Search Results (165)

Clozapine, a second-generation antipsychotic known for its effectiveness in treating resistant schizophrenia, is often linked with serious hematological side effects, particularly neutropenia and agranulocytosis. This review investigates the underlying pathophysiological mechanisms of clozapine-induced neutropenia (CIN) and agranulocytosis (CIA), outlines associated risk factors, and evaluates current clinical management strategies. Clozapine’s pharmacological profile, marked by its antagonism of dopamine D4 and serotonin receptors, contributes to both its therapeutic advantages and hematological toxicity. Epidemiological data show a prevalence of CIN and CIA at approximately 3.8% and 0.9%, respectively, with onset typically occurring within the first six months of treatment. Key risk factors include older age, Asian and African American ethnicity, female sex, and certain genetic predispositions. The development of CIN and CIA may involve bone marrow suppression and autoimmune mechanisms, although the exact processes remain partially understood. Clinical presentation often includes nonspecific symptoms such as fever and signs of infection, necessitating regular hematological monitoring in accordance with established guidelines. Management strategies include dosage adjustments, cessation of clozapine, and the administration of granulocyte colony-stimulating factors (G-CSF). Advances in pharmacogenomics show promise for predicting susceptibility to CIN and CIA, potentially improving patient safety. This review emphasizes the importance of vigilant monitoring and personalized treatment approaches to reduce the risks associated with clozapine therapy. Full article

Background/Objective: Candidemia is a serious complication following intensive chemotherapy and is associated with high mortality in pediatric patients. This study aimed to identify the factors associated with 28-day mortality in pediatric patients with candidemia. Methods: We retrospectively analyzed 63 pediatric patients diagnosed with acute leukemia and candidemia following intensive chemotherapy. Clinical characteristics, laboratory findings, and epidemiological data were collected. Antifungal susceptibility data were available for 60 patients. Kaplan–Meier survival analysis was used to estimate the 28-day mortality rate, and Cox regression was performed to identify prognostic factors. Results: The 28-day mortality rate among the 63 patients (57.1% male, median age 9.74 years) was 36.5%. Candida tropicalis was the predominant species (96.8%). Antifungal susceptibility rates were 100% for amphotericin B and caspofungin and 22.2% for fluconazole. The factors independently associated with reduced 28-day mortality were an absolute lymphocyte count (ALC) ≥ 0.2 G/L at the time of candidemia diagnosis (5.3% vs. 50% mortality; hazard ratio [HR] = 0.08; 95% confidence interval [CI], 0.01–0.61), the use of antifungal prophylaxis (AFP) (26.3% vs. 52%; HR 0.31; 95% CI, 0.13–0.74), and granulocyte transfusion (GTX) combined with granulocyte colony-stimulating factor (G-CSF) (20% vs. 47.4%; HR = 0.31; 95% CI, 0.11–0.85). Conclusions: Our findings suggest that an ALC ≥ 0.2 G/L, AFP, and the administration of a GTX combined with G-CSF may be considered favorable prognostic factors. Full article

Antibiotic therapy is essential for managing bacterial infections, but rare yet serious hematological complications such as leukopenia and agranulocytosis may occur. These conditions, although uncommon, require timely diagnosis and intervention, particularly in vulnerable populations such as postpartum patients. This case report describes a 31-year-old puerperal woman who developed agranulocytosis after extended antibiotic treatment for a presumed multidrug-resistant infection. Initially treated with ceftriaxone and metronidazole, her therapy was later escalated to include ciprofloxacin, amoxicillin–clavulanic acid, and vancomycin. Enterococcus spp. and Staphylococcus aureus were isolated from multiple sites, although no systemic infection was confirmed. Bone marrow findings were consistent with agranulocytosis in the recovery phase. Despite improvements in infection markers, her leukocyte count progressively declined, reaching a nadir of 1.61 × 10⁹/L on the 19th day of therapy. Granulocyte-colony stimulating factor (G-CSF) therapy was initiated, resulting in hematological recovery. The patient was discharged with normal inflammatory markers and leukocyte counts. This case highlights the importance of diagnostic precision, rational antibiotic use, and timely hematologic assessment during prolonged antimicrobial treatment. Full article

