Impact on natural history of atypical meningioma after changes in 2016 edition of the world health organization (WHO) classification of central nervous system tumors: a literature review.

Meningiomas and their WHO histological diagnostic criteria is complex, especially for grade 2 tumors presenting a interobserver discordance as high as 12.2%. The 2016 edition of the WHO Classification of CNS tumors recommended brain invasion as a stand-alone grading criterion for diagnosing an atypical grade 2 meningioma (AM). To provide an overview of the classification of 2016 WHO impact on the natural history of atypical meningioma (AM) relative to previous classification. To achieve this goal, we selected articles from the period 2017-2024 in Medline search on atypical meningiomas and analyzed them after following the following criteria: 1) reports with confirmed histopathological diagnosis according to WHO 2016 and or 2021 criteria; 2) series and case reports; 3) detailed and individualized clinical outcomes for AM; and 4) papers written in English; after that a total of 3445 patients reported in 67 manuscripts from worldwide centers from 2017 to March 2024 were analyzed. The patient's age at the time of surgery ranged from 1 month to 97 years (mean 52.28 ± 18.7 years). The most common tumor site was the convexity, accounting for 67.8%, followed by the skull base in 30.6%, ventricle in 1%, and spine in 0.6%; Gross total resection (GTR) was performed in 71.25% and subtotal resection (STR) in 28.75%; 1021 patients (29.63%) underwent adjuvant radiotherapy, and 22 patients (0.6%) were treated with adjuvant chemotherapy; tumor recurrence was reported in 1221 patients (35.44%) and 859 deaths (24.93%). 1) AM prevalence in females; 2) AM age distribution similar to the distribution of meningiomas in general; 3) AM recurrence rate of 35.44%, despite the high rate of GTR, which was higher than previously reported; 4) deepening knowledge in molecular mechanism of tumor progression will provide alternative therapeutic approaches for AM.

Consensus guidelines for the management of intracranial meningioma for low- and middle-income countries.

Intra-cranial meningiomas represent the most common type of extra-axial brain tumour in adults. Characteristically slow-growing and often asymptomatic, these tumours may only require observation in some cases. However, lesions that cause a significant mass effect necessitate intervention, primarily through surgical means. Additionally, in cases of significant unresectable low-grade residual meningioma or high-grade tumours, radiation therapy becomes essential. Notably, current management guidelines predominantly reflect data derived from high-income countries, failing to address constraints prevalent in the developing world, such as limited financial resources and restricted access to advanced surgical facilities. This manuscript introduces guidelines specifically tailored for the management of meningioma in patients from low- and middle-income countries, considering their unique healthcare challenges and resources.

The Molecular and Immunological Landscape of Meningiomas.

Meningiomas are the most common primary intracranial tumors in adults and typically have a slow-growing and benign nature. However, there is also a substantial subset of meningiomas that shows aggressive clinical behavior and is refractory to standard treatment modalities, which are still limited to surgery and/or radiotherapy. Despite intensive research, no systemic treatment options are yet available in the clinic for these challenging tumors, resulting in poor patient outcome. Intensive research on the molecular pathogenesis of meningiomas has led to improved diagnostic tools, but so far there is no standardized implementation for the molecular profiling of these tumors for clinical practice. Recent research advances have also focused on the immunophenotyping of meningiomas, leading to several clinical trials examining the use of immune checkpoint blockade therapy in patients with clinically aggressive subtypes. In this review, we aim to summarize the current knowledge on the molecular and immunological landscape of meningiomas in detail and provide current and progressive ideas for future directions.

Current immunotherapy techniques in meningioma.

