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Congenital enterovirus infection can be associated with a pro‐inflammatory state triggering haemophagocytic lymphohistiocytosis (HLH). Enteroviruses are also known to cause transient neutropenia in healthy children. Two infants presented with temperature instability, lethargy, thrombocytopaenia, hepatosplenomegaly and evidence of hyperinflammation in the setting of perinatal maternal rash and household contacts with gastrointestinal symptoms. Whilst HLH was successfully treated in both, protracted neutropenia persisted. Immune dysregulation with enterovirus in the neonatal period can provoke the generation of autoantibodies to hematologic cells giving rise to conditions such as autoimmune neutropenia. Sustained neutropaenia, after resolution of secondary infectious forms of HLH, requires investigation for underlying aetiologies.

Invasive fungal infection is a life-threatening complication of chemotherapy and neutropaenia in the haematology population. Trichoderma species rarely cause human disease but have been reported to cause invasive infection in the immunosuppressed. We present a case of invasive Trichoderma longibrachiatum pulmonary infection with fatal outcome in a neutropaenic patient with acute myeloid leukaemia. 2012 Elsevier Ltd. All rights reserved.

Introduction: Immune thrombocytopaenia (ITP), previously known as idiopathic thrombocytopaenic purpura, is an acquired autoimmune disorder characterised by immune-mediated platelet destruction. It has been observed that some paediatric patients with ITP treated with intravenous immunoglobulin (IVIG) developed neutropaenia. The aim of the study was to investigate the association between IVIG therapy and neutropaenia in paediatric ITP. Material and methods: The retrospective cohort study involved 123 children (79 girls, 44 boys) with immune thrombocytopaenia, aged 8.03 ±4.55 (0.8-17.9) years (mean ± standard deviation; range) who underwent IVIG in the Department of Haematology and Paediatric Oncology in Zabrze between April 2014 and December 2021. Correlations between age, sex, weight of patients, total IVIG dose, and neutrophil/platelet counts on administration day and 1, 2, and 3 days after IVIG treatment from official medical records were analysed. Results: The mean total dose of IVIG was 1.7 ±0.48 g/kg BW A significant increase in platelet level was observed usually on the first (67.5%) or second (20.3%) day after initial administration of intravenous immunoglobulins. After the course of IVIG, neutropaenia was observed in 50 subjects (40.7%). The neutropaenia occurred mostly (54%) on the first day after administration of IVIG. There was a positive correlation between the onset of neutropaenia and lower age of patients (p < 0.05). What is more, the decrease in the neutrophil count was more distinct in the group of subjects with neutropaenia. Conclusions: Intravenous immunoglobulin therapy in children with ITP can lead to neutropaenia. However, patients benefit noticeably from IVIG therapy, and neutropaenia in this case tends to be a transient, self-limiting condition. [ABSTRACT FROM AUTHOR]

Introduction: Acute leukaemias are complicated with numerous disease and treatment related medical complications. Infection is one of the major complications and is related to chemotherapy associated-neutropaenia. This study aims to identify medical complications in acute leukaemia patients during the induction chemotherapy period. Results: Medical complications were observed in patients receiving induction chemotherapy N=50. Infections and electrolyte disturbances were the most frequently observed complications (74% each) followed by chemotherapy induced neutropaenia (38%), alteration of liver functions (32%), steroid induced hyperglycaemia (28%) and bleeding (16%). Thrombosis and tumour lysis were detected at lesser frequencies (4% each). Among infections, the majority showed evidence of blood stream infection (27%) followed by pulmonary infections (24.3%). Gram negative organisms were the most frequently identified pathogen. Among the electrolyte disturbances, hypokalaemia (48%), hyponatraemia (48%), and hypocalcaemia (44%) were more prevalent. Mean duration from initiation of chemotherapy to neutrophil nadir was 10.05 days. Conclusions: Patients with acute leukaemia encounter a multitude of disease and treatment related medical complications during induction chemotherapy. Infection is the most common complication with higher rates of bacteraemia and gram-negative sepsis. This is likely to be a result of treatment related neutropaenia. However, further focused studies on neutropaenic sepsis during induction chemotherapy are recommended. Clinical vigilance, strict and improved infection control strategies are necessary to improve the outcome of these patients.

Abstract Background Glycogen storage disease type Ib (GSD Ib) is a severe disorder of carbohydrate metabolism due to bi-allelic variants in SLC37A4. It is associated with neutropaenia and neutrophil dysfunction, which has recently been attributed to the accumulation of 1,5-anhydroglucitol-6-phosphate (1,5AG6P) within neutrophils. Treatment with sodium-glucose co-transporter-2 (SGLT2) inhibitors, such as empagliflozin, is a novel therapy that reduces 1,5-anhydroglucitol (1,5AG) in plasma. Results We report our experience in treating 8 paediatric GSD Ib patients with empagliflozin with a cumulative treatment time greater than 12 years. Treatment with a median dose of 5 mg (0.22 mg/kg height weight) of empagliflozin resulted in improvement in bowel health, growth, and laboratory parameters. Plasma 1,5AG levels reduced by a median of 78%. Baseline 1,5AG levels in our cohort were higher than in adult patients with GSD Ib. Hypoglycaemia on empagliflozin treatment occurred in 50% of our cohort. Conclusion We report the largest single centre cohort of GSD Ib patients treated with empagliflozin to date. Treatment with SGLT2 inhibitors is a novel and favourable treatment option for neutropaenia and neutrophil dysfunction in GSD Ib. We suggest a low starting dose of empagliflozin with careful titration due to the risk of hypoglycaemia. The interpretation of 1,5AG levels and their role in treatment monitoring is yet to be established, and requires ongoing research.

Invasive fungal infection is a life-threatening complication of chemotherapy and neutropaenia in the haematology population. Trichoderma species rarely cause human disease but have been reported to cause invasive infection in the immunosuppressed. We present a case of invasive Trichoderma longibrachiatum pulmonary infection with fatal outcome in a neutropaenic patient with acute myeloid leukaemia. 2012 Elsevier Ltd. All rights reserved. [ABSTRACT FROM AUTHOR]

Abstract Glycogen storage disease type Ib (GSDIb) is characterized by hepatomegaly and fasting hypoglycaemia as well as neutropaenia and recurrent infections. We conducted a retrospective observational study on a cohort of patients with GSDIb across England. A total of 35 patients, with a median age of 9.1 years (range 1‐39 years), were included in the study. We examined the genotype and phenotype of all patients and reported 14 novel alleles. The phenotype of GSDIb in England involves a short fasting tolerance that extends into adulthood and a high prevalence of gastrointestinal symptoms. Growth is difficult to manage and neutropaenia and recurrent infections persist throughout life. Liver transplantation was performed in nine patients, which normalized fasting tolerance but did not correct neutropaenia. This is the first natural history study on the cohort of GSDIb patients in England.

