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BACKGROUND: Hematologic malignancies have been linked to inflammatory cytokine levels; however, whether a causal relationship exists between inflammatory cytokines and hematologic malignancies remains uncertain. This study aimed to explore the causal association between inflammatory cytokines and hematologic malignancies using Mendelian randomization (MR) analysis. METHODS: Summary statistics from genome-wide association studies of 41 inflammatory cytokines, C-reactive protein, and selected hematologic malignancies were obtained from the UK Biobank, YFS, FINRISK, and FinnGen consortia. The inverse-variance weighted (IVW) method with false discovery rate (FDR) adjustment was used as the primary MR method. The weighted median, MR-Egger regression, MR-Robust Adjusted Profile Score, and MR pleiotropy residual sum, and outlier methods were used as supplied analyses. MR-Egger intercept estimates and Cochran's Q test were used to assess pleiotropy and heterogeneity. Leave-one-out analysis and the MR Steiger test were used to assess sensitivity and the direction of causality. RESULTS: Although the primary IVW analysis indicated that some inflammatory cytokines were associated with risk of selected hematologic malignancies, no significant causal relationship between cytokines and selected hematologic malignancies was detected after FDR correction. CONCLUSION: Genetically predicted cytokine levels did not have a significant effect on the risk of the selected hematologic malignancies. Further research is warranted to confirm the potential association between cytokine levels and the risk of selected hematologic malignancies.
INTRODUCTION: Prolonged SARS-CoV-2 infection in hematologic patients may go unrecognized. The aim of the study is to describe the incidence, risk factors, viral evolution and clinical outcomes of prolonged SARS-CoV-2 infection in patients with hematologic malignancies. METHODS: This is a prospective, observational study. We performed a longitudinal follow-up rRT-PCR with cycle threshold (Ct) assessment until negativization to 500 patients diagnosed with hematologic malignancies who suffered SARS-CoV-2 infection between March 2020 and August 2023. We considered prolonged COVID-19 to a positive rRT-PCR with a Ct <35 beyond 30 days after microbiological diagnosis with the same viral variant. RESULTS: Prolonged SARS-CoV-2 infection is a complication in 44.8% (156/348) of patients diagnosed with hematologic malignancies with a median time of rRT-PCR positivity of 58 days (IQR 43-88). Active treatment with bispecific antibodies, anti-CD20 antibodies, BTK inhibitors and immunosuppressive drugs for GvHD are significantly associated with prolonged viral shedding; as well as lack of vaccination, lesser booster vaccine doses, absence of anti-S seroconversion after immunization, severe acute infection and delayed antiviral treatment. A 56.4% (88/156) of patients exhibit a pattern of remitting and relapsing symptoms and fluctuant viral load. During those exacerbations, 70.5% of patients experienced an increase in the severity of the acute infection and 34% developed pneumopathy, particularly organizing pneumonia. Persistent COVID-19 caused 54.5% (85/156) of patients to interrupt and 19.9% (31/156) to suspend indefinitely their hematologic treatments. Viral intra-host mutations across the entire viral genome, predominantly within the spike were detected in most patients with prolonged COVID-19, especially in those who received anti-SARS-CoV-2 mAb as sotrovimab (E340, R346, K356) and tixagevimab/cilgavimab (R346, K444 and G446). These substitutions are associated with reduced viral susceptibility. DISCUSSION: Prolonged SARS-CoV-2 infection in hematologic patients is frequent and leads to persistent viral replication, significant morbidity and the emergence of intra-host viral mutations. Optimizing treatments and monitoring viral clearance are medical needs for high-risk patients.
