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Abstract Background The management of febrile neutropenia (FN) in pediatric cancer patients has traditionally been conducted in a hospital setting. However, recent evidence has indicated that outpatient management of FN can be equally effective compared to inpatient care. Based on this evidence, we conducted a cost-minimization analysis (CMA) specifically focused on pediatric cancer patients in Mexico. Methods A piggy-back study was conducted during the execution of a non-inferiority clinical trial that compared outpatient treatment to inpatient treatment for FN in children with cancer. A CMA was performed from a societal perspective using patient-level data. In the previous study, we observed that step-down oral outpatient management of low-risk FN was as safe and effective as inpatient intravenous management. Direct and indirect costs were collected prospectively. The costs were adjusted for inflation and converted to US dollars, with values standardized to July 2022 costs. Statistical analysis using bootstrap methods was employed to obtain robust estimations for decision-making within the Mexican public health care system. Results A total of 117 FN episodes were analyzed, with 60 in the outpatient group and 57 in the inpatient group; however, complete cost data were available for only 115 FN episodes. The analysis revealed an average savings of $1,087 per FN episode managed on an outpatient basis, representing a significant 92% reduction in total cost per FN episode compared to inpatient treatment. Length of hospital stay and inpatient consultations emerged as the primary cost drivers within the inpatient care group. Conclusion This CMA demonstrates that the step-down outpatient management approach is cost-saving when compared to inpatient management of FN in pediatric cancer patients. The mean difference observed between the treatment groups provides support for decision-making within the public health care system, as outpatient management of FN allows for substantial cost savings without compromising patient health.

Aim. To evaluate the effectiveness and safety of Extimia® (empegfilgrastim, JSC "BIOCAD") in reducing the frequency, duration of neutropenia, the incidence of febrile neutropenia (FN) and infections caused by FN in patients with solid tumors receiving myelosuppressive therapy. Materials and methods. The paper presents the final results of a multicenter prospective observational post-marketing study of the safety and effectiveness of Extimia® (empegfilgrastim) in patients with solid tumors receiving cytotoxic therapy. For the primary prevention of FN, all patients received empegfilgrastim at 7.5 mg subcutaneously once per course of chemotherapy (CT) 24 hours after the end of CT administration. The primary endpoint included an assessment of the relative dose-intensity (RDI) of the CT courses administered. The endpoints of interest included the assessment of the RDI of CT courses by nosology and CT regimen, the frequency of dose-limiting neutropenia, and the incidence of all adverse events (AEs) in patients who received at least one dose of the study medication, including serious AEs. Results. From February 2021 to December 2022, 3218 patients with various malignancies were included in 41 study centers of the Russian Fede- ration. Of these, 3217 (99.97%) patients received at least one dose of the study drug, and 2663 (82.8%) patients were included in the RDI evaluation population according to the study protocol. The mean age in this group was 56.9 (18–84) years. RDI ≥85% was achieved in 2,415 (90.7%) patients. The mean RDI was 96.2%, with a median of 100%. FN risk factors were present in 1216 (45.7%) patients, with age ≥65 years being the most common risk factor at 761/2663 (28.6%). It should be noted that in patients younger than 65 years, the RDI was 91.5%, and in elderly patients (≥65 years) 88.7%. Dose-limiting neutropenia was reported in 19 (0.7%) patients. There were 74 cases of grade 3–4 AEs (according to CTCAE v.5) in 59 (1.8%) patients. The most common were neutropenia, anemia, and diarrhea in 19 (0.7%), 7 (0.2%), and 6 (0.2%) patients, respectively. Serious AEs were reported in 17 patients (0.5%). Conclusion. Primary prophylaxis of FN with long-acting granulocyte colony-stimulating factor empegfilgrastim effectively maintains RDI in various nosological and therapeutic groups of patients with different CT regimens in real-world clinical practice.

Abstract Background This study aimed to investigate the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) for primary prophylaxis of neutropenia in patients with cervical cancer receiving concurrent chemoradiotherapy. Methods In this prospective, single-center, single-arm study, we enrolled patients (18–70 years) with 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IIIC1r-IVA and IVB (distant metastasis only with inguinal lymph node metastasis) cervical cancer. Eligible patients should have normal function of the bone marrow (absolute neutrophil count (ANC) ≥ 2.0 × 109/L) and adequate hepatic and renal functions. Key exclusion criteria included: previous chemotherapy and/or radiotherapy; a history of bone marrow dysplasia or other hematopoietic abnormalities. All patients underwent radical radiotherapy (pelvic radiotherapy or extended-field irradiation) plus brachytherapy. The chemotherapy regimen included four cycles of 3-weekly paclitaxel and cisplatin. PEG-rhG-CSF was administered 48–72 h after each treatment cycle. Salvage granulocyte colony-stimulating factor (G-CSF) was only permitted in certain circumstances. The primary endpoint was the incidence of grade 3–4 neutropenia. The secondary endpoints included frequency of febrile neutropenia (FN), chemotherapy completion rate in cycles 2–4, time to complete radiotherapy, and safety. Results Overall, 52 patients were enrolled in this study from July 2019 to October 2020. The incidence of grade 3–4 neutropenia was 28.8%, with an average duration of grade 3–4 neutropenia persistence of 3.85 days (1–7 days). The incidence rate of FN was 3.8%. The chemotherapy completion rate was 94.2%, 82.7%, and 75.0% for cycles 2–4, respectively. The incidences of grade 3–4 neutropenia for cycles 1–4 were 9.6% (5/52), 8.2% (4/49), 14.0% (6/43), and 2.6% (1/39), respectively. All patients completed radiotherapy within 8 weeks (median, 48 days; range: 41–56 days), except one patient who withdrew consent and did not receive radiotherapy. Severe non-hematologic toxicity was not observed in any patient. Conclusion PEG-rhG-CSF is an effective and safe prophylactic treatment for neutropenia in patients with cervical cancer undergoing concurrent chemoradiotherapy. Trial registration Chinese Clinical Trial Registry, ChiCTR1900024494. Date of Registration:13/July/2019.

Neutropenia and elevated concentrations of hepatic transaminases often lead to referrals from emergency or outpatient departments to relevant specialists to diagnose underlying inborn errors of metabolism. Glycogen storage disease type (GSD) Ib, a rare congenital disorder of glucose metabolism caused by the SLC37A4 gene mutations, shows various manifestations, including persistent neutropenia and elevated hepatic transaminases. Empagliflozin has demonstrated its efficacy in treating GSD Ib-associated neutropenia by reducing the entry of 1,5-anhydroglucitol-6-phosphate into the neutrophils. This article reports successful empagliflozin therapy for GSD Ib-related neutropenia in 2 Korean adolescents. Diagnosing GSD Ib is complex and usually initiated by a referral from emergency or outpatient departments when there is a high index of suspicion. Once diagnosed, empagliflozin shows promising outcomes in restoring counts and function of the neutrophils without severe adverse effects in children with GSD Ib, supporting it as a safe and effective therapeutic option for GSD Ib-associated neutropenia.

Neutropenia refers to a decrease in the absolute neutrophil count according to age and race norms and poses a common concern in pediatric practice. Neutrophils serve as host defenders and act crucially in acute inflammation procedures. In this narrative review, we systematically present causes of neutropenia in childhood, mainly adopting the pathophysiological classification of Frater, thereby studying (1) neutropenia with reduced bone marrow reserve, (2) secondary neutropenia with reduced bone marrow reserve, and (3) neutropenia with normal bone marrow reserve. Different conditions in each category are thoroughly discussed and practically approached from the clinician’s point of view. Secondary mild to moderate neutropenia is usually benign due to childhood viral infections and is expected to resolve in 2–4 weeks. Bacterial and fungal agents are also associated with transient neutropenia, although fever with severe neutropenia constitutes a medical emergency. Drug-induced and immune neutropenias should be suspected following a careful history and a detailed clinical examination. Cytotoxic chemotherapies treating malignancies are responsible for severe neutropenia and neutropenic shock. Rare genetic neutropenias usually manifest with major infections early in life. Our review of taxonomies clinical findings and associates them to specific neutropenia disorders. We consequently propose a practical diagnostic algorithm for managing neutropenic children.

