Atypical pathogens presenting with pulmonary consolidations detected by cell-free DNA next-generation sequencing in patients with hematologic malignancies.

Identification of pathogens with pulmonary presentation in patients with hematologic malignancies may be challenging due to diagnostic difficulty related to the underlying malignancy and limitations of conventional microbiologic methods. Herein, we present a case series of three patients with pulmonary consolidations due to Legionella bozemanae necrotizing pneumonia, Pneumocystis jirovecii pneumonia, and disseminated Scedosporium infection, who were diagnosed by microbial cell-free DNA next-generation sequencing. We observed that this new sequencing modality was in agreement with gold-standard diagnostics, posing a potential solution to the problem of limited capability in diagnosing infections in hematological malignancy patients.

The Effect of Neutropenia and Filgrastim (G-CSF) on Cancer Patients With Coronavirus Disease 2019 (COVID-19) Infection.

BACKGROUND: Neutropenia is commonly encountered in cancer patients. Recombinant human granulocyte colony-stimulating factor (G-CSF, filgrastim), a cytokine that initiates proliferation and differentiation of mature granulocytes, is widely given to oncology patients to counteract neutropenia, reducing susceptibility to infection. However, the clinical impact of neutropenia and G-CSF use in cancer patients with coronavirus disease 2019 (COVID-19) remains unknown. METHODS: An observational cohort of 379 actively treated cancer patients with COVID-19 was assembled to investigate links between concurrent neutropenia and G-CSF administration on COVID-19-associated respiratory failure and death. These factors were encoded as time-dependent predictors in an extended Cox model, controlling for age and underlying cancer diagnosis. To determine whether the degree of granulocyte response to G-CSF affected outcomes, the degree of response to G-CSF, based on rise in absolute neutrophil count (ANC) 24 hours after growth factor administration, was also incorporated into a similar Cox model. RESULTS: In the setting of active COVID-19 infection, outpatient receipt of G-CSF led to an increased number of hospitalizations (hazard ratio [HR]: 3.54, 95% confidence interval [CI]: 1.25-10.0, P value: .017). Furthermore, among inpatients, G-CSF administration was associated with increased need for high levels of oxygen supplementation and death (HR: 3.56, 95% CI: 1.19-10.2, P value: .024). This effect was predominantly seen in patients that exhibited a high response to G-CSF based on their ANC increase post-G-CSF administration (HR: 7.78, 95% CI: 2.05-27.9, P value: .004). CONCLUSIONS: The potential risks versus benefits of G-CSF administration should be considered in neutropenic cancer patients with COVID-19, because G-CSF administration may lead to worsening clinical and respiratory status.

The Effect of Neutropenia and Filgrastim (G-CSF) in Cancer Patients With COVID-19 Infection.

BACKGROUND: Neutropenia is commonly encountered in cancer patients, and recombinant human granulocyte colony-stimulating factor (G-CSF, filgrastim) is widely given to oncology patients to counteract neutropenia and prevent infection. G-CSF is both a growth factor and cytokine that initiates proliferation and differentiation of mature granulocytes. However, the clinical impact of neutropenia and G-CSF use in cancer patients, who are also afflicted with coronavirus disease 2019 (COVID-19), remains unknown. METHODS: An observational cohort of 304 hospitalized patients with COVID-19 at Memorial Sloan Kettering Cancer Center was assembled to investigate links between concurrent neutropenia (N=55) and G-CSF administration (N=16) on COVID-19-associated respiratory failure and death. These factors were assessed as time-dependent predictors using an extended Cox model, controlling for age and underlying cancer diagnosis. To determine whether the degree of granulocyte response to G-CSF affected outcomes, a similar model was constructed with patients that received G-CSF, categorized into high- and low-response, based on the level of absolute neutrophil count (ANC) rise 24 hours after growth factor administration. RESULTS: Neutropenia (ANC < 1 K/mcL) during COVID-19 course was not independently associated with severe respiratory failure or death (HR: 0.71, 95% Cl: 0.34-1.50, P value: 0.367) in hospitalized COVID-19 patients. When controlling for neutropenia, G-CSF administration was associated with increased need for high oxygen supplementation and death (HR: 2.97, 95% CI: 1.06-8.28, P value: 0.038). This effect was predominantly seen in patients that exhibited a high response to G-CSF based on their ANC increase post-G-CSF administration (HR: 5.18, 95% CI: 1.61-16.64, P value: 0.006). CONCLUSION: Possible risks versus benefits of G-CSF administration should be weighed in neutropenic cancer patients with COVID-19 infection, as G-CSF may lead to worsening clinical and respiratory status in this setting.

Determinants of Severity in Cancer Patients with COVID-19 Illness.

New York State had 180,458 cases of SARS-CoV-2 and 9385 reported deaths as of April 10th, 2020. Patients with cancer comprised 8.4% of deceased individuals1. Population-based studies from China and Italy suggested a higher COVID-19 death rate in patients with cancer2,3, although there is a knowledge gap as to which aspects of cancer and its treatment confer risk of severe COVID-19 disease4. This information is critical to balance the competing safety considerations of reducing SARS-CoV-2 exposure and cancer treatment continuation. Since March 10th, 2020 Memorial Sloan Kettering Cancer Center performed diagnostic testing for SARS-CoV-2 in symptomatic patients. Overall, 40% out of 423 patients with cancer were hospitalized for COVID-19 illness, 20% developed severe respiratory illness, including 9% that required mechanical ventilation, and 9% that died. On multivariate analysis, age ≥ 65 years and treatment with immune checkpoint inhibitors (ICI) within 90 days were predictors for hospitalization and severe disease, while receipt of chemotherapy within 30 days and major surgery were not. Overall, COVID-19 illness is associated with higher rates of hospitalization and severe outcomes in patients with cancer. Association between ICI and COVID-19 outcomes will need interrogation in tumor-specific cohorts.

Determinants of COVID-19 disease severity in patients with cancer.

As of 10 April 2020, New York State had 180,458 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 9,385 reported deaths. Patients with cancer comprised 8.4% of deceased individuals1. Population-based studies from China and Italy suggested a higher coronavirus disease 2019 (COVID-19) death rate in patients with cancer2,3, although there is a knowledge gap as to which aspects of cancer and its treatment confer risk of severe COVID-194. This information is critical to balance the competing safety considerations of reducing SARS-CoV-2 exposure and cancer treatment continuation. From 10 March to 7 April 2020, 423 cases of symptomatic COVID-19 were diagnosed at Memorial Sloan Kettering Cancer Center (from a total of 2,035 patients with cancer tested). Of these, 40% were hospitalized for COVID-19, 20% developed severe respiratory illness (including 9% who required mechanical ventilation) and 12% died within 30 d. Age older than 65 years and treatment with immune checkpoint inhibitors (ICIs) were predictors for hospitalization and severe disease, whereas receipt of chemotherapy and major surgery were not. Overall, COVID-19 in patients with cancer is marked by substantial rates of hospitalization and severe outcomes. The association observed between ICI and COVID-19 outcomes in our study will need further interrogation in tumor-specific cohorts.