Background:Accurate classification of normal blood cells is a critical foundation for automated hematological analysis,including the detection of pathological conditions like leukemia.While convolutional neural networ...Background:Accurate classification of normal blood cells is a critical foundation for automated hematological analysis,including the detection of pathological conditions like leukemia.While convolutional neural networks(CNNs)excel in local feature extraction,their ability to capture global contextual relationships in complex cellular morphologies is limited.This study introduces a hybrid CNN-Transformer framework to enhance normal blood cell classification,laying the groundwork for future leukemia diagnostics.Methods:The proposed architecture integrates pre-trained CNNs(ResNet50,EfficientNetB3,InceptionV3,CustomCNN)with Vision Transformer(ViT)layers to combine local and global feature modeling.Four hybrid models were evaluated on the publicly available Blood Cell Images dataset from Kaggle,comprising 17,092 annotated normal blood cell images across eight classes.The models were trained using transfer learning,fine-tuning,and computational optimizations,including cross-model parameter sharing to reduce redundancy by reusing weights across CNN backbones and attention-guided layer pruning to eliminate low-contribution layers based on attention scores,improving efficiency without sacrificing accuracy.Results:The InceptionV3-ViT model achieved a weighted accuracy of 97.66%(accounting for class imbalance by weighting each class’s contribution),a macro F1-score of 0.98,and a ROC-AUC of 0.998.The framework excelled in distinguishing morphologically similar cell types demonstrating robustness and reliable calibration(ECE of 0.019).The framework addresses generalization challenges,including class imbalance and morphological similarities,ensuring robust performance across diverse cell types.Conclusion:The hybrid CNN-Transformer framework significantly improves normal blood cell classification by capturing multi-scale features and long-range dependencies.Its high accuracy,efficiency,and generalization position it as a strong baseline for automated hematological analysis,with potential for extension to leukemia subtype classification through future validation on pathological samples.展开更多
Background:Patients with hemato-oncological malignancies may respond insufficiently to vaccination,especially in terms of antibody titer.The antibody response depends on the type of malignancy as well as the type and ...Background:Patients with hemato-oncological malignancies may respond insufficiently to vaccination,especially in terms of antibody titer.The antibody response depends on the type of malignancy as well as the type and timing of treatment.We intended to evaluate this using real-world data from patients of our regional hospital.This study also considers the role of immune status,including T-cell activation markers,in predicting vaccination success.Methods:Seventeen patients of our hospital having a hematological malignancy were included in this study,including myeloma,lymphoma,as well as acute myeloid leukemia(AML)and chronic lymphoid leukemia(CLL).All patients were vaccinated against Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2)using Tozinameran following current recommendations.Circulating antibodies directed against the spike protein of SARS-CoV-2 were determined by a commercial immune assay.Immune status was determined from peripheral blood by flow cytometry.Both parameters were followed in fifteen patients who provided sufficient follow-up data for up to one year.Patients were categorized as responders or non-responders,and differences in diagnosis,treatment,and immune status were analyzed.Results:Antibody response depended on both diagnosis and treatment.Active treatment directed against B-cells,such as anti-Cluster of Differentiation 20(CD20)therapy,was associated with weak seroconversion.For CD38-as well as proteasome-directed therapies,the data suggest that responders as well as non-responders exist.Notably,low peripheral B-cell numbers and high CD3+HLADR+cell counts correlated withweak seroconversion upon vaccination.Conclusions:We suggest that peripheral immune status can be applied as a predictive biomarker for seroconversion upon vaccinations.展开更多
Hepatitis due to hepatitis B virus(HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximabc...Hepatitis due to hepatitis B virus(HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximabcontaining therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen(HBs Ag) and antibody to hepatitis B core antigen(antiHBc). Patients found to be positive for HBs Ag should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving highrisk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although there is currently limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBs Ag-positive patients receiving novel treatments, especially the Bruton tyrosine kinase inhibitors and the phosphatidylinositol 3-kinase inhibitors, which are B-cell receptor signaling modulators and reduce proliferation of malignant B-cells. Further studies are needed to clarify the risk of HBV reactivation with these agents and the best prophylactic strategy in the era of targeted therapy for hematological malignancies.展开更多
TMTP1, a 5-amino acid peptide NVVRQ, obtained by using the flagella peptide library screening in our previous studies, can be used for the labeling of malignant in situ and metastatic lesions, and even micro-metastase...TMTP1, a 5-amino acid peptide NVVRQ, obtained by using the flagella peptide library screening in our previous studies, can be used for the labeling of malignant in situ and metastatic lesions, and even micro-metastases. In this study, TMTP1 was assessed for its ability to specifically target the malignant hematopoietic cells and metastatic lesions of hematological malignancies. FITC-TMTP1 was chemically synthesized. Immunofluorescence assay and competitive test were carried out to determine the specific binding capacity of TMTPl to hematological malignant cell lines, including HL60, k562, SHI-1, Jurkat, Raji, El-4 and umbilical cord blood mononuclear cells. Mononuclear cells were isolated from the bone marrow of healthy subjects and patients with chronic myeloid leukemia. Then the cells were co-clutured with TMTP1 or scrambled peptides and the binding and affinity of TMTP1 peptide to the primary cells of hematological malignancies were flow cytometrically analyzed. The binding speci-ficity of TMTP1 to target hematological malignancies was measured in vivo by intravenous injection of FITC-conjugated TMTP1 into El-4 lymphoma-bearing mice. The results showed that TMTP1 specifi-cally bound to the cells of a series of hematological malignancies, including HL60, k562, Jurkat, Raji , El-4 and chronic myeloid leukemia primary cells but not to bone marrow mononuclear cells from healthy subjects. By contrast, TMTP1 could bind to the metastatic foci of lymphoma originating from the EL-4 cell line while the scrambled peptide failed to do so. Moreover, the occult metastases could be identified, with high specificity, by detecting FITC-TMTP1. We are led to conclude that TMTP1, as a novel tumor-homing peptide, can serve as a marker for primary malignant and metastatic lesions for the early diagnosis of hematological malignances and a carrier of anticancer drugs for cancer treatment.展开更多
