomycosis. Through a retrospective study, a pathology medical record search was performed from January 2004 to December 2020 at a single institution. A total of 9 patients were identified. Seven of 9 cases occurred in solid organ transplant recipients. All cases were located on the extremities. Six of 9 cases were clinically suspected to be squamous cell carcinoma. Seven of 9 cases were treated with surgical excision. Six of 9 patients were treated with oral antifungal medication. Four of 9 patients had received combination therapy. Eight of 9 patients had no recurrence of the disease after treatment. Chromoblastomycosis presents as verrucous papules or nodules and may clinically and histopathologically mimic squamous cell carcinoma. Immunosuppression is likely a risk factor for the development of chromoblastomycosis. This study highlights the importance of clinical awareness of this disease's clinical presentation and prevalence in immunosuppressed patient populations.

Cancer treatment delays among patients with cancer living with HIV during the COVID-19 pandemic in the United States.

131 Background: The COVID-19 pandemic led to care disruptions across the cancer continuum. It is unknown if immunosuppressed patients with cancer who may be at high risk for SARS-CoV-2 infection were disproportionately impacted. Our objective was to compare delays in cancer treatment initiation between people living with HIV (PLWH) and cancer, the general cancer population (GCP), and patients with cancer and a history of solid organ transplant (SOT), another immunosuppressed patient population. Methods: We used data from Flatiron Health electronic health record-derived de-identified database (2018-2021) comprised of US patients with cancer from 800 sites of care across the country. We included patients with lymphomas, myeloma, and melanoma, as well as cancers of the breast, lung, prostate, head & neck, and gynecologic or gastrointestinal systems. We calculated time to cancer treatment initiation (TTI) as the difference between the date of cancer diagnosis and the earliest date that one of the following treatments was recorded: cell based treatment, other local treatment, radiotherapy, surgery, systemic therapy, or transplant. 16.4%, 19.9%, and 13.3% of the GCP, PLWH, and SOT groups, respectively, did not have treatment information in the database. This may have been due to no receipt of treatment or lack of data in the medical record. All analyses reported were conducted among patients with available treatment data. PLWH and those with a history of SOT were selected using ICD 9/10 codes. After adjusting for age, sex, and metastatic disease (yes/no), we used a difference-in-difference analysis to compute TTI for each study group both prior to and during the COVID-19 pandemic. We then determined whether study group differences in cancer patient TTI (e.g., HIV-associated treatment delays) changed during the pandemic. Results: The sample included 181 PLWH, 65073 GCP patients, and 195 patients with a history of SOT. Overall, no significant delay in TTI was seen between the three groups pre-COVID. However, during the pandemic, the TTI was statistically significantly delayed for PLWH compared to the HIV-uninfected GCP (median TTI 41 days vs. 27 days, p = 0.0017). No significant difference was observed overall between the GCP and the SOT group (median TTI 27 days vs. 20 days, p = 0.376), evidence that COVID-related treatment delays were specific to PLWH. Difference in difference analysis revealed that, when compared to the GCP, there was a significant increase in TTI among PLWH over time, with delays increasing by almost one month during COVID [DID: 32.6 days (8.9-56.3); p = 0.007]. The increase in TTI for PLWH was consistent across treatment modalities, including surgery (DID: 55.1, 95% CI: 28.8-81.3, p < 0.001) and systemic therapy (DID: 30.4; 95% CI: 4.6-56.3, p = 0.021). Conclusions: PLWH and cancer experienced significant delays in cancer treatment initiation after diagnosis during the COVID-19 pandemic.

Relapse rate in children with nephrotic syndrome during the SARS-CoV-2 pandemic.

