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.

Neutropenia in Patients With Clozapine-Treated Schizophrenia: An Effect of Clozapine or a Consequence of SARS-CoV-2 Infection? A Systematic Review.

BACKGROUND: Clozapine is the only approved antipsychotic for treatment-resistant schizophrenia. Despite its therapeutic benefits, it is still widely underused, mainly because of its potential to cause agranulocytosis and neutropenia. Prescribing clozapine in COVID-19-positive patients became more challenging because of this potential side effect. This article is a review of literature on the risk of neutropenia associated with clozapine treatment in patients with COVID-19. AREAS OF UNCERTAINTY: In clozapine-treated COVID-19-positive patients, neutropenia was reported in some cases; is it a consequence of clozapine treatment or of SARS-Co2 infection? DATA SOURCES: Data were extracted from 2 databases: PubMed/MEDLINE and Google Scholar. We selected all original reports, from March 2020 until May 2022, on neutropenia associated with clozapine treatment in positive COVID-19 patients. Eleven studies were selected for the final analysis. THERAPEUTIC ADVANCES: Before the COVID-19 pandemic, neutropenia in clozapine-treated patients was reported in 3.8% of cases. During the pandemic, neutropenia rates seemed to be higher. As per the cause of neutropenia, studies reported contradictory results. We aim to clarify rates and causes of neutropenia in clozapine-treated COVID-19-positive patients. RESULTS: Three hundred eighty-eight articles were initially selected from the 2 databases. After excluding duplicates, unrelated articles, reviews, and guidelines, 11 studies were analyzed, all centered on clozapine treatment, COVID-19 infection, and associated neutropenia. CONCLUSIONS: Clozapine treatment in COVID-19-positive patients may be associated with a transient reduction of absolute neutrophils count, in some cases reaching neutropenia levels. Neutropenia rates reported in SARS-CoV-2-infected patients are higher than the prepandemic reports; therefore, we assume that the cause might be a result of the immunological interference between clozapine and SARS-CoV-2. Clozapine treatment needs to be continued whenever possible, with dose adjustments in relation to blood test results.

Clinical and Laboratory Findings of SARS-CoV-2 Infection in Children Younger than 6 Months Old: Neutropenia is More Common Not Lymphopenia.

BACKGROUND: Studies on age-related differences in clinical and laboratory features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited. We aimed to evaluate the demographic, clinical, laboratory findings of SARS-CoV-2 infection in children younger than 6 months old and compare them with older children. METHODS: A single-center retrospective study, including 209 confirmed SARS-CoV-2 infection cases, was conducted between 11 March 2020 and 1 September 2021. The case group consisted of 47 patients younger than 6 months old, whereas the control group consisted of 162 patients older than 6 months old. RESULTS: The mean age of the case group was 2.77 ± 1.52 months, and the control group was 101.89 ± 65.77 months. Cough was statistically higher in the control group, and poor feeding was higher in the case group (p = 0.043, 0.010). The underlying disease rate was statistically higher in the control group; however, the hospitalization rate was higher in the case group (p = 0.036, 0.001). The case group had significantly lower median values of the absolute neutrophil count, hemoglobin and higher median values of white blood cell, absolute lymphocyte count and platelet than the control group (p < 0.05). C-reactive protein, fibrinogen values were significantly lower, and procalcitonin, D-dimer, troponin T, N-terminal pro-B-type natriuretic peptide significantly higher in the case group (p < 0.05). Lymphopenia was more common in the control group, whereas neutropenia was more common in the case group (p = 0.001, 0.011). CONCLUSIONS: We showed that most children younger than 6 months old had mild and asymptomatic SARS-CoV-2 infection; however, the hospitalization rate was higher, and neutropenia was more common in older children. Lay summaryStudies on age-related differences in clinical and laboratory features on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pediatric patients are limited. We aimed to evaluate the demographic, clinical and laboratory findings of SARS-CoV-2 infection in children younger than 6 months old and compare them with older children. A single-center retrospective study was conducted, including 209 SARS-CoV-2 infection cases. The case group consisted of 47 patients younger than 6 months old, and the control group consisted of 162 patients older than 6 months old. Most children younger than 6 months old had mild and asymptomatic SARS-CoV-2 infection; however, the hospitalization rate was higher than older children. Neutropenia was more common in patients younger than 6 months than older children with SARS-CoV-2 infection, even if underlying diseases were excluded.

