First onset of persistent neutropenia in patient undergoing long-term clozapine treatment after vaccination against COVID-19 and SARS-CoV-2 infection in short interval - a case report. / Pierwszorazowa uporczywa neutropenia u pacjenta przewlekle leczonego klozapina po szczepieniu przeciwko COVID-19, krótko poprzedzajacym infekcje wirusem SARS-CoV-2 ­ opis przypadku.

Clozapine is one of the most effective antipsychotic drugs, but its use is limited due to the possibility of severe side effects, such as neutropenia and agranulocytosis. The risk of these complications is the highest at the beginning of the treatment, but they can occur later, particularly when additional risk factors are present. In the described case, either COVID-19 vaccination or the infection itself led to severe neutropenia, which recurred during subsequent independent trials of other antipsychotic drugs. The paper presents the case of a 23-year-old woman diagnosed with early-onset, treatment-resistant schizophrenia who had been undergoing clozapine treatment with satisfying outcome for over 10 years. A week after the first dose of an mRNA vaccine against COVID-19, the patient developed a severe SARS-CoV-2 infection and experienced an extreme neutropenia, followed by a change of treatment. Although the patient fully recovered from the infection, the re-stabilization of her mental state remained unsatisfactory. The introduction of various newly implemented antipsychotic drugs led to partial improvement or another decline in the neutrophil count, despite discontinuing the use of clozapine. The authors discuss a few possible pathomechanisms. Based on our current knowledge, this is the first reported case of persistent neutropenia triggered by various antipsychotic drugs following exposure to SARS-CoV-2 antigens.

Early and late complications of hematopoietic stem cell transplantation.

As autologous stem cell transplantation (ASCT) is increasingly frequent in some patients with multiple sclerosis (MS), the knowledge of its adverse effects is paramount. Early complications (within 30 from transplantation) are usually due to conditioning regimen and consequent neutropenia. They include infections and noninfectious complications, such as oral and intestinal mucositis, increases in liver enzymes, hemorrhagic cystitis, and worsening of neurologic symptoms. Infections in the early phase, particularly during neutropenia, are mainly of bacterial origin, such as bloodstream infections, pneumonia, central-venous catheter-related infections, urinary infections, and neutropenic typhlitis, followed by viral reactivations. Prophylaxis with acyclovir against reactivation of herpes simplex virus (HSV) and varicella-zoster virus (VZV) is recommended, while a preemptive strategy is used for cytomegalovirus (CMV) and Epstein-Barr virus (EBV) management. Fungal infections are infrequent and mainly caused by Candida, thus fluconazole prophylaxis is used in some centers. Late complications include secondary autoimmune diseases: hematologic, such as immune thrombocytopenic purpura, autoimmune hemolytic anemia, or acquired hemophilia, or nonhematologic, such as thyroiditis, rheumatoid arthritis, or Crohn's disease. Other late complications are endocrinopathies and gonadal dysfunction with possible consequences on fertility. Particularly in women over 32 years of age, the risk of infertility and premature ovarian insufficiency can be significant. Thus, reproductive counseling with fertility preservation techniques if required is mandatory before ASCT.

A multicenter, prospective, non-interventional real-world study to assess the effectiveness of mecapegfilgrastim in preventing neutropenia in patients with gastrointestinal cancer.

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.

Mecapegfilgrastim for the prophylaxis of chemotherapy-induced neutropenia in locally advanced nasopharyngeal carcinoma: A prospective phase II clinical study.

BACKGROUND: Induction chemotherapy of docetaxel plus cisplatin (TP) is myelosuppressive, leading to severe neutropenia and febrile neutropenia (FN). Herein, we aimed to investigate the efficacy and safety of mecapegfilgrastim in the prevention of neutropenia in patients with locally advanced nasopharyngeal carcinoma who received the TP regimen. METHODS: A total of 30 treatment-naive patients with locally advanced nasopharyngeal carcinoma were included in this study. Mecapegfilgrastim 6 mg was injected 24-48 h after the completion of induction chemotherapy with the TP regimen. RESULTS: The incidence of grade ≥3 neutropenia during the three induction chemotherapy cycles was 6.7% (95% CI, 0.8%-22.1%). In the first cycle of chemotherapy, the incidence of grade ≥3 neutropenia was 3.3% (95% CI, 0.1%-17.2%). No FN or antibiotic usage was reported. All 30 patients completed the induction chemotherapy cycles. CONCLUSION: Mecapegfilgrastim effectively reduced the incidence of chemotherapy-induced neutropenia and FN in patients with locally advanced nasopharyngeal carcinoma.