Abstract Objective This retrospective study aimed to investigate the factors influencing the occurrence of neutropenia in patients with endometrial cancer (EC) following adjuvant chemoradiotherapy (CRT). Methods Retrospective analysis of EC patients who underwent adjuvant CRT from January 2012 to June 2023 in the Department of Gynecology and Oncology of the First Affiliated Hospital of Shandong First Medical University. Neutropenia was defined as an Absolute Neutrophil Count (ANC) of peripheral blood neutrophils below 2 × 109/L. Factors affecting neutropenia in EC patients treated with CRT using Generalized Estimating Equation (GEE), and Logistic regression was used to further analyze the effect of adding radiotherapy to different chemotherapy cycles on neutropenia, so that patients receive optimal adjuvant CRT while the risk of neutropenia is appropriately controlled. Results A total of 144 patients met the inclusion criteria. They underwent 330 cycles of adjuvant chemotherapy, of whom 96 (66.7%) developed neutropenia, which occurred 140 times. The results of one-way GEE analysis showed that before CRT, White Blood Cell (WBC) (OR = 0.827; 95%CI, 0.701–0.976), ANC (OR = 0.749; 95%CI, 0.586–0.957), Absolute Monocyte Count (AMC) (OR = 0.047; 95%CI, 0.008–0.283), Blood Urea Nitrogen (BUN) (OR = 0.857; 95%CI, 0.741–0.991), platinum and docetaxel (platinum/docetaxel) dosing regimen (OR = 2.284; 95%CI, 1.130–4.618) were associated with neutropenia with adjuvant CRT for EC (p

Aim: We present a case of Ecthyma gangrenosum (EG) affecting left thigh in a child with acute lymphoblastic leukaemia (ALL) with an aim to raise awareness about this condition. Case presentation: A 7-year-old female child who presented with lethargy, pallor and lumps to inner lip was diagnosed with B-cell precursor ALL. She was started on treatment as per UKALL 2011 guidelines Regime B. On day 28, she developed neutropenic sepsis along with a new lesion in her left thigh. She was started on intravenous Meropenum, Gentamicin and Caspofungin. The clinical diagnosis of EG was made based on lesion progression, positive blood and wound swab & tissue cultures for Pseudomonas aeruginosa and patient's immunocompromised status. The wound healed with secondary intention following debridement. We present a series of photographs to demonstrate her remarkable improvement. Discussion: EG occurs in 1–30% of cases of Pseudomonas sepsis; other bacteria and fungi can be associated with this condition. It is identified more in oncology patients as seen in our patient. A multidisciplinary team approach should be provided in 3 stages with empirical antibiotics, followed by targeted antibiotics or antifungals & surgical debridement. Our patient was treated in similar fashion and made a good recovery. Conclusion: It is a rare skin condition associated with a high mortality. We suggest all clinicians to be vigilant about this condition to be able to provide accurate diagnosis and prompt treatment to improve the overall prognosis.

Introduction: Systemic lupus erythematosus (SLE), the commonest type of lupus, is an autoimmune multisystemic disorder that can affect any organ system of the body, especially blood vessels and connective tissues, causing widespread inflammation. Pediatric onset of SLE is a rare condition with more hematological involvement. Aim: This study was undertaken to observe various hematological abnormalities and their association with various autoantibodies present in pediatric SLE in Eastern India. Methodology: It was a single-centered, cross-sectional, observational, hospital-based study conducted in the Department of Pediatric Medicine in collaboration with the Department of Rheumatology in IPGME and R and SSKM Hospital, Kolkata. The duration of the study was 1.5 years, and a total of 30 children up to 12 years of age of either gender were enrolled. Study participants were evaluated for various parameters like demographic, hematological (anemia, neutropenia, leucopenia, lymphopenia, and thrombocytopenia), biochemical (CRP, Lactate dehydrogenase (LDH), and bilirubin), autoantibodies (anti-dsDNA, anti-Ro 52, and anti-Ribonucleoprotein [RNP]), and SLE related pathologies (Cutaneous, nephritis, serositis). Results: In the present study, most of the participants had arthritis, muscle pain (86.66%), and hematological involvement (80%). Among cytopenias, anemia was the commonest. dsDNA autoantibody was positive in most of the patients (83%), and about one-third suffered from autoimmune hemolytic anemia (AIHA). No association was observed between autoantibodies and various hematological manifestations. Conclusion: It can be concluded from the present study that anemia is the most common cytopenia in pediatric SLE, but there is no association between autoantibodies and these cytopenias. However, study on larger population may give better results.

Abstract Background Traditional dosing of chemotherapy drugs based on body surface area may overdose small dogs, leading to an increased frequency of adverse events (AEs). Hypothesis/Objectives Evaluate the frequency of hematologic and gastrointestinal AEs in dogs with newly diagnosed lymphoma treated with vincristine weighing ≤15 kg in comparison to dogs weighing >15 kg. We hypothesized that dogs weighing ≤15 kg would experience a higher frequency of AEs. Animals One hundred and thirty‐eight dogs with newly diagnosed lymphoma were treated with vincristine. Methods A multicenter retrospective study reviewing hematologic data and medical record information. Complete blood counts were performed no more than 24 hours before vincristine administration and then between 4 and 8 days post‐administration. Data were evaluated using logistic regression or ordinal logistic regression. Results Thirty‐eight dogs weighing ≤15 kg and 100 dogs weighing >15 kg were included. The median vincristine dose for both groups was 0.6 mg/m2. Seventeen (12.3%) instances of neutropenia occurred with no significant difference in overall frequency or grade between groups. Thirty initially asymptomatic substage A dogs (29.4%) experienced gastrointestinal AEs. Because of the widespread use of gastrointestinal supportive care medications, statistical comparison between groups could not be performed. Seven instances of hospitalization occurred (5.0%) and the risk of hospitalization did not differ significantly between groups (P = .37). Conclusions and Clinical Importance Vincristine dosed at ≤0.6 mg/m2 does not increase the risk of hematologic AEs in dogs weighing ≤15 kg.

Barth syndrome (BTHS) is a rare X-linked recessive genetic disorder characterized by a broad spectrum of clinical features including cardiomyopathy, skeletal myopathy, neutropenia, growth delay, and 3-methylglutaconic aciduria. This disease is caused by loss-of-function mutations in the TAFAZZIN gene located on chromosome Xq28, resulting in cardiolipin deficiency. Most patients are diagnosed in childhood, and the mortality rate is highest in the early years. We report a case of acute, life-threatening metabolic decompensation occurring one day after birth. A novel TAFAZZIN splice site mutation was identified in the patient, marking the first reported case of such a mutation in BTHS identified in China. The report aims to expand our understanding of the spectrum of TAFAZZIN mutations in BTHS.