As a rapidly progressing field in oncology,the adoptive transfer of T cells that have been genetically modified with chimeric antigen receptors(CARs)has shown striking efficacy in the management of hematological malig...As a rapidly progressing field in oncology,the adoptive transfer of T cells that have been genetically modified with chimeric antigen receptors(CARs)has shown striking efficacy in the management of hematological malignancies and has been reported in a number of clinical trials.of note,CAR T cell therapy has shown extraordinary potential,especially in relapsed/refractory patients.However,there are still challenges regarding the further development of this strategy,spanning from engineering and manufacturing issues,to limited applications,to accompanying toxicities.In this review,we will summarize the general knowledge of this novel method,including receptor composition,applications,adverse events and challenges.Additionally,we will propose several comprehensive recommendations.展开更多
AIM To investigate the prevalence and virological characteristics of occult hepatitis B virus(HBV)infections in patients with hematological malignancies in South Egypt.METHODS Serum samples were collected from 165 pat...AIM To investigate the prevalence and virological characteristics of occult hepatitis B virus(HBV)infections in patients with hematological malignancies in South Egypt.METHODS Serum samples were collected from 165 patients with hematological malignancies to monitor titers of HBV DNA,hepatitis B surface antigen(HBs Ag),and antibodies to HBV core(anti-HBc)and surface antigens.Serum samples negative for HBs Ag and positive for anti-HBc were subjected to nucleic acid extraction and HBV DNA detection by real-time polymerase chain reaction.DNA sequences spanning the S region were analyzed in cases with occult HBV infection.In vitro comparative study of constructed 1.24-fold wild type and S protein mutant HBV genotype D clones was further performed.RESULTS HBV DNA was detected in 23(42.6%)of 54 patients with hematological malignancies who were HBsA g negative,but anti-HBc positive,suggesting the presence of occult HBV infection.The complete HBV genome was retrieved from 6 occult HBV patients,and P120 T and S143 L were detected in 3 and 2 cases,respectively.Site directed mutagenesis was done to produce 1.24-fold genotype D clones with amino acid mutations T120 and L143.The in vitro analyses revealed that a lower level of extracellular HBsA g was detected by chemiluminescence enzyme immunoassay(CLEIA)with the clone containing T120 mutation,compared with the wild type or the clone with S143 L mutation despite the similar levels of extracellular and intracellular HBs Ag detected by Western blot.Southern blot experiments showed that the levels of intracellular HBV DNA were not different between these clones.CONCLUSION Occult HBV infection is common in patients with hematological malignancies and associated with P120 T and S143 L mutations.120 T mutation impairs the detection of HBsA g by CLEIA.展开更多
Chimeric antigen receptor T(CAR-T)cell therapy is the novel treatment strategy for hematological malignancies such as acute lymphoblastic leukemia(ALL),lymphoma and multiple myeloma.However,treatment-related toxicitie...Chimeric antigen receptor T(CAR-T)cell therapy is the novel treatment strategy for hematological malignancies such as acute lymphoblastic leukemia(ALL),lymphoma and multiple myeloma.However,treatment-related toxicities such as cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)have become significant hurdles to CAR-T treatment.Multiple strategies were established to alter the CAR structure on the genomic level to improve efficacy and reduce toxicities.Recently,the innovative gene-editing technology-clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated nuclease9(Cas9)system,which particularly exhibits preponderance in knock-in and knockout at specific sites,is widely utilized to manufacture CAR-T products.The application of CRISPR/Cas9 to CAR-T cell therapy has shown promising clinical results with minimal toxicity.In this review,we summarized the past achievements of CRISPR/Cas9 in CAR-T therapy and focused on the potential CAR-T targets.展开更多
Co-expression of immune checkpoint(IC)molecules can exacerbate T cell exhaustion in patients with hematological malignancies(HMs)and contribute to the immune escape of tumor cells,which is related to poor clinical out...Co-expression of immune checkpoint(IC)molecules can exacerbate T cell exhaustion in patients with hematological malignancies(HMs)and contribute to the immune escape of tumor cells,which is related to poor clinical outcome.It is worth establishing and optimizing an ideal prediction model based on the co-expression patterns of IC molecules to evaluate the immune status of HM patients and predict their clinical outcome.In this perspective,we summarize the co-expression patterns of IC molecules and their importance as biomarkers that predict the prognosis of patients with different HMs,providing new insights for designing dual IC blockades(ICBs).展开更多
The coronavirus disease 2019(COVID-19)is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Within a matter of months,this highly contagious novel virus has led to a g...The coronavirus disease 2019(COVID-19)is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Within a matter of months,this highly contagious novel virus has led to a global outbreak and is still spreading rapidly across continents.In patients with COVID-19,underlying chronic diseases and comorbidities are associated with dismal treatment outcomes.Owing to their immunosuppressive status,patients with hematological malignancies(HMs)are at an increased risk of infection and have a worse prognosis than patients without HMs.Accordingly,intensive attention should be paid to this cohort.In this review,we summarize and analyze specific clinical manifestations for patients with coexisting COVID-19 and HMs.Furthermore,we briefly de-scribe customized management strategies and interventions for this susceptible cohort.This review is intended to guide clinical practice.展开更多
