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Background. Given the limited collaborative international studies that evaluated COVID-19 in patients with cancer in comparison to patients without cancer, we aimed to determine the independent risk factors associated with increased 30-day mortality and the impact of novel treatment modalities in a large group of cancer and non-cancer patients with COVID-19 from multiple countries. Methods. We retrospectively collected de-identified data on cancer and non-cancer patients diagnosed with COVID-19 between January and November 2020, at 16 centers in Asia, Australia, Europe, North America, and South America. A logistic regression model was used to identify independent predictors of all-cause mortality within 30 days after COVID-19 diagnosis. Results. Of the total 4015 COVID-19 confirmed patients entered, we analyzed 3966 patients, 1115 cancer and 2851 non-cancer patients. Cancer patients were older than non-cancer patients (median age, 61 vs 50 years;p< 0.0001);more likely to be pancytopenic , had pulmonary disorders, hypertension, diabetes mellitus. In addition, they were more likely to present with higher inflammatory biomarkers (D-dimer, ferritin and procalcitonin), but were less likely to present with clinical symptoms. By multivariable logistic regression analysis, cancer was an independent risk factor for 30-day mortality (OR 1.46;95% CI 1.03 to 2.07;p=0.035). Older age (≥65 years) was the strongest predictor of 30-day mortality in all patients (OR 4.55;95% CI 3.34 to 6.20;p< 0.0001). Remdesivir was the only therapeutic agent independently associated with decreased 30-day mortality (OR 0.58;CI 0.39-0.88;p=0.009). Among patients on lowflow oxygen at admission, patients who received remdesivir had a lower 30-day mortality rate than those who were on high flow oxygen (5.9% vs 17.6%;p=0.03). Patients transfused with convalescent plasma within 1 day of diagnosis had a lower 30-day mortality rate than those transfused later (1% vs 7%, p=0.04). Conclusion. Cancer is an independent risk factor for increased 30-day all-cause mortality from COVID-19. Remdesivir, particularly in patients receiving low-flow oxygen, can reduce 30-day all-cause mortality, as well as convalescent plasma given early after COVID-19 diagnosis.
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Background. Several studies have shown that underlying cancer is a risk factor for progression of COVID-19 to severe illness and fatal outcome but there is very little data that specifies which underlying cancer puts this patient population at the highest risk. Methods. We retrospectively collected de-identified data on 1115 cancer patients diagnosed with COVID-19 between January and November 2020, at 12 centers in Asia, Australia, Europe, North America, and South America. Patient characteristics including age, type of malignancy (hematologic malignancy [HM], lung cancer, and non-lung cancer were determined in association with severe illness as well as all-cause mortality within 30 days after COVID-19 diagnosis. Results. By multivariable logistic regression analysis, independent risk factors for 30-day mortality in cancer patients included age > 65 (OR 6.64;95% CI 3.351to 12.55;p< 0.0001), ALC < 0.5 K/microliter (OR 2.10;95% CI 1.16 to 3.79;p=0.014), and anemia at < 10g/dl (OR 2.41;95% CI 1.30 to 4.44;p=0.005). Among cancer patients, the 30-day mortality rate was significantly higher in patients with lung cancer than in patients with non-lung cancer solid tumors, including those with lung metastases (22% vs 9%;p=0.001). Patients with HM tended to have higher 30-day mortality than patients with non-lung cancer solid tumors (13% vs 9% p=0.07) and tended to have a lower mortality rate than patients with lung cancer (p=0.07). Furthermore, HM patients were more likely to be lymphopenic and anemic at diagnosis as well as progress to LRTI and be placed on ventilatory support compared to non-lung cancer solid tumor patients ( p= or < 0.01). In addition, lung cancer and HM patients were more likely to develop hypoxia and require hospital admission than non-lung cancer solid tumor patients ( p=0.01). Conclusion. Lung cancer and HM patients are associated with the highest risk of progressing to severe disease and mortality in cancer patients with COVID-19. Hence, cancer patient population should be given the highest priority as far as prevention [vaccination with boosters if needed] as well as preemptive early therapy with monoclonal antibodies right after the onset of COVID-19.