Hematologic malignancies are cancers that affect the bone marrow, lymphatic system, and hematopoietic cells, resulting in various cancer subtypes and clinical manifestations. Currently, tissue biopsy in hematological malignancies is typically performed for genomic profiling and has limitations such as invasiveness, lengthy procedures, and high expense. On the other hand, liquid biopsy serves as an emerging tool used for examining the blood or other bodily fluids of patients, for the purpose of identifying genetic mutations, biomarkers, or cancer-related substances. Liquid biopsy biomarkers include circulating tumor DNA (ctDNA), microRNA (miRNA), and exosomes. In the context of hematological malignancies, these biomarkers offer valuable insights into disease etiology, enabling effective disease monitoring and guiding treatment decisions owing to their differential expression patterns. This review critically examines the recent advancements and effectiveness of liquid biopsy biomarkers in the areas of diagnosis, therapy, and monitoring. The challenges and future directions of liquid biopsy for hematological malignancies are also discussed.
OBJECTIVES: Criteria for visual examination of stained peripheral blood smear (PBS) differ among institutions in the United States and internationally. In an effort to standardize review criteria, the International Consensus Group for Hematology Review (ICGHR) proposed in 2005 a consensus list of rules for CBC findings that should trigger a review of automated cell counter results and potentially lead to further testing or blood smear review. The primary aim of this paper is to report on the published literature in the past 20 years regarding PBS review criteria and their ability to identify relevant peripheral blood abnormalities. METHODS: We performed a systematic review of the published literature from 2005 to 2025 to investigate and summarize PBS review criteria and performance in the context of automated hematology analyzers in clinical laboratories. RESULTS: Of 5351 citations, 68 studies met our search criteria. These studies included 22 countries and all major hematology analyzer manufacturers. Marked variability was observed in study populations, analyzer flagging criteria, details of PBS visual review, definitions of a "positive" smear, and approaches to statistical data analysis. Across studies, the blast flag sensitivity ranged from 18% to 100% while the blast flag specificity ranged from 17% to 100%. Wide ranges in sensitivity/specificity were also seen for atypical and/or abnormal lymphocyte flags across studies. For studies analyzing the same patient population, less striking variation was seen across instruments. CONCLUSIONS: This systematic review provides a 20-year overview of the literature, highlighting significant variability in PBS review criteria, dependence on study design and hematology analyzer, and the importance of developing harmonized evidence-based guidelines.
The increasing availability of genomic and transcriptomic sequencing has uncovered diverse genomic alterations and distinct gene expression profiles driving hematologic diseases, yet a data integration and sharing platform dedicated to hematology remains lacking. We developed the American Society of Hematology (ASH) HematOmics Program (ASHOP; ashop.hematology.org), a resource for exploring somatic alterations and gene fusions, transcriptomic results, and clinical data from 5960 patients spanning B-cell precursor and T-cell acute lymphoblastic leukemia, acute myeloid leukemia, myelodysplastic syndromes, and chronic lymphocytic leukemia. Users can explore genomic alteration landscapes and comutation patterns via lollipop and matrix plots and analyze significantly altered genes in user-defined subcohorts. Transcriptomes can be explored through interactive uniform manifold approximation and projections, clustering, differential expression, and pathway enrichment. Genomic, transcriptomic features, and clinical outcomes can be correlated in a user-driven manner or combined to precisely define study cohorts. We illustrate the following 4 use cases of ASHOP: (1) stratification of DUX4-rearranged B-cell leukemias into Early/Multipotent and Committed subgroups with distinct outcomes, (2) characterization of HOXA/HOXB expression patterns in acute myeloid leukemias, (3) correlating mutational burden with mismatch repair deficiency and mutational signatures, and (4) investigation of TP53 alteration landscape. ASHOP is an open-access resource to inform genomic and transcriptomic data interpretation for hematologic malignancies and will expand to support additional diseases and data modalities from the ASH community.