In fish, the innate immune system is crucial for rapid defense against pathogens. In this study, we performed transcriptome sequencing using next-generation sequencing (NGS) to identify and characterize granulocyte colony-stimulating factor (GCSF) and macrophage colony-stimulating factor (MCSF) in starry flounder (Platichthys stellatus). The GCSF gene (594 bp, 198 aa) features a conserved IL-6 domain, while the MCSF gene (621 bp, 207 aa) contains a predicted transmembrane region. Phylogenetic analysis confirmed high evolutionary conservation with other marine species. Quantitative real-time PCR revealed that GCSF is highly expressed in the skin, peripheral blood leukocytes, and muscle, with significant up-regulation in immune organs following Streptococcus parauberis infection; MCSF exhibited a similar tissue-specific expression pattern. Recombinant GCSF (rGCSF) was produced using a cell-free system and effectively enhanced leukocyte phagocytic activity at an optimal concentration of 150 μg/mL, without causing cytotoxicity in hemolytic assays. In contrast, rMCSF exhibited folding issues during purification. These findings highlight the potential of rGCSF as a molecular adjuvant to enhance immune responses in aquaculture. This study provides foundational knowledge for developing cytokine-based adjuvants, which could reduce antibiotic dependency and enhance vaccine efficacy in sustainable aquaculture systems. Full article

Background: Cephalosporins are considered safe antibiotics. However, serious hematological abnormalities may occur, although rarely, after their therapeutic use. Case Presentation: We present a case of pancytopenia in a 72-year-old female patient treated with ceftriaxone for a urinary tract infection. After five days of therapy, pancytopenia was observed. Other causes were excluded through extensive diagnostic evaluation, including immunological tests, viral serologies, bone marrow aspiration, and peripheral blood smear. The patient’s clinical condition significantly improved following the discontinuation of ceftriaxone and the administration of granulocyte colony-stimulating factor (G-CSF). Bone marrow findings revealed hypocellularity without malignant infiltration, and peripheral smear showed no dysplasia, blasts, or hemolysis. Conclusions: This case demonstrates that ceftriaxone, although widely regarded as a safe antibiotic, can induce rare but serious hematologic complications such as pancytopenia. A high index of suspicion is required when patients on antibiotic therapy develop unexplained cytopenias. Detailed medication history, exclusion of other causes, and prompt discontinuation of the suspected drug are essential. The patient’s favorable outcome supports the likelihood of an idiosyncratic, immune-mediated mechanism. Future research should explore pharmacogenomic screening in patients at increased risk, particularly involving HLA variants. Full article

Acute radiation syndrome (ARS) results from high-dose ionizing radiation (IR) exposure, with bone marrow (BM) being highly susceptible due to its proliferative activity. BM injury causes pancytopenia, leading to infections, anemia, and bleeding. Mesenchymal stem cells (MSCs) hold promise for ARS treatment because of their immunomodulatory, anti-inflammatory, and regenerative properties. However, challenges such as replicative senescence, poor survival, and engraftment in irradiated microenvironments limit their efficacy. This study evaluated rapamycin-preconditioned placenta-derived MSCs (rPD-MSCs) in a mouse ARS model. Rapamycin was selected for preconditioning due to its ability to induce autophagy and modulate cytokine secretion. We assessed rapamycin-dependent modulation of autophagy-related genes and proteins, as well as hematopoietic cytokines secretion in PD-MSCs, and evaluated morphological changes in blood and BM at 7 and 21 days post-irradiation in ICR/CD1 mice. Preconditioning with rapamycin alters the secretion of granulocyte colony-stimulating factor (G-CSF), stem cell factor (SCF), and Fms-related tyrosine kinase 3 ligand (Flt3LG) in PD-MSCs without affecting cell viability. rPD-MSCs better enhance hematopoietic recovery, restore bone marrow cellularity, and increase peripheral blood cell counts by elevating the secretion of hematopoietic cytokines compared to non-preconditioned cells. These results highlight rapamycin preconditioning as a promising strategy to enhance MSCs therapeutic potential for ARS, supporting further preclinical and clinical exploration. Full article