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Background. An increasing number of observational studies have reported the persistence of symptoms following recovery from acute COVID-19 disease. The long-term consequences of COVID-19 are not fully understood and there is no clear consensus on the definition of post-acute sequelae of SARS-CoV-2 infection (PASC). The reported prevalence of PASC widely varies from 10% up to 87%. The purpose of this study is to assess PASC in cancer patients following acute COVID-19 recovery. Methods. We assessed cancer patients at MD Anderson Cancer Center who were diagnosed with COVID-19 disease between March 1, 2020 and Sept 1, 2020. Using patient questionnaires and medical chart reviews we followed these patients from March 2020 till May 2021. Patient questionnaires were sent out remotely daily for 14 days after COVID-19 diagnosis then weekly for 3 months, and then monthly thereafter. Chart reviews were conducted for each patient hospital re-admission and emergency department visit. These admissions were classified as either COVID-19 related or non-related. The persistence or emergence of new COVID19-related symptoms were captured at each COVID-19 related admission. Results. We included 312 cancer patients with a median age of 57 years (18-86). The majority of patients had solid tumors (75%). Of the 312 patients, 188 (60%) reported long COVID-19 symptoms with a median duration of 7 months and up to 14 months after COVID-19 diagnosis. The most common symptoms reported included fatigue (82%), sleep disturbances (78%), myalgias (67%) and gastrointestinal symptoms (61%), followed by headache, altered smell or taste, dyspnea (47%) and cough (46%). A higher number of females reported a persistence of symptoms compared to males (63% vs 37%;p=0.036). Cancer type, neutropenia, lymphocytopenia, and hospital admission during acute COVID-19 disease were comparable in both groups and did not seem to contribute to a higher number of long-COVID-19 patients in our study group. Conclusion. Long-COVID occurs in 60% of cancer patients and may persist up to 14 months after acute illness. The most common symptoms are fatigue, sleep disturbance, myalgia and gastro-intestinal symptoms.
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Background. Procalcitonin (PCT) has been used to guide antimicrobial therapy in bacterial infections. With the wide spread use of empiric use of antibiotics in cancer patients admitted with COVID-19 disease, we aimed to evaluate the role of PCT in decreasing the duration of empiric antimicrobial therapy among cancer patients admitted with COVID-19. Methods. We conducted a retrospective study of cancer patients admitted to MD Anderson Cancer Center who had a PCT test done within 72 hours of admission following their COVID-19 diagnosis between March 1, 2020 and June 6, 2021. Patients were divided into 2 groups of PCT < 0.25 ng/mL and PCT >=0.25 ng/mL. We assessed pertinent cultures including blood and respiratory, as well as antibacterial use and duration of empiric antibacterial therapy. Results. We identified 544 patients with a median age of 62 years (range, 14-93). There were 312 (57%) patients that had at least one culture obtained from a sterile or infected site within 7 days following admission. None of the patients who had PCT< 0.25 had a positive culture whereas 41/111 (37%) patients with PCT >= 0.25 had at least one positive culture [P< 0.0001]. Among the 373 patients who had a PCT < 0.25, 129 (35%) patients received more than 72 hours of IV antibiotics compared to 87/171 (51%) among patients with PCT >=0.25 [P= 0.0003]. Conclusion. These results confirm the correlation between a PCT level greater than 0.25 and a documented bacterial infection. Furthermore, procalcitonin could be useful in enhancing antimicrobial stewardship in cancer patients with COVID-19 by reducing the duration of antimicrobial therapy beyond the initial empiric 72 hours until PCT results become available.