Efficacy, safety, and cost-effectiveness of pegylated PEG-rhg-CSF in pediatric patients receiving high-intensity chemotherapy: results from a phase II study.

Background: High-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. Methods: Treatment-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®). Results: Here, 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. Conclusion: Our 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.

Novelties for the management of cytomegalovirus after kidney transplantation / Nouveautés dans la prise en charge du cytomégalovirus après transplantation rénale.

Cytomegalovirus (CMV) infection is the main opportunistic infection observed after kidney transplantation. Despite the use of prevention strategies, CMV disease still occurs, especially in high-risk patients (donor seropositive/recipient seronegative). Patients may develop complicated CMV, i.e. recurrent, refractory or resistant CMV infection. CMV prevention relies on either universal prophylaxis or preemptive therapy. In high-risk patients, universal prophylaxis is usually preferred. Currently, valganciclovir is used in this setting. However, valganciclovir can be responsible for severe leucopenia and neutropenia. A novel anti-viral drug, letermovir, has been recently compared to valganciclovir. It was as efficient as valganciclovir to prevent CMV disease and induced less hematological side-effects. It is still not available in France in this indication. Recent studies suggest that immune monitoring by ELISPOT or Quantiferon can be useful to determine the duration of prophylaxis. Other studies suggest that prophylaxis may be skipped in CMV-seropositive kidney-transplant patients given mTOR inhibitors. Refractory CMV is defined by the lack of decrease of CMV DNAemia of at least 1 log10 at 2 weeks after effective treatment. In case of refractory CMV infection, drug resistant mutations should be looked for. Currently, maribavir is the gold standard therapy for refractory/resistant CMV. At 8 weeks therapy and 8 weeks later, it has been shown to be significantly more effective than other anti-viral drugs, i.e. high dose of ganciclovir, foscarnet or cidofovir. However, a high rate of relapse was observed after ceasing therapy. Hence, other therapeutic strategies should be evaluated in order to improve the sustained virological rate.

L'infection à cytomégalovirus (CMV) est la principale infection opportuniste après transplantation rénale. Malgré les stratégies préventives, il persiste des maladies à CMV, notamment chez les patients à haut risque (donneur séropositif/receveur séronégatif). Certains patients présentent des formes complexes avec des récurrences et des infections réfractaires et/ou résistantes aux antiviraux. La prévention de l'infection à CMV repose soit sur une prophylaxie universelle, soit sur une stratégie préemptive. Chez les patients à haut risque, la stratégie prophylactique est le plus souvent utilisée. Elle repose sur l'utilisation du valganciclovir, qui peut être responsable de leucopénies et de neutropénies sévères. Un nouvel antiviral, le létermovir, qui n'est pas encore disponible sur le marché en France dans cette indication, a montré une efficacité similaire au valganciclovir avec peu d'effets secondaires hématologiques. Des études récentes suggèrent l'intérêt de l'immuno-surveillance par ELISPOT ou Quantiféron pour guider la durée de la prophylaxie. D'autres études suggèrent également la possibilité de se passer d'un traitement prophylactique anti-CMV chez des transplantés rénaux CMV-séropositifs recevant des inhibiteurs de la mTOR. Le CMV réfractaire est défini par une absence de baisse de la charge virale d'au moins 1 log10 après deux semaines de traitement efficace. En cas d'absence de baisse de la charge virale, une recherche de mutations de résistance aux antiviraux doit être effectuée. Actuellement, le maribavir constitue le traitement de référence pour les formes réfractaires et résistantes. La clairance virale à la fin du traitement, ou huit semaines plus tard, est significativement supérieure à celle observée avec les autres antiviraux tels que le ganciclovir donné à forte dose, le foscarnet, ou le cidofovir. Cependant, le taux de rechute à l'arrêt du traitement par maribavir reste important. D'autres stratégies thérapeutiques doivent être évaluées pour améliorer ce taux de réponse virologique soutenue.