INTRODUCTION: Although meningiomas are the most common primary brain tumor, there are limited treatment options for recurrent or aggressive lesions. Compared to other brain tumors, meningiomas may be uniquely amenable to immunotherapy by virtue of their location outside the blood-brain barrier. AREAS COVERED: This review describes our current understanding of the immunology of the meninges, as well as immune cell infiltration and immune signaling in meningioma. Current literature on meningioma immunology and immunotherapy was comprehensively reviewed and summarized by a comprehensive search of MEDLINE (1/1/1990-6/1/2024). Further, we describe the current state of immunotherapeutic approaches, as well as potential future targets. Potential immunotherapeutic approaches include immune checkpoint inhibition, CAR-T approaches, tumor vaccine therapy, and immunogenic molecular markers. EXPERT OPINION: Meningioma immunotherapy is in early stages, as no immunotherapies are currently included in treatment guidelines. There is substantial heterogeneity in immune cell infiltration, immunogenicity, and immune escape across tumors, even within tumor grade. Furthering our understanding of meningioma immunology and tumor classification will allow for careful selection of tumors and patient populations that may benefit from primary or adjunctive immunotherapy for meningioma.

Decoding pediatric spinal tumors: a single-center retrospective case series on etiology, presentation, therapeutic strategies, and outcomes.

INTRODUCTION: Spinal tumors (ST) often result in dire prognosis, carrying risks such as permanent paralysis, sensory loss, and sphincter dysfunction. Data on their incidence and etiology in pediatric populations are markedly scant. Our study investigates the etiology, clinical manifestation, treatment, and outcomes of pediatric ST. METHODS: We conducted a retrospective review of our institutional pediatric oncology and neurosurgery database, examining 14 patients under 18 years admitted with ST due to oncological diseases since 2005. We analyzed the clinical presentations, evaluations, molecular diagnostics and treatments for these patients. RESULTS: The study spanned 15 years and included 14 pediatric patients, each diagnosed with distinct spinal tumor entity. The mean patient age was approximately 19.6 ± 10.1 months. Severe axial pain along the vertebral column was observed in 13 patients, while acute neurological deterioration manifested in 7 patients. As a first-line intervention, 13 patients underwent decompressive surgery through laminectomy and tumor resection, and only one patient received chemotherapy solely. Before surgery, seven patients were unable to walk; post-surgery, six of them regained their ability to ambulate. The diagnosis encompassed a range of neoplasms: two instances of Ewing sarcoma, 3 instances of teratoma, one case presenting an atypical teratoid Rhabdoid tumor, two instances each of low-grade astrocytoma and neuroblastoma, and single instances of ependymoma, meningioma, rhabdomyosarcoma, and embryonal tumors with multilayered rosettes (ETMRs). Three patients succumbed two years after initiating therapy. CONCLUSION: Despite their rarity, intraspinal tumors in pediatric patients pose substantial therapeutic challenges. The intertwined complexities of the disease entity and the patient's neurological status demand swift initiation of an individualized therapeutic strategy. This crucial step helps optimize outcomes for this patient cohort, who frequently grapple with debilitating health conditions. Inclusion of these patients within a registry is mandatory to optimize treatment outcomes due to their rarity in pediatric population.

Consensus guidelines for the management of primary supra-tentorial intraventricular tumour for low- and middle-income countries.

Almost any primary or metastatic brain tumour can manifest in intraventricular (IV) locations. These tumours may either originate within the ventricular system or extend into the IV space through growth. Such neoplasms represent a broad spectrum, with supratentorial IV tumours forming a heterogeneous group. This group includes primary ependymal tumours, central neurocytomas, choroid plexus tumours, and notably, meningiomas, as well as a variety of non-neoplastic, benign, glial, and metastatic lesions that can secondarily invade the IV compartment. Often presenting with nonspecific symptoms, these tumours can lead to delayed medical attention. The diversity in potential diagnoses, combined with their deep and complex locations, poses significant management challenges. This paper aims to delineate optimal management strategies, underscoring the importance of multidisciplinary care, especially in settings with limited resources, to effectively navigate the complexities associated with treating intraventricular brain tumours.

[Preoperative Embolization of Intracranial Meningioma].