BACKGROUND The mortality rate from septic shock in patients with hematological malignancies(HMs)remains significantly higher than that in patients without HMs.A longer resuscitation time would definitely be harmful be...BACKGROUND The mortality rate from septic shock in patients with hematological malignancies(HMs)remains significantly higher than that in patients without HMs.A longer resuscitation time would definitely be harmful because of the irreversibly immunocompromised status of the patients.Shortening the resuscitation time through continuous renal replacement therapy(CRRT)with oXiris^(■)would be an attractive strategy in managing such patients.AIM To explore the effects of CRRT and oXiris^(■)in shortening the resuscitation time and modifying the host response by reducing inflammation mediator levels.METHODS Forty-five patients with HM were diagnosed with septic shock and underwent CRRT between 2018 and 2022.Patients were divided into two groups based on the hemofilter used for CRRT(oXiris^(■)group,n=26;M150 group,n=19).We compared the number of days of negative and total fluid balance after 7 d of CRRT between the groups.The heart rate,norepinephrine dose,Sequential Organ Failure Assessment(SOFA)score,and blood lactic acid levels at different time points in the two groups were also compared.Blood levels of inflammatory mediators in the 26 patients in the oXiris^(■)group were measured to further infer the possible mechanism.RESULTS The average total fluid balance after 7 d of CRRT in the oXiris^(■)group was significantly lower than that of patients in the M150 hemofilter group.The SOFA scores of patients after CRRT with oXiris^(■)therapy were significantly lower than those before treatment on day 1(d1),d3 and d7 after CRRT;these parameters were also significantly lower than those of the control group on d7.The lac level after oXiris^(■)therapy was significantly lower than that before treatment on d3 and d7 after CRRT.There were no significant differences in the above parameters between the two groups at the other time points.In the oXiris^(■)group,procalcitonin levels decreased on d7,whereas interleukin-6 and tumor necrosis factor levels decreased significantly on d3 and d7 after treatment.CONCLUSION CRRT with oXiris^(■)hemofilter may improve hemodynamics by reducing inflammatory mediators and playing a role in shortening the resuscitation period and decreasing total fluid balance in the resuscitation phases.展开更多
In order to delineate the infectious status of HGV in pediatric hemato-logical patients and its clinical features, 38 children were studied for HGV by reverse transcription nested polymerase chain reaction (RT-nPCR). ...In order to delineate the infectious status of HGV in pediatric hemato-logical patients and its clinical features, 38 children were studied for HGV by reverse transcription nested polymerase chain reaction (RT-nPCR). The overall positive rate was 23. 68 %; the positive rate in 1-10 time transfusion recipients (mean 3. 26 times) was 3. 70 % while in over 10 time transfusion recipients (mean 20. 09 times) was 72. 73 %. A statistically significant difference was found between the two groups (P<0. 001). All HGV positive children showed diminished immunity and most were single HGV infection with no clinical and biochemical evidences of acute hepatitis. Our results suggest that HGV is one of the main causes of post-transfusion hepatic virus infection and the prevalence is related to transfusion times. Hematological malignancy maybe the most susceptible confluence of HGV.展开更多
In this editorial,we discussed the apparent discrepancy between the findings described by Colapietro et al,in their case report and data found in the literature.Colapietro et al reported a case of hepatitis B virus(HB...In this editorial,we discussed the apparent discrepancy between the findings described by Colapietro et al,in their case report and data found in the literature.Colapietro et al reported a case of hepatitis B virus(HBV)-related hepatic decompensation in a patient with chronic myeloid leukemia and a previously resolved HBV infection who was receiving Bruton’s tyrosine kinase(BTK)inhibitor therapy.First of all,we recapitulated the main aspects of the immune system involved in the response to HBV infection in order to underline the role of the innate and adaptive response,focusing our attention on the protective role of anti-HBs.We then carefully analyzed literature data on the risk of HBV reactivation(HBVr)in patients with previous HBV infection who were treated with either tyrosine kinase inhibitors or BTK inhibitors for their hematologic malignancies.Based on literature data,we suggested that several factors may contribute to the different risks of HBVr:The type of hematologic malignancy;the type of therapy(BTK inhibitors,especially second-generation,seem to be at a higher risk of HBVr than those with tyrosine kinase inhibitors);previous exposure to an anti-CD20 as first-line therapy;and ethnicity and HBV genotype.Therefore,the warning regarding HBVr in the specific setting of patients with hematologic malignancies requires further investigation.展开更多
Most tumor suppressor and growth-regulating proteins are transported via the plasmic nuclear transporter exportin 1(XPO1).Many malignancies have excessive XPO1 expression,which is associated with disease progression a...Most tumor suppressor and growth-regulating proteins are transported via the plasmic nuclear transporter exportin 1(XPO1).Many malignancies have excessive XPO1 expression,which is associated with disease progression and resistance to therapy.A novel class of anticancer medication called selective inhibitor of nuclear export(SINE)can down-regulate the levels of a number of antigenic proteins in the cytoplasm,activate tumor suppressor and other growth regulating proteins,and promote the nuclear retention and apoptosis of tumor cells.This article discusses the function of XPO1 in drug resistance and tumor development as well as the advancement of XPO1 inhibitor research for the treatment of hematological cancers.展开更多
Background: Hemopathies were rarely observed in major sickle cell disease patients some thirty years ago, probably due to the high mortality rate among the latter as a result of progressive complications. Thanks to ad...Background: Hemopathies were rarely observed in major sickle cell disease patients some thirty years ago, probably due to the high mortality rate among the latter as a result of progressive complications. Thanks to advances in the management of sickle cell disease, patients' life expectancy has increased considerably, exposing them more frequently to neoplasia, including hematological malignancies. The increased risk of leukemogenesis is multifactorial and linked to the pathophysiological mechanisms of the clinical manifestations of sickle cell disease. Study Setting: The clinical haematology department of campus teaching hospital and the paediatric onco-haematology unit of Sylvanus Olympio teaching hospital in Lomé were used as study settings. Observations: Four hematologic malignancies were collected in a cohort of 5847 major sickle cell syndromes. The median age of the patients was 31.25 years (extremes: 14 and 58 years) and they were predominantly female (sex ratio M/F = 0.25). Two were on background therapy with hydroxyurea. Among the four patients, there were two cases of acute lymphocytic leukemia, including ALL3 in a 58-year-old SS woman and T-ALL2 in a 12-year-old SC. Then, a case of lymphocytic lymphoma in a 20-year-old SS man was reported and finally a case of chronic myelocytic leukemia in a 33-year-old woman of Sβ+ thalassaemia phenotype. Conclusion: To further report this coexistence, it is therefore essential to systematically consider hematological malignancies during major sickle cell syndromes even if there are similarities in the symptomatology of these two serious pathological situations.展开更多