Risk factors for prolonged infection and secondary infection in pediatric severe sepsis.

PURPOSE: Sepsis causes significant worldwide morbidity and mortality. Inability to clear an infection and secondary infections are known complications in severe sepsis and likely result in worsened outcomes. We sought to characterize risk factors of these complications. METHODS: We performed a secondary analysis of clinical data from 401 subjects enrolled in the PHENOtyping sepsis-induced Multiple organ failure Study. We examined factors associated with prolonged infection, defined as infection that continued to be identified 7 days or more from initial identification, and secondary infection, defined as new infections identified ≥ 3 days from presentation. Multivariable adjustment was performed to examine laboratory markers of immune depression, with immunocompromised and immunocompetent subjects analyzed separately. RESULTS: Illness severity, immunocompromised status, invasive procedures, and site of infection were associated with secondary infection and/or prolonged infection. Persistent lymphopenia, defined as an absolute lymphocyte count (ALC) < 1000 cells/µL twice in the first five days, and persistent neutropenia, defined as absolute neutrophil count (ANC) < 1000 cells/µL twice in the first five days, were associated with secondary and prolonged infections. When adjusted in multivariable analysis, persistent lymphopenia remained associated with secondary infection in both immunocompromised (aOR = 14.19, 95% CI [2.69, 262.22] and immunocompetent subjects (aOR = 2.09, 95% CI [1.03, 4.17]). Persistent neutropenia was independently associated with secondary infection in immunocompromised subjects (aOR = 5.34, 95% CI [1.92, 15.84]). Secondary and prolonged infections were associated with worse outcomes, including death. CONCLUSIONS: Laboratory markers of immune suppression can be used to predict secondary infection. Lymphopenia is an independent risk factor in immunocompromised and immunocompetent patients for secondary infection.

Mucositis-associated bloodstream infections in adult haematology patients with fever during neutropenia: risk factors and the impact of mucositis severity.

PURPOSE: Haematology patients with high-risk neutropenia are prone to mucosal-barrier injury-associated laboratory-confirmed bloodstream infections (MBI-LCBI). We assessed risk factors for MBI-LCBI including candidaemia in neutropenic haematology patients with fever. METHODS: This prospective observational study was performed in six dedicated haematology units in the Netherlands. Eligible haematology patients had neutropenia < 500/mL for ≥ 7 days and had fever. MBI-LCBIs were classified according to Centers for Disease Control (CDC) definitions and were followed until the end of neutropenia > 500/mL or discharge. RESULTS: We included 416 patients from December 2014 until August 2019. We observed 63 MBI-LCBIs. Neither clinical mucositis scores nor the blood level of citrulline at fever onset was associated with MBI-LCBI. In the multivariable analysis, MASCC-score (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.05 to 1.29 per point decrease), intensive chemotherapy (OR 3·81, 95% CI 2.10 to 6.90) and Pichia kudriavzevii (formerly Candida krusei) colonisation (OR 5.40, 95% CI 1.75 to 16.7) were retained as risk factors for MBI-LCBI, while quinolone use seemed protective (OR 0.42, 95% CI 0.20 to 0.92). Citrulline level (OR 1.57, 95% CI 1.07 to 2.31 per µmol/L decrease), active chronic obstructive pulmonary disease (OR 15.4, 95% CI 1.61 to 14.7) and colonisation with fluconazole-resistant Candida (OR 8.54, 95% CI 1.51 to 48.4) were associated with candidaemia. CONCLUSION: In haematology patients with fever during neutropenia, hypocitrullinaemia at fever onset was associated with candidaemia, but not with bacterial MBI-LCBI. Patients with intensive chemotherapy with a low MASCC-score and colonisation with Pichia kudriavzevii had the highest risk of MBI-LCBI. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02149329) at 19-NOV-2014.

Protein Network Alterations in G-CSF Treated Severe Congenital Neutropenia Patients and Beneficial Effects of Oral Health Intervention.

