A novel t(X;21)(p11.4;q22.12) translocation adds to the role of BCOR and RUNX1 in myelodysplastic syndromes and acute myeloid leukemias.

In myeloid neoplasms, both fusion genes and gene mutations are well-established events identifying clinicopathological entities. In this study, we present a thus far undescribed t(X;21)(p11.4;q22.12) in five cases with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). The translocation was isolated or accompanied by additional changes. It did not generate any fusion gene or gene deregulation by aberrant juxtaposition with regulatory sequences. Molecular analysis by targeted next-generation sequencing showed that the translocation was accompanied by at least one somatic mutation in TET2, EZH2, RUNX1, ASXL1, SRSF2, ZRSR2, DNMT3A, and NRAS genes. Co-occurrence of deletion of RUNX1 in 21q22 and of BCOR in Xp11 was associated with t(X;21). BCOR haploinsufficiency corresponded to a significant hypo-expression in t(X;21) cases, compared to normal controls and to normal karyotype AML. By contrast, RUNX1 expression was not altered, suggesting a compensatory effect by the remaining allele. Whole transcriptome analysis showed that overexpression of HOXA9 differentiated t(X;21) from both controls and t(8;21)-positive AML. In conclusion, we characterized a new recurrent reciprocal t(X;21)(p11.4;q22.12) chromosome translocation in MDS and AML, generating simultaneous BCOR and RUNX1 deletions rather than a fusion gene at the genomic level.

Subsequent malignant neoplasms after primary hematological malignancy in adult patients.

Patients with primary hematological malignancy (HM) are at an elevated risk of subsequent malignant neoplasms (SMNs), which is a common concern after treatment of primary cancer. We identified 45,533 patients aged ≥20 years and diagnosed with primary HM in Finland from 1992 to 2019 from the Finnish Cancer Registry and estimated standardized incidence ratios (SIR) and excess absolute risks per 1000 person-years (EAR) for SMNs. A total of 6076 SMNs were found (4604 solid and 1472 hematological SMNs). The SIRs were higher for hematological SMNs (SIR 4.9, 95% confidence interval [CI] 4.7-5.2) compared to solid SMNs (SIR 1.5, 95% CI 1.4-1.5). The SIRs for hematological SMNs were highest in the young HM patients aged 20-39 years (SIR 9.2, 95% CI 6.8-12.2 in males and SIR 10.5, 95% CI 7.2-14.7 in females) and decreased by age of first primary HM. However, EARs for hematological SMNs were highest in the older patients, aged 60-79 years at their first primary HM (EAR 5.7/1000 and 4.7/1000 in male and female patients, respectively). In conclusion, the incidence of both hematological and solid SMNs were increased in hematological cancer patients. The relative risk (SIR) was highest among younger HM patients with hematological SMNs. The absolute second cancer burden reflected by high EAR arises from solid malignancies in older patients. Our results accentuate the need for vigilance in the surveillance of HM patients.

Investigation of polypharmacy, antimicrobial-related potential drug-drug interactions in patients with hematological malignancies.

PURPOSE: Drug-drug interactions (DDIs) occur when one drug interferes with the pharmacological activity of another and can lead to increased side effects. The purpose of this study was to examine potential interactions between antimicrobials and other drugs in patients with hematological malignancies (HMs). METHOD: The medications used by 233 patients with HMs before and during hospitalization in Ankara City Hospital Hematology Clinic services between January 2021 and July 2021 were examined. Potential DDIs (pDDIs) were identified through UptoDate, Drugs.com, and MedScape databases. The effects of major antimicrobial-related pDDIs on patients were examined. Agreement between the two interaction systems was judged based on the kappa test. SPSS R Version 4.0.2 was used in the statistical analysis of the data, p<.05 was considered significant. RESULTS: The prevalence of polypharmacy before hospitalization was determined as 22.7%. Diagnosed with acute leukemia and multiple myeloma, more antimicrobial-related pDDIs were detected during hospitalization (p<.001). A total of 758 antimicrobial-related pDDIs, which were in the major category in at least one of the three databases, were detected in 72.5% (169/233) of the participants. It was determined that the total hospitalization period of patients with major antimicrobial-related pDDIs was longer (p<.001). There was negligible agreement between UptoDate and Dugs.com and between Drugs.com and MedScape (kappa: 0.008 for both). There was no compatibility between UptoDate and MedScape (kappa<0). CONCLUSION: Interactions between antimicrobials and other drugs are undesirable problems. Further studies are required to evaluate the clinical and economic effects of the interactions on patients with HMs.