Background: Glycogen storage disease type Ib (GSD Ib) is a severe disorder of carbohydrate metabolism due to bi-allelic variants in SLC37A4. It is associated with neutropaenia and neutrophil dysfunction, which has recently been attributed to the accumulation of 1,5-anhydroglucitol-6-phosphate (1,5AG6P) within neutrophils. Treatment with sodium-glucose co-transporter-2 (SGLT2) inhibitors, such as empagliflozin, is a novel therapy that reduces 1,5-anhydroglucitol (1,5AG) in plasma.Results: We report our experience in treating 8 paediatric GSD Ib patients with empagliflozin with a cumulative treatment time greater than 12 years. Treatment with a median dose of 5 mg (0.22 mg/kg height weight) of empagliflozin resulted in improvement in bowel health, growth, and laboratory parameters. Plasma 1,5AG levels reduced by a median of 78%. Baseline 1,5AG levels in our cohort were higher than in adult patients with GSD Ib. Hypoglycaemia on empagliflozin treatment occurred in 50% of our cohort.Conclusion: We report the largest single centre cohort of GSD Ib patients treated with empagliflozin to date. Treatment with SGLT2 inhibitors is a novel and favourable treatment option for neutropaenia and neutrophil dysfunction in GSD Ib. We suggest a low starting dose of empagliflozin with careful titration due to the risk of hypoglycaemia. The interpretation of 1,5AG levels and their role in treatment monitoring is yet to be established, and requires ongoing research. [ABSTRACT FROM AUTHOR]

Neutropaenic enterocolitis is a rare, life-threatening disease, characterised by fever and abdominal pain in the setting of neutropaenia. Neutropaenic enterocolitis as a complication of medical therapy in patients with rheumatoid arthritis has rarely been reported. Here we describe a patient with rheumatoid arthritis, who developed neutropaenic enterocolitis following a single dose of methotrexate.

Background: Children with X-linked agammaglobulinaemia (XLA) usually present with pneumonia and otitis media caused by pyogenic bacteria. Rarely, ecthyma gangrenosum (EG), a known cutaneous manifestation of Pseudomonas septicaemia present in XLA as the first presenting features. We report three cases of EG caused by P. aeruginosa in previously healthy boys, leading to the diagnosis of XLA. In addition, we provide a brief literature review on those cases of EG where an underlying XLA was eventually diagnosed. Methods: Three paediatric cases admitted to the intensive care unit with P. aeruginosa septicaemia associated with ecthyma gangrenosum were reviewed retrospectively. Laboratory workup consisted of microbiological, haematological and immunological investigations were analysed. Results: The ages of the three patients were: one year and six months, three years and five months, and five years and six months. All patients had septic shock and required mechanical ventilation. P. aeruginosa was isolated in the blood and/or skin lesions of all patients. Underlying hypogammaglobulinaemia and neutropaenia were detected in all patients. Treatment consisted of combined antipseudomonal antimicrobial therapy and surgical debridement. All patients survived. Subsequent B-cell measurement and Bruton's tyrosine kinase (BTK) protein and genetic analysis confirmed the diagnosis of XLA. Twelve other similar reported cases were reviewed and analysed based on their clinical presentation, diagnosis and treatment. Conclusion: P. aeruginosa sepsis should be treated as early as possible. The most common risk factor for ecthyma gangrenosum in XLA patients is neutropaenia. In previously healthy children presenting with EG, immunological evaluation is important to rule out an underlying immunodeficiency. [ABSTRACT FROM AUTHOR]

Neutropaenic enterocolitis (NE) is a life-threatening condition characterised by an inflammation of the colon and/or the small bowel in the background of chemotherapy-induced neutropaenia. A 16-year-old girl with acute myeloblastic leukaemia (AML) developed fever, right-sided abdominal pain and tenderness with severe neutropaenia. Initial ultrasound findings suggested acute appendicitis for which she had surgery. She developed recurrent symptoms 3 weeks later. Abdominal computed tomography (CT) scan showed features of NE, but she succumbed to the illness. Another 17-year-old boy with AML developed fever and severe right-sided lower abdominal pain and tenderness, following completion of induction chemotherapy. He was neutropaenic and abdominal CT was typical of NE. He was managed nonoperatively and symptoms resolved. The diagnosis of NE can be a dilemma. A high index of suspicion is needed to avoid a misdiagnosis of acute appendicitis.

Wolcott-Rallison syndrome (WRS) is a rare autosomal recessive disorder. It is characterized by neonatal/ early onset non-autoimmune insulin dependent diabetes (permanent neonatal diabetes mellitus-PNDM) associated with spondyloepiphyseal dysplasia, tendency to skeletal fractures and growth retardation. We report a child with features of WRS, born to consanguineous parents and with an older sister having similar clinical features.

What is known and objective: Haematological toxicities such as neutropaenia are a common side effect of ganciclovir (GCV); however, risk factors for GCV‐induced neutropaenia have not been well established. Decision tree (DT) analysis is a typical technique of data mining consisting of a flow chart–like framework that shows various outcomes from a series of decisions. By following the flow chart, users can estimate combinations of risk factors that may increase the probability of certain events. In our previous study, we demonstrated the usefulness of this approach in the evaluation of adverse drug reactions. Therefore, we aimed to construct a risk prediction model of GCV‐induced neutropaenia including severity grade. Methods: We performed a retrospective study at the Hokkaido University Hospital and enrolled patients who received GCV between April 2008 and March 2018. Neutropaenia was defined as an absolute neutrophil count (ANC) <1500 cells/mm3 and a decrease to <75% relative to baseline. We classified the patients who developed neutropaenia in three groups (Grades 2‐4) based on the National Cancer Institute‐Common Terminology Criteria for Adverse Events. Data collection was achieved through the retrieval of medical records. We employed a chi‐squared automatic interaction detection algorithm to construct the DT model and compared the accuracies to the logistic regression model (a conventional statistical method) to evaluate the established model. Results and discussion: In total, 396 adult patients were included in the study; 61 (15.4%) developed neutropaenia. Three predictive factors (hematopoietic stem cell transplantation, baseline ANC <3854 cells/mm3 and duration of therapy ≥15 days) were extracted using the DT analysis to produce five subgroups, the incidence of neutropaenia ranged between 1.7% and 52.8%. In each subgroup, patients who developed neutropaenia were categorized based on the severity. The accuracies of each model were the same (84.6%), which indicated precision. What is new and conclusion: We successfully built a risk prediction model of GCV‐induced neutropaenia including severity grade. This model is expected to assist decision‐making in the clinical setting. [ABSTRACT FROM AUTHOR]

