Therapeutic Resistance in G-CSF Producing Lung Cancer With EGFR Mutation.

Background/Aim: Granulocyte colony-stimulating factor (G-CSF)-producing neoplasms are relatively rare; however, little is known on the clinical features of G-CSF-producing lung cancer harboring activating epidermal growth factor receptor (EGFR) mutations. Case Report: A 66-year-old female was definitively diagnosed with G-CSF-producing lung cancer that was positive for EGFR mutations. She repeatedly received epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as osimertinib and afatinib. However, she developed resistance to these molecular-targeting drugs within 2 to 3 months after immediate shrinkage. Thus, the patient was treated with chemoimmunotherapy including bevacizumab, and demonstrated a slight survival benefit. Conclusion: Overall, G-CSF-producing lung cancers positive for EGFR mutations were resistant to different treatment modalities. Clinicians should be attentive to the potential resistance of G-CSF-producing EGFR mutant lung cancer to EGFR-TKI therapy.

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.

Promotion of cardiac microtissue assembly within G-CSF-enriched collagen I-cardiogel hybrid hydrogel.

Tissue engineering as an interdisciplinary field of biomedical sciences has raised many hopes in the treatment of cardiovascular diseases as well as development of in vitro three-dimensional (3D) cardiac models. This study aimed to engineer a cardiac microtissue using a natural hybrid hydrogel enriched by granulocyte colony-stimulating factor (G-CSF), a bone marrow-derived growth factor. Cardiac ECM hydrogel (Cardiogel: CG) was mixed with collagen type I (ColI) to form the hybrid hydrogel, which was tested for mechanical and biological properties. Three cell types (cardiac progenitor cells, endothelial cells and cardiac fibroblasts) were co-cultured in the G-CSF-enriched hybrid hydrogel to form a 3D microtissue. ColI markedly improved the mechanical properties of CG in the hybrid form with a ratio of 1:1. The hybrid hydrogel demonstrated acceptable biocompatibility and improved retention of encapsulated human foreskin fibroblasts. Co-culture of three cell types in G-CSF enriched hybrid hydrogel, resulted in a faster 3D structure shaping and a well-cellularized microtissue with higher angiogenesis compared to growth factor-free hybrid hydrogel (control). Immunostaining confirmed the presence of CD31+ tube-like structures as well as vimentin+ cardiac fibroblasts and cTNT+ human pluripotent stem cells-derived cardiomyocytes. Bioinformatics analysis of signaling pathways related to the G-CSF receptor in cardiovascular lineage cells, identified target molecules. The in silico-identified STAT3, as one of the major molecules involved in G-CSF signaling of cardiac tissue, was upregulated in G-CSF compared to control. The G-CSF-enriched hybrid hydrogel could be a promising candidate for cardiac tissue engineering, as it facilitates tissue formation and angiogenesis.

Granulocyte Colony Stimulating Factor-Mobilized Peripheral Blood Mononuclear Cells: An Alternative Cellular Source for Chimeric Antigen Receptor Therapy.

Lymphocyte collection by apheresis for CAR-T production usually does not include blood mobilized using granulocyte colony stimulating factor (G-CSF) due to the widespread knowledge that it causes a decrease in the number and functionality of lymphocytes. However, it is used for stem cell transplant, which is a common treatment for hematological malignancies. The growing demand for CAR therapies (CAR-T and NK-CAR), both in research and clinics, makes it necessary to evaluate whether mobilized PBSC products may be potential candidates for use in such therapies. This review collects recent works that experimentally verify the role and functionality of T and NK lymphocytes and the generation of CAR-T from apheresis after G-CSF mobilization. As discussed, T cells do not vary significantly in their phenotype, the ratio of CD4+ and CD8+ remains constant, and the different sub-populations remain stable. In addition, the expansion and proliferation rates are invariant regardless of mobilization with G-CSF as well as the secretion of proinflammatory cytokines and the cytotoxic ability. Therefore, cells mobilized before apheresis are postulated as a new alternative source of T cells for adoptive therapies that will serve to alleviate high demand, increase availability, and take advantage of the substantial number of existing cryopreserved products.