Unusual Presentation of a Giant Cell Tumor of the Bone: A Case Report.

Bone giant cell tumors (GCTs) are rare, non-cancerous tumors that mostly affect the meta-epiphyseal region of long bones in the legs and arms. We are reporting a case of GCT of bone of a 14-year-old male; it usually occurs in the age group of 20-40 years. The presence of multinucleated giant cells and stromal cells in the proximal diaphysis of the left tibia serves as a distinguishing characteristic. The majority of GCTs are benign; they have the potential to induce bone loss and can be locally aggressive. Treatment options often include surgery, and in some cases, medications like denosumab may be used to help shrink the tumor or manage recurrent cases.

A Rare Case of Dual Metachronous Primary Malignancies, Chronic Myeloid Leukemia, and Tongue Carcinoma in a Patient With Long-Standing Systemic Lupus Erythematosus: A Case Report and Review of Literature.

Patients with long-standing autoimmune diseases like systemic lupus erythematosus (SLE) are at a higher risk of developing hematological malignancies. However, chronic myeloid leukemia (CML) has rarely been reported in patients with SLE. Advancements in medical diagnostics and treatment have led to the life expectancy of SLE and CML patients moving closer to that of the general population, and it is not uncommon to encounter more than one malignancy in a cancer survivor. Although squamous cell carcinoma (SCC) of the skin has been reported in CML patients, mucosal SCC of the head and neck has rarely only been reported in CML survivors. The objective of this case report is to share our experience in treating a patient with dual metachronous primary malignancies, CML, and tongue carcinoma, along with long-standing SLE, managed by a multidisciplinary team.

Genetic prediction of causal association between serum bilirubin and hematologic malignancies: a two-sample Mendelian randomized and bioinformatics study.

Introduction: An increasing number of cohort studies have shown a correlation between serum bilirubin and tumors, but no definitive causal relationship has been established between serum bilirubin and hematological malignancies.Therefore, the aim of the present study was to assess the causal relationship of serum bilirubin, including total bilirubin (TBIL) and direct bilirubin (DBIL), with hematological malignancies, including leukemia, lymphoma, and myeloma. Methods: We used a genome-wide association study (GWAS) collection of TBIL, DBIL, and hematological malignancies data. Using two-sample Mendelian randomization(MR), we assessed the impact of TBIL and DBIL on hematological malignancies. For this study, the inverse variance weighting method (IVW) was the primary method of MR analysis. In the sensitivity analysis, the weighted median method, MR Egger regression, and MR-PRESSO test were used. To understand the mechanisms behind TBIL and DBIL, we used three different approaches based on screening single nucleotide polymorphisms (SNPs) and their associated genes, followed by bioinformatics analysis. Results: The IVW test results showed evidence of effects of TBIL (odds ratio [OR]: 4.47, 95% confidence interval [CI]: 1.58-12.62) and DBIL (OR: 3.31, 95% CI: 1.08-10.18) on the risk of acute myeloid leukemia (AML).The findings from bioinformatics indicated that TBIL could potentially undergo xenobiotic metabolism through cytochrome P450 and contribute to chemical carcinogenesis. Discussion: In this study, two-sample MR analysis revealed a causal relationship between TBIL, DBIL, and AML.

Monitoring Humoral Response Following BNT162b2 mRNA Vaccination against SARS-CoV-2 in Hematopoietic Stem-Cell Transplantation Patients: A Single-Center Prospective Study along with a Brief Review of Current Literature.

Data on antibody response (AR) after vaccination against SARS-CoV2 in hematopoietic stem-cell transplantation setting (HSCT) were initially scarce, mainly due to the exclusion of such patients from approval studies. Shortly after the worldwide application of vaccination against SARS-CoV-2 in vulnerable populations such as patients with hematologic malignancies, limited single-center trials, including HSCT patients, were published. However, there was a great heterogeneity between them regarding the type of underlying malignancy, co-current treatment, type of vaccine, method of AR measurement, and time point of AR measurement. Herein, we present the results of a prospective study on AR after vaccination for SARS-CoV-2 using the BNT162b2 vaccine in a cohort of 54 HSCT recipients-mostly autologous from a single Unit-along with a broad review of the current literature. In our cohort, the AR positivity rate at 1 month was 80.8% and remained positive in 85.7% of patients at 3 months after vaccination. There were only nine non-responders, who were more heavily pretreated and more frequently hypogammaglobulinemic compared to responders. High antibody titers (AT), [AT ≥ 1000 U/mL], were detected in 38.5% and 30.6% of the patients at m1 and m3, respectively. A significant decline in AT between m1 and m3 was demonstrated-p < 0.0001; median AT1 and AT3 were 480.5 and 293 U/mL, respectively. A novel finding of our study was the negative impact of IgA hypogammaglobulinemia on response to vaccination. Other negative significant factors were treatment with anti-CD20 antibody at vaccination and vaccination within 18 months from HSCT. Our data indicate that HSCT recipients elicit a positive response to the BNT162b2 vaccine against SARS-CoV-2 when vaccinated at 6 months post-transplant, and vaccination should be offered to this patient population even within the post-pandemic COVID-19 era.