Patients hospitalised in intensive care units (ICU) are a group of patients characterised by a high risk of invasive fungal infections (IFI). Infections caused by yeast-like fungi Candida spp. predominate, however in patients with immunosuppression and other risk factors for IFI, moulds of the genus Aspergillus, particularly Aspergillus fumigatus, are relatively common etiological agents of lower respiratory tract mycoses. The diagnosis of invasive aspergillosis is made after the presence of hyphae in biopsy samples of the lung tissue is confirmed or the fungus is found in lower respiratory tract cultures. Either of these must also be accompanied by the presence of clinical symptoms. Diagnostic imaging (radiological, computed tomography or magnetic resonance imaging) as well as serological tests (detecting fungal antigens) play a supportive role and should be interpreted along with clinical symptoms and additional tests. A reliable diagnosis of invasive pulmonary aspergillosis depends on detection of fungal mycelium in a biopsy sample from the lungs or isolation of the fungus in a culture of the sample obtained from the lower respiratory tract. Culture of bronchoalveolar lavage fluid (BALF) remains the gold standard in laboratory diagnostics of invasive pulmonary aspergillosis. In accordance with the guidelines of ECIL-6, IDSA and ESCMID/ECMM/ERS, as well as expert groups, the strongest recommendations in therapy of invasive aspergillosis apply to the use of voriconazole. The results of in vitro antimicrobial susceptibility testing of Aspergillus isolates confirm that this antifungal agent represents an effective therapeutic option in treatment of invasive fungal infections of this etiology. [ABSTRACT FROM AUTHOR]

The objectives of this study were to describe the characteristics and natural history of beta‐lactam‐induced severe neutropaenia and to evaluate the risk of recurrences after another beta‐lactam readministration. Reports of pure agranulocytosis associated with a beta‐lactam exposure within the 10 days preceding the neutropaenia were extracted from the French Pharmacovigilance Database over the year 2010. Cases with another evident cause or more likely attributable to another drug were excluded. Data were analyzed for demographics, clinical and biological features, prognosis factors, granulocyte colony stimulating factors administration and outcome. Sixty‐two cases were included (median age: 65 years). The median duration of treatment before neutropaenia was 16 days. In 47% of cases, the diagnosis was made on a systematic blood cell count. The median neutrophil count at nadir was 0.125 × 109/L, and bone marrow examination evidenced features of neutrophilic maturation arrest or aplasia in 21 patients, hyperplasia of granulopoietic cells in three and normal findings in five. Three patients developed severe sepsis. All but one recovered a normal blood cell count within 2–56 days after beta‐lactam discontinuation. The last patient died from recurrent severe septic shock. No significant effect of granulocyte colony stimulating factor on the mean duration of haematological recovery was found. Among the 21 patients who later received another beta‐lactam, two experienced recurrence of the neutropaenia after receiving a beta‐lactam from another subfamily. Beta‐lactam‐induced agranulocytosis was usually observed after prolonged treatment, and severe complications are uncommon. In most patients, a subsequent treatment with another beta‐lactam was well tolerated. [ABSTRACT FROM AUTHOR]

Neutropaenic enterocolitis (NE) is a life-threatening condition characterised by an inflammation of the colon and/or the small bowel in the background of chemotherapy-induced neutropaenia. A 16-year-old girl with acute myeloblastic leukaemia (AML) developed fever, right-sided abdominal pain and tenderness with severe neutropaenia. Initial ultrasound findings suggested acute appendicitis for which she had surgery. She developed recurrent symptoms 3 weeks later. Abdominal computed tomography (CT) scan showed features of NE, but she succumbed to the illness. Another 17-year-old boy with AML developed fever and severe right-sided lower abdominal pain and tenderness, following completion of induction chemotherapy. He was neutropaenic and abdominal CT was typical of NE. He was managed nonoperatively and symptoms resolved. The diagnosis of NE can be a dilemma. A high index of suspicion is needed to avoid a misdiagnosis of acute appendicitis. [ABSTRACT FROM AUTHOR]

• Ocrelizumab and rituximab are monoclonal antibodies that target and deplete CD20-expressing B cells. • Both ocrelizumab and rituximab are used as disease modifying therapies in patients with MS. • Both agents are known to reduce peripheral lymphocyte counts. • In rare instances neutropaenia can occur with usage of rituximab or ocrelizumab. • As neutropaenia can be associated with severe infections, routine monitoring for neutrophil counts are warranted. Ocrelizumab is an anti-CD20 monoclonal antibody (mAb) that has been shown in phase 3 clinical trials to reduce relapses and disease progression in multiple sclerosis (MS) patients. Prior to the approval of ocrelizumab, rituximab, a chimeric anti-CD20 mAb was used to treat MS. Rituximab is still used to treat MS in many countries outside of Australia and remains mainstay of treatment of many non-MS neuroimmunological and systemic inflammatory diseases. Rituximab is currently used in neuromyelitis optica spectrum disorder (NMOSD) and autoimmune encephalitis, in addition to its widespread usage in hematological malignancies and systemic inflammatory diseases. Ocrelizumab is currently approved in Australia for treatment of relapsing-remitting MS (RRMS). Neutropaenia is a rare complication of both ocrelizumab and rituximab treatment. This case series reports 12 patients who have experienced neutropaenia following ocrelizumab or rituximab treatment and aims to characterize the clinical parameters of neutropaenia experienced by these patients, including the severity and duration of neutropaenia, length of hospital admission, the types of subsequent infections experienced and types of treatment necessary before patients reached count recovery. The unpredictability of neutropaenia and potential for serious infections highlight the need for continued hematological monitoring for patients on B-cell depleting therapies and calls for careful patient counselling to provide guidance on whether to continue such therapies in patients who have experienced related neutropaenia. [ABSTRACT FROM AUTHOR]

