Mortality in recipients of allogeneic haematopoietic cell transplantation in the era of cytomegalovirus primary prophylaxis: a single-centre retrospective experience.

OBJECTIVES: Allogeneic haematopoietic cell transplant (allo-HCT) recipients who are cytomegalovirus (CMV)-seronegative have better post-transplant outcomes than CMV-seropositive recipients. Letermovir (LTV) is approved for CMV primary prophylaxis in adults who are CMV-seropositive after allo-HCT, and its use is associated with improved long-term post-transplant outcomes. We analysed whether LTV has affected the relationship between CMV serostatus and post-transplant outcomes. METHODS: We conducted a retrospective single-centre cohort study of allo-HCT recipients, stratified according to donor (D) and recipient (R). CMV serostatus and the use of LTV: D-/R-, R+/LTV-, and R+/LTV+. Outcomes measured were all-cause and non-relapse mortality, clinically significant CMV infection, graft-versus-host disease, and relapse up to week 48 after allo-HCT. The D-/R- group served as the reference for comparisons in univariate, competing risk regression, and cumulative incidence functions. RESULTS: The analysis included 1071 consecutive allo-HCT recipients: 131 D-/R-, 557 R+/LTV-, and 383 R+/LTV+. All-cause mortality by day 100 was 6.1% for the D-/R- group, compared with 14.0% (p 0.024) and 7.8% (p 0.7) for the R+/LTV- and R+/LTV + groups, respectively. Non-relapse mortality by day 100 was 11.0%, 6.8% and 3.8% for R+/LTV-, R+/LTV+, and D-/R- groups, respectively, without significant difference. When including relapse as a competing event, the hazard ratio for non-relapse mortality was 1.83 (95% CI: 1.12-2.99, p 0.017) for R+/LTV- compared with D-/R- and 1.05 (95% CI 0.62-1.77, p 0.85) for R+/LTV + compared with D-/R-. DISCUSSION: CMV primary prophylaxis with LTV abrogated the mortality gap based on CMV serostatus, a protective effect that persisted after discontinuation of primary prophylaxis.

An international multicenter study comparing COVID-19 omicron outcomes in patients with hematological malignancies treated with obinutuzumab versus rituximab.

OBJECTIVES: Hematological malignancy (HM) patients treated with anti-CD20 monoclonal antibodies are at higher risk for severe COVID-19. A previous single-center study showed worse outcomes in patients treated with obinutuzumab compared to rituximab. We examined this hypothesis in a large international multicenter cohort. METHODS: We included HM patients from 15 centers, from five countries treated with anti-CD20, comparing those treated with obinutuzumab (O-G) to rituximab (R-G) between December 2021 and June 2022, when Omicron lineage was dominant. RESULTS: We collected data on 1048 patients. Within the R-G (n = 762, 73%), 191 (25%) contracted COVID-19 compared to 103 (36%) in the O-G. COVID-19 patients in the O-G were younger (61 ± 11.7 vs. 64 ± 14.5, p = 0.039), had more indolent HM diagnosis (aggressive lymphoma: 3.9% vs. 67.0%, p < 0.001), and most were on maintenance therapy at COVID-19 diagnosis (63.0% vs. 16.8%, p < 0.001). Severe-critical COVID-19 occurred in 31.1% of patients in the O-G and 22.5% in the R-G. In multivariable analysis, O-G had a 2.08-fold increased risk for severe-critical COVID-19 compared to R-G (95% CI 1.13-3.84), adjusted for Charlson comorbidity index, sex, and tixagevimab/cilgavimab (T-C) prophylaxis. Further analysis comparing O-G to R-G demonstrated increased hospitalizations (51.5% vs. 35.6% p = 0.008), ICU admissions (12.6% vs. 5.8%, p = 0.042), but the nonsignificant difference in COVID-19-related mortality (n = 10, 9.7% vs. n = 12, 6.3%, p = 0.293). CONCLUSIONS: Despite younger age and a more indolent HM diagnosis, patients receiving obinutuzumab had more severe COVID-19 outcomes than those receiving rituximab. Our findings underscore the need to evaluate the risk-benefit balance when considering obinutuzumab therapy for HM patients during respiratory viral outbreaks.

COVID-19 in cancer patients: The impact of vaccination on outcomes early in the pandemic.