Background: Granulocyte-colony stimulating factor (G-CSF) prophylaxis is widely used in gastrointestinal (GI) cancers. The use of G-CSF in GI cancers has not previously been investigated systematically in a meta-analysis. Thus, we systematically reviewed the literature to describe the G-CSF use and potential influence on long-term oncological outcomes in GI cancers. Method: The literature search of this systematic review and meta-analysis was conducted in PubMed, Embase, Cochrane Library and Web of Science. The PRISMA-P guidelines were followed. Studies that reported data on patients with GI cancers undergoing oncological treatment with G-CSF prophylaxis were included. Outcomes of interest were overall survival (OS), progression-free survival (PFS) and adverse events (AE), specifically neutropenia grade III/IV. A time-to-event random-effects meta-analysis was conducted. Risk of bias was assessed using the Newcastle–Ottawa Scale and the Cochrane Risk of Bias Tool for Randomized Controlled Trials (RoB) tool. Findings: In total, 2452 articles were screened for eligibility. Ultimately, 13 studies were included with a total patient number of 2673. The included studies indicated a positive association between OS and G-CSF prophylaxis (HR 0.72, 95% CI: 0.56–0.91, I²: 54%, low quality evidence). No significant relation between G-CSF use and PFS was found in the pooled analyses (HR 0.74, 95% CI: 0.51–1.08, I²: 73%, moderate quality evidence). However, a positive effect of G-CSF use was found in the retrospective cohorts reporting data on PFS (HR 0.50, 95% CI: 0.32–0.77, I²: 0%). A marked drop in neutropenia grade III/IV rates was observed in patients treated with G-CSF (risk ratio (RR) 0.46, 95% CI: 0.28–0.77, I²: 72%, high quality evidence). Interpretation: G-CSF prophylaxis provides a reduction in neutropenia grade III/IV in patients with GI cancers (high level of certainty) and a favorable OS (low certainty), while PFS is unaffected (moderate certainty). Studies on PFS and G-CSF use are nonetheless limited. Full article

Background: Thymoma-associated pure white cell aplasia (PWCA), characterized by agranulocytosis with absent myeloid precursors in the bone marrow in the setting of preserved erythropoiesis and megakaryopoiesis, is exceedingly rare, with only a few cases reported in the literature. We present a case of type-B2-thymoma-associated PWCA and immune reconstitution following marrow recovery. Case Presentation: A 75-year-old woman was incidentally found to have a concomitant mediastinal mass and peripheral leukopenia with absent granulocytes and monocytes. Bone marrow assessment was notable for a hypocellular marrow (<10%) with absent granulopoiesis and monopoiesis. Chest CT demonstrated a large lobulated anterior mediastinal mass, for which the patient underwent a video-assisted thoracoscopic thymectomy. Pathological evaluation of the mediastinal mass specimen revealed a type B2 thymoma. A tentative diagnosis of thymoma-associated PWCA was made, and the patient was started on cyclosporine/granulocyte-colony stimulating factor (G-CSF)/filgrastim therapy. Despite promising marrow recovery, she developed several comorbidities and had a leukemoid reaction, provoking concern for immune reconstitution following prolonged neutropenia and subsequent treatment. She passed away on post-operative day 15, and the results of a post-mortem bone marrow examination were consistent with granulocytic hyperplasia. Conclusions: This case of thymoma-associated PWCA heightens awareness regarding this entity, providing a note of caution regarding the possibility of immune reconstitution following treatment and marrow recovery. Full article

Drug delivery systems enhance drug efficacy while minimizing side effects. Liposomes, as well-studied and clinically approved carriers, offer biodegradability, biocompatibility, and low toxicity, making them suitable for delivering various pharmacological agents. Granulocyte colony-stimulating factor (G-CSF), a key growth factor, has shown therapeutic potential, particularly in infertility treatment. It effectively manages chronic and refractory endometritis by improving endometrial receptivity and increasing embryo implantation success. Studies indicate that G-CSF promotes endometrial growth and enhances the uterine microenvironment, benefiting patients with recurrent implantation failures and chronic endometritis. Encapsulation of G-CSF in liposomes enhances its stability, bioavailability, and controlled release. G-CSF-loaded liposomes were prepared using passive loading via the thin-film hydration method. The size of the liposomes, polydispersity index (PDI), and zeta potential were determined using dynamic and electrophoretic light scattering methods, and the encapsulation efficiency was measured using high-performance liquid chromatography. The morphology of the liposomes was established and confirmed using cryogenic transmission electron microscopy. The cytocompatibility of the G-CSF-loaded liposomes was evaluated on human dermal fibroblasts using an MTT assay. The G-CSF-loaded liposomes had an average particle size of 161.9 ± 9.9 nm, a PDI of 0.261 ± 0.03, and a zeta potential of +2.09 ± 0.10 mV, exhibiting high physical stability during long-term storage at +4 °C and 60% humidity. The passive loading method resulted in a 52.37 ± 3.64% encapsulation efficiency of the active substance. The analysis of cell viability revealed no cytotoxicity toward liposomes loaded with G-CSF and demonstrated a dose-dependent effect on the viability of human dermal fibroblasts. Thus, the obtained data confirm the successful preparation of G-CSF-loaded liposomes. However, to fully understand their effectiveness in biomedical applications, further research is needed, including an evaluation of their effectiveness in vivo. Such studies will help in determining the potential of these formulations for specific biomedical purposes and evaluating their safety and efficacy in living systems. Full article

