Afebrile chemotherapy-induced neutropenia: an international survey spots oncologists' routine clinical practice versus the standard of care and the impact of COVID-19.

INTRODUCTION: Afebrile chemotherapy-induced neutropenia represents a frequent clinical situation where chemotherapy protocol, patient's comorbidities, and disease status determine the risk of infection hence the management plan. Internationally distributed, this questionnaire aims to evaluate the routine practice and the impact of the COVID-19 pandemic on afebrile chemotherapy-induced neutropenia management. MATERIAL AND METHODS: Coordinators from Egypt, Morocco, Azerbaijan, and Russia developed a 12-item questionnaire using Google forms to explore how oncologists deal with afebrile chemotherapy-induced neutropenia. The link to the survey was available internationally through social media and to their local societies over the period from July to September 2021. RESULTS: We received 151 responses from 4 world regions: 58.9, 9.9, 11.3, and 15.2% from the Mena area, Russia, Europe, and Asia. The responses deviated from the guideline-driven practice as G-CSF was the most chosen option for intermediate risk that was statistically different based on the academic background of the treating physician. Half of the responders ignored patients and disease risk factors in the intermediate-risk cases that trend was statistically different based on the geographical distribution. The steroid was a valid option for intermediate and low-risk as per oncologists practicing in Russia. COVID-19 pandemic positively affected the rate of prescription of G-CSF as expected. CONCLUSION: The disparities in the routine practice of oncologists based on their geographical and academic backgrounds highlight the need to analyze the underlying obstacles that hinder guideline-based practice like workload or lack of the proper knowledge.

Efficacy and harms of tocilizumab for the treatment of COVID-19 patients: A systematic review and meta-analysis.

INTRODUCTION: We systematically assessed benefits and harms of tocilizumab (TCZ), which is an antibody blocking IL-6 receptors, in hospitalized COVID-19 patients. METHODS: Five electronic databases and two preprint webpages were searched until March 4, 2021. Randomized controlled trials (RCTs) and inverse probability treatment weighting (IPTW) cohorts assessing TCZ effects in hospitalized, COVID-19 adult patients were included. Primary outcomes were all-cause mortality, clinical worsening, clinical improvement, need for mechanical ventilation, and adverse events (AE). Inverse variance random-effects meta-analyses were performed with quality of evidence (QoE) evaluated using GRADE methodology. RESULTS: Nine RCTs (n = 7,021) and nine IPTW cohorts (n = 7,796) were included. TCZ significantly reduced all-cause mortality in RCTs (RR 0.89, 95%CI 0.81-0.98, p = 0.03; moderate QoE) and non-significantly in cohorts (RR 0.67, 95%CI 0.44-1.02, p = 0.08; very low QoE) vs. control (standard of care [SOC] or placebo). TCZ significantly reduced the need for mechanical ventilation (RR 0.80, 95%CI 0.71-0.90, p = 0.001; moderate QoE) and length of stay (MD -1.92 days, 95%CI -3.46 to -0.38, p = 0.01; low QoE) vs. control in RCTs. There was no significant difference in clinical improvement or worsening between treatments. AEs, severe AEs, bleeding and thrombotic events were similar between arms in RCTs, but there was higher neutropenia risk with TCZ (very low QoE). Subgroup analyses by disease severity or risk of bias (RoB) were consistent with main analyses. Quality of evidence was moderate to very low in both RCTs and cohorts. CONCLUSIONS: In comparison to SOC or placebo, TCZ reduced all-cause mortality in all studies and reduced mechanical ventilation and length of stay in RCTs in hospitalized COVID-19 patients. Other clinical outcomes were not significantly impacted. TCZ did not have effect on AEs, except a significant increased neutropenia risk in RCTs. TCZ has a potential role in the treatment of hospitalized COVID-19 patients.

Bacteremia in Children with Solid Tumors: Etiology, Antimicrobial Susceptibility, Factors Associated with Multidrug Resistance, and Mortality.

This retrospective study aims to describe the etiology and resistance patterns of pathogens causing bacteremia in children with solid tumors in a tertiary pediatric hematology-oncology center in Jerusalem, Israel (2011-2019). Factors associated with multidrug-resistant (MDR) bacteremia and mortality were analyzed. A total of 228 pathogens were isolated in 126 patients; 61.0% were gram-negative rods (GNR) and 38.2% were gram-positive cocci (GPC). The most common pathogens were Klebsiella pneumoniae (19.3%), Escherichia coli (17.5%), and coagulase-negative staphylococci (16.2%). The proportion of MDR-GNR was 18.2%, while the proportion of MDR-GPC was 55.2%. In logistic regression analysis, breakthrough bacteremia on a penicillin-group antibiotic (odds ratio [OR] 5.69, [95% confidence interval 1.42-22.76], p-value = 0.014) was associated and underlying diagnosis of neuroblastoma was inversely associated (OR 0.17, [0.04-0.81], p-value = 0.026) with MDR-GNR bacteremia; while the previous hospitalizations' duration (OR 1.032/day, [1.01-1.06], p-value = 0.007) and oncologic treatment intensity (OR 2.19, [1.08-4.45, p-value = 0.03) were associated with MDR-GPC bacteremia. Shock, prolonged profound neutropenia, and pediatric intensive care unit (PICU) admission were associated with 7-day mortality; and relapsed disease, oncologic treatment intensity, prolonged profound neutropenia, and PICU admission-with 30-day mortality in the univariate analyses. Empirical antibiotic choice should be based on factors associated with MDR infections in this specific population.

