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Topic Review
Related Factors of Anemia in Critically Ill Patients
Anemia is common in critically ill patients; almost 95% of patients admitted to intensive care units (ICUs) have hemoglobin levels below normal. Several causes may explain this phenomenon as well as the tendency to transfuse patients without adequate cause: due to a lack of adherence to protocols, lack of supervision, incomplete transfusion request forms, or a lack of knowledge about the indications, risks, and costs of transfusions. Daily sampling to monitor the coagulation parameters and the acid–base balance can aggravate anemia as the main iatrogenic factor in its production.
  • 607
  • 29 Mar 2022
Topic Review
ResRandSVM for Acute Lymphocytic Leukemia Blood Detection
Acute Lymphocytic Leukemia is a type of cancer that occurs when abnormal white blood cells are produced in the bone marrow which do not function properly, crowding out healthy cells and weakening the immunity of the body and thus its ability to resist infections. It spreads quickly in children’s bodies, and if not treated promptly it may lead to death. The manual detection of this disease is a tedious and slow task. Machine learning and deep learning techniques are faster than manual detection and more accurate.
  • 607
  • 10 Jul 2023
Topic Review
Inflammation in Sickle Cell Disease-Associated Pulmonary Complications
Sickle cell disease (SCD) is the most common monogenic blood disorder, affecting approximately 100,000 Americans and millions more worldwide. Cardiopulmonary complications are a major cause of morbidity and mortality in SCD, accounting for 32–70% of deaths. 
  • 606
  • 07 Mar 2023
Topic Review
Non-Transplant-Eligible Newly Diagnosed Multiple Myeloma
Multiple myeloma mainly affects the elderly, who are usually not eligible to intensive treatments such as autologous stem cell transplant. The advances in therapeutics have largely benefited elderly patients now renamed “non-transplant-eligible” (NTE) patients. Since the 1960s, and for several decades, chemotherapy was the only treatment for MM. Then, the field was marked by the emergence of targeted therapies in the 2000s, such as immunomodulating agents (thalidomide, lenalidomide, and pomalidomide) and proteasome inhibitors (bortezomib, carfilzomib, and ixazomib), which were the first steps towards an increase in survival. Thereafter, the apparition of monoclonal antibodies (mAbs) was considered a milestone in the treatment of MM for both transplant-eligible and NTE patients. Anti-CD38 mAbs can be safely administered to older patients with an impressive efficacy leading to a never-achieved-before survival rate with the triple association of anti-CD38 mAbs, lenalidomide, and dexamethasone.
  • 601
  • 30 Mar 2023
Topic Review
Targeting CML LSCs
Chronic myeloid leukemia stem cells (CML LSCs) are a rare and quiescent population that are resistant to tyrosine kinase inhibitors (TKI). When TKI therapy is discontinued in CML patients in deep, sustained and apparently stable molecular remission, these cells in approximately half of the cases restart to grow, resuming the leukemic process. The elimination of these TKI resistant leukemic stem cells is therefore an essential step in increasing the percentage of those patients who can reach a successful long-term treatment free remission (TFR). The understanding of the biology of the LSCs and the identification of the differences, phenotypic and/or metabolic, that could eventually allow them to be distinguished from the normal hematopoietic stem cells (HSCs) are therefore important steps in designing strategies to target LSCs in a rather selective way, sparing the normal counterparts.