Considerations for medical nutrition therapy management of the critically ill patient with hematological malignancies: A narrative review.

Patients with hematological malignancies (HMs) are more frequently admitted now than in the past to the intensive care unit (ICU) due to more aggressive approaches in primary therapy of HMs and the need for critical care support. Pathophysiological alterations derived from HMs and the different hematological therapies, such as chemotherapy, negatively affect gastrointestinal (GI) function, metabolism, and nutrition status. Further, malnutrition strongly influences outcomes and tolerance of the different hematological therapies. In consequence, these critically ill patients frequently present with malnutrition and pathophysiological alterations that create challenges for the delivery of medical nutrition therapy (MNT) in the ICU. Frequent screening, gauging tolerance, and monitoring nutrition status are mandatory to provide individualized MNT and achieve nutrition objectives. The present review discusses how HM impact GI function and nutrition status, the importance of MNT in patients with HM, and specific considerations for guidance in providing adequate MNT to these patients when admitted to the ICU.

INSPIRED Symposium Part 5: Expanding the Use of CAR T Cells in Children and Young Adults.

Chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable efficacy in relapsed/refractory (r/r) B cell malignancies, including in pediatric patients with acute lymphoblastic leukemia (ALL). Expanding this success to other hematologic and solid malignancies is an area of active research and, although challenges remain, novel solutions have led to significant progress over the past decade. Ongoing clinical trials for CAR T cell therapy for T cell malignancies and acute myeloid leukemia (AML) have highlighted challenges, including antigen specificity with off-tumor toxicity and persistence concerns. In T cell malignancies, notable challenges include CAR T cell fratricide and prolonged T cell aplasia, which are being addressed with strategies such as gene editing and suicide switch technologies. In AML, antigen identification remains a significant barrier, due to shared antigens across healthy hematopoietic progenitor cells and myeloid blasts. Strategies to limit persistence and circumvent the immunosuppressive tumor microenvironment (TME) created by AML are also being explored. CAR T cell therapies for central nervous system and solid tumors have several challenges, including tumor antigen heterogeneity, immunosuppressive and hypoxic TME, and potential for off-target toxicity. Numerous CAR T cell products have been designed to overcome these challenges, including "armored" CARs and CAR/T cell receptor (TCR) hybrids. Strategies to enhance CAR T cell delivery, augment CAR T cell performance in the TME, and ensure the safety of these products have shown promising results. In this manuscript, we will review the available evidence for CAR T cell use in T cell malignancies, AML, central nervous system (CNS), and non-CNS solid tumor malignancies, and recommend areas for future research.

Discovering needs for palliative care in children with cancer in Indonesia.

BACKGROUND: Although most children with cancer die in low- and middle-income countries, palliative care receives limited attention in these settings. This study explores parents' perspectives on experiences and needs of children dying from cancer. METHODS: Home visits were conducted to interview parents of children, who were treated for cancer at an Indonesian academic hospital and died between 2019 and 2020, using semi-structured questionnaires. RESULTS: Parents of 49 children (response rate 74%) were interviewed. While all children died in hospital, 37% of parents stated their child preferred to die at home. The most common symptoms during final illness were breathing difficulties (82%), pain (80%), and appetite loss (80%). Psychological symptoms received the least support from the medical team. No intervention was given to 46% of children with depression, 45% of children with anxiety, and 33% with sadness. Boys suffered more often from anxiety (68%) than girls (37%; p = .030). Parents (57%) were not always informed about their child's condition, and doctors gave confusing information (43%). The families' choice of treatment while dying was relieving pain or discomfort (39%) and extending life (33%), while for 29% it was unknown. However, many parents (51%) did not discuss these treatment wishes with doctors. Many children (45%) felt lonely wanting more interactions with school (71%), friends (63%), and family (57%). CONCLUSION: Relieving suffering of children with cancer requires regular physical, psychological, social, and spiritual needs assessment. Families should actively participate in deciding whether to extend life or relieve pain and discomfort. This can importantly improve the quality of life of children and families.

