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American Journal of Hematology Nov 2019Chronic lymphocytic leukemia (CLL) is the commonest leukemia in western countries. The disease typically occurs in elderly patients and has a highly variable clinical... (Review)
Review
DISEASE OVERVIEW
Chronic lymphocytic leukemia (CLL) is the commonest leukemia in western countries. The disease typically occurs in elderly patients and has a highly variable clinical course. Leukemic transformation is initiated by specific genomic alterations that impair apoptosis of clonal B-cells.
DIAGNOSIS
The diagnosis is established by blood counts, blood smears, and immunophenotyping of circulating B-lymphocytes, which identify a clonal B-cell population carrying the CD5 antigen, as well as typical B-cell markers.
PROGNOSIS
The two similar clinical staging systems, Rai and Binet, create prognostic information by using results of physical examination and blood counts. Various biological and genetic markers also have prognostic value. Deletions of the short arm of chromosome 17 (del [17p]) and/or mutations of the TP53 gene, predict resistance to chemoimmunotherapy and a shorter time to progression, with most targeted therapies. A comprehensive, international prognostic score (CLL-IPI) integrates genetic, biological and clinical variables to identify distinct risk groups of CLL patients.
THERAPY
Only patients with active or symptomatic disease, or with advanced Binet or Rai stages require therapy. When treatment is indicated, several options exist for most CLL patients: a combination of venetoclax with obinutuzumab, ibrutinib monotherapy, or chemoimmunotherapy. For physically fit patients younger than 65 (in particular when presenting with a mutated IGVH gene), chemoimmunotherapy with fludarabine, cyclophosphamide and rituximab remains a standard therapy, since it may have curative potential. At relapse, the initial treatment may be repeated, if the treatment-free interval exceeds 3 years. If the disease relapses earlier, therapy should be changed using an alternative regimen. Patients with a del (17p) or TP53 mutation are a different, high-risk category and should be treated with targeted agents. An allogeneic SCT may be considered in relapsing patients with TP53 mutations or del (17p), or patients that are refractory to inhibitor therapy.
FUTURE CHALLENGES
Targeted agents (ibrutinib, idelalisib, venetoclax, obinutuzumab) will be increasingly used in combination to allow for short, but potentially definitive therapies of CLL. It remains to be proven that they generate a superior outcome when compared to monotherapies with inhibitors of Bruton tyrosine kinase, which can also yield long-lasting remissions. Moreover, the optimal sequencing of drug combinations is unknown. Therefore, CLL patients should be treated in clinical trials whenever possible.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; B-Lymphocytes; Biomarkers, Tumor; Blood Cell Count; Chromosome Deletion; Combined Modality Therapy; Female; Forecasting; Hematopoietic Stem Cell Transplantation; Humans; Immunophenotyping; Immunotherapy; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Molecular Targeted Therapy; Mutation; Neoplasm Staging; Prognosis; Risk Assessment
PubMed: 31364186
DOI: 10.1002/ajh.25595 -
Acta Cytologica 2021
Topics: COVID-19; Host-Pathogen Interactions; Humans; Killer Cells, Natural; SARS-CoV-2; T-Lymphocytes, Helper-Inducer
PubMed: 32799199
DOI: 10.1159/000510110 -
Cureus Jun 2022A 34-year-old male presented with a gradual, painless decrease in distant vision in the left more than the right in the past 15 days. He had a history of an episode of...
A 34-year-old male presented with a gradual, painless decrease in distant vision in the left more than the right in the past 15 days. He had a history of an episode of fever seven days prior to ocular symptoms and had been treated with oral Cefixime and antipyretics. On detailed fundus examination, both eyes showed creamy white superficial lesions with ill-defined margins, suggestive of retinitis, with a few hemorrhages along the inferior arcade associated with sheathing of vessels and telangiectatic vessels near the lesion. Fundus fluorescein angiography (FFA) of both eyes in the venous phase depicted blocked fluorescence at the site of retinitis lesions with hyperfluorescence at their borders. Optical coherence tomography (OCT) of both eyes showed inner retinal layer hyper-reflectivity with neurosensory detachment (NSD) with hyper-reflective deposits in it and dilated choroidal vessels. The diagnosis of both eyes' post-fever retinitis (PFR) was made, and he was investigated for complete blood count, peripheral smear, erythrocyte sedimentation rate, and HIV Tridot test, which were normal. He was treated with intravitreal triamcinolone acetonide (2 mg/0.05 ml) in both eyes.
PubMed: 35915675
DOI: 10.7759/cureus.26429 -
Blood Cancer Journal Dec 2021Primary plasma cell leukemia (PCL) has a consistently ominous prognosis, even after progress in the last decades. PCL deserves a prompt identification to start the most...