Preoperative embolization(POE)of intracranial meningioma is performed worldwide. Although clear evidence of the effectiveness of POE has not been reported in the literature, the technique plays an important role in open surgery, especially for large or skull base meningiomas. The purposes of embolization include: 1)induction of tumor necrosis, resulting in a safer operation, 2)reduction in intraoperative bleeding, and 3)decrease in operative time. Knowledge of the functional vascular anatomy, embolic materials, and endovascular techniques is paramount to ensure safe embolization. Our standard procedure is as follows: 1)embolization is performed several days before open surgery; 2)in cases with strong peritumoral edema, steroid administration or embolization may be performed immediately prior to surgery; 3)patients undergo the procedure under local anesthesia; 4)the microcatheter is inserted as close as possible to the tumor; 5)particulate emboli are the first-line material; 6)embolization is occasionally performed with N-butyl cyanoacrylate(NBCA)glue; and 7)if possible, additional proximal feeder occlusion with coils is performed. The JR-NET study previous showed the situation regarding intracranial tumor embolization in Japan. Endovascular neurosurgeons should fully discuss the indications and strategies for POE with tumor neurosurgeons to ensure safe and effective procedures.

[Role of Pharmacotherapy in Treatment of Meningiomas].

Meningiomas constitute the most common primary tumors of the central nervous system. Despite maximum treatment, grade 2/3 meningiomas are associated with a high risk of recurrence. Stereotactic radiosurgery is the treatment of choice as adjuvant treatment for grade 2/3 meningiomas. Currently, pharmacotherapies, including molecular targeted therapy for various growth factors, their receptors, and the associated pathways, have shown limited effectiveness for management of refractory or recurrent meningiomas. Therefore, novel systemic treatment approaches are urgently required in such cases. Recent advances in genetics and epigenetics and the identification of specific genetic alterations have led to new classifications of these tumors and the development of therapeutic targets. Identification of targeted gene mutations may lead to precision-based medicine. Other therapeutic approaches such as immune checkpoint inhibitors rarely elicit a significant response in meningiomas with a high tumor mutation burden. Combination therapies that affect these multiple targets are also considered adjuvant therapeutic options. Comprehensive/in-depth research is warranted to investigate the safety and efficacy of other treatment strategies, including chimeric antigen receptor T-cells, oncolytic virus immunotherapy, and gene therapy. In this article, we review the current evidence regarding the efficacy of systemic treatments available in the literature and discuss recent and ongoing trials for meningiomas.

[Preoperative Embolization Performed Before Meningioma Resection Might Inhibit Tumor Recurrence].

Recent advances in endovascular treatment have improved the safety and efficacy of this procedure, and the number of cases in which preoperative embolization is performed is likely to increase. Preoperative tumor embolization is still a controversial treatment, and as long as it carries a risk of complications, its primary benefit of reducing blood loss during surgery may not be sufficient to justify treatment. We recently reported that preoperative embolization does not significantly increase complications, but may prolong recurrence-free survival. However, currently, tumor embolization is only a preoperative adjunctive therapy, and there is no evidence that it is a stand-alone option for meningioma treatment. Nevertheless, the possibility that tumor embolization alone can promote tumor shrinkage and reduce peripheral oedema has been reported, although the number of cases is small. Further research is needed, but in the future, tumor embolization may become an in-office treatment under certain conditions, such as in cases of poor general condition, multiple meningiomas, recurrent and refractory cases, difficult surgery and cases where re-irradiation is difficult after post-radiation therapy.

[Challenges to Overcome in Clinical Research on Meningiomas].