Background: Febrile neutropenia is one of the most serious adverse events in patients with hematological malignancies and chemotherapy. The routine use of fluoroquinolone prophylaxis in patients with hematological mal...Background: Febrile neutropenia is one of the most serious adverse events in patients with hematological malignancies and chemotherapy. The routine use of fluoroquinolone prophylaxis in patients with hematological malignancies is controversial. Therefore, we prospectively evaluated the efficacy and safety of prophylactic use of garenoxacin for febrile neutropenia. Patients and Methods: Consecutive adult patients with hematological malignancies who were at risk for chemotherapy-induced neutropenia lasting more than seven days were eligible for present study. They received oral garenoxacin (400 mg daily) from the neutrophil count decreased to less than 1000/μl and continued until the neutropenia had resolved. The primary endpoint was incidence of febrile neutropenia, and the secondary endpoints were the type and incidence of adverse events. Results: We enrolled 46 consecutive patients (median age, 59 years). The underlying diseases comprised acute myeloid leukemia (n = 17), acute lymphoblastic leukemia (n = 3), malignant lymphoma (n = 23), and multiple myeloma (n = 3). There were 23 febrile neutropenia episodes and 2 episodes of bacteremia. There were no grade 3 or 4 adverse events;however serum creatinine levels were significantly elevated after garenoxacin administration. The overall prophylactic efficacy of garenoxacin was 50%, and there were no infection-related deaths. Conclusions: Prophylactic use of garenoxacin is effective and safe in patients with hematological malignancies. (Clinical trial registration number: UMIN000004979).展开更多
Objective To investigate the efficiency and safety of allogeneic hematopoietic cell transplantation for malignant hematological diseases in patients older than 50 years of age. Methods From May 2002 to January 2010,35...Objective To investigate the efficiency and safety of allogeneic hematopoietic cell transplantation for malignant hematological diseases in patients older than 50 years of age. Methods From May 2002 to January 2010,35 patients P 】 50 years with malignant hematological diseases received allogeneic hematopoietic展开更多
Hematologic malignancies,including leukemia,lymphoma,and multiple myeloma,are hazardous diseases characterized by the uncontrolled proliferation of cancer cells.Dysregulated cell cycle resulting from genetic and epige...Hematologic malignancies,including leukemia,lymphoma,and multiple myeloma,are hazardous diseases characterized by the uncontrolled proliferation of cancer cells.Dysregulated cell cycle resulting from genetic and epigenetic abnormalities constitutes one of the central events.Importantly,cyclin-dependent kinases(CDKs),complexed with their functional partner cyclins,play dominating roles in cell cycle control.Yet,efforts in translating CDK inhibitors into clinical benefits have demonstrated disappointing outcomes.Recently,mounting evidence highlights the emerging significance of WEE1 G2 checkpoint kinase(WEE1)to modulate CDK activity,and correspondingly,a variety of therapeutic inhibitors have been developed to achieve clinical benefits.Thus,WEE1 may become a promising target to modulate the abnormal cell cycle.However,its function in hematologic diseases remains poorly elucidated.In this review,focusing on hematologic malignancies,we describe the biological structure of WEE1,emphasize the latest reported function of WEE1 in the carcinogenesis,progression,as well as prognosis,and finally summarize the therapeutic strategies by targeting WEE1.展开更多
Immuno-positron emission tomography(immuno-PET)is an innovative medical imaging technique that combines antibodies(Abs)or other immune-targeting molecules with positron-emitting radionuclides.By targeting antigens tha...Immuno-positron emission tomography(immuno-PET)is an innovative medical imaging technique that combines antibodies(Abs)or other immune-targeting molecules with positron-emitting radionuclides.By targeting antigens that are highly expressed in hematologic malignancies,immuno-PET has transformed diagnostic capabilities and enables precise monitoring of therapeutic responses through highly sensitive and specific tumor cell detection.Additionally,it plays a critical role in advancing therapeutic approaches by seamlessly linking diagnostic imaging with personalized treatment strategies.Its non-invasive nature and ability to provide whole-body imaging offer significant advantages over traditional diagnostic methods,especially for detecting minimal residual disease and guiding adaptive therapeutic interventions.In Ab-based immuno-PET,positronemitting radionuclides must have a half-life sufficient for slower pharmacokinetics and blood clearance of Abs.Recent studies have highlighted the advantages of long-lived radionuclides,such as 89Zr,which exhibit low positron energy and enable high sensitivity and resolution,making them particularly effective for tumor visualization and characterization.This review explores the current applications,recent advancements,and potential of immuno-PET for hematologic malignancies,emphasizing its pivotal role in improving patient outcomes and advancing precision medicine.展开更多
Since 1968 when the first successful hematopoietic stem cell transplantation(HSCT) was performed, transplant technique has developed rapidly for more than 50 years. In the past 20 years, the significant breakthroughs ...Since 1968 when the first successful hematopoietic stem cell transplantation(HSCT) was performed, transplant technique has developed rapidly for more than 50 years. In the past 20 years, the significant breakthroughs and widely use of haploidentical-related donor HSCT(e.g. Beijing Protocol) make everyone can have a donor(1), and the novel, reduced-toxicity transplant regimens help elderly patients receive HSCT safely(2).展开更多
Gastrointestinal bleeding(GIB)presents a significant challenge for patients with hematologic malignancies,especially those with severe thrombocytopenia.Although endoscopic intervention is frequently used in managing G...Gastrointestinal bleeding(GIB)presents a significant challenge for patients with hematologic malignancies,especially those with severe thrombocytopenia.Although endoscopic intervention is frequently used in managing GIB,its safety and effectiveness in this high-risk group remain unclear.A recent study by Alhumayyd et al provided insight into this issue.However,it has notable limitations,including its retrospective nature,small sample size,and failure to adjust for important confounding factors such as disease severity,hemodynamic status,and platelet function.The study’s findings indicated that urgent endoscopy may help decrease the incidence of recurrent bleeding;however,it did not show a clear benefit in terms of mortality.Future research ought to prioritize prospective,multicenter studies that employ standardized protocols and incorporate risk stratification models to better understand the impact of endoscopic treatment for GIB in these patients.Additionally,integrating platelet function assays could improve clinical decision-making.Addressing these research gaps is essential for improving patient outcomes and developing effective guidelines for managing GIB in individuals with thrombocytopenia.展开更多
基金the Deanship of Graduate Studies and Scientific Research at Najran University,Saudi Arabia,for their financial support through the Easy Track Research program,grant code(NU/EFP/MRC/13).