Background/Objectives: The objective of our study was to evaluate the safety and efficacy of granulocyte colony-stimulating factor (G-CSF) as primary prophylaxis in adult patients with acute myeloid leukemia (AML) undergoing intensive chemotherapy. Methods: We retrospectively analyzed 112 AML patients treated with intensive chemotherapy at Fondazione Policlinico Tor Vergata in Rome between January 2014 and March 2024. Patients were divided into G-CSF and non-G-CSF (nG-CSF) groups. We assessed the incidence of neutropenia, its severity and duration; duration of hospitalization and its costs; incidence of febrile neutropenia (FN) and septic shock; duration of antibiotic therapy (ABT) and antifungal therapy (AFT); complete remission (CR) rates; measurable residual disease (MRD) status; relapse rates; and outcomes. Results: G-CSF administration significantly reduced the duration of neutropenia (median 14 vs. 18 days, p < 0.05) and length of hospitalization (median 28 vs. 35 days, p < 0.05), in both induction and consolidation therapy. There were no significant differences in CR rates (73% vs. 67%, p = 0.64), MRD negativity achievement (52% vs. 48%, p = 0.68), leukemia relapse rates (43% vs. 62%, p = 0.14), or overall survival (OS) (median 16.7 vs. 12.3 months, p = 0.3) between G-CSF and nG-CSF groups. Thanks to a shorter hospitalization, the use of G-CSF led to €300,000 in savings over the last 4 years. Conclusions: Our findings support the safety of G-CSF in AML patients, demonstrating no adverse impact on treatment response. G-CSF abbreviated the duration of neutropenia and hospitalization, highlighting its potential clinical and cost-effective role in AML treatment. Full article

Chemotherapy-induced cytopenia (CIC) is characterized by neutropenia, anemia, and thrombocytopenia, which are common and serious complications in cancer treatment. These conditions affect approximately 60% of patients undergoing chemotherapy and can significantly impact quality of life, treatment continuity, and overall survival. The use of growth factors, including granulocyte colony-stimulating factors (GCSFs), erythropoietin-stimulating agents (ESAs), and thrombopoietin receptor agonists (TPO-RAs), has emerged as a promising strategy for managing CIC. However, the use of these growth factors must be approached with caution. This review provides an overview of the mechanisms, efficacy, and safety of growth factors in the management of CIC. Additionally, we discuss predictive markers for treatment response, potential risks, and highlight areas for future research. Full article

Feline Panleukopenia (FPL) infection is caused by feline panleukopenia virus (FPV), and it is considered one of the most severe cat’s infectious diseases. Since there is no specific antiviral treatment for FPL, the therapeutic protocol usually is focused on fluid therapy and supportive care. However, filgrastim, a granulocyte colony-stimulating factor (G-CSF) used in human medicine to treat neutropenia and leukopenia, has been lately used in treating FPV disease, providing promising results. During January 2022 and September 2024, twenty-two cats diagnosed with feline panleukopenia virus were subjected to filgrastim (Zarzio^®, Sandoz, Kundl, Austria) administration at a dose of 6 µg/kg for 3 consecutive days. The 4th day was a break day, and in the 5th day, the complete blood count was repeated. White blood cells, lymphocytes, monocytes, neutrophils and eosinophils parameters improved after Zarzio^® administration, with a significant statistical difference (p < 0.01) when their values between day 1 (pre Zarzio^® administration) and day 5 (post Zarzio^® administration) were analysed. However, red blood cells, haemoglobin, haematocrit and platelets parameters registered a considerable reduction from day 1 to day 5 with a significant statistical difference (p < 0.01), considered as post-administration side effects. In our study, the survival rate following Zarzio^® administration was 100%, suggesting that the protocol involving three doses is effective in restoring the leukopenia and neutropenia. Full article