Abstract Objectives Escherichia coli is the leading cause of bacteraemia. In an era of emerging multi-drug-resistant strains, development of effective preventative strategies will be informed by knowledge of strain diversity associated with specific infective syndromes/patient groups. We hypothesised that the number of virulence factor (VF) genes amongst bacteraemia isolates from neutropaenic patients would be lower than isolates from immunocompetent patients. Methods Immunocompetent and neutropaenic adults with E. coli bacteraemia were recruited prospectively and the source of bacteraemia determined. VF gene profiles were established in silico following whole genome sequencing. Results Isolates from individual patients were monoclonal. Strains from immunocompetent patients with urinary tract infective foci (UTIF) harboured more VF genes (median number of VF genes 16, range 8–24) than isolates from both immunocompetent patients with non-UTIF (10, 2–22, p = 0.0058) and neutropaenic patients with unknown focus of infection (NPUFI) (8, 3–13, p < 0.0001). Number of VF genes (OR 1.21, 95% CIs 1.01–1.46, p = 0.039) and urinary catheter/recurrent urinary tract infection (OR 12.82, 95% CIs 1.24–132.65, p = 0.032) were independent predictors of bacteraemia secondary to UTIF vs. non-UTIF in immunocompetent patients. papA, papC, papE/F, papG, agn43, tia, iut, fyuA, kpsM and sat were significantly more prevalent amongst UTIF- vs non-UTIF-originating isolates amongst immunocompetent patients, while papC, papE/F, papG, agn43, tia, fyuA, hlyA, usp and clb were significantly more prevalent amongst UTIF- vs NPUFI-associated isolates. Conclusions Bacteraemia-associated E. coli strains originating from UTIF have distinct VF gene profiles from strains associated with non-UTIF- and NPUFI. This diversity must be addressed in the design of future vaccines to ensure adequate coverage of strains responsible for site-specific disease. [ABSTRACT FROM AUTHOR]

Background: Artesunate is an antimalarial agent with broad anti-cancer activity in in vitro and animal experiments and case reports. Artesunate has not been studied in rigorous clinical trials for anticancer effects. Aim: To determine the anticancer effect and tolerability of oral artesunate in colorectal cancer (CRC). Methods: This was a single centre, randomised, double-blind, placebo-controlled trial. Patients planned for curative resection of biopsy confirmed single primary site CRC were randomised (n = 23) by computer-generated code supplied in opaque envelopes to receive preoperatively either 14 daily doses of oral artesunate (200 mg; n = 12) or placebo (n = 11). The primary outcome measure was the proportion of tumour cells undergoing apoptosis (significant if >7% showed Tunel staining). Secondary immunohistochemical outcomes assessed these tumour markers: VEGF, EGFR, c-MYC, CD31, Ki67 and p53, and clinical responses. Findings: 20 patients (artesunate = 9, placebo = 11) completed the trial per protocol. Randomization groups were comparable clinically and for tumour characteristics. Apoptosis in >7% of cells was seen in 67% and 55% of patients in artesunate and placebo groups, respectively. Using Bayesian analysis, the probabilities of an artesunate treatment effect reducing Ki67 and increasing CD31 expression were 0.89 and 0.79, respectively. During a median follow up of 42 months 1 patient in the artesunate and 6 patients in the placebo group developed recurrent CRC. Interpretation: Artesunate has anti-proliferative properties in CRC and is generally well tolerated.

The association of Pneumocystis jirovecii pneumonia (PJP) and acute myeloid leukaemia (AML) is not clearly defined. In our experience of 291 patients with AML, 20 (14 males and 6 females, median age 56) developed PJP (incidence 6.8%). Thirteen patients (65%) survived until discharge from hospital. We conclude that PJP is not uncommon among patients with AML. In clinical care of AML, awareness of PJP should be heightened and prophylaxis should be considered. [ABSTRACT FROM AUTHOR]

Interleukin-1 (IL-1) is the most important cytokine in the inflammation cascade activation in all tissues and is present in acute and chronic phases of inflammation. By blocking IL-1 binding to target cells, numerous inflammation processes are prevented. The use of autologous conditioned serum rich with IL-1 receptor antagonist protein (IL-1Ra) is a novel treatment method of tendon inflammation in domestic animals and humans. Injections of autologous conditioned serum (ACS) have demonstrated clinical efficacy and safety in animal models and humans in the treatment of osteoarthritis, disc prolapse and muscles and tendons injuries with low side effect. Neutropaenia, reduced white blood cell count, and infections or local irritations are described as side effects of IL-1 antagonist use in humans. Therefore, a study of blood changes in rabbits after local administration of IL-1Ra in the Achilles tendon tissue after iatrogenic inflammation was conducted. Interleukin-1 receptor antagonist protein was used to prevent and reduce tendon inflammation after longitudinal tenotomy. The study was done on 26 white Californian rabbits, divided into two equal groups consisting of 13 animals each; the experimental interleukin-1 receptor antagonist protein (irap) group, and the control group. In the irap group, autologous serum rich with IL-1Ra was used (Orthokine®vet irap, Alfa-Arthro, Croatia). Differences between two groups were considered significant as changes in the blood for certain blood elements at P < 0.01. The P value was P = 0.0153 for the white blood cells, P = 0.00153 for neutrophils, P = 0.00017 and for platelets. In the control group, an increased platelet count was noticed in 70% of blood samples and a decreased neutrophil count was found in all of the irap group samples at the end of the study in comparison to the initial blood count prior to application. [ABSTRACT FROM AUTHOR]

Late-onset neutropaenia is defined as an absolute neutrophil count of <1.5×10 3 cells/μL starting>4 weeks after the last dose of rituximab, in the absence of other identifiable causes. Late-onset neutropaenia is a rare adverse reaction to rituximab (observed in approximately 5% of patients). Rheumatic diseases constitute the main indication for rituximab; in these patients, neutropaenia appears after a mean of>28 days. Ocrelizumab is another monoclonal antibody that binds to CD20 (a glycosylated phosphoprotein mainly expressed on the membranes of B-lymphocytes); in January 2018, it was approved for the treatment of relapsing-remitting and primary progressive multiple sclerosis. We present a case of neutropaenia following intravenous infusion of ocrelizumab in a patient with primary progressive multiple sclerosis who presented with neutropaenic fever, herpetic stomatitis, and ecthyma gangrenosum only 20 days after infusion., (Copyright © 2021 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Non-typhoidal Salmonella (NTS) is an important pathogen that causes gastroenteritis, bacteraemia, and focal infections. Herein, we present our experience with bloodstream infections caused by Salmonella in paediatric leukaemia patients, which has been reported for the first time in both Europe and the US. According to our research, NTS might be a cause of serious infections in paediatric haematology- oncology patients. Following a low bacterial diet and increasing the hygiene of both the children and their surroundings would be beneficial in preventing these infections. [ABSTRACT FROM AUTHOR]