文摘Background:Accurate classification of normal blood cells is a critical foundation for automated hematological analysis,including the detection of pathological conditions like leukemia.While convolutional neural networks(CNNs)excel in local feature extraction,their ability to capture global contextual relationships in complex cellular morphologies is limited.This study introduces a hybrid CNN-Transformer framework to enhance normal blood cell classification,laying the groundwork for future leukemia diagnostics.Methods:The proposed architecture integrates pre-trained CNNs(ResNet50,EfficientNetB3,InceptionV3,CustomCNN)with Vision Transformer(ViT)layers to combine local and global feature modeling.Four hybrid models were evaluated on the publicly available Blood Cell Images dataset from Kaggle,comprising 17,092 annotated normal blood cell images across eight classes.The models were trained using transfer learning,fine-tuning,and computational optimizations,including cross-model parameter sharing to reduce redundancy by reusing weights across CNN backbones and attention-guided layer pruning to eliminate low-contribution layers based on attention scores,improving efficiency without sacrificing accuracy.Results:The InceptionV3-ViT model achieved a weighted accuracy of 97.66%(accounting for class imbalance by weighting each class’s contribution),a macro F1-score of 0.98,and a ROC-AUC of 0.998.The framework excelled in distinguishing morphologically similar cell types demonstrating robustness and reliable calibration(ECE of 0.019).The framework addresses generalization challenges,including class imbalance and morphological similarities,ensuring robust performance across diverse cell types.Conclusion:The hybrid CNN-Transformer framework significantly improves normal blood cell classification by capturing multi-scale features and long-range dependencies.Its high accuracy,efficiency,and generalization position it as a strong baseline for automated hematological analysis,with potential for extension to leukemia subtype classification through future validation on pathological samples.
基金supported by a grant of the Deutsche Forschungsgemeinschaft(DFG)to G.B.(#405833349).
文摘Background:Patients with hemato-oncological malignancies may respond insufficiently to vaccination,especially in terms of antibody titer.The antibody response depends on the type of malignancy as well as the type and timing of treatment.We intended to evaluate this using real-world data from patients of our regional hospital.This study also considers the role of immune status,including T-cell activation markers,in predicting vaccination success.Methods:Seventeen patients of our hospital having a hematological malignancy were included in this study,including myeloma,lymphoma,as well as acute myeloid leukemia(AML)and chronic lymphoid leukemia(CLL).All patients were vaccinated against Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2)using Tozinameran following current recommendations.Circulating antibodies directed against the spike protein of SARS-CoV-2 were determined by a commercial immune assay.Immune status was determined from peripheral blood by flow cytometry.Both parameters were followed in fifteen patients who provided sufficient follow-up data for up to one year.Patients were categorized as responders or non-responders,and differences in diagnosis,treatment,and immune status were analyzed.Results:Antibody response depended on both diagnosis and treatment.Active treatment directed against B-cells,such as anti-Cluster of Differentiation 20(CD20)therapy,was associated with weak seroconversion.For CD38-as well as proteasome-directed therapies,the data suggest that responders as well as non-responders exist.Notably,low peripheral B-cell numbers and high CD3+HLADR+cell counts correlated withweak seroconversion upon vaccination.Conclusions:We suggest that peripheral immune status can be applied as a predictive biomarker for seroconversion upon vaccinations.
文摘Hepatitis due to hepatitis B virus(HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximabcontaining therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen(HBs Ag) and antibody to hepatitis B core antigen(antiHBc). Patients found to be positive for HBs Ag should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving highrisk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although there is currently limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBs Ag-positive patients receiving novel treatments, especially the Bruton tyrosine kinase inhibitors and the phosphatidylinositol 3-kinase inhibitors, which are B-cell receptor signaling modulators and reduce proliferation of malignant B-cells. Further studies are needed to clarify the risk of HBV reactivation with these agents and the best prophylactic strategy in the era of targeted therapy for hematological malignancies.
基金supported by the National Science Foundation of China (No. 30800402)
文摘TMTP1, a 5-amino acid peptide NVVRQ, obtained by using the flagella peptide library screening in our previous studies, can be used for the labeling of malignant in situ and metastatic lesions, and even micro-metastases. In this study, TMTP1 was assessed for its ability to specifically target the malignant hematopoietic cells and metastatic lesions of hematological malignancies. FITC-TMTP1 was chemically synthesized. Immunofluorescence assay and competitive test were carried out to determine the specific binding capacity of TMTPl to hematological malignant cell lines, including HL60, k562, SHI-1, Jurkat, Raji, El-4 and umbilical cord blood mononuclear cells. Mononuclear cells were isolated from the bone marrow of healthy subjects and patients with chronic myeloid leukemia. Then the cells were co-clutured with TMTP1 or scrambled peptides and the binding and affinity of TMTP1 peptide to the primary cells of hematological malignancies were flow cytometrically analyzed. The binding speci-ficity of TMTP1 to target hematological malignancies was measured in vivo by intravenous injection of FITC-conjugated TMTP1 into El-4 lymphoma-bearing mice. The results showed that TMTP1 specifi-cally bound to the cells of a series of hematological malignancies, including HL60, k562, Jurkat, Raji , El-4 and chronic myeloid leukemia primary cells but not to bone marrow mononuclear cells from healthy subjects. By contrast, TMTP1 could bind to the metastatic foci of lymphoma originating from the EL-4 cell line while the scrambled peptide failed to do so. Moreover, the occult metastases could be identified, with high specificity, by detecting FITC-TMTP1. We are led to conclude that TMTP1, as a novel tumor-homing peptide, can serve as a marker for primary malignant and metastatic lesions for the early diagnosis of hematological malignances and a carrier of anticancer drugs for cancer treatment.