Abstract Background Mecapegfilgrastim, a long‐acting granulocyte‐colony stimulating factor has been approved for reducing the incidence of infection, particularly febrile neutropenia (FN), in China. Objective We conducted a multicenter prospective observational study to examine the safety and effectiveness of mecapegfilgrastim in preventing neutropenia in gastrointestinal patients receiving the chemotherapy, including S‐1/capecitabine‐based regimens or the fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI)/fluorouracil, leucovorin, and oxaliplatin (FOLFOX)/fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) regimens. Method Five hundred and sixty‐one gastrointestinal patients from 40 sites across China, between May 2019 and November 2021, were included. The administration of mecapegfilgrastim was prescribed at the discretion of local physicians. Results The most common adverse drug reactions (ADRs) of any grade for all patients was increased white blood cells (2.9%). Grade 3/4 ADRs were observed for anemia (0.2%), decreased white blood cells (0.2%), and decreased neutrophil count (0.2%). Among the 116 patients who received S‐1/capecitabine‐based chemotherapy throughout all cycles, ADRs of any grade included anemia (1.7%), myalgia (0.9%), and increased alanine aminotransferase (0.9%). No grade 3/4 ADRs were observed. In 414 cycles of patients who underwent S‐1/capecitabine‐based regimens, only one (0.2%) cycle experienced grade 4 neutropenia. In the FOLFIRINOX, FOLFOXIRI, and FOLFOX chemotherapy regimens, grade 4 neutropenia occurred in one (2.7%) of 37 cycles, four (4.7%) of 85 cycles, and two (1.2%) of 167 cycles, respectively. Conclusion In a real‐world setting, mecapegfilgrastim has proven effective in preventing severe neutropenia in gastrointestinal patients following chemotherapy. This includes commonly used moderate or high‐risk FN regimens or regimens containing S1/capecitabine, all of which have demonstrated favorable efficacy and safety profiles.

Abstract A previously healthy woman, 5 weeks pregnant, was admitted to the intensive care unit in critical condition for septic shock and acute respiratory distress syndrome due to methicillin‐resistant Staphylococcus aureus (MRSA) after being infected with Influenza for 3 days. The patient in this case suffered from severe sequelae due to necrotizing pneumonia and later died on the 20th day after admission. We would like to remind clinicians to be aware of this rare but serious diagnosis. The key is to begin appropriate treatment immediately because MRSA necrotizing pneumonia is mediated by toxins and once the toxins are released they cannot be limited by antibiotic treatments. Necrotizing pneumonia related to MRSA should be considered in young patients with pneumonia, sepsis, and neutropenia following seasonal influenza infection with rapidly progressive symptoms.

BackgroundHigh-intensity chemotherapy can cause life-threatening complications in pediatric patients. Therefore, this study investigated safety and efficacy of long-acting pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF; Jinyouli®) in children undergoing high-intensity chemotherapy.MethodsTreatment-naive patients received post-chemotherapy PEG-rhG-CSF as primary prophylaxis for two cycles. The primary endpoints were drug-related adverse events (AEs) and bone pain scores. Secondary endpoints included grade 3–4 neutropenia, duration of neutropenia recovery, absolute neutrophil count changes, febrile neutropenia (FN), reduced chemotherapy intensity, antibiotic usage, and AE severity. The cost-effectiveness of PEG-rhG-CSF was compared with that of rhG-CSF (Ruibai®).ResultsHere, 307 and 288 patients underwent one and two PEG-rhG-CSF cycles, respectively. Ninety-one patients experienced drug-related AEs, primarily bone pain (12.7%). Moreover, Grade 3–4 neutropenia and FN were observed. Median FN durations were 3.0 days in both cycles. No drug-related delays were observed during chemotherapy. One patient experienced grade 4 neutropenia-induced reduction in chemotherapy intensity during cycle 2. In total, 138 patients received antibiotics. PEG-rhG-CSF exhibited superior cost-effectiveness compared to rhG-CSF.ConclusionOur findings indicate that PEG-rhG-CSF is safe, efficient, and cost-effective in pediatric patients undergoing high-intensity chemotherapy, providing preliminary evidence warranting further randomized controlled trials.

Objective: to carry out a scoping review with the purpose of mapping the scientific evidence on the use of the neutropenic diet in neutropenic pediatric cancer patients. Source of data: The scoping review protocol was prepared in accordance with the PRISMA-ScR and the checklist before the literature search was performed. Articles on nutritional management in adults or on the treatment of other diseases, and articles that were not in Portuguese or English and published before the year 2000, were excluded. Data were extracted based on the Cochrane Consumer and Communication Review Group form. Summary of the findings: Three hundred and forty scientific articles were identified, with the final sample of this review consisting of nine studies. Although the neutropenic diet has been part of the nutritional management of pediatric cancer patients for more than 20 years, there is still great variation in the criteria for indicating use and starting and discontinuing it, as well as in the nutritional composition of the diet. Furthermore, there is no consensus on the impact of using a neutropenic diet on different clinical and nutritional outcomes. Conclusion: In the absence of guidelines that standardize the use of a neutropenic diet in pediatric patients with neutropenia, there are heterogeneous approaches reported in the literature, even within the same institution. The available literature presents an absence of evidence on the use, viability, and effectiveness of the neutropenic diet in oncological children with neutropenia. More studies are needed to identify the real impact of the neutropenic diet on clinical and nutritional outcomes.

Abstract Chronic disseminated candidiasis (CDC) is a severe but rarely seen fungal infection presenting in patients with hematologic malignancies after a prolonged duration of neutropenia. A high index of suspicion is required to diagnose CDC as standard culture workup is often negative. While tissue biopsy is the gold standard of diagnosis, it is frequently avoided in patients with profound cytopenias and increased bleeding risks. A presumptive diagnosis can be made in patients with recent neutropenia, persistent fevers unresponsive to antibiotics, imaging findings of hypoechoic, non-rim enhancing target-like lesions in the spleen and liver, and mycologic evidence. Here, we describe the case of an 18-year-old woman with relapsed B-cell acute lymphoblastic leukemia treated with re-induction chemotherapy who subsequently developed CDC with multi-organ involvement. The diagnosis was made based on clinical and radiologic features with positive tissue culture from a skin nodule and hepatic lesion. The patient was treated for a total course of 11 months with anti-fungal therapy, most notably amphotericin B and micafungin, and splenectomy. After initial diagnosis, the patient was monitored with monthly CT abdomen imaging that showed disease control after 5 months of anti-fungal therapy and splenectomy. The diagnosis, treatment, and common challenges of CDC are outlined here to assist with better understanding, diagnosis, and treatment of this rare condition.

Introduction: The introduction of immune checkpoint inhibitors (ICIs) has opened a new chapter in cancer treatment. Nevertheless, their use may result in immune-related adverse events (irAEs) with multifactorial determinants, complex mechanisms, and varying clinical implications. In specific cancer types, like melanoma, irAEs exhibit a complex relationship with patient outcomes. Case Presentation: We present a case of febrile neutropenia following ICI therapy in a patient with metastatic melanoma, underscoring the intricate clinical landscape associated with irAEs in the context of cancer immunotherapy. More specifically, a 68-year-old man was diagnosed with metastatic malignant melanoma and administered a combination of nivolumab and ipilimumab. However, after a single dose, the patient was hospitalized due to febrile neutropenia. The patient eventually recovered, but a diagnosis of myelosuppression related to prior immunotherapy led to treatment discontinuation. Subsequently, the patient transitioned to a second-line therapy. Conclusion: This case contributes to our comprehension of rare yet potentially severe hematological irAEs and their influence on immunotherapy outcomes. Such insights will guide future diagnostic and therapeutic strategies in the field of immunotherapy.