BACKGROUND AND AIM: Mucormycosis is a life-threatening invasive fungal infection. This study aimed to analyze the clinical characteristics of patients with hematologic malignancies complicated with mucormycosis. METHODS: This retrospective study investigated the clinical characteristics, epidemiological features, treatment, and prognosis of 46 patients with hematological diseases and Mucor infection as indicated by mNGS from August 28, 2020 to September 11, 2023. Metagenomic next-generation sequencing (mNGS) refers to the application of high-throughput sequencing technology for the comprehensive analysis of nucleic acid content in patient samples, facilitating the detection and characterization of microbial DNA and/or RNA, and then comparing and analyzing the results with an information database to determine the types of pathogenic microorganisms present in the sample. RESULTS: The median age of admission for the included patients was 49 years (9-78). Multivariate analysis identified age over 60 years (p = 0.006 < 0.05), high-dose corticosteroids (p = 0.001 < 0.05), neutropenia lasting more than 10 days (p = 0.041 < 0.05), and two or more Mucor infections (p = 0.004 < 0.05) were independent risk factors for OS in patients with hematological diseases. Moreover, differences between groups were analyzed using the Fisher exact probability method, and no significant difference was observed in the efficacy of various types of antifungal therapies. CONCLUSION: Patients with hematologic malignancies benefit greatly from early diagnosis and treatment when suspected of Mucor infection. mNGS is an important supplementary method for early diagnosis of Mucor infection. Moderated use of corticosteroids, reducing the duration of neutropenia, and enhancing autologous immune function are important measures to reduce patient mortality rate.
BACKGROUND: Patients with hematologic diseases are highly susceptible to infection. Conventional tests often have low sensitivity. Metagenomic next-generation sequencing (mNGS) can detect many pathogens at once, but its clinical value depends on how the results are interpreted. It is often hard to tell true infection from colonization or contamination. METHODS: We retrospectively studied hospitalized hematologic patients Only adult patients (≥18 years) who received mNGS for the first time. Detected organisms were reclassified using a clinical actionability system. We also analyzed the relationships between mNGS findings, host characteristics, and short-term outcomes. RESULTS: A total of 134 patients were included. At least one organism was detected in 87.3% of patients, but only 58.2% had highly actionable results. Bacteria were the most common findings, followed by viruses and fungi. Mixed detections were frequent. Actionable results were seen more often in respiratory specimens than in blood specimens. Viral detection was associated with immune status. Pathogen read counts were only weakly related to inflammatory markers and did not independently predict adverse outcomes. Age was the only independent risk factor for adverse outcome. CONCLUSION: mNGS had a high detection rate in hematologic patients, but not all positive findings were clinically important. Result interpretation should take specimen type and host status into account. Pathogen read counts alone were not useful for predicting short-term outcome.
INTRODUCTION: Morphologic examination of peripheral blood and bone marrow remains central to the diagnosis and classification of hematologic disorders. Conventional optical microscopy, however, is labor-intensive, dependent on operator expertise, and affected by interobserver variability. Digital morphology has developed from automated image acquisition and cell pre-classification into a broader field that includes whole-slide imaging, remote review, quantitative morphometry, and artificial intelligence-based analysis. CONTENT: This review examines current applications of digital morphology in peripheral blood, bone marrow aspirates, malaria detection, and body-fluid analysis. Commercial platforms are evaluated with particular attention to the distinction between raw automated pre-classification, expert digital post-classification, and comparison with independent optical microscopy. Digital systems generally perform well for common mature leukocyte populations but remain less reliable for rare or diagnostically critical cells, including blasts, abnormal lymphoid cells, plasma cells, and intermediate maturation stages. Research systems increasingly extend analysis from individual-cell classification to whole-slide, specimen-level, and patient-level assessment. SUMMARY: Digital morphology can improve standardization, image traceability, remote consultation, education, proficiency testing, quality assurance, and selected aspects of laboratory workflow. Its clinical value depends on appropriate validation, transparent reporting of reference methods, recognition of algorithm-specific failure modes, and clearly defined criteria for expert review and conventional microscopy. Human expertise remains essential not only for validating results but also for adapting cell taxonomies and interpretive rules to evolving classifications of hematologic diseases. OUTLOOK: Future progress will require representative multicenter datasets, harmonized morphologic terminology, external validation, interoperability with laboratory information systems, and continuous monitoring after software or hardware updates. Integration of morphology with quantitative hematology, flow cytometry, cytogenetics, genomics, and clinical data may support more comprehensive computational diagnosis. Digital platforms may also broaden access to specialist expertise, training, and quality programs in resource-limited institutions and regions, provided that infrastructure, governance, and professional competency are adequately supported.