PURPOSE: Severe congenital neutropenia (SCN) is a raredisorder characterized by diminished neutrophil levels. Despite granulocytecolony-stimulating factor (G-CSF) treatment, SCN patients remain still prone tosevere infections, including periodontal disease-a significant oral healthrisk. This study investigates the host proteome and metaproteome in saliva andgingival crevicular fluid (GCF) of G-CSF-treated patients. EXPERIMENTAL DESIGN: We used label-free quantitative proteomics on saliva and GCF samples from SCN patients before (n = 10, mean age: 10.7 ± 6.6 years) and after a 6-month oral hygiene intervention (n = 9,mean age: 11.6 ± 5.27 years), and from 12 healthy controls. RESULTS: We quantified 894 proteins in saliva (648 human,246 bacterial) and 756 proteins in GCF (493 human, 263 bacterial). Predominant bacterial genera included Streptococcus, Veillonella, Selenomonas, Corynebacterium, Porphyromonas, and Prevotella. SCN patients showed reduced antimicrobial peptides (AMPs) and elevated complement proteins compared tohealthy controls. Oral hygiene intervention improved oral epithelial conditionsand reduced both AMPs and complement proteins. CONCLUSIONS AND CLINICAL RELEVANCE: SCN patients have aunique proteomic profile with reduced AMPs and increased complement proteins, contributing to infection susceptibility. Oral hygiene intervention not onlyimproved oral health in SCN patients but also offers potential overall therapeuticbenefits.

Characteristics of oncology patients with fever and invasive bacterial infections diagnosed.

AIM: To describe the characteristics of febrile oncology patients seen in the Paediatric Emergency Department and microbiological characteristics of the invasive bacterial infections (IBIs) diagnosed. METHODS: We conducted a prospective observational study of febrile oncology patients seen between 2016 and 2022. We divided haematologic cancers by the aggressiveness of the chemotherapy received at the time. RESULTS: We included 418 episodes (272 haematologic cancers, 146 solid tumours). The median duration of fever was 2 h (interquartile range: 1-3) and 97.6% of patients were well-appearing on arrival. We diagnosed 61 IBIs (14.6%), including six episodes of bacterial sepsis. One other episode was coded as sepsis without microbiological confirmation, yielding seven episodes overall (1.7%). Rates of IBI and sepsis were higher among patients with high-risk haematologic cancers than those with low-risk haematologic cancers or solid tumours (22.9%, 5.4% and 10.3%, p < 0.01; 3.4%, 0% and 0.7%, p = 0.06, respectively). Leading causes were S. epidermidis (42.6%) and E. coli (14.7%). Gram-positive bacteria caused 67.2% of non-septic IBIs and 50% of septic episodes. CONCLUSION: Most febrile oncology patients are well-appearing and present with a very short history of fever. Prevalence of IBI and sepsis and the main disease-causing bacteria differ by cancer type and the presence of sepsis.

Hematological manifestation of Pediatric Systemic Lupus Erythematosus (SLE) - A single centered cross-sectional study.

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.

The impact of neutrophil count on the results of metagenomic next-generation sequencing in immunocompromised febrile children.

Metagenomic next-generation sequencing (mNGS) has revolutionized the detection of pathogens, particularly in immunocompromised individuals such as pediatric patients undergoing intensive chemotherapy and hematopoietic stem cell transplantation. This study aims to explore the impact of neutrophil count on the diagnostic efficacy of mNGS in diagnosing infections in pediatric patients with febrile diseases. We conducted a retrospective analysis of pediatric patients with febrile diseases in the hematology/oncology department from January 2019 to September 2022. The study included 387 patients with 516 febrile episodes. Analyzing data from 516 pediatric cases, our study found that 70.7 % had febrile neutropenia (FN) and 29.3 % had febrile without neutropenia (FWN). mNGS demonstrated a high positive detection rate of 84.9 %, compared to 29.7 % for conventional microbiological tests (CMT). While the positive detection rates of mNGS were similar in both FN and FWN groups, bacterial pathogens were more frequently detected in FN patients. Furthermore, the rate of identifying a "probable" microbial etiology was lower in the FN group (46.8 %) compared to the FWN group (65.6 %, p＜0.001). When analyzing the types of organisms and specimens, the "probable" identification rates were particularly lower for viruses and fungi detected by mNGS, as well as in blood and nasopharyngeal swab samples. These findings underscore the significant influence of neutrophil counts on mNGS results in pediatric febrile patients and highlight the necessity for tailored diagnostic approaches in this population.