Background: Guidelines on the use of haematopoietic colony-stimulating factors for patients having adjuvant chemotherapy for breast cancer are designed to minimise the risk of neutropaenic infection (Smith TJ, Khatcheressian J, Lyman GH et al. Update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol 2006; 3: 187-205; Aapro MS, Bohlius J, Cameron DA et al. Effect of primary prophylactic G-CSF use on systemic therapy administration for elderly breast cancer patients. Breast Cancer Res Treat 2011; 47: 8-32; Carlson RW, Allred DC, Anderson BO et al. Breast cancer. Clinical practice guidelines in oncology. J Natl Compr Canc Netw 2009; 7: 122-192). Non-randomised data suggest that the achievement of planned dose intensity (DI) may have an important effect on survival. This trial compared the effects of granulocyte colony-stimulating factor, GCSF, against standard management following a first neutropaenic event (NE) in achieving planned DI. Patients and methods: Adult patients receiving adjuvant or neoadjuvant chemotherapy were randomised following a first NE, defined as hospitalisation due to neutropaenic fever, an absolute neutrophil count (ANC) ≤1.5 x 109/l requiring treatment delay or dose reduction of 15% or more of planned dose. The study was initially planned to enrol 816 patients to detect a difference of 10%. This was difficult to achieve in the timeframe and the trial size was amended. Thus, 407 patients were randomly assigned to filgrastim for 7 days or pegfilgrastim versus standard care. The amended study was designed to have 80% power to detect an absolute difference of 14% of planned DI between the two groups. Results: Most regimens were anthracycline-based many of which included a sequential taxane and/or were in clinical trials. Around 82.7% had an NE in the first three cycles. A total of 401 had calculable relative dose intensity (RDI) data. A target of 85% planned RDI was achieved in only 50% of patients in the control arm compared with 75% in the GCSF arm (P < 0.0001). A secondary end point revealed a reduction in post-randomisation NEs, 65.7% controls versus 18.2% with GCSF. Conclusions: Secondary intervention with GCSF showed a statistically significant improvement in the achievement of adequate RDI in non-intensive regimens. This may have important clinical implications for outcome. [ABSTRACT FROM AUTHOR]

Background Neutropaenic patients are at a high risk of contracting severe infections. In particular, in these patients, parameters with a high negative predictive value are desirable for excluding infection or bacteraemia. This study evaluated sepsis biomarkers in neutropaenic patients suffering from systemic inflammatory response syndrome ( SIRS). Further, the predictive capacities of evaluated biomarkers in neutropaenic SIRS patients were compared to non-neutropaenic SIRS patients. Material and methods In this prospective observational cohort study, patients with clinically suspected sepsis were screened. The predictive capacities of procalcitonin ( PCT), C-reactive protein and lipopolysaccharide-binding protein ( LBP) in neutropaenic SIRS patients were evaluated in terms of their potential to identify infection or bacteraemia and were compared to results for non-neutropaenic SIRS patients. To select an appropriate control cohort, propensity score matching was applied, balancing confounding factors between neutropaenic and non-neutropaenic SIRS patients. Results Of 3370 prospectively screened patients with suspected infection, 51 patients suffered from neutropaenic SIRS. For the identification of infection, none of the assessed biomarkers presented a clinically relevant discriminatory potency. Lipopolysaccharide-binding protein and PCT demonstrated discriminatory capacity to discriminate between nonbacteraemic and bacteraemic SIRS in patients with neutropaenia [receiver-operating characteristics-area under the curves ( ROC- AUCs): 0·860, 0·818]. In neutropaenic SIRS patients, LBP had a significantly better ROC- AUC than in a comparable non-neutropaenic patient cohort for identifying bacteraemia ( P = 0·01). Conclusion In neutropaenic SIRS patients, none of the evaluated biomarkers was able to adequately identify infection. LBP and PCT presented a good performance in identifying bacteraemia. Therefore, these markers could be used for screening purposes to increase the pretest probability of blood culture analysis. [ABSTRACT FROM AUTHOR]

At the University Hospital of Cologne, in general two patient groups at high risk for invasive aspergillosis receive posaconazole prophylaxis: Acute myelogenous leukaemia patients during remission induction chemotherapy and allogeneic haematopoietic stem cell transplant recipients. Other patients at risk undergo serum galactomannan testing three times weekly. At 72-96 h of persisting fever despite broad-spectrum antibiotics, or at onset of lower respiratory tract symptoms a thoracic computed tomography ( CT) scan is performed. Without lung infiltrates on CT, IPA is ruled out. In lung infiltrates not suggestive for IPA mycological confirmation is pursued. In patients without posaconazole prophylaxis empiric caspofungin will be considered. CT findings typical for IPA prompt targeted treatment, and mycological confirmation. Bronchoalveolar lavage ( BAL) is most important for cultural identification and susceptibility testing, and facilitates diagnosing other pathogens. BAL performance is virtually independent of platelet counts. If despite suggestive infiltrates BAL does not yield the diagnosis, CT-guided biopsy follows as soon as platelet counts allow. Surgery can also be beneficial in diagnosis and treatment of IPA. If the diagnosis of IPA is not established, mucormycosis is a valid concern. In patients with breakthrough IPA during posaconazole prophylaxis liposomal amphotericin B is the drug of choice. If no posaconazole prophylaxis was given, voriconazole is the treatment of choice for IPA. [ABSTRACT FROM AUTHOR]

Aims Low rates of adjuvant chemotherapy use are frequently reported in older women with early breast cancer. One of the reasons for this may be the risk of febrile neutropaenia or the perception that older patients will probably not complete the chemotherapy course prescribed. There are no data regarding these adverse outcomes in routine clinical practice. Patients and methods We identified 128 patients aged 70 years or over who received neoadjuvant or adjuvant chemotherapy for early breast cancer in seven UK cancer centres between 2006 and 2012. Data were collected regarding standard clinical and pathological variables and treatment toxicity and outcomes. Results Twenty-four patients (19%) had an episode of febrile neutropaenia. Overall, 27 patients (21%) did not complete their planned therapy. Chemotherapy discontinuation was more common in those patients with an episode of febrile neutropaenia (46% versus 16%, P = 0.004). Thirty patients (23%) were admitted with chemotherapy-related complications. There were no treatment-related deaths. Conclusions The rates of febrile neutropaenia and treatment discontinuation are high in women aged 70 years or over receiving adjuvant chemotherapy for breast cancer. Close attention should be paid to the choice or regimen and the use of supportive therapies in this patient population. [ABSTRACT FROM AUTHOR]