BACKGROUND: With the rapid evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the development of effective and safe vaccines was of utmost importance to protect vulnerable individuals, including cancer patients. Studies comparing the clinical outcomes of cancer patients with or without vaccination against coronavirus disease 2019 (COVID-19) have not demonstrated clear benefit. We aimed to determine the protective effects of COVID-19 vaccination by comparing vaccinated and unvaccinated cancer patients after the initial phase of vaccine roll-out and to identify risk factors associated with hospitalization, severe COVID-19, and 30-day COVID-19 attributable mortality. METHODS: We performed a retrospective cohort study of cancer patients with COVID-19 diagnosed by polymerase chain reaction on nasal swabs between January 1, 2021 and July 30, 2021. Outcomes of interest included hospitalization, severe COVID-19, and 30-day COVID-19 attributable mortality. Univariate and multivariate analyses were performed to identify factors associated with clinical outcomes, using vaccination status as a variable of interest in all models. RESULTS: Key risk factors, such as age ≥ 60 years; comorbidities including diabetes mellitus, heart failure, and lung diseases; and specific cancer types (leukemia and lymphoma) were independently associated with hospital admission for COVID-19, severe COVID-19, and 30-day COVID-19 attributable mortality in cancer patients regardless of their vaccination status. Vaccinated patients were protected against severe COVID-19 but with no impact on hospitalization or mortality due to COVID-19. CONCLUSION: Our study highlights a significant benefit of COVID-19 vaccination for cancer patients-specifically its protection against severe COVID-19.

The impact of the COVID-19 pandemic on hospital-acquired infections at a comprehensive cancer center.

BACKGROUND: Robust infection prevention and control (IPC) measures were deployed across health care institutions at the start of the COVID-19 pandemic, resulting in increased use of personal protective equipment, enhanced contact precautions, and an emphasis on hand hygiene. Here, we evaluate the effect of enhanced IPC practices on the occurrence of various hospital-associated infections (HAIs) in a comprehensive cancer center. METHODS: From September 2016 through March 2022, we calculated the incidence rates (IRs) of HAIs for C. difficile infection, multidrug-resistant organisms, respiratory viral infections (RVIs), and device-related infections. We analyzed the incidence rate ratios for all HAIs during the periods before the pandemic, during the pandemic, at the time of the surges, and in COVID-19-designated wards. RESULTS: When comparing the prepandemic to the pandemic period, the IR across all MRDOs was similar. We observed a decrease in the IR of central line-associated bloodstream infections and a stable IR of catheter-associated urinary tract infections. A significant decrease was observed in the IR of C. difficile infection. The total IR of nosocomial RVIs decreased, as did for each respiratory virus. A similar IR of nosocomial RVIs between COVID-19 community surge versus nonsurge periods was observed except for SARS-CoV-2, RSV, and influenza. multidrug resistant organisms were 5 times more likely to occur on the COVID-19 wards compared with the non-COVID-19 wards. CONCLUSIONS: Implementing strict IPC measures during the COVID-19 pandemic in a cancer hospital led to a significant decrease in many HAIs and a reduction in nosocomial RVIs.

Respiratory Viral Infections in Recipients of Cellular Therapies: A Review of Incidence, Outcomes, Treatment, and Prevention.

Respiratory viral infections (RVIs) are of major clinical importance in immunocompromised patients and represent a substantial cause of morbidity and mortality in patients with hematologic malignancies and those who have undergone hematopoietic cell transplantation. Similarly, patients receiving immunotherapy with CD19-targeted chimeric antigen receptor-modified T cells, natural killer cells, and genetically modified T-cell receptors are susceptible to RVIs and progression to lower respiratory tract infections. In adoptive cellular therapy recipients, this enhanced susceptibility to RVIs results from previous chemotherapy regimens such as lymphocyte-depleting chemotherapy conditioning regimens, underlying B-cell malignancies, immune-related toxicities, and secondary prolonged, profound hypogammaglobulinemia. The aggregated risk factors for RVIs have both immediate and long-term consequences. This review summarizes the current literature on the pathogenesis, epidemiology, and clinical aspects of RVIs that are unique to recipients of adoptive cellular therapy, the preventive and therapeutic options for common RVIs, and appropriate infection control and preventive strategies.

COVID-19 Vaccination in Patients With Cancer and Recipients of Cellular Therapy.

COVID-19 continues to disproportionately affect patients with cancer because of their underlying immunocompromised state. Strategies to mitigate the impact of COVID-19 on patients with cancer include vaccination, which has demonstrated some level of protection, at least against serious complications such as respiratory failure and death, with limited safety concerns. In this narrative review, we discuss the current COVID-19 vaccines that are available in the United States, the published data regarding vaccine efficacy and safety in patients with cancer, current vaccination guidelines, and future directions.