In contrast to other cancer research areas, the development of chemotherapy and radiotherapy for meningiomas has been challenging, lacking standardized criteria for assessing treatment response and progression. Although efforts by RANO have proposed evaluation criteria, a consensus on effective evaluation parameters for meningiomas remains elusive. This paper underscores the importance of establishing efficacy endpoints in clinical trials, compares efficacy assessment in meningioma research with other solid tumor areas, and outlines the challenges ahead in meningioma research. Recent analyses revealed the absence of consensus on efficacy endpoints in meningioma trials, complicating trial design and hindering cross-trial comparisons. The unique anatomical constraints and histological variability of meningiomas pose challenges in determining appropriate efficacy measures. To address these challenges, future research must focus on accumulating prognostic data, standardizing evaluation criteria, and considering multiple endpoints in trial designs. Akin to other cancer areas, investigating targeted therapies and establishing international consensus on efficacy endpoints are crucial steps forward.

Immune Checkpoint Inhibition for High Grade Meningiomas: A Systematic Review.

BACKGROUND: World Health Organization grade II/III meningiomas frequently recur despite maximal safe surgical resection and adjuvant radiation. Notoriously resistant to medical therapy, no well-established guidelines for pharmacologic treatment currently exist. In recent years, a small number of clinical trials have investigated immune checkpoint inhibitors (ICIs) for patients with recurrent grade II/III meningiomas. We reviewed the existing literature to 1) summarize the clinical responses that have been observed and 2) identify tumor genomic characteristics that may predict a better response to ICI therapy. METHODS: PubMed was searched following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to include studies reporting clinical data for recurrent grade II or grade III meningiomas treated with ICIs. Clinical features, available tumor genomics, and outcomes were analyzed. RESULTS: Four studies were included comprising 59 patients; 74.6% had World Health Organization grade II meningiomas and 25.4% had grade III meningiomas. Thirt-two patients (54%) received nivolumab, 26 (44%) received pembrolizumab, and 1 (2%) received an ICI not named. While tumor genomic data was not consistently reported across studies, favorable response was most associated with mismatch repair deficiency and high tumor mutational burden. Common adverse effects included liver/pancreas enzyme elevations (11.5%), fatigue (11.5%), and leukopenia/infection (9%). CONCLUSIONS: Checkpoint inhibitors represent a promising investigational therapy for patients with recurrent grade II/III meningiomas. These drugs may be more efficacious for tumors with mismatch repair deficiency or high tumor mutational burden. Future investigations would benefit from research consortia with prospective enrollments of patients, descriptive characterization of tumor genomics, and standardized assessment of radiographic response.

Joint EANM/EANO/RANO/SNMMI practice guideline/procedure standards for diagnostics and therapy (theranostics) of meningiomas using radiolabeled somatostatin receptor ligands: version 1.0.

PURPOSE: To provide practice guideline/procedure standards for diagnostics and therapy (theranostics) of meningiomas using radiolabeled somatostatin receptor (SSTR) ligands. METHODS: This joint practice guideline/procedure standard was collaboratively developed by the European Association of Nuclear Medicine (EANM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the European Association of Neurooncology (EANO), and the PET task force of the Response Assessment in Neurooncology Working Group (PET/RANO). RESULTS: Positron emission tomography (PET) using somatostatin receptor (SSTR) ligands can detect meningioma tissue with high sensitivity and specificity and may provide clinically relevant information beyond that obtained from structural magnetic resonance imaging (MRI) or computed tomography (CT) imaging alone. SSTR-directed PET imaging can be particularly useful for differential diagnosis, delineation of meningioma extent, detection of osseous involvement, and the differentiation between posttherapeutic scar tissue and tumour recurrence. Moreover, SSTR-peptide receptor radionuclide therapy (PRRT) is an emerging investigational treatment approach for meningioma. CONCLUSION: These practice guidelines will define procedure standards for the application of PET imaging in patients with meningiomas and related SSTR-targeted PRRTs in routine practice and clinical trials and will help to harmonize data acquisition and interpretation across centers, facilitate comparability of studies, and to collect larger databases. The current document provides additional information to the evidence-based recommendations from the PET/RANO Working Group regarding the utilization of PET imaging in meningiomas Galldiks (Neuro Oncol. 2017;19(12):1576-87). The information provided should be considered in the context of local conditions and regulations.