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Background. The purpose of this study was to compare chest computed tomography (CT) scan findings in cancer versus non-cancer patients with COVID-19 infection. We sought to assess the correlation between radiologic patterns of COVID-19 pneumonia, clinical course, and outcomes. Methods. We performed a retrospective study of COVID-19 positive cancer and non-cancer pts who had chest CT scans at the time of diagnosis, at our hospital and 16 other centers in Asia, Australia, Europe, North America and South America, between March, 2020 and November, 2020. Patients' age, underlying diseases, symptoms, laboratory studies, and radiologic findings consisting of bilateral ground-glass opacities (GGOs), multifocal organizing pneumonia (MOP) were collected in association with clinical outcomes. Results. We identified 426 pts with cancer and 622 non-cancer pts. Thereafter, cancer pts were analyzed into 3 distinct groups and similar to non-cancer pts: GGOs group (n=224, 54%), GGOs+MOP group (n=61, 14.6%), and a third group of neither GGOs or MOP (n=131, 31.4%) in cancer pts, and in non-cancer pts: GGOs group (n=387, 62.8%), GGOs +MOP group (n=100, 16.2%), and a third group of neither GGOs or MOP (n=129, 21%). The median patients' age was 54 in non-cancer pts vs 62 in cancer pts (p< 0.001) and there were more males in the non-cancer group 57% vs 47% (p=0.001). Cough was more prevalent in non-cancer pts, 71% vs 59% (p< 0.001) and similar to fever (73% vs 57%, p< 0.001). Neutropenia < 0.5 k/μL and lymphocytopenia < 1 k/μL were more frequent in cancer pts (p< 0.001). In cancer pts, there was no statistically significance difference between the 3 groups (hospital admission, mechanical ventilation, readmission within 30 days, and mortality), except pts who required non-invasive (NI) ventilation were more frequent in the GGOs group, 55% (p=0.005). In non-cancer, pts with GGOs +MOP have higher hospital admission, ICU transfer, NI- and mechanical ventilation compared to the 2 other groups (p< 0.001). While readmission to hospital or mortality rate within 30 days were similar between the 3 groups. Conclusion. This study reveals that non-cancer pts tended to have more radiologic findings on chest CT scan compared to cancer pts at the time of COVID-19 diagnosis and were associated with more worrisome COVID-19-related clinical outcomes.
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Background. Bamlanivimab is a monoclonal antibody that was granted an emergency use authorization by the US Food and Drug Administration in November 2020 for patients with mild to moderate coronavirus disease 2019 (COVID-19). It initially showed promising results with decreasing hospitalizations and return emergency department visits in immunocompetent patients. We evaluated the role of bamlanivimab in the cancer patient population. Methods. We conducted a retrospective matched study of all cancer patients diagnosed with mild to moderate COVID-19 who received bamlanivimab in our acute cancer care center (ACCC) from December 2020 to February 2021. These patients were compared to a control group of cancer patients who presented to our ACCC and were diagnosed with mild to moderate COVID-19 from March to November 2020 before the introduction of bamlanivimab. Control patients were matched by age and underlying malignancy. All patients had a baseline oxygen saturation ≥ 94% and an absolute neutrophil count > 500 mm3. Demographics, clinical characteristics, and outcome that included COVID-related admissions, oxygen desaturation, ICU admission and 30-day mortality were compared in both groups. Results. A total of 108 patients were analyzed with 54 patients in each group, of which 59% consisted of hematologic malignancies, and 33% were ≥ 65 years. The presenting symptoms were similar in both groups and mainly consisted of cough, fever, and dyspnea. Patients who received bamlanivimab were less likely to be admitted to the hospital (24% vs. 91%;p< 0.0001), experience oxygen desaturation < 94% during follow-up (11% vs 44%;p=0.0001), require oxygen supplement (7% vs. 44%;p< 0.0001), or be admitted to the ICU (4% vs 15%;p=0.046). No 30-day mortality was observed in the bamlanivimab group with 2 (4%) occurring in the control group. However, the difference was not significant. Conclusion. Bamlanivimab decreased hospital and ICU admissions in cancer patients. In addition, bamlanivimab reduced oxygen requirement and the risk of hypoxia and progression to severe disease in this patient population.