Abstract Ramucirumab plus docetaxel (RD) can cause febrile neutropenia (FN), which frequently requires the prophylactic administration of pegfilgrastim. However, the effects of prophylactic pegfilgrastim on FN prevention, therapeutic efficacy, and prognosis after RD have not been fully evaluated in patients with advanced non-small-cell lung cancer (NSCLC). Two hundred and eighty-eight patients with advanced NSCLC who received RD as second-line therapy after platinum-based chemotherapy plus PD-1 blockade were included. Patients were divided into groups with and without prophylactic pegfilgrastim, and adverse events, efficacy, and prognosis were compared between both groups. Of the 288 patients, 247 received prophylactic pegfilgrastim and 41 did not. The frequency of grade 3/4 neutropenia was 62 patients (25.1%) in the pegfilgrastim group and 28 (68.3%) in the control group (p

Abstract Inherited Metabolic Diseases (IMD) encompass a diverse group of rare genetic conditions that, despite their individual rarity, collectively affect a substantial proportion, estimated at as much as 1 in 784 live births. Among their wide-ranging clinical manifestations, cytopenia stands out as a prominent feature. Consequently, IMD should be considered a potential diagnosis when evaluating patients presenting with cytopenia. However, it is essential to note that the existing scientific literature pertaining to the link between IMD and cytopenia is limited, primarily comprising case reports and case series. This paucity of data may contribute to the inadequate recognition of the association between IMD and cytopenia, potentially leading to underdiagnosis. In this review, we synthesize our findings from a literature analysis along with our clinical expertise to offer a comprehensive insight into the clinical presentation of IMD cases associated with cytopenia. Furthermore, we introduce a structured diagnostic approach underpinned by decision-making algorithms, with the aim of enhancing the early identification and management of IMD-related cytopenia.

(1) Background: Aspergillus spp. is a widely distributed filamentous fungus in the environment due to its high sporulation capacity. Currently, invasive aspergillosis (IA) is the most common invasive fungal infection in patients with hematologic malignancies, with high rates of mortality and morbidity. The multifactorial nature of the disease requires appropriate risk stratification to enable the most appropriate preventive measures to be adapted and implemented according to the characteristics of the patient. In this sense, the present research aims to identify recent risk factors and environmental control measures against invasive aspergillosis to establish preventive actions to reduce the incidence of invasive aspergillosis in hospitals. (2) Methods: We conducted a qualitative systematic review of the scientific literature on environmental risk factors and preventive measures for invasive aspergillosis in patients with hematologic malignancies. The Medline, Cochrane, and Scopus databases were consulted, following the PRISMA and STROBE guidelines. (3) Results: Adequate implementation of environmental control measures is presented as the most efficient intervention in terms of prevention to decrease the incidence of invasive aspergillosis in hospitals. Neutropenia, fungal contamination, insufficient environmental control measures in hospital and home settings, length of hospital stay, and anemia, are identified as independent risk factors. We show that HEPA, LAF, and Plasmair® systems are suitable methods to reduce the concentration of airborne fungal spores. Antifungal prophylaxis did not significantly influence IA reduction in our study. (4) Conclusions: Proper professional training and environmental control measures in hospitals are essential for the prevention of invasive aspergillosis. We should optimize risk stratification for patients with hematologic malignancies. Antifungal prophylaxis should be complementary to environmental control measures and should never be substituted for the latter. Studies should also be undertaken to evaluate the efficiency of environmental control measures against IA at patients’ homes.

Background To evaluate the risk of neutropenia during treatment with anti-IL-23 antibodies in patients with psoriasis.Method We conducted an observational study with cohort design using MID-NET® in Japan. We identified patients with psoriasis who were newly prescribed anti-IL-23 antibodies, anti-IL-17-antibodies, adalimumab, or apremilast between January 1, 2009, and March 31, 2021. We estimated the adjusted hazard ratio (aHR) of anti-IL-23 antibodies compared to that of anti-IL-17 antibodies, adalimumab, or apremilast, for the risk of grade 2 (neutrophil count < 1,500/μL) or grade 3 (neutrophil count < 1,000/μL) neutropenia.Results Overall, 287 patients on anti-IL-23 antibodies, 189 patients on anti-IL-17 antibodies, 293 patients on adalimumab, and 540 patients on apremilast were included. Compared with anti-IL-17 antibodies, the aHR (95% confidence interval (CI)) of anti-IL-23 antibodies was 0.83 (0.27–2.51) for grade 2 and 0.40 (0.02–7.60) for grade 3 neutropenia; that when compared with adalimumab was 0.76 (0.28–2.06) for grade 2 but was not calculated for grade 3 as no cases were found; and that compared with apremilast was 3.88 (0.62–24.48) for grade 2 and 0.43 (0.02–11.63) for grade 3 neutropenia.Conclusion No clear increase in the risk of neutropenia with anti-IL-23 antibodies was observed.

Immune checkpoint inhibitors (ICIs) demonstrate unique advantages in the treatment of lung cancer and are widely used in the era of immunotherapy. However, ICIs can cause adverse reactions. Hematological toxicities induced by immunotherapy are relatively rare. Agranulocytosis, a rare hematologic adverse event associated with immune checkpoint inhibitors, has received limited attention in terms of treatment and patient demographics. Herein, we report the case of a 68-year-old male with non-small cell lung cancer(NSCLC) who received two cycles of programmed cell death-1 (PD-1) antibody sintilimab immunotherapy combined with albumin-bound paclitaxel and carboplatin chemotherapy and one cycle of sintilimab monotherapy. He was diagnosed with grade 4 neutropenia and sepsis (with symptoms of fever and chills) after the first two cycles of treatment. Teicoplanin was promptly initiated as antimicrobial therapy. The patient presented with sudden high fever and developed agranulocytosis on the day of the third cycle of treatment initiation, characterized by an absolute neutrophil count of 0.0×109/L. The patient was treated with granulocyte colony-stimulating factor but did not show improvement. He was then treated with corticosteroids, and absolute neutrophil counts gradually returned to normal levels. To the best of our knowledge, this is the first reported case of sintilimab-induced agranulocytosis in a patient with NSCLC. Sintilimab-induced severe neutropenia or agranulocytosis is a rare side effect that should be distinguished from chemotherapy-induced neutropenia and treated promptly with appropriate therapies; otherwise, the condition may worsen.

IntroductionGlycogen storage disease type 1b (GSD-1b) is characterized by neutropenia and neutrophil dysfunction generated by the accumulation of 1,5-anhydroglucitol-6-phosphate in neutrophils. Sodium-glucose co-transporter 2 inhibitors, such as empagliflozin, facilitate the removal of this toxic metabolite and ameliorate neutropenia-related symptoms, including severe infections and inflammatory bowel disease (IBD). Our case series presents the treatment of three pediatric GSD-1b patients with empagliflozin over a follow-up of three years; the most extended reported follow-up period to date.Cases descriptionA retrospective analysis of empagliflozin treatment of three pediatric GSD-1b patients (two male and one female; ages at treatment initiation: 4.5, 2.5 and 6 years) was performed. Clinical and laboratory data from a symmetrical period of up to three years before and after the therapy introduction was reported. Data on the clinical course of the treatment, IBD activity, the need for antibiotic treatment and hospitalizations, neutrophil count and function, and markers of inflammation were assessed. Prior the introduction of empagliflozin, patients had recurrent oral mucosa lesions and infections, abdominal pain, and anemia. During empagliflozin treatment, the resolution of aphthous stomatitis, termination of abdominal pain, reduced frequency and severity of infections, anemia resolution, increased appetite, and improved wound healing was observed in all patients, as well as an increased body mass index in two of them. In a patient with IBD, long-term deep remission was confirmed. An increased and stabilized neutrophil count and an improved neutrophil function enabled the discontinuation of G-CSF treatment in all patients. A trend of decreasing inflammation markers was detected.ConclusionsDuring the three-year follow-up period, empagliflozin treatment significantly improved clinical symptoms and increased the neutrophil count and function, suggesting that targeted metabolic treatment could improve the immune function in GSD-1b patients.