INTRODUCTION: Breast cancer develops in breast tissues, in ducts and lobules. It affects both genders, though it is uncommon in men. Hematological variations are important considerations and deficiencies in metals can negatively impact human health. Cadmium is highly toxic and plays role in breast cancer progression. This study was designed for hematological variations and cadmium induced toxicity in mice and humans causing breast cancer. METHODS: Mice, obtained from local supplier, housed at university laboratory for 11 weeks, exposed to cadmium. Following dissection, blood and organs were harvested for examination. Histological analysis of liver and mammary gland tissues was conducted. RESULTS: Affected mice had higher Hb, RBC, HCT, MCV, and MCH, while humans showed lower Hb, HCT, and MCV but similar RBC and MCH. Other blood values also show changes. Histopathology revealed changes in mammary glands (higher cadmium led to increased fat deposition, degeneration of alveolar epithelial cells, and a reduction in alveolar milk lumen size, indicating compromised glandular function) and liver damage (vacuolation, lipid accumulation, fibrosis, and collagen deposition, was noticeable with prolonged cadmium). These changes causes liver fibrosis and impaired mammary gland function. DISCUSSION: The cadmium exposure induces distinct hematological alterations and severe tissues damage, reflecting species-specific responses. The observed liver fibrosis and mammary gland dysfunction emphasize cadmium's potential to compromise critical organ functions over time. CONCLUSION: Significant effects of cadmium exposure in mice were observed. Histological damage was seen in mammary glands and liver. Further research on protective measures and dose-response relationships for cadmium exposure is needed.
Europe's firs Hemalog D was installed in the Hematology Laboratory of the Franco-Musulman Hospital at Bobigny, just outside Paris, in March 1975. The authors' experience with the apparatus since that date has enabled them to analyze the significance of "alarms", "high peroxidase", "large unstained cells", "remainder" and "low rate" in patients with and without hematologic disorders. On the basis of these results it has been possible to define the fate of the various blood cells in the Hemalog D, the role of the apparatus in the ivestigation of hematologic disorders and the type of "cooperation" between the hematologist and the Hemalog D.
Hematologic emergencies may be defined as sudden or unexpected life-threatening events in clinical hematology and oncology which require immediate action predominantly based on clinical judgements and supported only by investigations that can be expected to produce results rapidly. It is convenient to classify these emergencies according to disorders affecting the erythrocytes; leukocytes; platelets; hemostasis; defence mechanisms against infection; the respiratory system; and emergencies related to drugs used for the treatment of neoplasia. A proposed classification is outlined. Part of treatment of hematologic emergencies is to ensure that the cicumstances which caused them will not recur in the same patient or those with similar disorders.
Hematological parameters of a carp, Cirrhina mrigala, are reported here. Haematocrit ranged from 29.0 to 44.0%. The range of hemoglobin was 7.06 to 11.86 g/100 ml of blood, and the total number of erythrocytes varied from 1.7 to 3.0 million/mm3 of the blood, both hemoglobin and erythrocyte concentrations being higher in males than in the females. Mean ESR was 1.88 mm/h, with higher ESR in females (2.05 mm/h) than in the males (1.67 mm/h). The clotting time in males (41.0 seconds) was lower than in the females (63.5 seconds). Hematological values varied with the size and weight of the fishes. Variations in hematological parameters with season and in fishes of different maturation states were quite apparent.