  • 599
  • 21 Dec 2021
Topic Review
LncRNAs in ALL Classification, Pathogenesis and Treatment
The coding regions account for only a small part of the human genome, and the remaining vast majority of the regions generate large amounts of non-coding RNAs. Although non-coding RNAs do not code for any protein, they are suggested to work as either tumor suppressers or oncogenes through modulating the expression of genes and functions of proteins at transcriptional, posttranscriptional and post-translational levels. Acute Lymphoblastic Leukemia (ALL) originates from malignant transformed B/T-precursor-stage lymphoid progenitors in the bone marrow (BM). The pathogenesis of ALL is closely associated with aberrant genetic alterations that block lymphoid differentiation and drive abnormal cell proliferation as well as survival. While treatment of pediatric ALL represents a major success story in chemotherapy-based elimination of a malignancy, adult ALL remains a devastating disease with relatively poor prognosis. Thus, novel aspects in the pathogenesis and progression of ALL, especially in the adult population, need to be further explored. Accumulating evidence indicated that genetic changes alone are rarely sufficient for development of ALL. Recent advances in cytogenic and sequencing technologies revealed epigenetic alterations including that of non-coding RNAs as cooperating events in ALL etiology and progression, which might provide new options for managing the disease in the future.
  • 597
  • 18 May 2022
Topic Review
Single-Cell Next-Generation Sequencing
Single-cell DNA sequencing is a laboratory technique that analyzes the genetic content of individual cells. In the context of genetically diverse hematological cancers such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), the traditional approach of analyzing genetic material, which typically involves bulk samples of leukemia cells, may miss important mutations that may not be present in all cells.
  • 597
  • 12 Jul 2023
Topic Review
Targeted Therapies for Chronic Lymphocytic Leukemia
The management of chronic lymphocytic leukemia (CLL) is based on symptom severity and includes various types of targeted therapies, including rituximab, obinutuzumab, ibrutinib, acalabrutinib, zanubrutinib, idelalisib, and venetoclax. These therapies rely on the recognition of specific peptides presented by human leukocyte antigen (HLA)  on the surface of tumor cells by T cells, leading to an immune response. The therapeutic landscape for CLL is diverse and encompasses multiple therapeutic options, including chemotherapy, immunotherapy, radiation therapy, and stem-cell transplantation. There are several FDA-approved targeted therapies for CLL, including rituximab, ibrutinib, idelalisib, venetoclax, and acalabrutinib. Despite their high efficacy, the complex biology of CLL allows malignant cells to develop resistance mechanisms to these targeted therapies.
  • 596
  • 12 Jun 2023
Topic Review
Pediatric Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma
Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) is an aggressive T-cell lymphoma characterized by large T-cells with strong CD30 and ALK expression. Although conventional chemotherapy is effective in most patients, approximately 30% experience a relapse or refractory disease and have a poor prognosis. Several risk factors associated with poor prognosis have been identified in pediatric ALK-positive ALCL. These include morphological patterns with the small cell variant or lymphohistiocytic variant, leukemic presentation, the presence of minimal disseminated disease, or involvement of the central nervous system. Relapsed or refractory ALK-positive ALCL is often resistant to conventional chemotherapy; therefore, salvage therapy is required. In recent years, targeted therapies such as ALK inhibitors and brentuximab vedotin (BV) have been developed. ALK inhibitors block the continuous activation of ALK kinase, a driver mutation that leads to cell proliferation in ALK-positive ALCL. Additionally, BV is an antibody–drug conjugate that targets CD30-positive cells. Both ALK inhibitors and BV have displayed dramatic effects in chemoresistant ALK-positive ALCL. Weekly vinblastine treatment and hematopoietic stem cell transplantation have also been reported to be effective therapies. 
  • 587
  • 29 Dec 2023
Topic Review
Invasive Mucormycosis in Patients with Hematological Malignancies
The incidence rate of invasive mucormycosis (IM) in patients with hematological malignancies (HMs) is increasing year by year, ranging from 0.07% to 4.29%, and the mortality rate is mostly higher than 50%. With the ongoing pandemic of COVID-19, COVID-19-associated mucormycosis (CAM) also became a global health threat.