Abstract: We examined the performance of a real-time polymerase chain reaction (PCR) test (SeptiFast) for early detection of bloodstream infection in febrile neutropaenic patients. Blood samples from 201 patients were screened for pathogens by blood culture and by PCR on the first day of fever. PCR results were available earlier (median 3 days for bacteria, 5 days fungal pathogens; P ≤ 0.01). The sensitivity (0.74) and specificity (0.96) of the PCR test were acceptable for Gram negatives when culture was considered the gold standard, but sensitivity of the test was poorer for Gram-positive organisms (0.39). The PCR assay also led to 22.9% of invalid results. SeptiFast speeds the microbiological diagnosis of bloodstream infection in neutropaenic patients. However, the frequent failure of instrumental control procedures, the relatively poor sensitivity of the test, and the lack of phenotypic data on antimicrobial susceptibility associated with its high costs suggest that this assay cannot replace the blood cultures. [Copyright &y& Elsevier]

Objective: Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in preterm infants born prior to 32 weeks gestation or with a birth weight less than 1500 grams. In this article, we review hematological abnormalities associated with NEC. Methods: A literature search was performed using the databases PubMed, EMBASE, and Scopus, and the electronic archive of abstracts presented at the annual meetings of the Pediatric Academic Societies. Results: Thrombocytopenia, disseminated intravascular coagulation, increased or decreased neutrophil counts, and hemolytic anemia are frequent events in NEC. Conclusions: NEC is associated with several hematological abnormalities, which may play a direct or indirect role in the pathogenesis of gut mucosal injury, and may also carry important prognostic information. [ABSTRACT FROM AUTHOR]

Background In patients with chronic hepatitis C virus ( HCV) infection, the presence of peripheral blood cytopaenia may represent an obstacle to pegylated interferon and ribavirin treatment. Aims To evaluate the prevalence of anaemia, neutropaenia and thrombocytopaenia potentially limiting initiation of pegylated interferon and ribavirin treatment in patients with chronic HCV infection who were otherwise eligible for antiviral therapy. Methods We studied 3059 consecutive anti- HCV and HCV- RNA positive patients referred to our centre to be evaluated for antiviral therapy from June 2002 to May 2011. The European Association for the Study of Liver HCV guidelines were applied to assess eligibility for antiviral therapy. Results In the study cohort, 1,521 patients (49.7%) were not eligible for treatment because of reasons different from haematological abnormalities. In the remaining 1,538 patients the overall prevalence of any peripheral blood cytopaenia potentially preventing patients from being treated with antiviral therapy was 15.1%. In particular, anaemia (haemoglobin level < 12 g/dL for women, <13 g/dL for men) was a relative contraindication to treatment in 8.9% (137/1,538) of the patients, while thrombocytopaenia (platelet count cut-off, 90 × 109/L) and neutropaenia (absolute neutrophil count < 1.5 × 109/L) limited treatment in 6.5% (100/1358) and 3.2% (48/1358) of patients respectively. These haematological abnormalities were more prevalent in patients with older age ( P < 0.004) and cirrhosis ( P < 0.001). Conclusions The presence of peripheral blood cytopaenia may potentially limit initiation of antiviral therapy in one in every seven patients with chronic HCV infection who are otherwise eligible for treatment. [ABSTRACT FROM AUTHOR]

Background: There is uncertainty whether low-risk episodes of febrile neutropaenia (FN) in adult cancer patients are best managed in the in- or outpatient setting.Methods: A Monte Carlo cost-utility model was created to compare four treatment strategies for low-risk FN: (1) treatment in hospital with intravenous antibiotics (HospIV); (2) early discharge after 48 h in-patient observation, followed by oral outpatient treatment (EarlyDC); (3) outpatient management with IV antibiotics (HomeIV); and (4) outpatient management with oral antibiotics (HomePO). The model used a health-care payer perspective and a time horizon of one FN episode. Outcome measures were quality-adjusted FN episodes (QAFNE), costs (Canadian dollars) and incremental cost-effectiveness ratios (ICER). Parameter uncertainty was assessed with probabilistic sensitivity analyses.Results: HomePO was cost saving ($3470 vs $4183), but less effective (0.65 QAFNE vs 0.72 QAFNE) than HomeIV. The corresponding ICER was $10,186 per QAFNE. Both EarlyDC ($6115; 0.66 QAFNE) and HospIV ($13,557; 0.62 QAFNE) were dominated strategies. At a willingness-to-pay (WTP) threshold of $4,000 per QAFNE, HomePO and HomeIV were cost effective in 54 and 38% of simulations, respectively.Interpretation: For adult cancer patients with an episode of low-risk FN, treatment in hospital is more expensive and less effective than outpatient strategies. [ABSTRACT FROM AUTHOR]

White cell counts at rest might be lower in athletes participating in selected endurance-type sports. Here, we analysed blood tests of elite athletes collected over a 10-year period. Reference ranges were established for 14 female and 14 male sports involving 3,679 samples from 937 females and 4,654 samples from 1,310 males. Total white blood cell counts and counts of neutrophils, lymphocytes and monocytes were quantified. Each sport was scaled (1-5) for its perceived metabolic stress (aerobic-anaerobic) and mechanical stress (concentric-eccentric) by 13 sports physiologists. Substantially lower total white cell and neutrophil counts were observed in aerobic sports of cycling and triathlon (~16% of test results below the normal reference range) compared with team or skill-based sports such as water polo, cricket and volleyball. Mechanical stress of sports had less effect on the distribution of cell counts. The lower white cell counts in athletes in aerobic sports probably represent an adaptive response, not underlying pathology. [ABSTRACT FROM AUTHOR]

SAMPHAO S., EREMIN J.M. & EREMIN O. (2010) European Journal of Cancer Care 19, 707-713 Oncological emergencies: clinical importance and principles of management Oncological emergencies are common conditions associated with significant morbidity and mortality. Delay in diagnosis and treatment can result in unfavourable outcomes. Cancer itself, cancer-related hormones or cytokines, or treatment effects can cause emergency problems. Febrile neutropaenia, frequently associated with chemotherapy, can lead to life-threatening conditions. Treatment requires systematic evaluation and early empirical antibiotics. Hypercalcaemia of malignancy is the most common metabolic emergency in cancer patients. Non-specific clinical features may cause delay in diagnosis and increase morbidity and mortality. Treatment includes active fluid resuscitation, diuretics and intravenous bisphosphonates. Superior vena cava syndrome is usually caused by external compression. Computerised tomography is useful to confirm diagnosis, evaluate the extent of disease and guide invasive tissue diagnosis. Treatment and prognosis depend on the underlying malignancies. Spinal cord compression is a true emergency due to risk of permanent neurological impairment. Localised back pain is the most common presenting symptom while late presentation of neurological deficit is associated with irreversible outcomes. Magnetic resonance imaging is the investigation of choice. Treatment includes corticosteroids, radiotherapy and/or decompressive surgery. [ABSTRACT FROM AUTHOR]