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.

Granulocyte colony stimulating factor (G-CSF)-induced aortitis in a patient undergoing adjuvant chemotherapy for breast cancer.

Granulocyte colony stimulating factor (G-CSF) is used to prevent febrile neutropenia post chemotherapy. Usually well tolerated with minimal side effects but aortitis is an extremely rare side effect previously reported. A 64-year-old woman treated with adjuvant chemotherapy including G-CSF for left breast cancer was admitted with fevers, neutropenia and markedly raised inflammatory markers after 7 days of her first cycle. Initially diagnosed with neutropenic sepsis, she did not respond to broad spectrum antibiotics with subsequent CT imaging revealing marked periaortic inflammatory changes consistent with aortitis and periaortitis. Extensive investigations for other causes of large vessel vasculitis were negative and G-CSF was the only causative factor. She rapidly responded to steroids with almost complete resolution of inflammatory changes on repeat imaging within 4 weeks and no recurrence on tapering of steroids. This diagnosis must be considered in patients presenting with fever and raised inflammatory markers post G-CSF treatment.

Self-limiting severe neutropenia in a patient with COVID-19.

Neutropenia is a rare haematological complication of COVID-19 infection in immunocompetent patients. There is sparse literature on neutropenia in patients with COVID-19, except a few case reports. We encountered a similar case in an intensive care unit that developed severe neutropenia on day 24 of illness. Neutropenia resolved spontaneously on 4th day of its appearance. The patient was isolated and kept under close observation, antibiotics were upgraded and strict asepsis was maintained. Thus, we observed in a patient with no comorbidities and uncomplicated neutropenia that strict measures to prevent infection may suffice and the undue risk of hematopoietic therapy can be avoided. An expert opinion should always be sought in such cases as the presence of complications may require an aggressive approach.

Delayed, transient and self-resolving neutropenia following COVID-19 pneumonia.

A novel coronaravirus, identified as SARS-CoV-2, spread throughout the world in 2020. The COVID-19 pandemic has led to many discoveries and clinical manifestations. A young patient is presented with new, self-resolving neutropenia presenting weeks after a prolonged hospital stay for COVID-19 pneumonia. Workup included analysis for underlying infection, nutritional abnormalities, malignancy, medication and toxin exposure, all of which were negative. From 2020 to the present, few reports have described neutropenia associated with a recent COVID-19 infection. In particular, no reports have described a delayed presentation of neutropenia. The authors would like to propose that the significant inflammatory response associated with COVID-19 is likely what led to this patient's postviral neutropenia. Furthermore, in young healthy patients, bone marrow biopsy may be deferred and a watchful-waiting approach may be taken to assess for neutropenia resolution.

Oncologic immunomodulatory agents in patients with cancer and COVID-19.

Corticosteroids, anti-CD20 agents, immunotherapies, and cytotoxic chemotherapy are commonly used in the treatment of patients with cancer. It is unclear how these agents affect patients with cancer who are infected with SARS-CoV-2. We retrospectively investigated associations between SARS-CoV-2-associated respiratory failure or death with receipt of the aforementioned medications and with pre-COVID-19 neutropenia. The study included all cancer patients diagnosed with SARS-CoV-2 at Memorial Sloan Kettering Cancer Center until June 2, 2020 (N = 820). We controlled for cancer-related characteristics known to predispose to worse COVID-19 as well as level of respiratory support during corticosteroid administration. Corticosteroid administration was associated with worse outcomes prior to use of supplemental oxygen; no statistically significant difference was observed in sicker cohorts. In patients with metastatic thoracic cancer, 9 of 25 (36%) and 10 of 31 (32%) had respiratory failure or death among those who did and did not receive immunotherapy, respectively. Seven of 23 (30%) and 52 of 187 (28%) patients with hematologic cancer had respiratory failure or death among those who did and did not receive anti-CD20 therapy, respectively. Chemotherapy itself was not associated with worse outcomes, but pre-COVID-19 neutropenia was associated with worse COVID-19 course. Relative prevalence of chemotherapy-associated neutropenia in previous studies may account for different conclusions regarding the risks of chemotherapy in patients with COVID-19. In the absence of prospective studies and evidence-based guidelines, our data may aid providers looking to assess the risks and benefits of these agents in caring for cancer patients in the COVID-19 era.

COVID-19 in Neonates and Infants: Progression and Recovery.

Between March 10, 2020 and April 17, 2020, of 8/70 (11.4%) SARS-CoV-2 positive infants that presented, 5/8 (63%) developed fever, 4/8 (50%) had lower respiratory tract involvement, 2/8 (25%) had neutropenia and thrombocytosis, and 4/8 infants (50%) were treated for suspected sepsis with broad-spectrum antibiotics. Only 1/8 (13%) required pediatric intensive care. All patients were eventually discharged home well.