  • 585
  • 30 May 2023
Topic Review
Hematopoietic Stem Cell Transplant
Hematopoietic stem cell transplantation (HSCT) or Bone marrow transplantation is a medical procedure in the field of hematology and oncology that involves transplantation of hematopoietic stem cells (HSC). It is most often performed for people with diseases of the blood or bone marrow, or certain types of cancer. Bone marrow transplantation was pioneered at the Fred Hutchinson Cancer Research Center from the 1950s through the 1970s by E. Donnall Thomas, whose work was later recognized with a Nobel Prize in Physiology and Medicine. Dr. Thomas' work showed that bone marrow cells infused intravenously could repopulate the bone marrow and produce new blood cells. His work also reduced the likelihood of developing a life-threatening complication called Graft-versus-host disease. Since the early 1990s and the availability of the stem cell growth factors GM-CSF and G-CSF, most hematopoeitic stem cell transplantation procedures have been performed with stem cells collected from the peripheral blood. Collecting stem cells provides a bigger graft, and does not require that the donor be subjected to general anesthesia to collect the graft. Hematopoeitic stem cell transplantation remains a risky procedure and has always been reserved for patients with life threatening diseases.
  • 583
  • 11 Nov 2022
Topic Review
Krüppel-Like Factor 1 in Erythropoiesis
Krüppel-like factor 1 (KLF1) is an erythroid-specific transcription factor that plays a crucial role in erythropoiesis. Isolated for the first time from mouse erythroleukemia cell line (MEL), it was originally named erythroid Krüppel-like factor (EKLF). When related Krüppel-like factors were subsequently identified, the nomenclature was changed to KLF1 to reflect the order of discovery. The human KLF1 gene is located on chromosome 19p13.2, whilst the mouse Klf1 gene is located on chromosome 8. KLF1 is a master erythroid gene regulator whose relevance in erythroid development and haemoglobin switching became clear as soon as the first Klf1 KO mouse models were characterised. The process of erythropoiesis occurs in different organs during mammalian embryonic development. Primitive erythropoiesis occurs in the yolk sac, in which primitive erythroid precursors (i.e., erythroid-colony-forming cells, Ery-CFCs) arise and further differentiate in the bloodstream. Definitive erythropoiesis occurs in the foetal liver until birth and subsequently in the bone marrow. Definitive erythroblasts mature in specialised niches called erythroblastic islands, which are characterised by the central macrophages of erythroid islands (CMEIs) surrounded by maturing erythroblasts, which play a fundamental role in erythropoiesis homeostasis and nuclei digestion. Both Ery-CFC and definitive erythroid progenitors (BFU-E/CFU-E), undergo a further phase of differentiation, called terminal erythropoiesis starting from large nucleated cells, proerythroblasts, that differentiate to basophil, then polychromatic and, finally, orthochromatic erythroblasts.
  • 582
  • 20 Oct 2022
Topic Review
CD123 in Blastic Plasmacytoid Dendritic Cell Neoplasm
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic cancer originating from the malignant transformation of plasmacytoid dendritic cell precursors. The exploration of combinations such as CD123-targeted immunotherapies with azacitidine and venetoclax is suggested to enhance antineoplastic responses and improve survival rates in BPDCN patients.
  • 581
  • 30 Jan 2024
Topic Review
Microbiome Environments and Lymphomagenesis
The gut microbiome is increasingly being recognized as an important immunologic environment, with direct links to the host immune system. The scale of the gut microbiome’s genomic repertoire extends the capacity of its host’s genome by providing additional metabolic output, and the close communication between gut microbiota and mucosal immune cells provides a continued opportunity for immune education. The relationship between the gut microbiome and the host immune system has important implications for oncologic disease, including lymphoma, a malignancy derived from within the immune system itself.
  • 576
  • 28 Feb 2023
Topic Review
Infections Secondary to Targeted Therapies in Hematological Malignancies
Concurrent infections in hematological malignancies (HM) are major contributors to adverse clinical outcomes, including prolonged hospitalization and reduced life expectancy. Individuals diagnosed with HM are particularly susceptible to infectious pathogens due to immunosuppression, which can either be inherent to the hematological disorder or induced by specific therapeutic strategies. The treatment paradigm for HM has witnessed a tremendous shift, from broad-spectrum treatment approaches to more specific targeted therapies. The therapeutic landscape of HM is constantly evolving due to the advent of novel targeted therapies and the enhanced utilization of these agents for treatment purposes. By initiating unique molecular pathways, these agents hinder the proliferation of malignant cells, consequently affecting innate and adaptive immunity, which increases the risk of infectious complications.