Shorter donor leukocyte telomere length is associated with poor peripheral blood stem cell mobilization induced by granulocyte colony-stimulating factor.

BACKGROUND/PURPOSE: Insufficient numbers of peripheral blood stem cells (PBSC) after granulocyte colony-stimulating factor (G-CSF) mobilization occurs in a significant proportion of PBSC collections, often from older age donors. Telomere length (TL) is often used as an indicator of an individual's biological age. This study aimed to investigate the relationship between donors' leukocyte TL and the outcome of G-CSF-induced PBSC mobilization in healthy unrelated donors. METHODS: Donors' leukocyte TLs and the outcome of G-CSF-induced PBSC mobilization, as assessed by pre-harvest CD34+ cell counts, were analyzed in 39 healthy PBSC donors. TL in a non-mobilized general population (n = 90) was included as a control group. G-CSF mobilization effect was categorized into three groups according to pre-harvest CD34+ cell count: poor (≤25/µL, PMD), intermediate (between 25 and 180/µL), and good (≥180/µl, GMD). RESULTS: Leukocyte TL of PBSC donors correlated well with pre-harvest CD34+ cell counts (r = 0.645, p < 0.001). Leukocyte TLs of PMDs (n = 8) were significantly shorter than those of GMDs (n = 9) and non-mobilization controls (p < 0.05). Moreover, all PMD TLs were below the 50th percentile, and 62.5% of PMDs had TLs below the 10th percentile of age-matched control participants. In contrast, no GMD TLs were below the 10th percentile; in fact, 33.3% (3/9) of them were above the 90th percentile. CONCLUSION: Our results indicate that shorter donor leukocyte TL is associated with poor G-CSF-induced PBSC mobilization. TL, which represents a donor's biological age, could be a potential predictor for mobilization outcome.

Mesenchymal-epithelial transition factor exon 14 skipping mutation-positive granulocyte colony-stimulating factor-producing lung adenocarcinoma mimicking lung abscess: A case report.

Granulocyte colony-stimulating factor (G-CSF)-producing lung tumours are rare, with their imaging features and effective treatments remaining elusive. Similarly, mesenchymal-epithelial transition (MET) exon 14 skipping mutations are also uncommon. Herein, we report a case of G-CSF-producing lung adenocarcinoma positive for a MET exon 14 skipping mutation, mimicking lung abscess. A 61-year-old man presented with cough and high fever. Contrast-enhanced chest computed tomography revealed a mass with a cavity and internal fluid accumulation. The patient initially underwent diagnostic treatment for a lung abscess but was ultimately diagnosed with lung adenocarcinoma positive for a MET exon 14 skipping mutation. Following tepotinib therapy, the primary lesion shrank, and serum G-CSF levels decreased, leading to a diagnosis of G-CSF-producing lung cancer. G-CSF-producing lung tumours can present imaging findings that mimic lung abscesses. Tepotinib therapy may be effective for patients with MET exon 14 skipping mutation, including those with G-CSF-producing lung cancer.

Comparing machine learning screening approaches using clinical data and cytokine profiles for COVID-19 in resource-limited and resource-abundant settings.

Accurate screening of COVID-19 infection status for symptomatic patients is a critical public health task. Although molecular and antigen tests now exist for COVID-19, in resource-limited settings, screening tests are often not available. Furthermore, during the early stages of the pandemic tests were not available in any capacity. We utilized an automated machine learning (ML) approach to train and evaluate thousands of models on a clinical dataset consisting of commonly available clinical and laboratory data, along with cytokine profiles for patients (n = 150). These models were then further tested for generalizability on an out-of-sample secondary dataset (n = 120). We were able to develop a ML model for rapid and reliable screening of patients as COVID-19 positive or negative using three approaches: commonly available clinical and laboratory data, a cytokine profile, and a combination of the common data and cytokine profile. Of the tens of thousands of models automatically tested for the three approaches, all three approaches demonstrated > 92% sensitivity and > 88 specificity while our highest performing model achieved 95.6% sensitivity and 98.1% specificity. These models represent a potential effective deployable solution for COVID-19 status classification for symptomatic patients in resource-limited settings and provide proof-of-concept for rapid development of screening tools for novel emerging infectious diseases.