基金the Key Program of the National Natural Science Foundation(NNSF)of China(No.81230052 and No.81630006).
文摘As a rapidly progressing field in oncology,the adoptive transfer of T cells that have been genetically modified with chimeric antigen receptors(CARs)has shown striking efficacy in the management of hematological malignancies and has been reported in a number of clinical trials.of note,CAR T cell therapy has shown extraordinary potential,especially in relapsed/refractory patients.However,there are still challenges regarding the further development of this strategy,spanning from engineering and manufacturing issues,to limited applications,to accompanying toxicities.In this review,we will summarize the general knowledge of this novel method,including receptor composition,applications,adverse events and challenges.Additionally,we will propose several comprehensive recommendations.
基金Supported by Japan Society for the Promotion of Science,No.15H05289
文摘AIM To investigate the prevalence and virological characteristics of occult hepatitis B virus(HBV)infections in patients with hematological malignancies in South Egypt.METHODS Serum samples were collected from 165 patients with hematological malignancies to monitor titers of HBV DNA,hepatitis B surface antigen(HBs Ag),and antibodies to HBV core(anti-HBc)and surface antigens.Serum samples negative for HBs Ag and positive for anti-HBc were subjected to nucleic acid extraction and HBV DNA detection by real-time polymerase chain reaction.DNA sequences spanning the S region were analyzed in cases with occult HBV infection.In vitro comparative study of constructed 1.24-fold wild type and S protein mutant HBV genotype D clones was further performed.RESULTS HBV DNA was detected in 23(42.6%)of 54 patients with hematological malignancies who were HBsA g negative,but anti-HBc positive,suggesting the presence of occult HBV infection.The complete HBV genome was retrieved from 6 occult HBV patients,and P120 T and S143 L were detected in 3 and 2 cases,respectively.Site directed mutagenesis was done to produce 1.24-fold genotype D clones with amino acid mutations T120 and L143.The in vitro analyses revealed that a lower level of extracellular HBsA g was detected by chemiluminescence enzyme immunoassay(CLEIA)with the clone containing T120 mutation,compared with the wild type or the clone with S143 L mutation despite the similar levels of extracellular and intracellular HBs Ag detected by Western blot.Southern blot experiments showed that the levels of intracellular HBV DNA were not different between these clones.CONCLUSION Occult HBV infection is common in patients with hematological malignancies and associated with P120 T and S143 L mutations.120 T mutation impairs the detection of HBsA g by CLEIA.
基金the National Natural Science Foundation of China(No.81230014,No.81470341,No.81520108002 and No.81500157)the Key Project of Science and Technology Department of Zhejiang Province(No.2018C03016-2)the Key Research and Development Program of Zhejiang Province(No.2019C03016).
文摘Chimeric antigen receptor T(CAR-T)cell therapy is the novel treatment strategy for hematological malignancies such as acute lymphoblastic leukemia(ALL),lymphoma and multiple myeloma.However,treatment-related toxicities such as cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)have become significant hurdles to CAR-T treatment.Multiple strategies were established to alter the CAR structure on the genomic level to improve efficacy and reduce toxicities.Recently,the innovative gene-editing technology-clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated nuclease9(Cas9)system,which particularly exhibits preponderance in knock-in and knockout at specific sites,is widely utilized to manufacture CAR-T products.The application of CRISPR/Cas9 to CAR-T cell therapy has shown promising clinical results with minimal toxicity.In this review,we summarized the past achievements of CRISPR/Cas9 in CAR-T therapy and focused on the potential CAR-T targets.
基金supported by grants from the National Natural Science Foundation of China(No.82293630,No.82293632 and No.82070152)the Guangdong Natural Science Foundation(No.2023A1515012968)Medical Scientific Research Foundation of Guangdong Province(No.A2023330)。
文摘Co-expression of immune checkpoint(IC)molecules can exacerbate T cell exhaustion in patients with hematological malignancies(HMs)and contribute to the immune escape of tumor cells,which is related to poor clinical outcome.It is worth establishing and optimizing an ideal prediction model based on the co-expression patterns of IC molecules to evaluate the immune status of HM patients and predict their clinical outcome.In this perspective,we summarize the co-expression patterns of IC molecules and their importance as biomarkers that predict the prognosis of patients with different HMs,providing new insights for designing dual IC blockades(ICBs).
基金Project supported by the National Natural Science Foundation of China(Nos.81770201 , 81730008)。
文摘The coronavirus disease 2019(COVID-19)is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Within a matter of months,this highly contagious novel virus has led to a global outbreak and is still spreading rapidly across continents.In patients with COVID-19,underlying chronic diseases and comorbidities are associated with dismal treatment outcomes.Owing to their immunosuppressive status,patients with hematological malignancies(HMs)are at an increased risk of infection and have a worse prognosis than patients without HMs.Accordingly,intensive attention should be paid to this cohort.In this review,we summarize and analyze specific clinical manifestations for patients with coexisting COVID-19 and HMs.Furthermore,we briefly de-scribe customized management strategies and interventions for this susceptible cohort.This review is intended to guide clinical practice.
基金Hebei Health Science and Education Project,No.20200852.