Incidental occurrence of neutropenia in children hospitalised for COVID-19.

BACKGROUND: Investigations on haematological alterations in paediatric COVID-19 have been focused mostly on lymphocytes and clotting profiles. Neutropenia has been occasionally reported and its course and impact on the disease have not been elucidated. The aim of this study was to describe the epidemiology, course, and impact of neutropenia in children with COVID-19 hospitalised in a tertiary care referral paediatric ward. METHODS: A single-centre retrospective study was conducted. Hospitalised children between 1 month and 18 years with confirmed COVID-19 and neutropenia were included and compared to non neutropenic patients. Complete blood picture with differential blood count, serum biochemistry, clotting profiles were performed; clinical data, length of hospitalisation, and prescription of drugs were collected. RESULTS: Twelve out of 95 patients (12.63%) with documented SARS-CoV-2 infection were neutropenic and met the inclusion criteria. The mean age was 161 days (range 38-490 days). The mean duration of symptoms in neutropenic children was 3.82 days, while the mean length of hospitalisation was 7.67 days. These findings were not significantly different in the two study groups. All patients had mild clinical manifestations and were discharged without sequelae. CONCLUSIONS: We provided the first comprehensive study on neutropenia in mild paediatric COVID-19 infection. Our findings show that the main features of this haematological disorder in COVID-19 are analogous to the well-known transient benign neutropenia associated with other common viral infections. In our setting, neutropenia does not emerge as a potential negative prognostic factor in paediatric COVID-19.

SARS-CoV-2 in children with cancer or after haematopoietic stem cell transplant: An analysis of 131 patients.

PURPOSE: There are limited data on SARS-CoV-2 (COVID-19) infection in children with cancer or after haematopoietic stem cell transplant (HSCT). We describe the severity and outcomes of SARS-COV-2 in these patients and identify factors associated with severe disease. METHODS: This was a multinational, observational study of children (aged <19 years) with cancer or HSCT and SARS-CoV-2 confirmed by polymerase chain reaction. COVID-19 was classified as asymptomatic, mild, moderate, severe or critical (≥1 organ support). Exact polytomous regression was used to determine the relationship between clinical variables and disease severity. RESULTS: One hundred and thirty-one patients with COVID-19 across 10 countries were identified (median age 8 years). Seventy-eight (60%) had leukaemia/lymphoma, 48 (37%) had solid tumour and five had primary immunodeficiency and HSCT. Fever (71%), cough (47%) and coryza (29%) were the most frequent symptoms. The median duration of detectable virus was 16 days (range, 1-79 days). Forty-nine patients (37%) were hospitalised for COVID-19 symptoms, and 15 (11%) required intensive care unit-level care. Chemotherapy was delayed/modified in 35% of patients. COVID-19 was asymptomatic in 32% of patients, mild in 47%, moderate in 8%, severe in 4% and critical in 9%. In 124 patients (95%), a full recovery was documented, and four (3%) died due to COVID-19. Any comorbidity (odds ratio, 2.94; 95% confidence interval [CI], 1.81-5.21), any coinfection (1.74; 95% CI 1.03-3.03) and severe baseline neutropenia (1.82; 95% CI 1.13-3.09) were independently and significantly associated with increasing disease severity. CONCLUSION: Although most children with cancer had asymptomatic/mild disease, 13% had severe COVID-19 and 3% died. Comorbidity, coinfection and neutropenia may increase the risk of severe disease. Our data may help management decisions in this vulnerable population.

Neutropenia in adult acute myeloid leukemia patients represents a powerful risk factor for COVID-19 related mortality.

Patients with hematological malignancies are at risk for poor outcomes when diagnosed with coronavirus disease 2019 (COVID-19). It remains unclear whether cytopenias and specific leukemia subtypes play a role in the clinical course of COVID-19 infection. Here, we report outcomes and their clinical/laboratory predictors for 65 patients with acute and chronic leukemias diagnosed with COVID-19 between 8 March 2020 and 19 May 2020 at Memorial Sloan Kettering Cancer Center in New York City. Most patients had CLL (38%) or AML (26%). A total of 14 (22%) patients required high flow nasal cannula or were intubated for mechanical ventilation and 11 patients (17%) died. A diagnosis of AML (OR 4.7, p=.028), active treatment within the last 3 months (OR 5.22, p=.047), neutropenia within seven days prior and up to 28 days after SARS-CoV-2 diagnosis (11.75, p=.001) and ≥3 comorbidities (OR 6.55, p=.019) were associated with increased odds of death.