Feasible Influence of G-CSF on Clinical Pregnancy Outcome in Oocyte Donation Cycles for Patients with Recurrent Implantation Failure.

Background and Objectives: The aim of our single-center cohort study was the determination of the influence of the intrauterine lavage of granulocyte colony-stimulating growth factor (G-CSF) on clinical pregnancy rate in patients with a history of implantation failure older than 40 years. Materials and Methods: The study was conducted in Ferticare Prague SE between May 2018 and June 2020. Overall, 115 patients were distributed into two arms, with 48 subjects in the experimental and 67 in the control arm. All women have had a previous history of unsuccessful history of infertility treatment with their own genetic material and at least one ineffective cycle with the donated oocytes. The experimental arm underwent the intrauterine lavage of 0.5 mL of pure G-CSF from 120 to 48 h prior to embryo transfer. Results: The clinical pregnancy rate was 63.3% in the experimental arm and 47.8% in the control arm (p = 0.097 for Pearsonߣs χ2, and p = 0.133 for Fisher's exact test). However, the mean endometrial thickness on the day of embryo transfer did not appear to be statistically different (p = 0.139). Only the difference in endometrium thickness growth was statistically significant (p = 0.023). The increase in pregnancy rate is still encouraging for the future, even if it is not significant. Conclusion: Our study suggests the trend of increased pregnancy rate after the intrauterine G-CSF lavage in the interval of 120-48 h prior to embryo transfer.

Effectiveness and safety of primary prophylaxis with G-CSF during chemotherapy for invasive breast cancer: a systematic review and meta-analysis from Clinical Practice Guidelines for the Use of G-CSF 2022.

INTRODUCTION: Chemotherapy for breast cancer can cause neutropenia, increasing the risk of febrile neutropenia (FN) and serious infections. The use of granulocyte colony-stimulating factors (G-CSF) as primary prophylaxis has been explored to mitigate these risks. To evaluate the efficacy and safety of primary G-CSF prophylaxis in patients with invasive breast cancer undergoing chemotherapy. METHODS: A systematic literature review was conducted according to the "Minds Handbook for Clinical Practice Guideline Development" using PubMed, Ichushi-Web, and the Cochrane Library databases. Randomized controlled trials (RCTs) and cohort studies assessing using G-CSF as primary prophylaxis in invasive breast cancer were included. The primary outcomes were overall survival (OS) and FN incidence. Meta-analyses were performed for outcomes with sufficient data. RESULTS: Eight RCTs were included in the qualitative analysis, and five RCTs were meta-analyzed for FN incidence. The meta-analysis showed a significant reduction in FN incidence with primary G-CSF prophylaxis (risk difference [RD] = 0.22, 95% CI: 0.01-0.43, p = 0.04). Evidence for improvement in OS with G-CSF was inconclusive. Four RCTs suggested a tendency for increased pain with G-CSF, but statistical significance was not reported. CONCLUSIONS: Primary prophylactic use of G-CSF is strongly recommended for breast cancer patients undergoing chemotherapy, as it has been shown to reduce the incidence of FN. While the impact on OS is unclear, the benefits of reducing FN are considered to outweigh the potential harm of increased pain.

Effectiveness and safety of granulocyte colony-stimulating factor priming regimen for acute myeloid leukemia: A systematic review and meta-analysis of the Clinical Practice Guideline for the use of G-CSF 2022 from the Japan Society of Clinical Oncology.