BackgroundViral upper respiratory tract infections trigger nephrotic syndrome relapses. Few data exist on the impact of the SARS-CoV-2 pandemic on the risk of relapse in children with idiopathic nephrotic syndrome (INS).MethodsIn a Belgian and Italian cohort of children with INS, we performed a retrospective analysis on the number and duration of relapses observed in 3 different periods in 2020: first COVID period, February 15–May 31; second COVID period, June 1–September 14; third COVID period, September 15–December 31. Relapse rates were compared to those of the previous 5 years (PRECOVID period). For the years 2019 and 2020, all causes and INS relapse-related hospitalizations were recorded. Hospitalizations and deaths due to SARS-CoV-2 infection were also recorded. In the Belgian cohort, SARS-CoV-2 serologies were performed.ResultsA total of 218 patients were enrolled, and 29 (13.3%) were diagnosed with new-onset INS during the COVID period. Relapse rates per 1000 person-days were as follows: 3.2 in the PRECOVID period, 2.7 in the first COVID period, 3.3 in the second COVID period, and 3.0 in the third COVID period. The incidence rate ratio for the total COVID period was 0.9 (95%CI 0.76 to 1.06; P = 0.21) as compared to the PRECOVID period. During 2020, both the proportion of patients hospitalized for recurrence (14.2% vs. 7.6% in 2019; P = 0.03) and the rate of hospitalization for recurrence (IRR 1.97 (95%CI 1.35 to 2.88); P = 0.013) were higher compared to 2019. In December 2020, anti-SARS-CoV-2 antibodies were detected in 31% of the Belgian cohort. Patients with positive and negative SARS-CoV-2 serology did not differ significantly in relapse rate (2.4 versus 4.2 per 1000 person-days). The number of new INS cases remained similar between 2020, 2019, and 2018.ConclusionThe first year of the SARS-CoV-2 pandemic did not significantly affect the relapse rate in children with INS. No serious infections were reported in this population of immunosuppressed patients.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary informationSupplementary InformationThe online version contains supplementary material available at 10.1007/s00467-022-05702-2.

Essential Oils in Respiratory Mycosis: A Review

Respiratory mycosis is a major health concern, due to the expanding population of immunosuppressed and immunocompromised patients and the increasing resistance to conventional antifungals and their undesired side-effects, thus justifying the development of new therapeutic strategies. Plant metabolites, namely essential oils, represent promising preventive/therapeutic strategies due to their widely reported antifungal potential. However, regarding fungal infections of the respiratory tract, information is disperse and no updated compilation on current knowledge is available. Therefore, the present review aims to gather and systematize relevant information on the antifungal effects of several essential oils and volatile compounds against the main type of respiratory mycosis that impact health care systems. Particular attention is paid to Aspergillus fumigatus, the main pathogen involved in aspergillosis, Candida auris, currently emerging as a major pathogen in certain parts of the world, and Cryptococcus neoformans, one of the main pathogens involved in pulmonary cryptococcosis. Furthermore, the main mechanisms of action underlying essential oils’ antifungal effects and current limitations in clinical translation are presented. Overall, essential oils rich in phenolic compounds seem to be very effective but clinical translation requires more comprehensive in vivo studies and human trials to assess the efficacy and tolerability of these compounds in respiratory mycosis.

Corynebacterium striatum-Got Worse by a Pandemic?

The role of Corynebacterium striatum has been demonstrated in different nosocomial infections. An increasing number of publications have demonstrated its virulence in the respiratory tract, especially in the immunosuppressed patient population. The number of these patients has increased significantly during the COVID-19 pandemic. For this reason, we aimed to investigate the prevalence and antimicrobial resistance pattern of this species between 2012 and 2021 at the Clinical Center of the University of Szeged, Hungary. Altogether, 498 positive samples were included from 312 patients during the study period. On the isolates, 4529 antibiotic susceptibility tests were performed. Our data revealed that the prevalence of C. striatum increased during the COVID-19 pandemic, the rise occurred in respiratory, blood culture, and superficial samples. During the study period, the rifampicin resistance significantly increased, but others have also changed dynamically, including linezolid. The species occurred with diverse and changing co-pathogens in the COVID-19 era. However, the increasing rifampicin and linezolid resistance of C. striatum was probably not due to the most commonly isolated co-pathogens. Based on resistance predictions, vancomycin is likely to remain the only effective agent currently in use by 2030.