Letter to editor: single-cell transcriptome analysis upon ECM-remodeling meningioma cells of published cases.

This letter offers a nuanced evaluation of the recent study on single-cell transcriptome analysis of ECM-remodeling meningioma cells. While acknowledging the positive aspects, such as enhanced understanding of tumor heterogeneity and identification of potential therapeutic targets, it also highlights potential limitations, including challenges in data interpretation and validation.The focus on ECM-remodeling may inadvertently overshadow other critical aspects of tumor biology, necessitating a more holistic approach. The abstract concludes by emphasizing the importance of considering the broader context of tumor heterogeneity and microenvironmental influences in future research endeavors to improve clinical outcomes for patients with meningioma and other malignancies.

Neoadjuvant Chemotherapy in Locally Advanced Sinonasal Teratocarcinosarcoma a Rare Malignancy: An Audit From an Academic Tertiary Care Centre in India.

AIMS: Sinonasal teratocarcinosarcomas (SNTCS) are rare sinonasal malignancies, the incidence of which is less than 1% of all tumors. There is limited data available on SNTCS's, often as case reports and small case series. The management of SNTCS is complicated because of its location, locally aggressive biology, difficulty in achieving complete resection, and limited data on chemotherapy in these malignancies. This audit was performed to understand the role of neoadjuvant chemotherapy (NACT) in SNTCS's, its ability to downstage the disease, achieve complete resection, and impact on long-term survival outcomes. METHODS: This was a retrospective analysis of a prospectively maintained database approved by the Institutional Ethics Committee (IEC). The baseline characteristics, the extent of tumor, Kadish stage, NACT regimen, and adverse events were extracted from the Electronic Medical Records and the patient's case file. Patients with baseline extensive/inoperable disease were referred for NACT from the multidisciplinary joint clinic followed by response assessment (RECIST v1.1). Patients underwent skull-base surgery if respectable post-completion of NACT, however, if deemed unresectable were treated with non-surgical modalities or palliative therapies. RESULTS: The data of 27 patients were evaluated from the year 2015-2022. The median age was 42 years (IQR:30-56) and 85.2% (n = 23) were males. The ECOG-PS was 0-1 in 88.8% (n = 24) patients. All 27 patients received NACT in view of extensive disease at presentation. 74.1% (n = 20) patients received Cisplatin-Etoposide and 25.9% (n = 7) received other chemotherapy regimens. The median number of chemotherapy cycles was 2(IQR:2-3). 96.3% patients (n = 26) completed the planned NACT cycles. 70.4% (n = 19) patients achieved a partial response in post-NACT imaging. 77.8% (n = 18) underwent surgery, 18.5% (n = 5) received CTRT, and 7.4% (n = 2) received definitive-RT alone. The median PFS and OS of the cohort was 19months (95%CI:12.0-25.6) and 23months (95%CI:5.94-40.06) respectively. CONCLUSION: NACT is safe, feasible, and effective with significant response rates, leading to effective downstaging, resectability and improved survival in patients with locally advanced SNTCS's.

Secondary hematological malignancies in patients with sarcoma: A single­center retrospective study.

The present retrospective study investigated the clinical features and prognosis of secondary hematological malignancies (SHMs) in patients with sarcoma at Korea Cancer Center Hospital (Seoul, South Korea). Patients who had been diagnosed with SHMs after having received treatment for sarcoma between January 2000 and May 2023 were enrolled. Clinical data were collected from the patients' medical records. Clinical characteristics were analyzed, including SHM incidence, type and prognosis. Of 2,953 patients with sarcoma, 18 (0.6%) were diagnosed with SHMs. Their median age at the time of sarcoma diagnosis was 39.5 (range, 9-72) years, and 74% (n=14) of these patients were male. The histological features of sarcoma varied, with osteosarcoma diagnosed in nine patients (50%). All patients with sarcoma underwent surgical treatment, and 16 (88.8%) received chemotherapy. The most common type of SHMs was acute myeloid leukemia (n=6; 33.3%), followed by myelodysplastic syndrome (n=5; 27.7%). The median latency period between the sarcoma diagnosis and SHM identification was 30 (range, 11-121) months. A total of 13 (72.2%) patients received treatment for the SHM. The median overall survival after SHM diagnosis was 15.7 (range, 0.4-154.9) months. The incidence of SHMs in sarcoma in the present study was consistent with that reported previously. The presence of SHMs was associated with a poor patient prognosis, especially if treatment for SHMs was not administered.