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RATIONALE: Bronchiolitis obliterans syndrome (BOS) is the most common form of chronic lung allograft dysfunction, and the major limitation of long-term survival post lung transplantation (LTx). BOS affects up to 50% of LTx recipients within 5 years post-transplant. Currently there are no therapies indicated specifically for BOS. The most common treatment is augmentation of systemic immunosuppression, which has limited efficacy and is associated with deleterious long-term side effects. To address the goal of optimizing immunosuppression as a treatment for BOS, a novel liposomal formulation of cyclosporine A (L-CsA) delivered with an investigational eFlow® Technology nebulizer system (PARI Pharma GmbH) is being investigated. The objective of these two trials is to assess the efficacy and safety of inhaled L-CsA added to standard of Care (SoC) immunosuppression, in adult patients with single (SLT) and double lung transplantation (DLT). METHODS: Adult patients who received a SLT or DLT at least 12 months prior to screening, diagnosed with clinically defined BOS by FEV1 between 85-60% of personal best after transplant are eligible for inclusion. Patients are randomized 1:1 to L-CsA-i (5mg dose for SLT;10mg dose for DLT) twice daily plus SoC or SoC alone. After informed consent has been obtained, a Screening Visit is carried out to check general eligibility for participation. At the Randomization Visit, inclusion and exclusion criteria will be reevaluated and spirometry performed. Safety and tolerability will be assessed by physical examination, vital signs, adverse event reporting, and clinical laboratory parameters at every visit. A total of 11 visits throughout the 48-week treatment period will be performed. At completion of trial period, patients from both treatment groups could be eligible to continue in an open-label extension trial (BOSTON-3). The primary endpoint for both trials is the mean absolute change in FEV1 (mL) from baseline to Week 48 between the treatment groups. Secondary endpoints for both trials include mean change in FEV1/FVC from baseline to Week 48 and time to progression of BOS. The latter endpoint will be assessed in a pooled analysis of both trials. CONCLUSIONS: These phase III trials will help characterize the safety and efficacy of L-CsA-i as add-on therapy to SoC in BOS patients. Despite the COVID-19 pandemic, BOSTON-1 and BOSTON-2 are ongoing, ensuring the integrity of data collection and safety of enrolled patients. .
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Background: Our objective was to describe the clinical course, risk factors and outcomes of patients infected with COVID-19 around the globe comparing cancer to non-cancer patients. Methods: We conducted a retrospective cohort study of COVID-19 confirmed cases through an international multicenter collaboration including 17 centers around the world including the United States of America, Brazil, Europe, Far East, Middle East and Australia from January to date. We evaluated the patients' clinical characteristics, clinical course of the disease, hospitalization and outcome. Death was considered to be COVID-associated if it occurred within 30 days from the time of diagnosis. Results: Preliminary data on 571 patients included 186 cancer patients and 385 non-cancer patients. Cancer patients were more likely to have COPD and received steroids but were less likely to have COVID-related symptoms compared to non-cancer patients (84% vs 97%, p< 0.0001). The rate of pneumonia with hypoxia, non-invasive ventilation and mechanical ventilation were similar in both groups. Despite the fact that hospital admissions were significantly higher in non-cancer patients (70% vs 56%, p< 0.001), promising antiviral and immune-related therapy including remdesivir, convalescent plasma and immunomodulators were more commonly used in cancer patients compared to non-cancer patients (P=0.04). Cancer patients had a higher COVIDassociated mortality rate compared to non-cancer patients (20% vs 11%, p=0.006). Conclusion: Despite the fact that cancer patients received more frequent antiviral and immune-related therapy, the mortality rate among cancer patients was significantly higher than non-cancer patients.