ObjectivesIn this study, we compared the dynamic changes in body composition during XELOX/SOX chemotherapy in patients with gastric cancer. Furthermore, we investigated the potential impact of these changes on the occurrence of toxic side effects.MethodsPatients with gastric cancer who received adjuvant or first-line XELOX/SOX chemotherapy between January 2020 and June 2023 were enrolled. The Brief Conghua Scale was used to assess energy intake, and nutritional management was carried out with reference to the Chinese Guidelines for Nutritional Therapy of Cancer 2020. The NRS 2002 Nutritional Risk Screening Scale, PG-SGA scale, bioelectrical impedance analysis, and dynamic changes in lumbar 3 vertebral skeletal muscle index were compared between baseline and post-chemotherapy in the study. The neutropenia was evaluated using the Common Terminology Criteria for Adverse Events V.5.0, developed by the National Institutes of Health.ResultsDynamic follow-up was completed in 39 cases, with a mean follow-up time of 117.62 ± 43.38 days. The incidence of sarcopenia increased significantly after chemotherapy, escalating from 46.2% to 51.3%. After chemotherapy, the mean L3SMI decreased from 36.00 cm2/m2 to 34.99 cm2/m2. Furthermore, when compared to pre-chemotherapy values, the body composition indexes body mass index (BMI), SL3, fat mass free index (FFMI), lean body mass (LBM), and body surface area (BSA) were significantly reduced after chemotherapy. Regardless of baseline or post-chemotherapy status, the incidence of grade ≥ 3 neutropenia was significantly higher in the sarcopenia group than in the non-sarcopenia group. Furthermore, when the skeletal muscle index decreased during chemotherapy, the incidence of grade ≥ 3 neutropenia was significantly higher in both the sarcopenia and non-sarcopenia groups compared to baseline. When the incidence of grade ≥ 3 neutropenia in the post-chemotherapy sarcopenia group was compared to baseline status, the increase was significantly higher in the sarcopenia group than in the maintenance/increase group.ConclusionsSkeletal muscle mass decreased progressively during XELOX/SOX chemotherapy in gastric cancer patients, followed by a higher incidence of grade ≥ 3 neutropenia.

Key Clinical Message Adalimumab has become essential for managing various chronic inflammatory diseases, including inflammatory bowel disease (IBD). While hematologic complications of adalimumab therapy are rare, they can have significant clinical implications. This report highlights the importance of recognizing and monitoring for neutropenia in patients receiving adalimumab treatment. We also describe the potential mechanisms and management strategies for this adverse event.

Key Clinical Message COVID‐19 infection may increase the likelihood of neutropenia in patients already on clozapine. In clozapine treated patients experiencing COVID‐19 associated neutropenia, adjunct therapy with lithium can be considered.

Objective To explore the risk factors for neutropenia (grade 2 or higher) during postoperative adjuvant radiotherapy for breast cancer. Methods A total of 93 patients with breast cancer treated by postoperative adjuvant radiotherapy in Shaanxi Provincial People’s Hospital from January 2018 to December 2020 were assigned to a control group (no neutropenia or grade 1 neutropenia, n=62) and an observation group (grade 2 or higher neutropenia, n=31). The clinical data of the two groups were analyzed by univariate and logistic regression analyses to determine the independent risk factors for grade 2 or higher neutropenia, and the predictive efficacy of risk factors was established by the receiver operating characteristic (ROC) curve. Results The univariate analysis results showed that there were significant differences between the two groups in molecular types of breast cancer, white blood cell count and absolute neutrophil count at the first visit, proportion of patients with grade 4 myelosuppression during chemotherapy, white blood cell count, absolute neutrophil count, hemoglobin before radiotherapy, planning target volume (PTV), mean radiotherapy dose to the sternum (Dmean), and ratio of volume exposed to radiation greater than 20 Gy to total vo-lume and ratio of volume exposed to radiation greater than 30 Gy to total volume in the sternum (χ2=4.511,9.900,t=2.286-9.900,P733.28 mL and sternum Dmean >2 213.5 cGy are independent risk factors for grade 2 or higher neutropenia during postoperative adjuvant radiotherapy for breast cancer, and the combination of the two indices can improve the predictive efficacy for the occurrence of neutropenia.

Aim. To assess the proportion and profile of patients at high risk of febrile neutropenia (FN) receiving cytotoxic chemotherapy (CT), as well as the incidence of FN and dose-limiting neutropenia after one cycle of CT. Materials and methods. The paper presents the results of the FLAME study, the first Russian observational study in patients with solid tumors who received only cytotoxic CT or a combination with targeted, immuno-oncological drugs. By random sampling, the study retrospectively included 500 patients with a median age of 59 years (18–83 years) from 25 medical institutions in the Russian Federation. Results. CT regimens with a high (20%) risk of FN were received by 25.2% (126/500) of patients; 53% (265/500) of patients had intermediate risk, and half of them (132/265 [49.8%]) had at least one additional risk FN factor following international NCCN guidelines. Thus, a high risk of FN, according to the therapy and the assessment of individual prognostic adverse factors, was noted in 51.6% (258/500) of patients. 36.8% (95/258) of patients with high risk for FN received primary prophylaxis with granulocyte colony-stimulating factors. Conclusion. The study showed a significant proportion of patients with a high risk of FN, and most of them do not receive primary prophylaxis of FN.

Abstract Background Several studies have reported an association between severe neutropenia and long-term survival in patients treated with trifluridine-tipiracil (TAS-102). Because some of these studies failed to address immortality time bias, however, their findings should be interpreted with caution. Additionally, the association between severe neutropenia and survival in patients receiving TAS-102 in combination with bevacizumab (Bmab) remains unclear. Patients and methods We conducted a single-center retrospective cohort study in patients with colorectal cancer who received Bmab + TAS-102. We compared overall survival (OS) between patients who developed grade ≥ 3 neutropenia during the treatment period and those who did not. To account for immortal time bias, we used two approaches, time-varying Cox regression and landmark analysis. Results Median OS was 15.3 months [95% CI: 14.1–NA] in patients with grade ≥ 3 neutropenia and 10.0 months [95% CI: 8.1–NA] in those without. In time-varying Cox regression, onset grade ≥ 3 neutropenia was significantly related to longer survival after adjustment for age and modified Glasgow Prognostic Score. Additionally, 30-, 60-, 90-, and 120-day landmark analysis showed that grade ≥ 3 neutropenia was associated with longer survival after adjustment for age and modified Glasgow Prognostic Score, with respective HRs of 0.30 [0.10–0.90], 0.65 [0.30–1.42], 0.39 [0.17–0.90], and 0.41 [0.18–0.95]. Conclusion We identified an association between long-term survival and the development of severe neutropenia during the early cycle of Bmab + TAS-102 using an approach that addressed immortality time bias.

Abstract Background Neutropenia is the most important cause of life-threatening invasive fungal infections (IFIs). Here, we studied the frequency and antifungal susceptibility profiles of Candida species that colonized or caused infections among neutropenic patients with solid or hematological malignancies. Methods A total of 362 clinical samples were collected from 138 patients. After initial isolation using a mix of mycological methods, isolates were screened using chromogenic culture media. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was applied for molecular identification. Positive or suspected cases were confirmed using the reference method of sequencing. Antifungal susceptibility testing for voriconazole and caspofungin was carried out using the microbroth dilution method. An in-silico assay was applied for phylogenetic analysis. Results Thirty-four Candida strains were isolated. C. albicans (47.06%) and C. glabrata (29.41%) were the most frequent strains. Antifungal treatment reduced the chance of Candida colonization by almost 76% in neutropenic patients (OR: 1.759; 95% CI: 1.349 to 2.390; p value: 0.000). An unusual and non-resistant strain, C. lambica, was reported from the bloodstream of a 56-year-old man with hematologic malignancy (HM). Eight isolates were non-susceptible, and one isolate was resistant to voriconazole. Also, four isolates were non-susceptible to caspofungin. Conclusion We can conclude that there is a cause-and-effect relationship between neutropenia, HM background, and Candida species separated from neutropenic patients, which can lead to possible infections. Further and repetitive studies are recommended using different molecular methods for better prediction and management of fungal infections in neutropenic patients.