Long-Term Survival of Patients With Cancer, Sepsis, and Vasopressor Requirements Based on Lactate Levels.

A prospective cohort study was conducted to evaluate the 1-year survival of cancer patients with sepsis and vasopressor requirements. Eligible patients were admitted a Comprehensive Cancer Center's ICU and were compared based on their admission lactate levels. Of the 132 included patients, 87 (66%) had high lactate (HL; > 2.0 mmol/L), and 45 (34%) had normal lactate (NL; ≤ 2.0 mmol/L). The 1-year survival rates of the two groups were similar (HL 16% vs. NL 18%; p = 0.0921). After adjustment for ICU baseline characteristics, HL was not significantly associated with a 1-year survival (Hazards ratio, 1.39; 95% CI, 0.94-2.05). Critically ill cancer patients with sepsis and vasopressor requirements, regardless of the lactate level, had 1-year survival of less than 20%. Large multicenter cancer registries would enable to confirm our findings and better understand the long-term trajectories of sepsis in this vulnerable population.

Peripheral helper T cells in human diseases.

Peripheral helper T cells (Tph) are a specialized subset of CD4+ T cells with the ability to help B cells and induce antibody production. Although usually located in ectopic lymphoid-like structures (ELS), inside the peripheral blood, Tph cells can also be identified. The aberrant proliferation and functions of Tph cells are commonly found in the patients with disease. In this review, first we will summarize the biological characteristics of Tph cells, such as the expression of surface molecules, transcription factors and cytokines, and discuss its B cell help functions. Tph cells also have roles in a wide range of human diseases, including autoimmune diseases, infectious diseases, malignancies etc. Therefore, there is a strong interest in targeting Tph cells to improve treat strategies of human diseases.

Fertility preservation in hematological cancer patients.

Among adolescents and young adults, hematological malignancies are the most common malignancies. Although the survival rate of hematological malignancies in young patients has been dramatically improved, due to the continuous improvement and development of tumor diagnosis and treatment options, cytotoxic therapies can significantly reduce a patient's reproductive capacity and cause irreversible infertility. The most two established solutions are embryo cryopreservation and oocyte cryopreservation which can be considered in single female. Sperm or testicular tissue cryopreservation in adult male are feasible approaches that must be considered before gonadotoxic therapy. A comprehensive consultation with reproductive specialists when once diagnosed is a significantly issue which would help those survivors who want to have children. In this article, we review germ cell toxicity, which happens during the treatment of hematological malignancies, and aims to propose safety, efficacy fertility preservation methods in younger patients with hematological malignancies.

A new concept for mandible reconstruction after oncological resection: Multisegment virtual surgical planning.

PURPOSE: Virtual surgical planning (VSP) is good for three dimensional reconstructions in maxillofacial surgery, but it is not problem-free completely especially when the resection margins cannot be affirmed in preoperative period. We aimed to obtain an ideal reconstruction with elaborating VSP to be prepared for adverse conditions during surgery and to proceed the oncological resections step- by- step with A, B, and C resection planes. PATIENTS AND METHODS: Four patients undergoing multisegment VSP for the primary mandible malignancies were included in the study. The first resection margin was detected as plan A in VSP, and plans of B and C were also prepared considering the tumor- positive result of intraoperative frozen section procedure. RESULTS: Following the tumor resection, margins were extended to the plan B in two patients, and plan C in one patient in accordance with the results of the frozen section procedure.Histogram comparison of the localizations of osteotomies in mandible and fibula, and positions of the implants were calculated at a confidence level of 95 % (p > 0.95) and mean difference was found -0.55 mm, while standard deviation was 1.76 mm. CONCLUSION: Multisegment virtual surgical planning seems to achieve the optimal reconstruction with the staged resection preventing redundant removal of tumor- free structures like bone and teeth.

A novel potent class I HDAC inhibitor reverses the STAT4/p66Shc apoptotic defect in B cells from chronic lymphocytic leukemia patients.