Primary plasma cell leukemia (PCL) has a consistently ominous prognosis, even after progress in the last decades. PCL deserves a prompt identification to start the most effective treatment for this ultra-high-risk disease. The aim of this position paper is to revisit the diagnosis of PCL according to the presence of circulating plasma cells in patients otherwise meeting diagnostic criteria of multiple myeloma. We could identify two retrospective series where the question about what number of circulating plasma cells in peripheral blood should be used for defining PCL. The presence of ≥5% circulating plasma cells in patients with MM had a similar adverse prognostic impact as the previously defined PCL. Therefore, PCL should be defined by the presence of 5% or more circulating plasma cells in peripheral blood smears in patients otherwise diagnosed with symptomatic multiple myeloma.
Topics: Aged; Female; Humans; Leukemia, Plasma Cell; Male; Multiple Myeloma; Plasma Cells; Prognosis; Retrospective Studies
PubMed: 34857730
DOI: 10.1038/s41408-021-00587-0 -
Frontiers in Oncology 2019Acute myeloid leukemia (AML) represents 80% of adult leukemias and 15-20% of childhood leukemias. AML are characterized by the presence of 20% blasts or more in the bone... (Review)
Review
Acute myeloid leukemia (AML) represents 80% of adult leukemias and 15-20% of childhood leukemias. AML are characterized by the presence of 20% blasts or more in the bone marrow, or defining cytogenetic abnormalities. Laboratory diagnoses of myelodysplastic syndromes (MDS) depend on morphological changes based on dysplasia in peripheral blood and bone marrow, including peripheral blood smears, bone marrow aspirate smears, and bone marrow biopsies. As leukemic cells are not functional, the patient develops anemia, neutropenia, and thrombocytopenia, leading to fatigue, recurrent infections, and hemorrhage. The genetic background and associated mutations in AML blasts determine the clinical course of the disease. Over the last decade, non-coding RNAs transcripts that do not codify for proteins but play a role in regulation of functions have been shown to have multiple applications in the diagnosis, prognosis and therapeutic approach of various types of cancers, including myeloid malignancies. After a comprehensive review of current literature, we found reports of multiple long non-coding RNAs (lncRNAs) that can differentiate between AML types and how their exogenous modulation can dramatically change the behavior of AML cells. These lncRNAs include: H19, LINC00877, RP11-84C10, CRINDE, RP11848P1.3, ZNF667-AS1, AC111000.4-202, SFMBT2, LINC02082-201, MEG3, AC009495.2, PVT1, HOTTIP, SNHG5, and CCAT1. In addition, by performing an analysis on available AML data in The Cancer Genome Atlas (TCGA), we found 10 lncRNAs with significantly differential expression between patients in favorable, intermediate/normal, or poor cytogenetic risk categories. These are: DANCR, PRDM16-DT, SNHG6, OIP5-AS1, SNHG16, JPX, FTX, KCNQ1OT1, TP73-AS1, and GAS5. The identification of a molecular signature based on lncRNAs has the potential for have deep clinical significance, as it could potentially help better define the evolution from low-grade MDS to high-grade MDS to AML, changing the course of therapy. This would allow clinicians to provide a more personalized, patient-tailored therapeutic approach, moving from transfusion-based therapy, as is the case for low-grade MDS, to the introduction of azacytidine-based chemotherapy or allogeneic stem cell transplantation, which is the current treatment for high-grade MDS.
PubMed: 31681586
DOI: 10.3389/fonc.2019.01048 -
Movement Disorders Clinical Practice Feb 2021Movement disorders can be associated with or caused by hematological abnormalities. The objective of this review is to highlight features that will aid in the... (Review)
Review
BACKGROUND
Movement disorders can be associated with or caused by hematological abnormalities. The objective of this review is to highlight features that will aid in the clinician's recognition and treatment of these disorders.
METHODS
MESH terms relevant to movement disorders and hematologic diseases were searched to identify conditions included in this narrative, educational review.
RESULTS
Several conditions were identified, and they were organized by hematologic categories to include red blood cell abnormalities, white blood cell abnormalities, disorders of clotting and bleeding, hematologic malignancies, and others.
CONCLUSIONS
This review will increase providers' understanding of disorders that include movement disorders and hematologic abnormalities. Basic hematologic laboratories can aid in assessment of these disorders, to include complete blood count/hemogram and peripheral blood smear. Recognition is key, especially in the setting of underlying malignancy, vitamin deficiency, or other disorder in which treatment is available.