Published data on Japanese leukemia patients with a preleukemic hematological disorder were assessed. The reexamined cases were from the "Japona Centra Revuo Medicina" reported during the period from 1952 to 1971. Among preleukemic hematological disorders, hypoplastic anemia was the most frequently reported (41 of 62 cases). These "hypoplastic preleukemia" patients were rather elderly and terminated mostly in atypical myelocytic leukemia. The chief hematological feature of the hypoplastic preleukemia cases was the coexistence of a relative erythroid hyperplasia and a slight increase of myeloblasts in the bone marrow that was unusual in hypoplastic anemia. The presence of pancytopenia and hypocellular marrow with a relative erythroid hyperplasia combined with a slight increase of myeloblasts probably indicates hypoplastic preleukemia that terminates later in acute leukemia.
Patients with hematologic malignancies (HMs) are particularly vulnerable to coronavirus disease 2019 (COVID-19) because of underlying immune dysfunction and treatment-related immunosuppression. However, proteomic features associated with different clinical trajectories in this population remain insufficiently characterized. We performed serum proteomic analysis in 40 HM patients with COVID-19 and 15 healthy controls. Compared with controls, HM patients showed impaired immune-related responses during the acute phase of COVID-19. Acute-phase proteomic patterns differed across outcome groups; however, because outcome groups were closely intertwined with initial COVID-19 severity, ICU admission, and systemic illness, and because multivariable adjustment was not performed due to the limited sample size, these patterns should be interpreted as severity- and outcome-associated profiles rather than independent trajectory-specific markers. Fatal cases showed evidence of dysregulated immune activation, whereas patients later classified as having long COVID exhibited broader suppression of immune-related pathways. In addition to immune alterations, pathways related to platelet activation and cardiac-related dysfunction were associated with adverse clinical trajectories. Enzyme-linked immunosorbent assay validation supported the association of selected proteins with outcome groups during acute infection. These findings provide a proteomic overview of COVID-19 in HM patients and offer a basis for future mechanistic studies and larger external validation cohorts.IMPORTANCEPatients with hematologic malignancies are highly vulnerable to severe coronavirus disease 2019 (COVID-19), acute death, and long COVID due to preexisting immune dysfunction. However, the proteomic signatures linked to adverse clinical trajectories remain poorly understood. Our serum proteomic study identifies distinct acute-phase immune profiles associated with different outcomes: broad immune suppression characterizes long COVID, while dysregulated immune activation is associated with fatal cases. Platelet activation and cardiac-related pathways are also linked to poor outcomes. These findings provide key molecular insights for this high-risk population, supporting future biomarker development, risk stratification, and targeted clinical management.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT05683353.
One hundred sixty-five patients with operative prostatic disease were investigated for hematologic abnormalities. The tests were useful in the clinical management of 6 (3.7 per cent) patients. Preoperative hematologic screening tests are recommended in patients with prostatic cancer, potential sepsis, and in patients with a known bleeding tendency.
32P is effective therapy for polycythemia and primary thrombocytosis. The Polycythemia Vera Study Group is comparing radioactive phosphorus with alkylating agents to determine relative efficacy. Less well investigated is the effectiveness of 32P vs. busulfan in chronic granulocytic leukemia. Endolymphatic administration of radiopharmaceuticals may play a role in the therapy of infradiaphragmatic lymphoma. Among the radionuclides that have at times been used in hematology are 32P, 198Au 24Na, 76As, 89Sr, 52Mb, 54Mn, 91Y, 95Zr, 95Cb, 111Ag, 109Pd, 131I, 185W, and 192Ir. As stated, 32P has proven single most efficacious agent. The hematologic diseases that have been treated include both malignant and benign conditions. Among the malignant conditions are polycythemia vera, agnogenic myeloid metaplasia, thrombocythemia, leukemia, Hodgkin's disease, and multiple myeloma. Hemophilia, and Osler--Weber--Rendu disease are among the benign entities in which the agents have been tried. Polycythemia and thrombocythemia remain those in which the greatest success has been achieved.