Management Approaches in WHO Grade III Meningioma: A National Oncology Trainees' Collaborative for Healthcare Research (NOTCH) UK Multi-Centre Retrospective Study.

AIMS: WHO Grade 3 (G3) meningiomas are rare tumours with limited data to guide management. This retrospective study documents UK management approaches across 14 centres over 11 years. MATERIALS AND METHODS: Patients with WHO G3 meningioma between 01/01/2008 and 31/12/2018 were identified. Data were collected on demographics, management strategy, adjuvant radiotherapy, approach in recurrence setting and survival. RESULTS: 84 patients were identified. 21.4% transformed from lower-grade disease. 96.4% underwent primary surgical resection, with 20.8% having evidence of residual disease on their post-op MRI. 59.3% of patients underwent adjuvant radiotherapy (RT) following surgical resection. Overall median PFS and OS were 12.6 months and 28.2 months, respectively. Median OS in the group who underwent complete surgical resection was 34.9 months, compared to 27.5 months for those who had incomplete resection (HR 0.58, 95% CI 0.27-1.23, p = 0.15). Median OS was 33.1 months for those who underwent adjuvant RT and 14.0 months for those who did not (HR 0.48, 95% CI 0.27-0.84, p = 0.004). Median adjuvant RT dose delivered was 60Gy (range 12Gy-60Gy), 45.8% of adjuvant RT was delivered using IMRT. At disease relapse, 31% underwent salvage surgery and 29.3% underwent salvage RT. Of those treated with salvage RT, 64.7% were re-treats and all were treated with hypofractionated RT. CONCLUSION: Surgery continues to be the preferred primary management strategy. Post-operative MRI within 48 hours is indicated to assess presence of residual disease and guide further surgical options. Adjuvant radiotherapy plays an important part of the management paradigm in these patients with the data supporting an attached survival advantage. Further surgery and re-irradiation is an option in the disease recurrence setting with radiosurgery frequently utilised in this context.

Meningioma: International Consortium on Meningiomas consensus review on scientific advances and treatment paradigms for clinicians, researchers, and patients.

Meningiomas are the most common primary intracranial tumors in adults and are increasing in incidence due to the aging population and increased access to neuroimaging. While most exhibit nonmalignant behavior, a subset of meningiomas are biologically aggressive and are associated with treatment resistance, resulting in significant neurologic morbidity and even mortality. In recent years, meaningful advances in our understanding of the biology of these tumors have led to the incorporation of molecular biomarkers into their grading and prognostication. However, unlike other central nervous system (CNS) tumors, a unified molecular taxonomy for meningiomas has not yet been established and remains an overarching goal of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy-Not Official World Health Organization (cIMPACT-NOW) working group. Additionally, clinical equipoise still remains on how specific meningioma cases and patient populations should be optimally managed. To address these existing gaps, members of the International Consortium on Meningiomas including field-leading experts, have prepared this comprehensive consensus narrative review directed toward clinicians, researchers, and patients. Included in this manuscript are detailed overviews of proposed molecular classifications, novel biomarkers, contemporary treatment strategies, trials on systemic therapies, health-related quality-of-life studies, and management strategies for unique meningioma patient populations. In each section, we discuss the current state of knowledge as well as ongoing clinical and research challenges to road map future directions for further investigation.

Comprehensive assessment of atypical and anaplastic pediatric meningiomas utilizing national cancer database: a retrospective cohort study.