Abstract SARS-CoV-2 vaccination is strongly recommended, particularly for fragile patients such as those undergoing active oncological treatments. It is crucial to conduct post-marketing surveillance in this patient population. In our study, we conducted a retrospective analysis of real-world data, including 136 patients who received SARS-CoV-2 vaccines and were undergoing anticancer treatments between March 1st and June 30th, 2021. All patients received mRNA vaccines, namely Pfizer-BioNTech’s COMIRNATY (BNT162b2 mRNA) and Moderna’s mRNA-1273 COVID-19 vaccines. We collected blood samples from the patients one week to 10 days before and after vaccine administration to assess full blood count with white cell differentials. Additionally, we monitored serology titers to detect any previous SARS-CoV-2 infection before hospital admission and tracked changes over time. Our findings revealed a significant occurrence of leukopenia following both the first and second vaccine doses among patients receiving chemotherapy and chemo-immunotherapy. Importantly, this effect was independent of demographic factors such as sex, age, and Body Mass Index. In the chemo-immunotherapy treated group, we observed that concomitant immune-mediated diseases were significantly associated with leukopenia following the second vaccine dose. Notably, in healthy subjects, transient neutropenia was recognized as an adverse event following vaccination. The observed lymphocytopenia during SARS-CoV-2 infection, combined with the impact on leukocyte counts observed in our study, underscores the need for larger post-marketing surveillance studies. Despite a treatment delay occurring in 6.6% of patients, the administration of mRNA vaccines did not have a significant impact on the treatment schedule in our series. These findings from a real-world setting provide valuable insights and suggest avenues for further prospective studies to explore potential complex interactions specific to this patient population.

Abstract Background The intravenous form of fosfomycin, a bactericide antibiotic used to treat multiresistant bacterial infections is little prescribed. The most common reported adverse effects are hypokaliemia and hypernatremia. We describe a case of agranulocytosis, a rarely described side effect that may be fatal. Case presentation A 45 year-old woman was admitted to the intensive care unit for post-surgical meningitis following meningioma resection. Meropenem and vancomycin were first introduced. A DRESS-syndrom with meropenem was suspected. Neutropenia was diagnosed three days after the introduction of parenteral fosfomycin and agranulocytosis four days later. Eosinophilia was also observed. A bone marrow aspiration was performed showing a disappearance of the neutrophil granulocyte line and a significant eosinophilia. Meropenem was discontinued. Fosfomycin was maintained and filgrastim was added. As filgrastim had no effect, the relationship with fosfomycin was suspected, so it was then withheld. An increase of the neutrophil count was observed. Because of the complexity of the case, the unfavorable course of the illness and the urgent need for revision surgery, a rechallenge with fosfomycin was done followed by a decrease of the neutrophil count. Conclusion This is the third paper reporting agranulocytosis induced by fosfomycin, and the first detailed description of a case. Based on chronological and semiological criteria and bibliographic data, the event was qualified as probable with the Naranjo adverse drug probability scale. Literature data is scarce. The summary of product characteristics mentions that only a few cases of transient neutropenia and agranulocytosis have been reported. An analysis of the FDA Adverse Event Reporting System Database highlighted a higher than expected frequency of agranulocytosis in patients treated with fosfomycin. Parenteral fosfomycin is often used in patients receiving other medications, so that it is rarely the only suspect. In our case, the results of the bone marrow aspiration, the sudden drop of the neutrophil count with concomitant eosinophilia and the absence of improvement despite the dose decrease, point towards an immuno-allergic mechanism. However, the overlap between the suspected DRESS induced by meropenem and the agranulocytosis do not allow to conclude with certainty on the causality. Awareness should be raised about this side effect.

Objective: Recurrent oral ulcers and severe periodontal diseases in patients with quantitative or qualitative neutrophil defects highlight the important role of neutrophils in maintaining oral mucosal barrier homeostasis. Recurrent aphthous stomatitis (RAS) is a common oral mucosal disease affecting up to 25% of the population, yet its etiopathogenesis remains unclear, and management is unsatisfactory. This review aims to gain insight into the pathogenesis of RAS. Design: This narrative review examines the characteristics of oral and blood neutrophils, the associations between neutrophil defects and the occurrence of oral ulcers, and the evidence for the involvement of neutrophils in RAS. To conduct the review, relevant literature was searched in PubMed and Google Scholar, which was then thoroughly reviewed and critically appraised. Results: Neutropenia, specifically a decrease in the number of oral neutrophils, impaired extravasation, and defective ROS production appear to be associated with oral ulcers, while defects in granule enzymes or NETosis are unlikely to have a link to oral ulcers. The review of the histopathology of RAS shows that neutrophils are concentrated in the denuded area but are latecomers to the scene and early leavers. However, the evidence for the involvement of neutrophils in the pathogenesis of RAS is inconsistent, leading to the proposal of two different scenarios involving either impaired or hyperactive neutrophils in the pathogenesis of RAS.

Resistant schizoaffective disorder has persistent psychotic symptoms and intermittent mood swings. A satisfying method for treating these patients is the use of the antipsychotic drug clozapine, but its use is limited due to significant side effects such as leukopenia and neutropenia. Lithium carbonate is another psychiatric drug that reduces these side effects. We hypothesized that lithium, along with clozapine, in addition to controlling side effects, could have a dual effect on mood episodes in schizoaffective disorder, and used it in a chronic case. The patient was a 48-year-old man with a 20-year history of the disease. Therefore, the use of lithium along with clozapine is recommended in refractory schizoaffective patients.

Abstract Neutropenia is the most common hematological toxicity of concurrent chemoradiotherapy (CCRT), and leads to subsequent treatment delays and/or dose reductions. Neutropenia often advances to febrile neutropenia and serious infections, which can affect the prognosis and safety of patients. The reasonable prevention and management of neutropenia is vital for patients with malignancies undergoing CCRT. Pegylated recombinant human granulocyte colony‐stimulating factor (PEG‐rhG‐CSF), a long‐acting recombinant human granulocyte colony‐stimulating factor, can prevent and treat neutropenia in more convenient clinical settings. Based on relevant guidelines and the most recent clinical data, the Chinese Association for Therapeutic Radiation Oncologists, China Society for Radiation Oncology, and Chinese Association of Radiation Therapy have evaluated the safety and efficacy of PEG‐rhG‐CSF during CCRT, clearly defined the clinical pathway and route of administration for the prevention and treatment of neutropenia, and formed a Chinese expert consensus on PEG‐rhG‐CSF application during CCRT, with the goal of promoting the reasonable clinical use of this treatment.

Abstract Background Additional efficacious immunomodulatory treatment is needed for the management of immune‐mediated disease in horses. Mycophenolate mofetil (MMF) is an immunosuppressive drug that warrants assessment as a viable therapeutic agent for horses. Hypothesis/Objectives To evaluate the pharmacokinetics (PK) of multiple‐day oral dosing of MMF in healthy horses and to determine the tolerability of this dosing regimen. Animals Six healthy Standardbred mares. Methods Horses received MMF 10 mg/kg PO q12h for 7 days in the fed state. Serial sampling was performed over 12 hours on Days 1 and 7 with trough samples collected every 24 hours, immediately before morning drug administration. Noncompartmental PK analyses were performed to determine primary PK parameters, followed by calculation of geometric means and coefficients of variation. A CBC, serum biochemical profile, physical examination, and fecal scoring were used to assess dose tolerability. Results Seven days of treatment resulted in a mycophenolic acid (MPA) area under the curve (AUC0‐12) of 12 594 h × ng/mL (8567‐19 488 h × ng/mL) and terminal half‐life (T1/2) of 11.3 hours (7.5‐15.9 hours), yielding minor metabolite accumulation in all horses treated. Salmonellosis was detected in the feces of 2 horses by Day 7, and all horses developed myelosuppression, hyperbilirubinemia, hyporexia, decreased gastrointestinal motility, and decreased fecal output by the seventh day of treatment. Conclusion and Clinical Importance Administration of MMF at 10 mg/kg PO q12h resulted in hematologic and clinical toxicity within 1 week of treatment. A decreased MMF dose, frequency, or both is needed to avoid colic. Drug monitoring should include frequent hemograms, serum biochemical profiles, and strict biosecurity protocols.