BACKGROUND: The outcomes of relapsed or refractory acute myeloid leukemia (AML) remain poor. Although the concomitant use of granulocyte colony-stimulating factor (G-CSF) and anti-chemotherapeutic agents has been investigated to improve the antileukemic effect on AML, its usefulness remains controversial. This study aimed to investigate the effects of G-CSF priming as a remission induction therapy or salvage chemotherapy. METHODS: We performed a thorough literature search for studies related to the priming effect of G-CSF using PubMed, Ichushi-Web, and the Cochrane Library. A qualitative analysis of the pooled data was performed, and risk ratios (RRs) with confidence intervals (CIs) were calculated and summarized. RESULTS: Two reviewers independently extracted and accessed the 278 records identified during the initial screening, and 62 full-text articles were assessed for eligibility in second screening. Eleven studies were included in the qualitative analysis and 10 in the meta-analysis. A systematic review revealed that priming with G-CSF did not correlate with an improvement in response rate and overall survival (OS). The result of the meta-analysis revealed the tendency for lower relapse rate in the G-CSF priming groups without inter-study heterogeneity [RR, 0.91 (95% CI 0.82-1.01), p = 0.08; I2 = 4%, p = 0.35]. In specific populations, including patients with intermediate cytogenetic risk and those receiving high-dose cytarabine, the G-CSF priming regimen prolonged OS. CONCLUSIONS: G-CSF priming in combination with intensive remission induction treatment is not universally effective in patients with AML. Further studies are required to identify the patient cohort for which G-CSF priming is recommended.

Leveraging G-CSF prescribing in the outpatient setting: considerations beyond clinical factors-a questionnaire study.

PURPOSE: This study aims to delineate G-CSF treatment practices, assess decision criteria, and measure their implementation in ambulatory settings for patients with breast (BC), lung (LC), or gastrointestinal cancers (GIC), beyond standard recommendations. METHODS: In this non-interventional, cross-sectional, multicenter study, clinical cases were presented using conversational interfaces (chatbots), simulating a conversation with one or more virtual interlocutors through voice or text exchange. The clinical simulations were configured by four parameters: types of cancer, risk of FN related to chemotherapy and comorbidities, access to care, and therapy setting (adjuvant/neoadjuvant/metastatic). RESULTS: The questionnaire was completed by 102 physicians. Most practitioners (84.5%) reported prescribing G-CSF, regardless of tumor type. G-CSF was prescribed more frequently for adjuvant/neoadjuvant therapy than for metastatic cases. The type of chemotherapy was cited as the first reason for prescribing G-CSF, with access to care being the second. Regarding the type of chemotherapy, physicians do not consider this factor alone, but combined with comorbidities and age (56.7% of cases). Pegfilgrastim long-acting was prescribed in most cases of BC and LC (70.1% and 86%, respectively), while filgrastim short-acting was named in the majority of cases of GIC (61.7%); 76.3% of physicians prescribed G-CSF as primary prophylaxis. CONCLUSIONS: Our findings suggest that recommended practices are broadly followed. In the majority of cases, G-CSF is prescribed as primary prophylaxis. In addition, physicians seem more inclined to prescribe G-CSF to adjuvant/neoadjuvant patients rather than metastatic patients. Finally, the type of chemotherapy tends to be a more significant determining factor than the patient's background.

Protection of neutrophils by bone marrow mesenchymal stromal cells is enhanced by tumor-associated inflammatory cytokines.