PURPOSE: To examine demographic and clinical characteristics and their association with survival in grade 2 and 3 pediatric meningiomas in a large cohort using the National Cancer Database (NCDB). METHODS: We conducted a comprehensive analysis using data from NCDB between 2004 to 2018. Tumor-specific data included tumor grade and size. Treatment details, including surgical resection, extent of resection, and radiotherapy, were gathered. Our analytic approach incorporated logistic and Poisson regression, Kaplan-Meier survival estimates, and Cox proportional hazards models. RESULTS: Among the included 239 patients aged 0-21 years, age category distribution was significantly different between grade 2 and grade 3 tumors (p = 0.018). For grade 2 meningiomas, 51.5% of patients were female, and 76.7% were white. 85.3% of patients with grade 2 meningiomas underwent surgical resection, of which 67% underwent gross total resection. Overall survival (OS) was significantly different between resected and non-resected patients (p = 0.048). Uninsured patients were over seven times as likely to have prolonged length of stay (LOS) versus those with private insurance (OR = 7.663, p = 0.014). For grade 3 meningiomas, 51.4% of patients were male, and 82.9% were white. 91.4% of patients with grade 3 meningiomas underwent surgical resection, of which 53.3% underwent subtotal resection. OS was not significantly different between resected and non-resected patients (p = 0.659). CONCLUSION: In summary, there were significant differences in age, maximum tumor dimension, unplanned readmission, radiotherapy, and treatment combinations between grade 2 and 3 meningiomas. These findings highlight the intricacies of managing pediatric meningiomas and emphasize the necessity for tailored therapeutic approaches to enhance outcomes in the future.

Related mechanisms, current treatments, and new perspectives in meningioma.

Meningiomas are non-glial tumors that are the most common primary brain tumors in adults. Although meningioma can possibly be cured with surgical excision, variations in atypical/anaplastic meningioma have a high recurrence rate and a poor prognosis. As a result, it is critical to develop novel therapeutic options for high-grade meningiomas. This review highlights the current histology of meningiomas, prevalent genetic and molecular changes, and the most extensively researched signaling pathways and therapies in meningiomas. It also reviews current clinical studies and novel meningioma treatments, including immunotherapy, microRNAs, cancer stem cell methods, and targeted interventions within the glycolysis pathway. Through the examination of the complex landscape of meningioma biology and the highlighting of promising therapeutic pathways, this review opens the way for future research efforts aimed at improving patient outcomes in this prevalent intracranial tumor entity.

Evolving concepts in meningioma management in the era of genomics.

Meningioma is the most common type of primary brain tumor. Surgical resection followed by surveillance is the first-line treatment for the majority of symptomatic meningiomas; however, recent advances in molecular sequencing, DNA methylation, proteomics, and single-cell sequencing provide insights into further characterizing this heterogeneous group of tumors with a wide range of prognoses. A subset of these tumors are highly aggressive and cause severe morbidity and mortality. Therefore, identifying those individuals with a poor prognosis and intervening are critical. This review aims to help readers interpret the molecular profiling of meningiomas to identify patients with worse prognoses and guide the management and strategy for surveillance.

Relevance of the Foramen of Vesalius for Preoperative Tumor Embolization in Skull Base Meningioma.

OBJECTIVE: The objective of this study was to investigate the role of the foramen of Vesalius (FV) in the pathogenesis of skull base meningioma by analyzing data from various multi-image modalities. METHODS: For this single-center retrospective study, 39 consecutive patients with skull base meningioma who underwent tumor resection between January 2020 and March 2023 were enrolled. The anatomical and pathological characteristics of the FV were evaluated using computed tomography and 3-dimensional digital subtraction angiography. The clinical significance of the FV in tumor hemodynamics and treatment, such as preoperative tumor embolization, was investigated using the 3-dimensional digital subtraction angiography/computed tomography fusion images. RESULTS: We identified FV in 52% (17/27) of the finally included patients. In 10 (30%) patients, the FV was found bilaterally with no significant variation in appearance between the healthy and tumor-affected sides (P = 0.786). The mean FV diameter was significantly larger on the tumor-affected side (P = 0.010). No significant anatomical differences, like duplication and partial assimilation with the foramen ovale, were observed between the 2 sides. The FV was involved in venous skull base perfusion around the tumor in 9 cases. In 4 cases where it was the pathway for tumor feeders, preoperative tumor embolization via the FV resulted in disappearance of the tumor stain. No complications associated with endovascular treatment were observed. CONCLUSIONS: This study elucidated the anatomical asymmetry of the FV and its role in the hemodynamics of skull base meningioma. Our findings highlight the significance of performing anatomical and pathological evaluations of the FV in determining treatment strategies, including preoperative embolization, for skull base lesions.