Prioritizing SARS-CoV-2 testing in a highly immunosuppressed patient population

Background: The NIH Clinical Center implemented multiple testing protocols to facilitate early detection and isolation of SARS-CoV-2 infected patients and rooming-in family members (RIFMs). Beginning in February 2020, all symptomatic patients were tested; in March 2020, all patients were tested prior to aerosol-generating procedures (AGPs); and in May 2020, all patients and RIFMs were tested on admission. We sought to determine the value of SARS-CoV-2 testing practices in our hospital. Methods: Respiratory specimens collected March 2020 through June 2021 tested for SARS-CoV-2 by RT-PCR were reviewed, and corresponding patient clinical and demographic variables were collected. Repeated tests from SARS-CoV-2–positive persons were excluded from the data. Results associated with multiple testing indications were assigned the highest priority reason based on a predetermined hierarchy. Data were analyzed using the χ2 test and logistic regression. Results: Of 12,706 results from 5,704 patients, primary testing reasons were pre-AGP (n = 5,387, 43.0%), admission (n = 2,733; 21.8%), and symptomatic testing (n = 2,701; 21.6%). Overall, 159 tests (1.25%) were positive for SARS-CoV-2. Asymptomatic patients tested on admission were 1.8 times more likely to be positive than outpatients tested for any reason (P = .003) and 4.2 times more likely than asymptomatic inpatients tested prior to AGP (P = .003). Within asymptomatic pre-AGP testing, there was no difference between inpatients (0.46%) and outpatients (0.65%). Hispanic patients were 1.9 times more likely to be positive. (p Conclusions: At a hospital with a geographically broad referral base, admissions COVID-19 testing was far more fruitful than pre-AGP testing of inpatients. Pre-AGP used the most testing resources yet had the lowest yield. Admissions testing remains beneficial regardless of community transmission rates, while testing prior to AGP could be pared back when community rates of COVID-19 are low and redeployed when community rates rise. Conclusions: Our findings that Hispanic persons had higher risk and that transplant patients had lower risk of testing positive suggests differences in the extent to which each subgroup may have been able to shelter from COVID-19 in the community during this earlier phase of the pandemic. Keeping immunocompromised patients safe from COVID-19 while they undergo longitudinal care involves layered precautions in the hospital and in the community that must evolve in response to evidence and epidemiological trends.Funding: NoneDisclosures: None

Različiti oblici infekcije mikobakterijama kod bolesnika na anti-TNF terapiji - prikazi bolesnika

Biological agents, including TNF-alpha antagonists, have been used in treatment of autoimmune diseases for over 20 years. Due to impaired T-cell immunity and blocked effects of TNF-alpha mediator, patients receiving this therapy have increased risk of developing tuberculosis or other non-tuberculous mycobacterial infections. Both tuberculosis and other mycobacterial infections may occur anytime in patients who have ever used these medicines, even after the first injection. Most often we see activation of latent tuberculosis confirmed by screening tests. IGRA tests (QuantiFERON and T-SPOT.TB) are significantly more sensitive and specific for testing population of immunosuppressed patients, in comparison to tuberculosis skin test. There are contemporary recommendations for diagnosing, monitoring, chemoprophylaxis and treatment of latent and active tuberculosis in adults and children in case of planning administration of TNF-alpha antagonists or in cases when these drugs have already been used. Prevention of active tuberculosis via diagnosing LTBI and use of chemoprophylaxis is the crucial component of the strategy of World Health Organization for elimination of TB (End TB Strategy).

Candidiasis as Secondary Infection in Post COVID-19: A New Problem?

Introduction: Severe Acute Respiratory Syndrome (SARS-CoV-2) can develop into post COVID-19 with one of its main attentions being secondary infection. Candidiasis as fungal pneumonia is one of secondary infection in post COVID-19. It is hard to diagnose and has high mortality. We present a case of candidiasis as fungal pneumonia in post COVID-19 patient.Case: A 47-year-old woman came to the emergency room with major complaints of dyspnoea and jaundice since her second day at home after being discharged from having COVID-19. She previously finished her COVID treatment and tested negative 2 times. She had severe sepsis and her sputum culture was positive for non-albicans Candida. She received anti-fungal treatment and her condition was getting better and her chest X-ray showed less infiltrates than before.Discussion: Fungal respiratory infections generate concern in the expanding population of immunosuppressed patients like COVID-19 patient. The mortality from COVID-19 associated candidiasis is high (19-40%) as one of fungal infection. Marked immune dysregulation in COVID-19 makes system immune becomes impaired, it also harms lung epithelium. In this patient, diagnosis and treatment were challenging.Conclusion: Post COVID-19 is a condition that should be given more attention, especially when it develops secondary infection. Candidiasis as fungal pneumonia is hard to diagnose and can quickly become severe sepsis and has high mortality. Health practitioners should recognize it as soon as possible and give the best treatment for the patient.

Checkpoint inhibition in immunosuppressed or immunocompromised patients with advanced cutaneous squamous cell carcinoma (CSCC): Data from prospective CemiplimAb-rwlc Survivorship and Epidemiology (C.A.S.E.) study.