Cytomegalovirus infection in transplant recipients: newly approved additions to our armamentarium.

BACKGROUND: The burden that cytomegalovirus (CMV) portends for haematopoietic and solid-organ transplant recipients cannot be understated. Valganciclovir and ganciclovir have successfully been used for prevention and treatment of CMV infections, although with serious side effects such as leucopenia and some development of resistance. Until recently, available therapies for ganciclovir-resistant CMV have significant toxicities. Although advances have been made in the field, the unmet medical needs for effective and well-tolerated therapies are significant. OBJECTIVES: This review aims to summarise the current and emerging CMV antiviral drugs and discusses future perspectives in the field. SOURCES: We searched for relevant articles with pertinent keywords: "Cytomegalovirus OR CMV", "Transplant" and "Antiviral". Articles published after 2019 were given preference. Articles were reviewed by the authors for relevance and impact to the subject of interest. CONTENT: We outline in this review current advances in prophylaxis of CMV infection with letermovir, breakthrough CMV infections while on or after prophylaxis, the development of resistant and refractory CMV infections, and the newly approved anti-CMV agent, maribavir, in haematopoietic and solid-organ transplant recipients. IMPLICATIONS: Prevention of CMV infections after transplant has improved greatly over the past few years. Despite major advancements, breakthrough CMV infections and development of refractory and resistant CMV infections remain major complications post transplantation. We highlight emerging therapeutics that tolerably and effectively prevent and treat CMV infections, especially refractory and resistant cases.

Nosocomial COVID-19 at a comprehensive cancer center during the first year of the pandemic: Lessons learned.

BACKGROUND: The spread of coronavirus disease 2019 (COVID-19) in health care settings endangers patients with cancer. As knowledge of the transmission of COVID-19 emerged, strategies for preventing nosocomial COVID-19 were updated. We describe our early experience with nosocomial respiratory viral infections (RVIs) at a cancer center in the first year of the pandemic (March 2020-March 2021). METHODS: Nosocomial RVIs were identified through our infection control prospective surveillance program, which conducted epidemiologic investigations of all microbiologically documented RVIs. Data was presented as frequencies and percentages or medians and ranges. RESULTS: A total of 35 of 3944 (0.9%) documented RVIs were determined to have been nosocomial acquired. Majority of RVIs were due to SARS CoV-2 (13/35; 37%) or by rhinovirus/enterovirus (12/35; 34%). A cluster investigation of the first 3 patients with nosocomial COVID-19 determined that transmission most likely occurred from employees to patients. Five patients (38%) required mechanical ventilation and 4 (31%) died during the same hospital encounter. CONCLUSIONS: Our investigation of the cluster led to enhancement of our infection control measures. The implications of COVID-19 vaccination on infection control policies is still unclear and further studies are needed to delineate its impact on the transmission of COVID-19 in a hospital setting.

Taking a Closer Look: Clinical and Histopathological Characteristics of Culture-Positive versus Culture-Negative Pulmonary Mucormycosis.

The cultural recovery of Mucorales from hyphae-laden tissue is poor, and the clinical implications of culture positivity are scarcely studied. Therefore, we compared clinical and histopathological characteristics of culture-positive and culture-negative histology-proven pulmonary mucormycosis cases among cancer patients. Histology specimens were blindly reviewed by a thoracic pathologist and graded on four histopathologic features: hyphal quantity, tissue necrosis, tissue invasion, and vascular invasion. Twenty cases with a corresponding fungal culture were identified; five were culture-positive, and fifteen were culture-negative. Although no statistically significant differences were found, culture-positive patients were more likely to exhibit a high burden of necrosis and have a high burden of hyphae but tended to have less vascular invasion than culture-negative patients. In terms of clinical characteristics, culture-positive patients were more likely to have acute myeloid leukemia (60% vs. 27%, p = 0.19), a history of hematopoietic cell transplant (80% vs. 53%, p = 0.31), severe lymphopenia (absolute lymphocyte count ≤ 500/µL, 100% vs. 73%, p = 0.36), and monocytopenia (absolute monocyte count ≤100/µL, 60% vs. 20%, p = 0.11). Forty-two-day all-cause mortality was comparable between culture-positive and culture-negative patients (60% and 53%, p = 0.80). This pilot study represents the first comprehensive histopathological scoring method to examine the relationship between histopathologic features, culture positivity, and clinical features of pulmonary mucormycosis.

Infectious Complications Among Patients With AML Treated With Immune Checkpoint Inhibitors.