Abstract Agranulocytosis is a rare and life-threatening side effect of antithyroid drugs (ATD); it has been reported in

A triad of symptoms characterises Felty's syndrome: seropositive rheumatoid arthritis (RA), splenomegaly and neutropenia. The treatment of Felty's syndrome is based on using classic synthetic and biological disease-modifying drugs (DMARDs). In this article, we present a case of a patient with Felty's syndrome who was treated with biologic treatment. A systematic search of the literature on the electronic medical database was conducted. The drugs from the DMARD group, despite reducing the activity of the disease, may cause significant clinical complications. It is important to know about the diagnosis, differentiation and treatment of neutropenia and the prevention of febrile neutropenia. The article discusses the current therapeutic possibilities using both classical and biologic DMARDs.

Severe chronic neutropenia is classified as severe congenital, cyclic, autoimmune, or idiopathic. However, there is a lot of uncertainty regarding the diagnosis of severe congenital neutropenia (SCN) and chronic idiopathic neutropenia, and this uncertainty affects further evaluations and treatments. A 20-year-old man presented with fever and knee abrasions after a bicycle accident. On admission, his initial absolute neutrophil count (ANC) was 30/µL. He had no medical history of persistent severe neutropenia with periodic oscillation of ANC. Although his fever resolved after appropriate antibiotic therapy, ANC remained at 80/µL. Bone marrow (BM) aspiration and biopsy were performed, and a BM smear showed myeloid maturation arrest. Moreover, genetic mutation test results showed a heterozygous missense variant in exon 4 of the neutrophil elastase ELANE: c597+1G>C (pV190-F199del). The patient was diagnosed with SCN. After discharge, we routinely checked his ANC level and monitored any signs of infection with minimum use of granulocyte colony-stimulating factor (G-CSF), considering its potential risk of leukemic transformation. Considering that SCN can be fatal, timely diagnosis and appropriate management with G-CSF are essential. We report the case of a patient with SCN caused by ELANE mutation who had atypical clinical manifestations. For a more accurate diagnosis and treatment of severe chronic neutropenia, further studies are needed to elucidate the various clinical features of ELANE.

Abstract Background Neutropenic children with hematological diseases were associated with higher morbidity of carbapenem-resistant enterobacteriaceae (CRE) blood-stream infection (BSI) or colonization. But it was still murky regarding clinical characteristics, antimicrobial susceptibility, and outcomes of CRE-BSI in these patients. We aimed to identify the potential risk factors for subsequent bacteremia and clinical outcome caused by CRE-BSI. Methods Between 2008 and 2020, 2,465 consecutive neutropenic children were enrolled. The incidence and characteristics of CRE-BSI were explored in CRE-colonizers versus non-colonizers. Survival analysis was performed and risk factors for CRE-BSI and 30-day mortality were evaluated. Results CRE-carriers were identified in 59/2465 (2.39%) neutropenic children and19/59 (32.2%) developed CRE-BSI, while 12/2406 (0.5%) of non-carriers developed CRE-BSI (P

Shuyun Wang,1 Yan Song,1 Nan Shi,1,2 Donghong Yin,1 Jianbang Kang,1 Wanni Cai,2 Jinju Duan1 1Department of Pharmacy, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Department of Pharmacy, School of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of ChinaCorrespondence: Jinju Duan, Department of Pharmacy, Second Hospital of Shanxi Medical University, Wuyi Road, Xinghualing District, Taiyuan, Shanxi, People’s Republic of China, Tel +86 13834653172, Email duanjinju@163.comPurpose: The aim of this study was to investigate the current epidemiology, its changes during the study years, and inflammatory biomarkers of bacterial bloodstream infections (BSIs) in neutropenic patients with hematological malignancies. We assessed mortality risk factors and multidrug-resistant (MDR) gram-negative BSI predictors.Patients and Methods: We conducted a retrospective study from January 2015 to December 2021, which included adult neutropenic oncohematological patients with confirmed BSIs. We used univariable and multivariable analyses to analyze the risk factors. Each index’s reliability for bacterial BSI diagnosis was assessed using the receiver-operating characteristic curve and area under the curve.Results: A total of 514 isolates were obtained from the 452 patients. The average mortality was 17.71%. Gram-negative organisms were the predominant causes of BSI. Escherichia coli was the most common microorganism (49.90%). The overall variation trend of the isolation rate of MDR and carbapenem-resistant gram-negative bacteria increased. Multivariate analysis indicated that: 1) neutropenia that lasted for more than 7 days, patients ≥ 60 years of age, septic shock, hospitalization for > 20 days, BSI with a carbapenem-resistant strain, and treatment with linezolid or vancomycin in infections lasting less than 30 days were independent mortality risk factors; 2) severe neutropenia exceeding 7 days, unreasonable empirical therapy, and receipt of aminoglycosides or 3rd or 4th generation cephalosporins in infections lasting less than 30 days were independent risk factors of MDR gram-negative bacteria. Procalcitonin, absolute neutrophil count, and white blood cell indicate higher diagnostic accuracy for BSIs. Moreover, bacteria time to detection was better at differentiating Gram-negative and Gram-positive bacterial infections.Conclusion: We analyzed the risk factors for BSI neutropenic patients with hematological malignancies, the distribution of bacteria, antibiotic resistance, and the changes in clinical parameters. This single-center retrospective study may provide clinicians with novel insights into the diagnosis and treatment of BSI to improve future clinical outcomes.Keywords: bloodstream infection, neutropenia, hematological malignancy, pathogens distribution, antibiotic susceptibility, risk factors

Ribosomopathies are defined as inherited diseases in which ribosomal factors are mutated. In general, they present multiorgan symptoms. In spite of the fact that in cellular models, ribosomal insufficiency leads to a reduced rate of oncogenic transformation, patients affected by ribosomopathies present a paradoxical increase in cancer incidence. Several hypotheses that explain this paradox have been formulated, mostly on the assumption that altered ribosomes in a stem cell induce compensatory changes that lead to a cancer cell. For instance, the lack of a specific ribosomal protein can lead to the generation of an abnormal ribosome, an oncoribosome, that itself leads to altered translation and increased tumorigenesis. Alternatively, the presence of ribosomal stress may induce compensatory proliferation that in turns selects the loss of tumor suppressors such as p53. However, modern views on cancer have shifted the focus from the cancer cell to the tumor microenvironment. In particular, it is evident that human lymphocytes are able to eliminate mutant cells and contribute to the maintenance of cancer-free tissues. Indeed, many tumors develop in conditions of reduced immune surveillance. In this review, we summarize the current evidence and attempt to explain cancer and ribosomopathies from the perspective of the microenvironment.

In the present study, the influence of previous immune checkpoint inhibitor (ICI) therapy with ramucirumab (RAM) + docetaxel (DTX) therapy on the occurrence of severe neutropenia in patients with non-small cell lung cancer (NSCLC) was evaluated, taking into account the influences of cytotoxic chemotherapy used in pretreatment. The study participants included patients who received a combination therapy of RAM and DTX as cancer chemotherapy for NSCLC. The influences of previous ICI treatment and pretreatment with cytotoxic anticancer agents on the development of grade ≥ 3 neutropenia were analysed. A total of 89 patients, including 50 with and 39 without a history of ICI treatment, were analysed. Kaplan-Meier curves showed a significant difference in the influence of previous ICI treatment on the development of grade ≥ 3 neutropenia (p = 0.006). Moreover, Cox regression analysis identified a history of ICI treatment and prophylactic administration of G-CSF as factors associated with the development of grade ≥ 3 neutropenia (p = 0.018 and p < 0.001, respectively). This study found that previous treatment with ICIs reduced the incidence of grade ≥ 3 neutropenia after RAM + DTX therapy in patients with NSCLC, regardless of the influences of pretreatment with cytotoxic anticancer agents.