  • 572
  • 12 Jun 2023
Topic Review
COVID-19 and Adult Acute Leukemia
The majority of publications regarding SARS-CoV-2 infections in adult patients with acute leukemia (AL) refer to hematological patients in general and are not focused on acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). Overall, SARS-CoV-2-associated mortality ranges from 20–52% in patients with adult AL. AML patients have a particularly high COVID-19-related mortality. Of note, most of the available data relate to the pre-vaccination era and to variants before Omicron. The impact of COVID-19 infections on AL treatment is rarely reported. Treatment delay does not appear to be associated with an increased risk of relapse, whereas therapy discontinuation was associated with worse outcomes in AML patients. Therefore, the recommendations suggest delaying systemic AL treatment in SARS-CoV-2-positive patients until SARS-CoV-2 negativity, if immediate AL treatment is not required. It is recommended to offer vaccination to all AL patients; the reported antibody responses are around 80–96%. Seronegative patients should additionally receive prophylactic administration of anti-SARS-CoV-2 monoclonal antibodies. Patients with AL infected with SARS-CoV-2 should be treated early with antiviral therapy to prevent disease progression and enable the rapid elimination of the virus.
  • 571
  • 11 Aug 2022
Topic Review
Predisposing Factors of B-Cell Non-Hodgkin’s Lymphoma
In pSS, chronic antigenic stimulation gradually drives the evolution from polyclonal B-cell expansion to oligoclonal/monoclonal B-cell predominance to malignant B-cell transformation. Thus, most pSS-related lymphomas are B-cell non-Hodgkin lymphomas (NHLs), with mucosa-associated lymphoid tissue (MALT) lymphomas predominating, followed by diffuse large B-cell lymphomas (DLBCLs) and nodal marginal zone lymphomas (NMZLs).
  • 570
  • 10 Nov 2022
Topic Review
Non-Coding RNAs in Myelodysplastic Neoplasms
Myelodysplastic syndromes or neoplasms (MDS) are a heterogeneous group of myeloid clonal disorders characterized by peripheral blood cytopenias, blood and marrow cell dysplasia, and increased risk of evolution to acute myeloid leukemia (AML). Non-coding RNAs, especially microRNAs and long non-coding RNAs, serve as regulators of normal and malignant hematopoiesis and have been implicated in carcinogenesis.
  • 568
  • 16 Oct 2023
Biography
Jan Evangelista Dyr
Jan was born on 24 September 1946 in Prague, Czechoslovakia. He obtained his undergraduate degree in Macromolecular Chemistry from the University of Chemistry and Technology in Prague in 1969. Then, he earned a Ph.D. in Physical Chemistry in 1978 from Charles University and a DrSc. in Chemistry in 1994 from the Academy of Sciences of the Czech Republic. In 1984 he became the Head of the Departm
  • 561
  • 31 Aug 2022
Topic Review
Autologous Stem Cell Transplantation in Multiple Myeloma
Multiple myeloma (MM) is a clonal plasma cells hematologic malignancy. The introduction of high-dose therapy in the 1990s as well as the development of drugs such as thalidomide, lenalidomide, and bortezomib in the 2000s led to an impressive improvement in outcome of patients with multiple myeloma (MM) eligible for autologous stem cell transplantation (ASCT). Clinical trials conducted in the first ten years of the twenty-first century established as standard therapy for these patients a therapeutic approach including induction, single or double ASCT, consolidation, and maintenance therapy. More recently, incorporating second-generation proteasome inhibitors carfilzomib and monoclonal antibody daratumumab into each phase of treatment significantly improved the efficacy of ASCT in terms of measurable residual disease (MRD) negativity, Progression Free Survival (PFS), and Overall Survival (OS). 
  • 557
  • 07 Mar 2022
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