文摘BACKGROUND The mortality rate from septic shock in patients with hematological malignancies(HMs)remains significantly higher than that in patients without HMs.A longer resuscitation time would definitely be harmful because of the irreversibly immunocompromised status of the patients.Shortening the resuscitation time through continuous renal replacement therapy(CRRT)with oXiris^(■)would be an attractive strategy in managing such patients.AIM To explore the effects of CRRT and oXiris^(■)in shortening the resuscitation time and modifying the host response by reducing inflammation mediator levels.METHODS Forty-five patients with HM were diagnosed with septic shock and underwent CRRT between 2018 and 2022.Patients were divided into two groups based on the hemofilter used for CRRT(oXiris^(■)group,n=26;M150 group,n=19).We compared the number of days of negative and total fluid balance after 7 d of CRRT between the groups.The heart rate,norepinephrine dose,Sequential Organ Failure Assessment(SOFA)score,and blood lactic acid levels at different time points in the two groups were also compared.Blood levels of inflammatory mediators in the 26 patients in the oXiris^(■)group were measured to further infer the possible mechanism.RESULTS The average total fluid balance after 7 d of CRRT in the oXiris^(■)group was significantly lower than that of patients in the M150 hemofilter group.The SOFA scores of patients after CRRT with oXiris^(■)therapy were significantly lower than those before treatment on day 1(d1),d3 and d7 after CRRT;these parameters were also significantly lower than those of the control group on d7.The lac level after oXiris^(■)therapy was significantly lower than that before treatment on d3 and d7 after CRRT.There were no significant differences in the above parameters between the two groups at the other time points.In the oXiris^(■)group,procalcitonin levels decreased on d7,whereas interleukin-6 and tumor necrosis factor levels decreased significantly on d3 and d7 after treatment.CONCLUSION CRRT with oXiris^(■)hemofilter may improve hemodynamics by reducing inflammatory mediators and playing a role in shortening the resuscitation period and decreasing total fluid balance in the resuscitation phases.
文摘In order to delineate the infectious status of HGV in pediatric hemato-logical patients and its clinical features, 38 children were studied for HGV by reverse transcription nested polymerase chain reaction (RT-nPCR). The overall positive rate was 23. 68 %; the positive rate in 1-10 time transfusion recipients (mean 3. 26 times) was 3. 70 % while in over 10 time transfusion recipients (mean 20. 09 times) was 72. 73 %. A statistically significant difference was found between the two groups (P<0. 001). All HGV positive children showed diminished immunity and most were single HGV infection with no clinical and biochemical evidences of acute hepatitis. Our results suggest that HGV is one of the main causes of post-transfusion hepatic virus infection and the prevalence is related to transfusion times. Hematological malignancy maybe the most susceptible confluence of HGV.
文摘In this editorial,we discussed the apparent discrepancy between the findings described by Colapietro et al,in their case report and data found in the literature.Colapietro et al reported a case of hepatitis B virus(HBV)-related hepatic decompensation in a patient with chronic myeloid leukemia and a previously resolved HBV infection who was receiving Bruton’s tyrosine kinase(BTK)inhibitor therapy.First of all,we recapitulated the main aspects of the immune system involved in the response to HBV infection in order to underline the role of the innate and adaptive response,focusing our attention on the protective role of anti-HBs.We then carefully analyzed literature data on the risk of HBV reactivation(HBVr)in patients with previous HBV infection who were treated with either tyrosine kinase inhibitors or BTK inhibitors for their hematologic malignancies.Based on literature data,we suggested that several factors may contribute to the different risks of HBVr:The type of hematologic malignancy;the type of therapy(BTK inhibitors,especially second-generation,seem to be at a higher risk of HBVr than those with tyrosine kinase inhibitors);previous exposure to an anti-CD20 as first-line therapy;and ethnicity and HBV genotype.Therefore,the warning regarding HBVr in the specific setting of patients with hematologic malignancies requires further investigation.
基金National Natural Science Foundation Project(No.81970190)Shaanxi Provincial Social Development Public Relations Key Project(No.2019ZDLSF02-02)National Medical Center Transformation Project(No.2020ZKMC01)。
文摘Most tumor suppressor and growth-regulating proteins are transported via the plasmic nuclear transporter exportin 1(XPO1).Many malignancies have excessive XPO1 expression,which is associated with disease progression and resistance to therapy.A novel class of anticancer medication called selective inhibitor of nuclear export(SINE)can down-regulate the levels of a number of antigenic proteins in the cytoplasm,activate tumor suppressor and other growth regulating proteins,and promote the nuclear retention and apoptosis of tumor cells.This article discusses the function of XPO1 in drug resistance and tumor development as well as the advancement of XPO1 inhibitor research for the treatment of hematological cancers.
文摘Background: Hemopathies were rarely observed in major sickle cell disease patients some thirty years ago, probably due to the high mortality rate among the latter as a result of progressive complications. Thanks to advances in the management of sickle cell disease, patients' life expectancy has increased considerably, exposing them more frequently to neoplasia, including hematological malignancies. The increased risk of leukemogenesis is multifactorial and linked to the pathophysiological mechanisms of the clinical manifestations of sickle cell disease. Study Setting: The clinical haematology department of campus teaching hospital and the paediatric onco-haematology unit of Sylvanus Olympio teaching hospital in Lomé were used as study settings. Observations: Four hematologic malignancies were collected in a cohort of 5847 major sickle cell syndromes. The median age of the patients was 31.25 years (extremes: 14 and 58 years) and they were predominantly female (sex ratio M/F = 0.25). Two were on background therapy with hydroxyurea. Among the four patients, there were two cases of acute lymphocytic leukemia, including ALL3 in a 58-year-old SS woman and T-ALL2 in a 12-year-old SC. Then, a case of lymphocytic lymphoma in a 20-year-old SS man was reported and finally a case of chronic myelocytic leukemia in a 33-year-old woman of Sβ+ thalassaemia phenotype. Conclusion: To further report this coexistence, it is therefore essential to systematically consider hematological malignancies during major sickle cell syndromes even if there are similarities in the symptomatology of these two serious pathological situations.