Mesenchymal stromal/stem cells (MSCs), which are distributed in many tissues including bone marrow, have been reported to play a critical role in tumor development. While bone marrow, the primary site for hematopoiesis, is important for establishing the immune system, whether MSCs in the bone marrow can promote tumor growth via influencing hematopoiesis remains unclear. We observed that the numbers of MSCs and neutrophils were increased in bone marrow in tumor-bearing mice. Moreover, co-culture assay showed that MSCs strongly protected neutrophils from apoptosis and induced their maturation. G-CSF and GM-CSF have been well-documented to be associated with neutrophil formation. We found a remarkably increased level of G-CSF, but not GM-CSF, in the supernatant of MSCs and the serum of tumor-bearing mice. The G-CSF expression can be enhanced with inflammatory cytokines (IFNγ and TNFα) stimulation. Furthermore, we found that IFNγ and TNFα-treated MSCs enhanced their capability of promoting neutrophil survival and maturation. Our results indicate that MSCs display robustly protective effects on neutrophils to contribute to tumor growth in bone niches.

Optimizing autologous stem cell collections for patients with multiple myeloma receiving G-CSF and Plerixafor: A single center project.

BACKGROUND: Increasing indications for cellular therapy collections have stressed our healthcare system, with autologous collections having a longer than desired wait time until apheresis collection. This quality improvement initiative was undertaken to accommodate more patients within existing resources. STUDY DESIGN AND METHODS: Patients with multiple myeloma who underwent autologous peripheral blood stem cell collection from October 2022 to April 2023 were included. Demographic, mobilization, laboratory, and apheresis data were retrospectively collected from the medical record. RESULTS: This cohort included 120 patients (49.2% male), with a median age of 60 years. All received G-CSF and 95% received pre-emptive Plerixafor approximately 18 hours pre-collection. Most (79%) had collection goals of at least 8 × 106/kg CD34 cells, with 63% over 70 years old having this high collection goal (despite 20 years of institutional data showing <1% over 70 years old have a second transplant). With collection efficiencies of 55.9%, 44% of patients achieved their collection goal in a single day apheresis collection. A platelet count <150 × 103/µL on the day of collection was a predictor for poor mobilization; among 27 patients with a low baseline platelet count, 17 did not achieve the collection goal and 2 failed to collect a transplantable dose. CONCLUSIONS: With minor collection goal adjustments, 15% of all collection appointments could have been avoided over this 6-month period. Other strategies to accommodate more patients include mobilization modifications (Plerixafor timing or substituting a longer acting drug), utilizing platelet counts to predict mobilization, and modifying apheresis collection volumes or schedule templates.

Dataset of cell viability and analytes released by cancer cell lines exposed to low pH and conditioned medium.

Cancer cells influence their microenvironment by secreting factors that promote tumour growth and survival while evading immune-mediated destruction. We previously determined the expression of secreted factors in breast and oesophageal squamous cell carcinoma cell lines (MCF-7 and WHCO6, respectively) using Luminex assays. These cells were subsequently treated with low pH medium to mimic in vivo acid exposure, and the effects on cell viability, proliferation, and secretion of cytokines, chemokines and growth factors were described [1]. Here, we present the datasets from these experiments in addition to data obtained from treating cell lines with conditioned medium from apoptotic cell cultures.

Balancing Benefits and Risks: A Literature Review on Hypersensitivity Reactions to Human G-CSF (Granulocyte Colony-Stimulating Factor).

Human granulocyte colony-stimulating factor (G-CSF) is a granulopoietic growth factor used in the treatment of neutropenia following chemotherapy, myeloablative treatment, or healthy donors preparing for allogeneic transplantation. Few hypersensitivity reactions (HRs) have been reported, and its true prevalence is unknown. We aimed to systematically characterize G-CSF-induced HRs while including a comprehensive list of adverse reactions. We reviewed articles published before January 2024 by searching in the PubMed, Embase, Cochrane Library, and Web of Science databases using a combination of the keywords listed, selected the ones needed, and extracted relevant data. The search resulted in 68 entries, 17 relevant to our study and 7 others found from manually searching bibliographic sources. A total of 40 cases of G-CSF-induced HR were described and classified as immediate (29) or delayed (11). Immediate ones were mostly caused by filgrastim (13 minimum), with at least 9 being grade 5 on the WAO anaphylaxis scale. Delayed reactions were mostly maculopapular exanthemas and allowed for the continuation of G-CSF. Reactions after first exposure frequently appeared and were present in at least 11 of the 40 cases. Only five desensitization protocols have been found concerning the topic at hand in the analyzed data. We believe this study brings to light the research interest in this topic that could benefit from further exploration, and propose regular updating to include the most recently published evidence.