BACKGROUND: The incidence and spectrum of infections in acute myeloid leukemia (AML) patients treated with immune checkpoint inhibitors (CPIs) in combination with a hypomethylating agents (HMAs) is not known. Nivolumab is a PD-1 checkpoint inhibitor approved in many solid tumors and lymphoma. MATERIALS/METHODS: We performed a retrospective cohort study of 75 adult patients at MD Anderson Cancer Center with relapsed/refractory AML treated with azacitidine and nivolumab or with nivolumab and ipilimumab from March 2016 through March 2020 and described the infectious complications that occurred during their treatment. RESULTS: Sixty-four (85%) patients developed an infection during the study period, and bacterial infections were by far the most common type of infection. A comparison of risk factors and characteristic between the 75 patients on CPIs who developed infection and those who did not found that corticosteroid use (odds ratio [OR], 28; 95% confidence interval [CI], 1.6-490; P =.02) and lymphopenia (OR, 4; 95% CI, 1-15.5; P =.04) were significantly associated with infections. CONCLUSION: Patient with relapsed/refractory AML treated with salvage CPI-based therapy were more likely to develop infections when treated with corticosteroids in the setting of an immune-related adverse event, compared to those who were not.

Emerging Fungal Infections.

Various uncommon fungal pathogens have been increasingly identified as causes of disseminated and invasive fungal disease (IFD) worldwide. Growing recognition and clinical knowledge of these emerging fungal pathogens has occurred through improved molecular diagnostics, nucleic sequence databases, and taxonomic reclassification of medically significant fungi. However, emerging fungal diseases carry significant morbidity and mortality and, due to a paucity of published literature, the collective clinical experience with these fungi is often limited. In this review, we focus on unusual emerging fungal pathogens not extensively covered elsewhere in this issue of Infectious Diseases Clinics of North America.

The Burden of Neurocysticercosis at a Single New York Hospital.

Neurocysticercosis (NCC), a disease caused by the larval pork tapeworm Taenia solium, has emerged as an important infection in the United States. In this study, we describe the spectrum of NCC infection in eastern Long Island, where there is a growing population of immigrants from endemic countries. A retrospective study was designed to identify patients diagnosed with NCC using ICD-9 and ICD-10 codes in the electronic medical records at Stony Brook University Hospital between 2005 and 2016. We identified 52 patients (56% male, median age: 35 years) diagnosed with NCC in the only tertiary medical center in Suffolk County. Twenty-five cases were reported in the last three years of the study. Forty-eight (94%) patients self-identified as Hispanic or Latino in the electronic medical record. Twenty-two (44%) and 28 (56%) patients had parenchymal and extraparenchymal lesions, respectively. Nineteen (41.3%) patients presented with seizures to the emergency department. Six patients (11.7%) had hydrocephalus, and five of them required frequent hospitalizations and neurosurgical interventions, including permanent ventriculoperitoneal shunts or temporary external ventricular drains. No deaths were reported. The minimum accumulated estimated cost of NCC hospitalizations during the study period for all patients was approximately 1.4 million United States dollars (USD). In conclusion, NCC predominantly affects young, Hispanic immigrants in Eastern Long Island, particularly in zip codes correlating to predominantly Hispanic communities. The number of cases diagnosed increased at an alarming rate during the study period. Our study suggests a growing need for screening high-risk patients and connecting patients to care in hopes of providing early intervention and treatment to avoid potentially detrimental neurological sequelae.

Invasive Fungal Infections at Presentation of Untreated Hematologic Malignancies: Rare and Elusive.

Invasive fungal infections (IFIs) are a feared complication of hematologic malignancy (HM) treatment. Infrequently, the diagnosis of a new IFI contemporaneously with a new untreated HM has been sporadically described in case reports. We performed a comprehensive search of published literature and reviewed cases describing this synchronous disease phenomenon.

Postacute COVID-19: An Overview and Approach to Classification.

As the coronavirus disease 2019 (COVID-19) pandemic has progressed, a large volume of literature has developed delineating the clinical manifestations of acute infection. Recent reports have also started to describe persistent symptoms extending beyond the period of initial illness or hospitalization. Anecdotes of different signs and symptoms occurring after acute infection have also arisen in the lay press. Here we describe the current existing medical literature on the emerging concept of postacute COVID-19 and suggest an approach to classifying different manifestations of the syndrome. We also review long-term clinical manifestations observed in patients who recovered from infection due to other epidemic coronaviruses and briefly discuss potential mechanisms driving the phenomenon of postacute COVID-19.