Background: Perioperative FLOT (5-fluorouracil, oxaliplatin and docetaxel) is a standard of care for patients with locally advanced gastro-oesophageal adenocarcinoma (GEA) in Western guidelines, but its use is limited in Asian patients. We report outcomes from a single Asian centre of perioperative FLOT with concomitant granulocyte colony-stimulating factor (GCSF) prophylaxis. Methods: A retrospective analysis of all 56 stage II to III GEA patients treated with perioperative FLOT at the National Cancer Centre Singapore between June 2017 and February 2024 was performed. All patients were discussed at a multidisciplinary tumour board, underwent preoperative laparoscopic staging, and received prophylactic GCSF with perioperative FLOT. Surgery was performed across four partner institutions. The primary endpoints were the tolerability of FLOT and pathological complete response (pCR). A univariate analysis of factors associated with survival and adverse events was also performed. Results: Overall, 33 patients (58.9%) completed eight cycles of pre- and postoperative FLOT, and 92.9% underwent resection. The commonest grade 3 to 4 adverse events (AEs) were diarrhoea (10.7%) and neutropenia (5.6%). The 30- and 90-day postoperative mortality rates were 0% and 1.9%, respectively. In resected tumours, the pCR was 15.4%. The median DFS was 27.5 months, but the median OS was not reached. The values for 1-, 2-, and 3-year DFS were 74.6%, 61.0%, and 46.5%, respectively. The values for 1-, 2-, and 3-year OS were 85.0%, 67.4%, and 61.0%, respectively. In the univariate analysis of patients who underwent resection, an ECOG status of 0 was associated with better DFS, while ypN0, R0 resection, and pathological stages 0-II were associated with better DFS and OS. Patients ≥ 65 years benefited from FLOT similarly to those <65 years in terms of DFS (HR 1.03; p = 0.940) and OS (HR 1.08; p = 0.869), with similar rates of grade 3 to 4 AEs. Patients with a higher housing index (HI) were less likely to experience ≥grade 3 AEs compared to those with a lower HI (OR 0.16, p = 0.029). Conclusions: This study presents a unique real-world Asian experience of perioperative FLOT with prophylactic GCSF use, with low rates of G3 to 4 neutropenia. The tolerability of FLOT was similar to that reported in Western populations. Furthermore, similar survival and rates of grade 3 to 4 AEs were observed in elderly patients. Patients of lower socioeconomic status were more likely to experience severe AEs, highlighting the need to proactively support vulnerable groups during treatment. Full article

Background/Objectives: Neutropenia is a frequent complication among solid organ transplant (SOT) recipients receiving immunosuppressive therapy and antimicrobial prophylaxis. However, there are limited studies analysing the frequency and impact of neutropenia in lung transplant recipients (LTRs). Our aim was to analyse the frequency of neutropenia, the need for granulocyte colony-stimulating factor (GCSF) treatment within the first 18 months post-transplant and its association with acute rejection, chronic lung allograft dysfunction (CLAD), overall survival and the development of infections. Methods: This observational and retrospective study recruited 305 patients who underwent lung transplantation between 2009 and 2019, with outpatient quarterly follow-up during the first 18 months post-surgery.Results: During this period, 51.8% of patients experienced at least one episode of neutropenia. Neutropenia was classified as mild in 50.57% of cases, moderate in 36.88% and severe in 12.54%. GCSF treatment was indicated in 23.28% of patients, with a mean dose of 3.53 units. No statistically significant association was observed between neutropenia or its severity and the development of acute rejection, CLAD or overall survival. However, the patients who received GCSF treatment had a higher mortality rate compared to those who did not. Sixteen patients (5.25%) developed infections during neutropenia, with bacterial infections being the most common. Conclusions: Neutropenia is common in the first 18 months after lung transplantation and most episodes are mild. We did not find an association between neutropenia and acute rejection, CLAD, or mortality. However, the use of GCSF were associated with worse post-transplant survival. Full article

The skin microenvironment created by keratinocytes (KC) influences the stress responses of melanocytes (MC) to UVB insults. This study employed RNA sequencing analysis as well as in vitro and in vivo models to elucidate the underlying mechanisms. Our RNA-Seq analysis revealed a statistically significant upregulation of GCSF and CCL20 genes in UVB-irradiated KC, correlating with the protective effects of KC on MC responses to UVB exposure. Recombinant GCSF and CCL20 exhibited the most pronounced modulation of UVB-induced MC responses. These effects included the attenuation of apoptosis and reduction of ROS formation, along with the upregulation of tyrosinase and tyrosinase-related protein-1, which are involved in the melanogenic pathway. ELISA was also used to confirm that UVB could induce the secretion of GCSF and CCL20 from KC. A similar correlation between GCSF and CCL20 expression in KC and tyrosinase levels in MC was observed in UVB-irradiated mouse skin. Our study provides novel insights into the protective role of GCSF and CCL20 in the paracrine effects of KC on UVB-induced MC damage through the modulation of stress response pathways, the MITF-tyrosinase axis, and the regulation of p53. These findings have implications for the development of pharmacological strategies targeting KC-derived paracrine factors for the prevention of skin photodamage. Full article