Case report: A rare case of anti-PD-1 sintilimab-induced agranulocytosis/severe neutropenia in non-small cell lung cancer and literature review.

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.

Novel biomarkers to identify complicated course of febrile neutropenia in hematological patients receiving intensive chemotherapy.

Febrile neutropenia (FN) is a common consequence of intensive chemotherapy in hematological patients. More than 90% of the patients with acute myeloid leukemia (AML) develop FN, and 5%-10% of them die from subsequent sepsis. FN is very common also in autologous stem cell transplant recipients, but the risk of death is lower than in AML patients. In this review, we discuss biomarkers that have been evaluated for diagnostic and prognostic purposes in hematological patients with FN. In general, novel biomarkers have provided little benefit over traditional inflammatory biomarkers, such as C-reactive protein and procalcitonin. The utility of most biomarkers in hematological patients with FN has been evaluated in only a few small studies. Although some of them appear promising, much more data is needed before they can be implemented in the clinical evaluation of FN patients. Currently, close patient follow-up is key to detect complicated course of FN and the need for further interventions such as intensive care unit admission. Scoring systems such as q-SOFA (Quick Sequential Organ Failure Assessment) or NEWS (National Early Warning Sign) combined with traditional and/or novel biomarkers may provide added value in the clinical evaluation of FN patients.

Risk of neutropenia in psoriasis patients prescribed anti-IL-23 antibody in comparison with anti-IL-17 antibody or adalimumab based on real-world data from the MID-NET® in Japan.

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.

Optimized high-dose granulocyte transfusions for the treatment of infections in neutropenic patients: A single-center retrospective analysis.

BACKGROUND: Granulocyte transfusions for patients with prolonged neutropenia and severe infections has been a controversial practice. Previous studies suggest a benefit of high-dose granulocyte transfusions (≥0.6 × 109/kg), although, until recently, the consistent production of high-dose units has been challenging. Here, we present our experience and results utilizing high-dose granulocyte transfusions at a large, tertiary academic medical center for the treatment of infections in adult, neutropenic patients. STUDY DESIGN/METHODS: A retrospective chart review (2018-2021) was conducted for all patients who received high-dose granulocyte transfusions from donors stimulated with granulocyte colony-stimulating factor (G-CSF) and dexamethasone. Gathered parameters included patient demographics, clinical history, infection status, dose, clinical outcomes, pre- and post-absolute neutrophil count (ANC), and transfusion times including time between granulocyte collection, administration, and posttransfusion ANC count. Gathered parameters were summarized using descriptive statistics, outcomes were assessed utilizing Kaplan-Meier curves/log-rank/regression testing. RESULTS: Totally 28 adult, neutropenic patients refractory to antimicrobial agents and/or G-CSF received a total of 173 granulocyte concentrates. Median ANC increased from 0.7 × 109/L pre-transfusion to 1.6 × 109/L posttransfusion. The mean granulocyte yield was 77.4 × 109 resulting in an average dose per kilogram of 0.90 × 109 ± 0.30 × 109 granulocytes. Composite day 42 survival and microbial response was 42.9% (n = 12/28) without significant adverse reactions. DISCUSSION: Here, we demonstrate the successful and safe implementation of high-dose granulocyte transfusions for neutropenic patients. Given the rapid and consistent production, distribution, and improved granulocyte quality, further investigations to determine the clinical efficacy of G-CSF primed granulocyte transfusions is now possible.

PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome: A case report and review of the literature.

PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome is a rare autoinflammatory disorder often arising in pediatric patients. We present a case of an 18-year-old female with a past medical history of growth failure, immunoglobulin A nephropathy, and inflammatory arthritis who presented to a pediatric dermatology clinic with findings of acne, psoriasiform dermatitis, and hidradenitis suppurativa, whose clinical, genetic, and laboratory findings were most consistent with PAMI syndrome. We conducted a literature review to better characterize this rare condition in the context of dermatologic findings. Recognition of the distinctive skin findings seen in PAMI syndrome can help distinguish it from other inflammatory disorders, enabling expedited diagnosis and treatment.