A systematic review of extraneural meningioma metastasis: timing, evolution and outlook.

PURPOSE: Extraneural meningioma metastasis is a rare occurrence and may pose a clinical challenge due to its unclear prognosis. In this systematic review, we analyze patient demographics, clinical characteristics, management strategies, and outcomes. METHODS: PubMed, EMBASE, Scopus, Cochrane, and Web of Science databases were searched from inception to February 23, 2024 for cases of metastatic meningioma according to PRISMA guidelines. Descriptive statistics, Mann-Whitney U test, Fisher's exact tests, Kaplan-Meier curves, and log-rank tests were used for selected analyses. RESULTS: A total of 288 patients (52% male) were included with an average age of 49 years at meningioma diagnosis. Tumors were distributed across WHO grade 1 (38%), 2 (36%), and 3 (26%). Most patients experienced intracranial recurrence (79%) and mean time to first metastasis was approximately 8 years. No change in WHO grade between primary and metastasis was observed for most cases (65%). Treatment of the initial metastasis was most often with surgery (43%), chemotherapy (20%), or no treatment (14%). Half of the patients were alive (50%) with an average follow-up of 3 years following metastasis. Overall median survival was 36 months for the entire cohort. This differed significantly between WHO grade 1 versus 2/3 meningioma primaries (168 vs. 15 months, p < 0.005). CONCLUSION: Metastatic meningioma appears to be associated with more positive prognosis than other brain tumor types with extra-neural metastasis or metastasis in general. This is particularly true for cases arising from a WHO grade 1 meningioma.

A randomized control trial for evaluation of transfusion related immuno-modulation in patients with meningioma.

BACKGROUND: Blood transfusion necessity in neurosurgery varies based on surgical type, blood loss, and patient anemia. Leukocytes in red blood cells (RBCs) component release pro-inflammatory cytokines during storage, contributing to transfusion-related immunomodulation (TRIM). Our aim was to examine the impact of the leukocyte content in transfused PRBCs on patients undergoing neurosurgery for meningioma tumours. STUDY DESIGN AND METHODS: This prospective randomized controlled trial conducted from 2018 to 2020 by dividing patients randomly into non-leukoreduced (NLR) (n = 65) and leuko-reduced (LR) (n = 65) groups based on PRBCs received during surgery and hospital stay. Hospital and ICU stays, mechanical ventilation duration, and postoperative bacterial infections were observed. Hematological parameters and cytokine levels (IL-10, INF-gamma, and FAS-L) were assessed at pre-transfusion, 24 h, and 7 days post-transfusion. Data analysis included Mann-Whitney U test, Friedman test, Fisher's chi-square test, with statistical significance at p < 0.05. RESULTS: In our study, ICU and hospital stay duration showed no significant difference (p = 0.06) between groups. However, NLR group had longer mean mechanical ventilation (18 ± 40.1 h) than the LR group (12.8 ± 8.6 h). Both groups showed statistically significant increase in Fas-L level on days 1 and 7 (p < 0.05). The IL-10 levels rose 43% in the NLR group, while and decreased by 7% the LR group on day 1. On day 7, IL-10 increased by 75% in NLR and decreased by 40% in LR, with no significance (p > 0.05). CONCLUSION: In conclusion, leukoreduction appeared to offer some immune response protection in term of reducing mechanical ventilation timings and cytokine level changes.