9547 Background: Immunosuppressed and/or immunocompromised patients are at increased risk for solid tumors and cutaneous malignancies. Limited data exist on the safety and effectiveness of immune checkpoint inhibitors (ICIs) in these patients because they are frequently excluded from clinical trials. Here, we describe the safety and effectiveness results from the initial cohort of immunosuppressed and/or immunocompromised patients with advanced CSCC enrolled in the C.A.S.E. study (NCT03836105). Methods: C.A.S.E. is a prospective, real-world, multi-center, longitudinal study evaluating the effectiveness, safety, quality of life, and survivorship in patients with advanced CSCC treated with cemiplimab. Patients received cemiplimab 350 mg intravenously every 3 weeks per routine standard of care. Patient demographics, disease characteristics, immunosuppression, and relevant medical history were collected. Immunosuppressive regimens varied amongst patients. Investigator assessment of objective response rate (ORR), safety, and tolerability was conducted. Data from 26 immunosuppressed and/or immunocompromised patients with advanced CSCC treated with cemiplimab are presented. Recruitment is ongoing. Results: As of November 17, 2020, 121 patients were enrolled in the C.A.S.E. study, of which 26 patients (median age: 74 years [IQR: 71-84]; 85% male; 89% Caucasian) were designated as immunocompromised or immunosuppressed due to a history of solid organ transplant (n = 6), autoimmune disorder (n = 11), or hematologic malignancy (n = 9). Median duration of cemiplimab exposure was 14 months (IQR: 9.1–42, range: 0, 67). Among 19 immunocompromised or immunosuppressed patients who enrolled in C.A.S.E. prior to their third dose of cemiplimab, ORR per investigator assessment was 47% (95% CI: 24–71); 1 (5%) patient had complete response; 8 (42%) had partial response. One patient had a treatment-related serious adverse reaction of organ transplant rejection. One (3.8%) patient discontinued treatment due to increased alanine aminotransferase (not treatment-related). Immune-related AEs (irAEs) occurred in 23% of patients. No treatment-related AEs led to death. Conclusions: The safety, tolerability, and effectiveness of cemiplimab in this initial cohort of immunosuppressed and/or immunocompromised patients with advanced CSCC appear to be consistent with those observed in clinical trials that excluded these patients. Further follow-up and additional data would add to our general understanding of safety and effectiveness of anti-PD1 therapy in immunocompromised and/or immunosuppressed patient populations overall. Clinical trial information: NCT03836105.

Discovery of 5-Nitro-6-thiocyanatopyrimidines as Inhibitors of Cryptococcus neoformans and Cryptococcus gattii.

Opportunistic infections from pathogenic fungi present a major challenge to healthcare because of a very limited arsenal of antifungal drugs, an increasing population of immunosuppressed patients, and increased prevalence of resistant clinical strains due to overuse of the few available antifungals. Cryptococcal meningitis is a life-threatening opportunistic fungal infection caused by one of two species in the Cryptococcus genus, Cryptococcus neoformans and Cryptococcus gattii. Eighty percent of cryptococcosis diseases are caused by C. neoformans that is endemic in the environment. The standard of care is limited to old antifungals, and under a high standard of care, mortality remains between 10 and 30%. We have identified a series of 5-nitro-6-thiocyanatopyrimidine antifungal drug candidates using in vitro and computational machine learning approaches. These compounds can inhibit C. neoformans growth at submicromolar levels, are effective against fluconazole-resistant C. neoformans and a clinical strain of C. gattii, and are not antagonistic with currently approved antifungals.

Is denosumab associated with an increased risk for infection in patients with low bone mineral density? A systematic review and meta-analysis of randomized controlled trials.

Denosumab increases bone mineral density through inhibition of the receptor activator of nuclear factor κ-Β ligand (RANKL). RANKL has known immunomodulatory effect. The largest study to date that reviewed denosumab efficacy in osteoporosis demonstrated an increased incidence of serious adverse events of infection (SAEI). We aimed to further evaluate risk of infection and SAEI in denosumab-treated patients. PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science were searched for randomized controlled trials. Studies comparing denosumab 60mg every 6months with placebo or bisphosphonate for treatment of low bone mineral density were included. Trials were excluded for use of denosumab in cancer patients treated for skeletal-related events, immunosuppressed patient populations, or for comparison to teriparatide. Risk ratios (RR) with a 95% confidence interval (CI) were pooled using a fixed effects model, or a random effects model if heterogeneity occurred. Twenty-four randomized controlled trials (20470 patients) were analyzed. An increased incidence of any infection (RR 1.11; 95% CI 1.02-1.20; P=0.02) was observed in denosumab-treated patients compared with bisphosphonates, but not when compared with placebo. In contrast, a higher incidence of SAEI (RR 1.21; 95% CI 1.03-1.43; P=0.02) was seen with denosumab when compared with placebo, but not compared with bisphosphonates. Denosumab-treated patients with low bone mineral density have slightly increased incidence of SAEI compared with placebo, but not when compared with bisphosphonates. Application of these results requires consideration of the entire body of data available regarding denosumab safety.