Neutropenia Induced by Ceftriaxone and Meropenem.

Neutropenia by non-chemotherapy drugs is an extremely rare idiosyncratic life-threatening drug reaction. Ceftriaxone and meropenem are widely used broad-spectrum antibiotics and are generally safe and well tolerated. The authors present a case of neutropenia induced by ceftriaxone and meropenem in an adult patient. The resolution of neutropenia occurred within 48 hours of ceftriaxone and meropenem being discontinued. Although antibiotic-induced neutropenia is uncommon, clinicians should be mindful of this adverse drug effect because of its potential development of severe neutropenia, septicaemia, septic shock, deep-seated infections and even death. Therefore, neutropenic sepsis treatment should be initiated without delay, particularly if the patient becomes septic and febrile. Granulocyte-colony stimulation factor (G-CSF) may be administered to facilitate the recovery process with daily monitoring of neutrophil count. Mortalities from antibiotic-induced neutropenia remain rare, with a range of 2.5-5%. LEARNING POINTS: Beta-lactam antibiotics and cabapenem are widely prescribed antibiotics for the treatment of various infections, but they can uncommonly cause neutropenia as adverse effects.Severe neutropenia may lead to severe life-threatening sepsis, shock and even death.Drug-induced neutropenia typically improves with the cessation of offending agents, supportive treatment and granulocyte-colony stimulating factor (G-CSF) which may shorten the recovery time.

Moxibustion combined with guasha therapy for recurrent neutropenia following multiple cycles of chemotherapy of ovarian cancer: A case report.

Neutropenia, a common side effect of chemotherapy for ovarian cancer, was observed in a 47-year-old female patient undergoing a six-cycle chemotherapy regimen. She experienced recurrent neutropenia and leukopenia but refused granulocyte colony-stimulating factor (G-CSF) due to severe bone pain and high costs. Moxibustion combined with guasha therapy (MGT) was administered each time neutropenia occurred. The treatment involved guasha therapy on the bladder meridian (BL) and the governor vessel (GV), followed by moxibustion at Zhongwan (CV 12), Guanyuan (CV 4), and Shenzhu (GV 12) points over 2-3 days. This approach led to the recovery of neutrophil and leukocyte counts, enabling the patient to complete six chemotherapy cycles without G-CSF. These findings suggest that MGT may enhance neutrophil and leukocyte counts in patients with chemotherapy-induced myelosuppression, presenting a potential alternative for those intolerant to G-CSF. However, further high-quality research is needed to confirm its efficacy.

Diagnostic performance of the CellaVision preclassification neutrophil count - time to bypass the reclassification?

OBJECTIVES: The objective of this study was to perform a method comparison between the CellaVision preclassification neutrophil count and the reclassification neutrophil count performed by trained laboratory technicians, and to evaluate the diagnostic performance of the preclassification neutrophil count at clinical decision levels. METHODS: We retrospectively identified patient samples through 2019-2022 in which the differential count was performed on Cellavision (n = 4,354). Data on sample characteristics and leukocyte- and differential counts was extracted from the electronic medical journal. For each sample, data containing the pre- and reclassification leukocyte classification, respectively, was extracted from the Cellavision software. Method comparison between the pre-and reclassification neutrophil count was performed using Bland Altman analysis. Diagnostic performance of the preclassification neutrophil count was evaluated according to four pre-specified categories of results with the reclassification as reference method. RESULTS: The median difference between the pre- and reclassification neutrophil count was 0.044 x 109/L. The preclassification neutrophil count categorised 95.6% of all samples correctly according to the four categories. The sensitivity, specificity, positive predictive value and negative predictive value for detecting neutrophilia > 7.00 x 109/L was 98.8%, 97.2%, 95.8%, and 99.2%, respectively. In samples with leukopenia (n = 543), the sensitivity, specificity, positive predictive value and negative predictive value for detecting severe neutropenia (< 0.50 x 109/L) was 97.7%, 99.1%, 98.6%, and 98.5%, respectively. CONCLUSION: The diagnostic performance of the CellaVision preclassification neutrophil count was satisfactory. The preclassification neutrophil count may be released to the electronic medical journal to improve turnaround time and benefit laboratory management.