Therapeutic use of granulocyte colony-stimulating factor (G-CSF) in patients with febrile neutropenia: a comprehensive systematic review for clinical practice guidelines for the use of G-CSF 2022 from the Japan Society of Clinical Oncology.

BACKGROUND: Febrile neutropenia represents a critical oncologic emergency, and its management is pivotal in cancer therapy. In several guidelines, the use of granulocyte colony-stimulating factor (G-CSF) in patients with chemotherapy-induced febrile neutropenia is not routinely recommended except in high-risk cases. The Japan Society of Clinical Oncology has updated its clinical practice guidelines for the use of G-CSF, incorporating a systematic review to address this clinical question. METHODS: The systematic review was conducted by performing a comprehensive literature search across PubMed, the Cochrane Library, and Ichushi-Web, focusing on publications from January 1990 to December 2019. Selected studies included randomized controlled trials (RCTs), non-RCTs, and cohort and case-control studies. Evaluated outcomes included overall survival, infection-related mortality, hospitalization duration, quality of life, and pain. RESULTS: The initial search yielded 332 records. Following two rounds of screening, two records were selected for both qualitative and quantitative synthesis including meta-analysis. Regarding infection-related mortality, the event to case ratio was 5:134 (3.73%) in the G-CSF group versus 6:129 (4.65%) in the non-G-CSF group, resulting in a relative risk of 0.83 (95% confidence interval, 0.27-2.58; p = 0.54), which was not statistically significant. Only median values for hospitalization duration were available from the two RCTs, precluding a meta-analysis. For overall survival, quality of life, and pain, no suitable studies were found for analysis, rendering their assessment unfeasible. CONCLUSION: A weak recommendation is made that G-CSF treatment not be administered to patients with febrile neutropenia during cancer chemotherapy. G-CSF treatment can be considered for patients at high risk.

Subcutaneous injection granulocyte colony-stimulating factor (G-CSF) is superior to intrauterine infusion on patients with recurrent implantation failure: A systematic review and network meta-analysis.

Although both subcutaneous injection and intrauterine infusion of granulocyte colony-stimulating factor (G-CSF) have been reported to improve pregnancy outcomes in patients with recurrent implantation failure (RIF), how to administer it is still no consensus. The study aimed to investigate which administration route is optimal. We searched PubMed, Embase, the Cochrane Library (CENTRAL), Web of Science, and China National Knowledge Internet (CNKI) from inception to April 10, 2023, with language in both English and Chinese. The randomized controlled trials (RCTs) compared the effectiveness of G-CSF to treat patients with RIF were included in this network meta-analysis (NMA). The odds ratio (OR) and 95% confidence interval (CI) in pregnancy outcomes (implantation rate, IR; clinical pregnancy rate, CPR; live birth rate, LBR; miscarriage rate, MR; ectopic pregnancy rate, EPR) were summarized by NMA with a random-effects model. A total of 1360 RIF patients from 14 RCTs were included in this NMA, with no publication bias and small sample effects. No direct evidence compared the effectiveness of different administration routes of G-CSF on IR, LBR and MR. Both subcutaneous injection and intrauterine infusion of G-CSF increased the IR (OR = 2.81, 95% CI: 1.10-7.24; OR = 2.15, 95% CI: 1.50-3.07, respectively) and CPR (OR = 2.79, 95% CI: 1.86-4.17; OR = 1.74, 95% CI: 1.30-2.33, respectively) in patients with RIF. According to SUCRA, subcutaneous injection is more likely to be the optimal medication administration route. However, more high-quality studies were also needed to support these, especially IR and LBR.