Chronic Lymphocytic Leukemia (CLL) patients have a defective expression of the proapoptotic protein p66Shc and of its transcriptional factor STAT4, which evoke molecular abnormalities, impairing apoptosis and worsening disease prognosis and severity. p66Shc expression is epigenetically controlled and transcriptionally modulated by STAT4; epigenetic modifiers are deregulated in CLL cells and specific histone deacetylases (HDACs) like HDAC1, are overexpressed. Reactivation of STAT4/p66Shc expression may represent an attractive and challenging strategy to reverse CLL apoptosis defects. New selective class I HDAC inhibitors (HDACis, 6a-g) were developed with increased potency over existing agents and preferentially interfering with the CLL-relevant isoform HDAC1, to unveil the role of class I HDACs in the upregulation of STAT4 expression, which upregulates p66Shc expression and hence normalizes CLL cell apoptosis. 6c (chlopynostat) was identified as a potent HDAC1i with a superior profile over entinostat. 6c induces marked apoptosis of CLL cells compared with SAHA, which was associated with an upregulation of STAT4/p66Shc protein expression. The role of HDAC1, but not HDAC3, in the epigenetic upregulation of STAT4/p66Shc was demonstrated for the first time in CLL cells and was validated in siRNA-induced HDAC1/HDAC3 knock-down EBV-B cells. To sum up, HDAC1 inhibition is necessary to reactivate STAT4/p66Shc expression in patients with CLL. 6c is one of the most potent HDAC1is known to date and represents a novel pharmacological tool for reversing the impairment of the STAT4/p66Shc apoptotic machinery.

Inhibition of Acyl-CoA Synthetase Long Chain Isozymes Decreases Multiple Myeloma Cell Proliferation and Causes Mitochondrial Dysfunction.

Multiple myeloma (MM) is an incurable cancer of plasma cells with a 5-year survival rate of 59%. Dysregulation of fatty acid (FA) metabolism is associated with MM development and progression; however, the underlying mechanisms remain unclear. Acyl-CoA synthetase long-chain family members (ACSLs) convert free long-chain fatty acids into fatty acyl-CoA esters and play key roles in catabolic and anabolic fatty acid metabolism. The Cancer Dependency Map data suggested that ACSL3 and ACSL4 were among the top 25% Hallmark Fatty Acid Metabolism genes that support MM fitness. Here, we show that inhibition of ACSLs in human myeloma cell lines using the pharmacological inhibitor Triascin C (TriC) causes apoptosis and decreases proliferation in a dose- and time-dependent manner. RNA-seq of MM.1S cells treated with TriC for 24 h showed a significant enrichment in apoptosis, ferroptosis, and ER stress. Proteomics of MM.1S cells treated with TriC for 48 h revealed that mitochondrial dysfunction and oxidative phosphorylation were significantly enriched pathways of interest, consistent with our observations of decreased mitochondrial membrane potential and increased mitochondrial superoxide levels. Interestingly, MM.1S cells treated with TriC for 24 h also showed decreased mitochondrial ATP production rates and overall lower cellular respiration.

Investigating bleeding adverse events associated with BTK inhibitors in the food and drug administration adverse event reporting system (FAERS).

BACKGROUND: This study analyzed the bleeding adverse events (AEs) resulting from the treatment of B-cell lymphoma with Bruton tyrosine kinase (BTK) inhibitors, according to reports in the US Food and Drug Administration's Adverse Event Reporting System (FAERS). METHODS: Bleeding AEs associated with BTK inhibitors (including ibrutinib, zanubrutinib, and acalabrutinib) from the first quarter of 2013 to the third quarter of 2023 were extracted. Reporting odds ratio (ROR) and proportional reporting ratio (PRR) were reported. Preferred Terms (PTs) of Medical Dictionary for Regulatory Activities (MedDRA) terms were mapped to System Organ Class terms (SOC) terms and analyzed bleeding AEs associated with three BTK inhibitors. RESULTS: A total of 463 cases of bleeding AEs were included. Contusion, subcutaneous hemorrhage, hematuria, and cerebral hemorrhage were included in PTs. Blood urine was present and subdural hematoma were also reported. The incidence of bleeding AEs was higher with ibrutinib (Case number = 10,696) than with zanubrutinib (Case number = 213) and acalabrutinib (Case number = 314). CONCLUSION: Our findings indicate that bleeding AEs linked to BTK inhibitors in various conditions underscore the need for cautious clinical decision-making, particularly in nervous system disorders, injuries, poisoning, surgical complications, vascular disorders, and others.