There is an increased risk of infection in patients with neutropaenia, especially in those with neutrophil counts of less than 0·5 × 109/L, and neutropaenia-associated infection remains a limiting factor in treating malignancy especially of haematopoietic origin. Transfusing donor neutrophils is a logical approach to these problems, but granulocyte transfusion (GTx), a practice first advocated in the 1960s, is underused and although now enjoying resurgence, remains controversial. The aim of this study was to determine the practical aspects of GTx and clinical responses in patients receiving them. This is an observational retrospective review of GTx in patients undergoing therapy for predominantly haematological malignancies. We reviewed blood bank records and identified patients who received therapeutic granulocytes procured by leukapheresis and linked these recipients with their granulocyte donors. We determined the reasons for GTx and their clinical and relevant haematological responses to the transfusions. We identified 22 patients receiving at least three continuous days of GTx and who had adequate clinical and haematological data. Most donors were relatives and ABO matched with their respective recipients. Mean age of the patients was 28·8 years. Severe aplastic anaemia was the most common diagnosis, occurring in 9 patients (40·9%), followed by acute myeloid leukaemia in 6 (27·3%). Disseminated fungal infection was the most common reason for GTx, occurring in 16 patients (73%), followed by febrile neutropaenia in 7 patients. Fifteen (68·2%) patients showed clinical improvement. This uncontrolled retrospective observational study provides some evidence that procurement and use of GTx is safe for both donors and recipients and is probably an effective supportive therapy for patients with febrile neutropaenia [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Patients with febrile neutropaenia (FN) can be stratified according to their risk of significant complications, allowing reduced intensity therapy for low risk (LR) episodes. Serious events are very rare in low risk episodes making randomised trials difficult. Introduction of new evidence-based guidelines followed by re-auditing of the outcome is an alternative strategy. Methods: New guidelines for the management of LR FN were implemented in 4 specialist paediatric oncology centres (POCs) and in their associated shared care units (POSCUs). All patients commenced empirical intravenous antibiotic therapy and after 48h those with blood culture negative episodes designated LR were eligible for discharge on oral co-amoxiclav. Prospective data collection on FN episodes in all treatment centres was undertaken over a 1-year period. Results: Seven hundred and sixty two eligible episodes of FN were recorded in 368 patients; 213 episodes were initiated in POCs and 549 episodes were initiated in POSCUs. In 40% of episodes no clinical or microbiological focus of infection was found. At 48h, 212 (27%) episodes were classified as LR and 143 of these (19%) were managed on the LR protocol. There was a low hospital readmission rate (8/143 episodes; 5.6%), no intensive care admissions and no deaths in LR episodes. Almost all LR episodes (209/212) occurred in the shared care setting. Conclusions: Rapid step-down to oral antibiotics was a feasible and safe management strategy for LR FN in the shared care setting in England. [Copyright &y& Elsevier]

Abstract: We retrospectively analysed 153 patients with metastatic colorectal cancer who received FOLFOX with or without bevacizumab as first-line chemotherapy. Several background characteristics and chemotherapy features (grade of neutropaenia, use of bevacizumab or irinotecan, re-introduction of FOLFOX, and tumour progression) as time-varying covariates were analysed as potential prognostic factors. Of the 153 patients, mild neutropaenia (grade 1–2) occurred in 60 patients (39%) and severe neutropaenia (grade 3–4) occurred in 46 patients (30%). The other 47 patients (31%) did not experience neutropaenia. According to a multivariate Cox model with time-varying covariates, hazard ratios (HRs) of death were 0.55 (95% confidence interval (CI), 0.31–0.98; P =0.044) for patients with mild neutropaenia and 0.35 (95% CI, 0.18–0.66; P =0.002) for those with severe neutropaenia. Both mild and severe neutropaenia during chemotherapy are associated with improved survival in patients with MCRC. Prospective trials are required to assess whether dosing adjustments based on neutropaenia may improve chemotherapy efficacy. [Copyright &y& Elsevier]

The objective of this study was to assess the efficacy of an injection of 100 μg/kg of pegfilgrastim in haematopoietic recovery and mobilization in children following 32 courses of chemotherapy. End points were duration of neutropaenia, myeloid recovery and PBMC collection. Neutropaenia lasted a mean of 4.7 days (±2.13 days). Myeloid recovery occurred at a median of 10 days (inter quartile range (IQR) 8–11). Febrile neutropaenia complicated 13 courses (40.6%). Mobilization was observed in 20 out of 26 assessable courses (76.9%). The rise in CD34+ cells occurred at a median of 6 days (IQR 4–7) after PEG and remained >20 per μl for 6 days (IQR 4–8), with a median value of 80 per μl (IQR 48–170.5). The median CD34+ cell peak was 165 per μl (IQR 82.5–331), 9 days (range 6–14) after PEG. PBMC were collected on average at day +5 (+4 to +9) after PEG. In 93.3% of collections, at least 3 × 106 per kg CD34+ cells were collected through a single apheresis. Myeloid recovery occurred in all cases within 15 days, without concomitant thrombocytopaenia. The incidence of primary febrile episodes is in line with data in the literature and with our own historical experience. A long-lasting period of circulating CD34+ cells allowed for more accurate scheduling of apheresis.Bone Marrow Transplantation (2008) 42, 507–513; doi:10.1038/bmt.2008.206; published online 21 July 2008 [ABSTRACT FROM AUTHOR]

In 2005, 224 patients received adjuvant/neoadjuvant chemotherapy for breast cancer in a single institution according to daily practices. Regimens consisted of epirubicin-based chemotherapy (FEC100, four or six cycles), or three cycles of FEC100 followed by three cycles of docetaxel. An absolute blood count was carried out every 3 weeks, 1-3 days before planned chemotherapy cycle. Overall, 1238 cycles were delivered. An absolute neutrophil count (ANC) <1.5 x 10(9) l(-1) before planned chemotherapy was found in 171 cycles. Of these, 130 cycles (76%) were delivered as planned regardless of whether ANC levels recovered, and 41 (24%) were delayed. None of these patients developed a febrile neutropaenia. Haematopoietic support (granulocyte colony-stimulating factor (G-CSF)) was required in 12 cycles. We found that the majority of patients with an ANC <1.5 x 10(9) l(-1) before planned chemotherapy received planned doses, without complications and need for G-CSF. [ABSTRACT FROM AUTHOR]