Characteristics and outcomes of COVID-19 infection in 45 patients with breast cancer: A multi-center retrospective study in Hubei, China.

BACKGROUND: The COVID-19 pandemic is a significant worldwide health crisis. Breast cancer patients with COVID-19 are fragile and require particular clinical care. This study aimed to identify the clinical characteristics of breast cancer patients with COVID-19 and the risks associated with anti-cancer treatment. METHODS: The medical records of breast cancer patients with laboratory-confirmed COVID-19 were collected among 9559 COVID-19 patients from seven designated hospitals from 13th January to 18th March 2020 in Hubei, China. Univariate and multivariate analyses were performed to assess risk factors for COVID-19 severity. RESULTS: Of the 45 breast cancer patients with COVID-19, 33 (73.3%) developed non-severe COVID-19, while 12 (26.7%) developed severe COVID-19, of which 3 (6.7%) patients died. The median age was 62 years, and 3 (6.7%) patients had stage IV breast cancer. Univariate analysis showed that age over 75 and the Eastern Cooperative Oncology Group (ECOG) score were associated with COVID-19 disease severity (P < 0.05). Multivariate analysis showed that patients who received chemotherapy within 7 days had a significantly higher risk for severe COVID-19 (logistic regression model: RR = 13.886, 95% CI 1.014-190.243, P = 0.049; Cox proportional hazards model: HR = 13.909, 95% CI 1.086-178.150, P = 0.043), with more pronounced neutropenia and higher LDH, CRP and procalcitonin levels than other patients (P < 0.05). CONCLUSIONS: In our breast cancer cohort, the severity of COVID-19 could be associated with baseline factors such as age over 75 and ECOG scores. Chemotherapy within 7 days before symptom onset could be a risk factor for severe COVID-19, reflected by neutropenia and elevated LDH, CRP and procalcitonin levels.

Perioperative neutropenia is not an independent risk factor for infectious complications of central venous line placement in children: A propensity score-matched analysis.

BACKGROUND: The infectious risk of central venous line (CVL) placement in children with neutropenia (absolute neutrophil count [ANC] <500/mm3) is not well defined. This study aims to investigate the early (≤30 days) and late (>30 days) infectious complications of CVLs placed in pediatric patients with and without neutropenia. METHODS: A retrospective review was conducted of all CVLs placed by pediatric surgeons at two institutions from 2010 to 2017. Multivariable logistic regression was performed to identify risk factors for line infection. Propensity score-matched cohorts of patients with and without neutropenia were compared in a 1:1 ratio. Wilcoxon rank-sum, Chi-square, Fisher's exact, and log-rank tests were also performed. RESULTS: Review identified 1,102 CVLs placed in 937 patients. Fifty-four patients were neutropenic at the time of placement. Multivariable analysis demonstrated tunneled catheters and subclavian access as associated with line infection. The propensity score-matched cohort included 94 patients, 47 from each group. Demographic and preoperative data were similar between the groups (p > 0.05). Patients with neutropenia were no more likely to develop early (4.3% vs. 2.1%, p = 1.000) or late (19.1% vs. 17.0%, p = 1.000) infectious complications than patients without neutropenia, with similar median time to infection (141 vs. 222 days, p = 0.370). CONCLUSION: A policy of selective CVL placement in neutropenic patients with standardized postoperative line maintenance is safe. Future directions include defining criteria by which neutropenic patients could be prospectively selected for safe CVL placement. LEVEL OF EVIDENCE: II - Retrospective cohort study.

A possible increased risk of metamizole-associated neutropenia among COVID-19 patients.

Metamizole is commonly used as analgesic and antipyretic drug. The use of metamizole is prohibited in several countries due to its rare side effect of neutropenia and even agranulocytosis. Among the many symptoms of COVID-19, fever and diffuse pain predominant and therefore it can be assumed that metamizole may be widely used in the current epidemic period. So far, there have been no reports on the safety of metamizole in COVID-19 patients. We describe a series of 3 patients who developed severe neutropenia under metamizole treatment, raising a concern of a possible increased risk of this side effect among COVID-19 patients.