Bartonella henselae is associated with numerous clinical syndromes in people. Cats are the definitive hosts for B. henselae, develop high levels of bacteremia, and are associated with human infections, particularly in the presence of Ctenocephalides felis. Several antibiotic protocols used for the treatment of B. henselae infection in cats have failed to clear bacteremia. The purpose of this study was to assess the safety and efficacy of a high-dose pradofloxacin protocol to eliminate B. henselae bacteremia. Bartonella henselae infection was initiated in 8 cats by intravenous inoculation of infected feline blood and then pradofloxacin was administered at 7.5 mg/kg, PO, twice daily for 28 days, starting 12 weeks after inoculation. Complete blood cell counts were performed prior to pradofloxacin administration and then every 2 weeks for 10 weeks. Bartonella PCR assay was performed prior to pradofloxacin administration and approximately every 2 weeks for 10 weeks and then weekly for 4 weeks. Methylprednisolone acetate (5 mg/kg) was administered by intramuscular injection to all cats on week 10. The cats remained normal and none developed a hematocrit, platelet count, lymphocyte count, or neutrophil count outside of the normal reference ranges. In the one month prior to pradofloxacin administration, all cats were PCR-positive for Bartonella DNA on at least two of four sample dates; after pradofloxacin administration, all cats were negative for B. henselae DNA in blood on all nine sample dates. The protocol appears to be safe and failure to amplify B. henselae DNA from the blood after the administration of pradofloxacin and one dose of methylprednisolone acetate suggests either an antibiotic effect or the organism was cleared spontaneously.

Venetoclax is a Bcl-2 homology domain 3 (BH3) mimetic currently approved for the treatment of chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) that has proven to be highly effective in reinstating apoptosis in leukemic cells through the highly selective inhibition of the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2). Clinically, venetoclax has provided lasting remissions through the inhibition of CLL and AML blasts. However, this activity has often come at the cost of grade III/IV neutropenia due to hematopoietic cells’ dependence on Bcl-2 for survival. As life-threatening infections are an important complication in these patients, an effective management of neutropenia is indispensable to maximize patient outcomes. While there is general consensus over dose reduction and scheduling modifications to minimize the risk of neutropenia, the impact of these modifications on survival is uncertain. Moreover, guidelines do not yet adequately account for patient-specific and disease-specific risk factors that may predict toxicity, or the role combination treatment plays in exacerbating neutropenia. The objective of this review is to discuss the venetoclax-induced mechanism of hematological toxicity, the potential predictive risk factors that affect patient vulnerability to neutropenia, and the current consensus on practices for management of neutropenia.

Abstract Aims Neutrophils play a pivotal in immunity and inflammation. We aim to investigate the prevalence of neutropenia in the United States. Methods In this cross-sectional study, participants from the National Health and Nutrition Examination Survey (NHANES) (2011–2018) were enrolled. Demographic information, hematologic measurements, smoking status of all participants were collected for all participants. All statistical analyses were performed utilizing the NHANES survey weights. Covariate-adjusted linear regression was used to compare hematologic indices in different population grouped by age, sex, ethnicity, and smoking. We also employed multivariate-logistic regression to estimate the weighted odds ratio with a 95% confidence interval and predict the neutropenia risk among. Results 32,102 participants from NHANES survey were included, represented 286.6 million multiracial population in the United States. Black participants had lower mean leukocyte count (mean difference (MD): 0.71 × 109/L; P

Abstract Background Clozapine is the treatment of choice in refractory psychosis. In most countries, clozapine must be stopped indefinitely if white blood cells fall below a defined threshold during routine monitoring. Despite evidence of severe adverse consequences of clozapine discontinuation, published accounts on the lived experiences and perspectives of patients and carers are scarce. Method We completed semi-structured interviews with patients (n = 4) and family carers (n = 4) on experiences of clozapine cessation following suspected drug-induced neutropenia. Interviews were audio-recorded, transcribed and analysed thematically. Results The two overarching themes comprised:(i) stress of clozapine below threshold neutrophil results and (ii) patient and carer priorities. Conclusions There is a suggested need for evidence-based pharmacological and psychological approaches to support patients and carers after clozapine cessation. Such approaches will minimise the potentially negative physical and emotional sequela in the aftermath of a below threshold neutrophil result and reduce the likelihood of experiencing additional health and social inequalities after clozapine discontinuation.

Abstract Objectives To determine the clinical and laboratory differences between leukemic arthritis (LA) and juvenile idiopathic arthritis (JIA) at the onset of the disease. Material and methods Patients under 16 years of age, both genders, who presented for the first time to the pediatric rheumatology service with a diagnosis of probable JIA, with arthritis and without peripheral blood blasts, in which the final diagnosis was acute lymphoblastic leukemia (ALL) or JIA. The clinical and laboratory characteristics of the patients were compared, chi-square and relative risk were used for categorical variables, and the Mann–Whitney U and T-test for the comparison of means between groups. A binary logistic regression model was developed to differentiate leukemic arthritis from JIA. Results A total of 76 patients, 14 with LA and 62 with JIA, were analyzed. The mean age at diagnosis was lower in the leukemic arthritis group, the female gender prevailed in the JIA group, and the time to onset of symptoms was lower in the leukemic arthritis group. Patients with leukemic arthritis showed increased pain intensity, fever, weight loss, nocturnal diaphoresis, lymph node enlargement, hepatosplenomegaly, and pain that did not improve with analgesic administration. Laboratory parameters with statistical significance were the presence of anemia, leukopenia, and neutropenia. The platelet count was significant but in a low normal value, compared to the JIA. A binary logistic regression model was developed to differentiate leukemic arthritis from JIA. The probability associated with the statistic (Chi-square) was 0.000, and the Cox and Snell R2 and Nagelkerke R2 values were 0.615 and 1, respectively. The developed model correctly classified 100% of the cases. Conclusions The diagnosis of acute lymphoblastic leukemia should be ruled out in patients who present with arthritis and hematological alterations, mainly leukopenia and neutropenia, with joint pain disproportionate to the degree of arthritis, predominantly at night and that does not improve with the use of analgesics, fever, lymph nodes, and hepatosplenomegaly. Criteria are suggested to differentiate both diseases.

Here, we describe a case of temporary severe neutropenia after atezolizumab monotherapy and its treatment course. Atezolizumab monotherapy was introduced as a 6th-line treatment for a man in his late 60s, who was diagnosed with stage Ⅳ lung adenocarcinoma. The first treatment cycle was administered during hospitalization, and the patient presented with a fever of 37.8°C on the first day. The fever resolved after the administration of acetaminophen and naproxen, and the white blood cell count, neutrophil count, and other white blood cell fractions were normal. However, grade 3 leukopenia and grade 4 neutropenia appeared at the beginning of the third cycle, and treatment was discontinued. After treatment, monocyte count in the leukocyte fraction increased from approximately 10% to 25.6%. Lenograstim 100 μg subcutaneous injection and oral levofloxacin 500 mg once daily were started of onset of neutropenia, and he was hospitalized the next day. Laboratory findings upon admission showed a significant improvement to 5,300/µL for leukocytes and 3,376/µL for neutrophils. Lenograstim was discontinued, with no further decrease in the neutrophil count. Atezolizumab therapy was resumed, and there was no further reduction in leukocyte, neutrophil, or leukocyte fractions over about a 2-year period. Concomitant drugs were maintained during the atezolizumab treatment, suggesting that they did not induce neutropenia. In conclusion, we observed temporary severe neutropenia during atezolizumab monotherapy. Neutrophil recovery with cautious monitoring has enabled longer efficacy. We should consider temporary symptom occurrence in cases of haematological immune-related adverse events.