Atraumatic splenic rupture secondary to granulocyte-colony stimulating factor medication exposure.

Hematopoietic hormones such as granulocyte-colony stimulating factors are commonly used prevent neutropenia in patients undergoing chemotherapy and to prepare patients for bone marrow donations. In rare cases, splenic injury can result from exposure to this medication. We present the case of a 30-year-old man who presented to the emergency department the day after a bone marrow donation procedure complaining of severe, acute onset left upper quadrant abdominal pain, radiating to the shoulder. Neither the patient nor his family reported any abdominal trauma prior to or following the marrow donation procedure. An initial bedside ultrasound examination was positive for peritoneal fluid and distortion of the normal splenic architecture, raising suspicion for possible intraabdominal or splenic injury. An emergent confirmatory CT with contrast of the abdomen confirmed the initial ultrasound examination suspicion of an atraumatic splenic rupture and with evidence of venous bleeding but without active arterial extravasation. An emergent trauma surgery consultation was placed, and he underwent embolization with an uneventful recovery. This case report highlights the need for a high index of suspicion for atraumatic splenic rupture in patients exposed to these types of granulocyte-colony stimulating factors.

IL-23 regulation of myeloid cell biology during inflammation.

Interleukin (IL)-23 is implicated in the pathogenesis of several inflammatory diseases and is usually linked with helper T cell (Th17) biology. However, there is some data linking IL-23 with innate immune biology in such diseases. We therefore examined the effects of IL-23p19 genetic deletion and/or neutralization on in vitro macrophage activation and in an innate immune-driven peritonitis model. We report that endogenous IL-23 was required for maximal macrophage activation by zymosan as determined by pro-inflammatory cytokine production, including a dramatic upregulation of granulocyte-colony stimulating factor (G-CSF). Furthermore, both IL-23p19 genetic deletion and neutralization in zymosan-induced peritonitis (ZIP) led to a specific reduction in the neutrophil numbers, as well as a reduction in the G-CSF levels in exudate fluids. We conclude that endogenous IL-23 can contribute significantly to macrophage activation during an inflammatory response, mostly likely via an autocrine/paracrine mechanism; of note, endogenous IL-23 can directly up-regulate macrophage G-CSF expression, which in turn is likely to contribute to the regulation of IL-23-dependent neutrophil number and function during an inflammatory response, with potential significance for IL-23 targeting particularly in neutrophil-associated inflammatory diseases.

Comparison of two autologous hematopoietic stem cell mobilization strategies in patients with multiple myeloma: CE plus G-CSF versus G-CSF only: A single-center retrospective analysis.

BACKGROUND: Despite recent advances in the treatment of multiple myeloma, high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (ASCT) remains an essential therapeutic keystone. As for the stem cell mobilization procedure, different regimens have been established, usually consisting of a cycle of chemotherapy followed by application of granulocyte-colony stimulating factor (G-CSF), although febrile neutropenia is a common complication. Following national guidelines, our institution decided to primarily use G-CSF only mobilization during the COVID-19 pandemic to minimize the patients' risk of infection and to reduce the burden on the health system. STUDY DESIGN AND METHODS: In this retrospective single-center analysis, the efficacy and safety of G-CSF only mobilization was evaluated and compared to a historic control cohort undergoing chemotherapy-based mobilization by cyclophosphamide and etoposide (CE) plus G-CSF. RESULTS: Although G-CSF only was associated with a higher need for plerixafor administration (p < .0001) and a higher number of apheresis sessions per patient (p = .0002), we were able to collect the target dose of hematopoietic stem cells in the majority of our patients. CE mobilization achieved higher hematopoietic stem cell yields (p = .0015) and shorter apheresis sessions (p < .0001) yet was accompanied by an increased risk of febrile neutropenia (p < .0001). There was no difference in engraftment after ASCT. DISCUSSION: G-CSF only mobilization is a useful option in selected patients with comorbidities and an increased risk of serious infections, especially in the wintertime or in future pandemics.