Infections during neutropaenia contribute still significantly to mortality and morbidity after high-dose therapy and autologous stem cell transplantation. Further acceleration of haemopoietic recovery seems impossible for biological reasons. Another approach to shorten neutropaenia could be to remove drugs from high-dose therapy protocols with strong contribution to immunosuppression and neutropaenia and unproven antineoplastic activity. In this retrospective matched-pair analysis, conventional busulphan/cyclophosphamide (Bu/Cy) high-dose therapy was compared to single-agent busulphan conditioning before autologous stem cell transplantation. This modification led to a significant shorter neutropaenic interval by protraction of cell decrease and to a significant mitigation of neutropaenia. After single-agent busulphan conditioning, leucocytes dropped below 1/nl at median 1.5 days later when compared to the patients from the busulphanBu/Cy control group (P=0.001). In a significant percentage of patients (n=6, 60%) leucocytes did not fall below 0.5 cells/nl at any time. In contrast, all patients from the Bu/Cy control group experienced deep neutropaenia (P=0.004). Thrombocytopaenia and requirement for transfusions of platelets or red cells were not influenced. Antineoplastic activity seemed to be preserved as determined by survival analysis. In conclusion, modification of high-dose regimen with the intention to shorten neutropaenia with preserved antitumour activity could be an approach to reduce infection-related morbidity and mortality and to consider economic necessities.Bone Marrow Transplantation (2006) 37, 1087–1091. doi:10.1038/sj.bmt.1705390; published online 8 May 2006 [ABSTRACT FROM AUTHOR]

Ultrasound-guided percutaneous insertion of a long-term tunneled central venous catheter (TCVC) is now a very common procedure, but catheter-related sepsis remains a significant problem. This study aims to review our results concerning this complication. Fifty-seven central venous catheters were inserted into 50 patients percutaneously under ultrasound guidance in Queen Elizabeth hospital for between 1 March 2003 and 30 April 2004. Data was retrospectively collected and analysed from hospital records. This study had a successful placement rate of 100%. The overall complication rate was 31% (18 out of 57), comprised of four mechanical complications (all occurring within 30 days of insertion). There was no complication documented within the first 24 h. Fourteen patients developed infective complications, and of these eight patients were classified as catheter-related sepsis, all requiring premature removal of their catheters. There were in total 6161 catheter days, with the incidence rate of catheter-related sepsis of 1.2 per 1000 catheter days. The infecting organisms were heterogeneous, with the majority being Gram-positive cocci (47%). Our study found that patients who developed neutropaenia within 30 days after insertion were significantly associated with catheter-related sepsis ( P < 0.05). Insertion of TCVC under ultrasound guidance is a safe method with a high success rate. Incidence of catheter-related sepsis of TCVC under percutaneous guidance was comparable to the open method. Neutropaenia developing within 30 days after ultrasound-guided percutaneous insertion of central venous catheter may be associated with increased risk of catheter-related sepsis. [ABSTRACT FROM AUTHOR]

Thrombocytopaenia occurs during necrotizing enterocolitis (NEC), and nadir platelet count is associated with extent of disease. In paediatric meningococcal disease, the product of neutrophil and platelet count at admission is prognostically useful. We therefore aimed to determine whether the first full blood count (FBC) after diagnosis of NEC is useful as a score for poor outcome and severity of disease. Between 1987 to 2001, neutrophils (N), platelets (P) and their product (PN) was available in 187 neonates treated for NEC at our institution. Neonates with NEC were grouped according to the extent of disease (no gangrene, focal, multifocal and pan-intestinal). Data were not normally distributed so Mann-Whitney U test or analysis of variance (ANOVA) on logged data were used ( p<0.05 was considered significant). Receiver operating characteristics (ROC) curves were used to examine the relationship between specificity and sensitivity. A perfect test would have an ROC curve area of 1. Initial P count and PN product of non-survivors were both significantly lower than in survivors ( p<0.0001), whereas N was not different ( p<0.08). Low Log(10)PN was significantly associated with greater extent of disease (ANOVA; no gangrene vs multifocal, p<0.01, vs panintestinal, p<0.0005), suggesting that the initial FBC could be prognostically useful. Area under the ROC survival curve for neutrophils was 0.58, for platelets 0.75 and for PN product 0.71; thus, although no test performed extremely well, initial platelet count and NP product could be useful in evaluating disease severity in neonates with NEC and for further monitoring. [ABSTRACT FROM AUTHOR]

A patient with acquired immune deficiency syndrome (AIDS) with bilateral cytomegaloviral (CMV) retinitis who had become neutropaenic from intravenous gancyclovir, was treated with a total of 16 intravitreal 2 mg/0.l ml doses of gancyclovir in each eye under topical anaesthesia. The injections were well tolerated with no evidence of retinal toxicity. A moderate vitreous haze which did not affect vision was the only complication. The patient retained useful vision until the time of his death, three months later. [ABSTRACT FROM AUTHOR]

Late-onset neutropaenia is defined as an absolute neutrophil count of <1.5×10 3 cells/μL starting>4 weeks after the last dose of rituximab, in the absence of other identifiable causes. Late-onset neutropaenia is a rare adverse reaction to rituximab (observed in approximately 5% of patients). Rheumatic diseases constitute the main indication for rituximab; in these patients, neutropaenia appears after a mean of>28 days. Ocrelizumab is another monoclonal antibody that binds to CD20 (a glycosylated phosphoprotein mainly expressed on the membranes of B-lymphocytes); in January 2018, it was approved for the treatment of relapsing-remitting and primary progressive multiple sclerosis. We present a case of neutropaenia following intravenous infusion of ocrelizumab in a patient with primary progressive multiple sclerosis who presented with neutropaenic fever, herpetic stomatitis, and ecthyma gangrenosum only 20 days after infusion., (Copyright © 2021 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Clozapine is associated with haematological side effects, including neutropaenia, which can signal impending life-threatening agranulocytosis. Patients with COVID-19 infection frequently experience lymphopaenia, but not neutropaenia. We present 13 patients established on clozapine who developed COVID-19 infection. There were no significant differences in total white cell or neutrophil counts between pre-COVID-19, intra-COVID-19 or post-COVID-19 periods. We therefore suggest that patients who develop COVID-19 should generally have their clozapine treatment continued. Patients taking clozapine who develop neutroapaenia during COVID-19 infection should be investigated and monitored as in normal practice, because changes in neutrophil counts cannot be assumed to be due to the viral infection., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)