PubMed: 33553488
DOI: 10.1002/mdc3.13129 -
Medical & Biological Engineering &... Sep 2022Anemia is a blood disorder which is caused due to inadequate red blood cells and hemoglobin concentration. It occurs in all phases of life cycle but is more dominant in... (Review)
Review
Anemia is a blood disorder which is caused due to inadequate red blood cells and hemoglobin concentration. It occurs in all phases of life cycle but is more dominant in pregnant women and infants. According to the survey conducted by the World Health Organization (WHO) (McLean et al., Public Health Nutr 12(4):444-454, 2009), anemia affects 1.62 billion people constituting 24.8% of the population and is considered the world's second leading cause of illness. The Peripheral Blood Smear (PBS) examination plays an important role in evaluating hematological disorders. Anemia is diagnosed using PBS. Being the most powerful analytical tool, manual analysis approach is still in use even though it is tedious, prone to errors, time-consuming and requires qualified laboratorians. It is evident that there is a need for an inexpensive, automatic and robust technique to detect RBC disorders from PBS. Automation of PBS analysis is very active field of research that motivated many research groups to develop methods using image processing. In this paper, we present a review of the methods used to analyze the characteristics of RBC from PBS images using image processing techniques. We have categorized these methods into three groups based on approaches such as RBC segmentation, RBC classification and detection of anemia, and classification of anemia. The outcome of this review has been presented as a list of observations.
Topics: Anemia; Erythrocyte Count; Erythrocytes; Female; Hematologic Tests; Humans; Image Processing, Computer-Assisted; Pregnancy
PubMed: 35838854
DOI: 10.1007/s11517-022-02614-z -
BME Frontiers 2022. We present a fully automated hematological analysis framework based on single-channel (single-wavelength), label-free deep-ultraviolet (UV) microscopy that serves as a...
. We present a fully automated hematological analysis framework based on single-channel (single-wavelength), label-free deep-ultraviolet (UV) microscopy that serves as a fast, cost-effective alternative to conventional hematology analyzers. . Hematological analysis is essential for the diagnosis and monitoring of several diseases but requires complex systems operated by trained personnel, costly chemical reagents, and lengthy protocols. Label-free techniques eliminate the need for staining or additional preprocessing and can lead to faster analysis and a simpler workflow. In this work, we leverage the unique capabilities of deep-UV microscopy as a label-free, molecular imaging technique to develop a deep learning-based pipeline that enables virtual staining, segmentation, classification, and counting of white blood cells (WBCs) in single-channel images of peripheral blood smears. . We train independent deep networks to virtually stain and segment grayscale images of smears. The segmented images are then used to train a classifier to yield a quantitative five-part WBC differential. Our virtual staining scheme accurately recapitulates the appearance of cells under conventional Giemsa staining, the gold standard in hematology. The trained cellular and nuclear segmentation networks achieve high accuracy, and the classifier can achieve a quantitative five-part differential on unseen test data. . This proposed automated hematology analysis framework could greatly simplify and improve current complete blood count and blood smear analysis and lead to the development of a simple, fast, and low-cost, point-of-care hematology analyzer.
PubMed: 37850166
DOI: 10.34133/2022/9853606 -
Proceedings of the National Academy of... Jun 2020Hematological analysis, via a complete blood count (CBC) and microscopy, is critical for screening, diagnosing, and monitoring blood conditions and diseases but requires...
Hematological analysis, via a complete blood count (CBC) and microscopy, is critical for screening, diagnosing, and monitoring blood conditions and diseases but requires complex equipment, multiple chemical reagents, laborious system calibration and procedures, and highly trained personnel for operation. Here we introduce a hematological assay based on label-free molecular imaging with deep-ultraviolet microscopy that can provide fast quantitative information of key hematological parameters to facilitate and improve hematological analysis. We demonstrate that this label-free approach yields 1) a quantitative five-part white blood cell differential, 2) quantitative red blood cell and hemoglobin characterization, 3) clear identification of platelets, and 4) detailed subcellular morphology. Analysis of tens of thousands of live cells is achieved in minutes without any sample preparation. Finally, we introduce a pseudocolorization scheme that accurately recapitulates the appearance of cells under conventional staining protocols for microscopic analysis of blood smears and bone marrow aspirates. Diagnostic efficacy is evaluated by a panel of hematologists performing a blind analysis of blood smears from healthy donors and thrombocytopenic and sickle cell disease patients. This work has significant implications toward simplifying and improving CBC and blood smear analysis, which is currently performed manually via bright-field microscopy, and toward the development of a low-cost, easy-to-use, and fast hematological analyzer as a point-of-care device and for low-resource settings.
Topics: Blood Cell Count; Blood Cells; Equipment Design; Humans; Microscopy, Ultraviolet; Molecular Imaging; Point-of-Care Systems
PubMed: 32561645
DOI: 10.1073/pnas.2001404117