文摘Background: Febrile neutropenia is one of the most serious adverse events in patients with hematological malignancies and chemotherapy. The routine use of fluoroquinolone prophylaxis in patients with hematological malignancies is controversial. Therefore, we prospectively evaluated the efficacy and safety of prophylactic use of garenoxacin for febrile neutropenia. Patients and Methods: Consecutive adult patients with hematological malignancies who were at risk for chemotherapy-induced neutropenia lasting more than seven days were eligible for present study. They received oral garenoxacin (400 mg daily) from the neutrophil count decreased to less than 1000/μl and continued until the neutropenia had resolved. The primary endpoint was incidence of febrile neutropenia, and the secondary endpoints were the type and incidence of adverse events. Results: We enrolled 46 consecutive patients (median age, 59 years). The underlying diseases comprised acute myeloid leukemia (n = 17), acute lymphoblastic leukemia (n = 3), malignant lymphoma (n = 23), and multiple myeloma (n = 3). There were 23 febrile neutropenia episodes and 2 episodes of bacteremia. There were no grade 3 or 4 adverse events;however serum creatinine levels were significantly elevated after garenoxacin administration. The overall prophylactic efficacy of garenoxacin was 50%, and there were no infection-related deaths. Conclusions: Prophylactic use of garenoxacin is effective and safe in patients with hematological malignancies. (Clinical trial registration number: UMIN000004979).
文摘Objective To investigate the efficiency and safety of allogeneic hematopoietic cell transplantation for malignant hematological diseases in patients older than 50 years of age. Methods From May 2002 to January 2010,35 patients P 】 50 years with malignant hematological diseases received allogeneic hematopoietic
基金supported by grants from the National Natural Science Foundation of China(No.81920108004,82270127,82203880)the Hunan Provincial Natural Science Foundation of China(No.2023JJ30928,2024JJ3037)+2 种基金the Changsha Municipal Natural Sci-Science Foundation(No.kq2208382)the Fellowship of the China Postdoctoral Science Foundation(No.2023T160740)the Hunan Province Clinical Medical Technology Innovation Guidance Project(No.2021SK50917,2023SK4056)。
文摘Hematologic malignancies,including leukemia,lymphoma,and multiple myeloma,are hazardous diseases characterized by the uncontrolled proliferation of cancer cells.Dysregulated cell cycle resulting from genetic and epigenetic abnormalities constitutes one of the central events.Importantly,cyclin-dependent kinases(CDKs),complexed with their functional partner cyclins,play dominating roles in cell cycle control.Yet,efforts in translating CDK inhibitors into clinical benefits have demonstrated disappointing outcomes.Recently,mounting evidence highlights the emerging significance of WEE1 G2 checkpoint kinase(WEE1)to modulate CDK activity,and correspondingly,a variety of therapeutic inhibitors have been developed to achieve clinical benefits.Thus,WEE1 may become a promising target to modulate the abnormal cell cycle.However,its function in hematologic diseases remains poorly elucidated.In this review,focusing on hematologic malignancies,we describe the biological structure of WEE1,emphasize the latest reported function of WEE1 in the carcinogenesis,progression,as well as prognosis,and finally summarize the therapeutic strategies by targeting WEE1.
文摘Immuno-positron emission tomography(immuno-PET)is an innovative medical imaging technique that combines antibodies(Abs)or other immune-targeting molecules with positron-emitting radionuclides.By targeting antigens that are highly expressed in hematologic malignancies,immuno-PET has transformed diagnostic capabilities and enables precise monitoring of therapeutic responses through highly sensitive and specific tumor cell detection.Additionally,it plays a critical role in advancing therapeutic approaches by seamlessly linking diagnostic imaging with personalized treatment strategies.Its non-invasive nature and ability to provide whole-body imaging offer significant advantages over traditional diagnostic methods,especially for detecting minimal residual disease and guiding adaptive therapeutic interventions.In Ab-based immuno-PET,positronemitting radionuclides must have a half-life sufficient for slower pharmacokinetics and blood clearance of Abs.Recent studies have highlighted the advantages of long-lived radionuclides,such as 89Zr,which exhibit low positron energy and enable high sensitivity and resolution,making them particularly effective for tumor visualization and characterization.This review explores the current applications,recent advancements,and potential of immuno-PET for hematologic malignancies,emphasizing its pivotal role in improving patient outcomes and advancing precision medicine.
文摘Since 1968 when the first successful hematopoietic stem cell transplantation(HSCT) was performed, transplant technique has developed rapidly for more than 50 years. In the past 20 years, the significant breakthroughs and widely use of haploidentical-related donor HSCT(e.g. Beijing Protocol) make everyone can have a donor(1), and the novel, reduced-toxicity transplant regimens help elderly patients receive HSCT safely(2).
文摘Gastrointestinal bleeding(GIB)presents a significant challenge for patients with hematologic malignancies,especially those with severe thrombocytopenia.Although endoscopic intervention is frequently used in managing GIB,its safety and effectiveness in this high-risk group remain unclear.A recent study by Alhumayyd et al provided insight into this issue.However,it has notable limitations,including its retrospective nature,small sample size,and failure to adjust for important confounding factors such as disease severity,hemodynamic status,and platelet function.The study’s findings indicated that urgent endoscopy may help decrease the incidence of recurrent bleeding;however,it did not show a clear benefit in terms of mortality.Future research ought to prioritize prospective,multicenter studies that employ standardized protocols and incorporate risk stratification models to better understand the impact of endoscopic treatment for GIB in these patients.Additionally,integrating platelet function assays could improve clinical decision-making.Addressing these research gaps is essential for improving patient outcomes and developing effective guidelines for managing GIB in individuals with thrombocytopenia.