Janus Kinase Inhibitors and Non-Melanoma Skin Cancer.

JAK (janus kinase) inhibitors are becoming increasingly prescribed for various conditions from dermatologic diseases to graft versus host disease in bone marrow transplant recipients. This class of drugs has been found to be truly life-changing for many, though they are not without potential adverse effects. While JAK inhibitors have not been shown to significantly increase the risk of non-melanoma skin cancer (NMSC) in large scale clinical trials, NMSC is one of the most concerning possible adverse events, and there have been several reported cases of aggressive squamous cell carcinomas, especially in our already immunosuppressed patient populations. In these patients, it is incredibly important that patients are on the lowest possible dosage of the JAK inhibitor. In addition, these patients must be routinely screened by a dermatologist with a comprehensive skin exam to ensure early detection if skin cancer was to develop. For those patients diagnosed with skin cancer, early intervention is key to optimize outcomes, and at times, multi-disciplinary care coordination is needed. In the future, large-scale studies with longer follow-up of patients would help determine whether JAK inhibitors significantly increase the risk of NMSC.

524 Evaluating the utility of post-surgical radiation for high-risk cutaneous squamous cell carcinoma in immunosuppressed patients

Cutaneous squamous cell carcinoma (cSCC) that presents with high-risk features such as perineural invasion is associated with a poor outcome. The National Comprehensive Cancer Network recommends consideration of post-surgical radiation for these aggressive tumors. However, the supporting evidence for this recommendation is limited for immunosuppressed patients. Recent studies demonstrated inferior outcomes of cSCC in immunosuppressed patients treated with adjuvant radiation compared with immunocompetent patients that also received radiation, highlighting the uncertain benefit of post-surgical radiation therapy in the immunosuppressed patient population.

Abiotrophia and Granulicatella Infections in Cancer Patients: A Single-Center Chart Review Study

Objectives: Nutritionally Variant Streptococci (NVS) comprise two primary genera that have been identified from human specimens, particularly the Abiotrophia and Granulicatella species. These infections are often complicated to manage due to the difficulty identifying these organisms, indolent course of disease, and variable resistance to common antimicrobial agents. The wide breadth of disease presentations involving these organisms has not been fully elucidated, particularly in the immunosuppressed cancer patient population. Method: We performed a retrospective chart review on 28 patients from an academic cancer center with positive NVS cultures, from January 2012 to July 2018. We reviewed patient characteristics, culture data, immunodeficiency status, response to antibiotic therapy, and outcomes of infection. Results: Of twenty-eight patients, fifteen patients developed bacteremia from either Abiotrophia or Granulicatella species, while thirteen patients had positive wound or body fluid cultures. Most patients with bacteremia had underlying hematologic malignancies and neutropenia. Patients with positive wound or body fluid cultures had an invasive procedure at the related site. Intravenous (IV) vancomycin was the most common agent used, and all but two patients were treated with multiple antibiotic regimens. Conclusions: Infections with NVS have been reported with a variety of clinically infectious presentations and should be considered in cancer patients with neutropenia or in patients who have undergone invasive procedures. Bacteremia was the most common complication, especially in the setting of hematologic malignancy and neutropenia. Focal body site infection was also a common complication related to invasive procedures in immunocompetent patients. Overall mortality was low and related to complications of septic shock. J Microbiol Infect Dis 2020; 10(2):89-97.

Hematological Malignancies and HBV Reactivation Risk: Suggestions for Clinical Management.

It is well known that hepatitis B virus reactivation (HBVr) can occur among patients undergoing treatment for hematological malignancies (HM). The evaluation of HBVr risk in patients undergoing immunosuppressive treatments is a multidimensional process, which includes conducting an accurate clinical history and physical examination, consideration of the virological categories, of the medication chosen to treat these hematological malignancies and the degree of immunosuppression induced. Once the risk of reactivation has been defined, it is crucial to adopt adequate management strategies (should reactivation occur). The purpose of treatment is to prevent dire clinical consequences of HBVr such as acute/fulminant hepatitis, and liver failure. Treatment will be instituted according to the indications and evidence provided by current international recommendations and to prevent interruption of lifesaving anti-neoplastic treatments. In this paper, we will present the available data regarding the risk of HBVr in this special population of immunosuppressed patients and explore the relevance of effective prevention and management of this potentially life-threatening event. A computerized literature search was performed using appropriate terms to discover relevant articles. Current evidence supports the policy of universal HBV testing of patients scheduled to undergo treatment for hematological malignancies, and clinicians should be aware of the inherent risk of viral reactivation among the different virological categories and classes of immunosuppressive drugs.