Review Highlights

  • REVIEW2024-03-08

    0 178 57

    Genomic testing for germline predisposition to hematologic malignancies

    Sang Mee Hwang

    Blood Res 2024; 59():
    Abstract

    Abstract : Germline predisposition (GPD) to hematological malignancies has gained interest because of the increased use of genetic testing in this field. Recent studies have suggested that GPD is underrecognized and requires appropriate genomic testing for an accurate diagnosis. Identification of GPD significantly affects patient management and has diverse implications for family members. This review discusses the reasons for testing GPD in hematologic malignancies and explores the considerations necessary for appropriate genomic testing. The aim is to provide insights into how these genetic insights can inform treatment strategies and genetic counseling, ultimately enhancing patient care.

  • REVIEW2024-03-06

    0 215 55

    The role of next-generation sequencing in hematologic malignancies

    Young‑Uk Cho

    Blood Res 2024; 59():
    Abstract

    Abstract : Next-generation sequencing (NGS) allows high-throughput detection of molecular changes in tumors. Over the past 15 years, NGS has rapidly evolved from a promising research tool to a core component of the clinical laboratory. Sequencing of tumor cells provides an important step in detecting somatic driver mutations that not only characterize the disease but also influence treatment decisions. For patients with hematologic malignancies, NGS has been used for accurate classification and diagnosis based on genetic alterations. The recently revised World Health Organization classification and the European LeukemiaNet recommendations for acute myeloid leukemia consider genetic abnormalities as a top priority for diagnosis, prognostication, monitoring of measurable residual disease, and treatment choice. This review aims to present the role and utility of various NGS approaches for the diagnosis, treatment, and follow-up of hemato-oncology patients.

  • REVIEW2024-02-13

    0 557 102

    Genomic technologies for detecting structural variations in hematologic malignancies

    Mi‑Ae Jang

    Blood Res 2024; 59():
    Abstract

    Abstract : Genomic structural variations in myeloid, lymphoid, and plasma cell neoplasms can provide key diagnostic, prognostic, and therapeutic information while elucidating the underlying disease biology. Several molecular diagnostic approaches play a central role in evaluating hematological malignancies. Traditional cytogenetic diagnostic assays, such as chromosome banding and fluorescence in situ hybridization, are essential components of the current diagnostic workup that guide clinical care for most hematologic malignancies. However, each assay has inherent limitations, including limited resolution for detecting small structural variations and low coverage, and can only detect alterations in the target regions. Recently, the rapid expansion and increasing availability of novel and comprehensive genomic technologies have led to their use in clinical laboratories for clinical management and translational research. This review aims to describe the clinical relevance of structural variations in hematologic malignancies and introduce genomic technologies that may facilitate personalized tumor characterization and treatment.

  • Review Article2023-12-31

    2 940 381

    Recent advances in cellular immunotherapy for lymphoid malignancies

    Haerim Chung, Hyunsoo Cho

    Blood Res 2023; 58(4): 166-172
    Abstract

    Abstract : Cellular immunotherapy with chimeric antigen receptor (CAR) T-cells has revolutionized the treatment of lymphoid malignancies. This review addresses the need for CAR expression in our endogenous T-cells to kill tumor cells with a focus on the basic principles of T-cell receptor recognition of major histocompatibility complex-peptide complexes. We review the factors associated with CAR T-cell outcomes and recent efforts to employ CAR T-cells in earlier lines of therapy. We also discuss the value of bispecific T-cell engagers as off-the-shelf products with better toxicity profiles. Finally, natural killer cells are discussed as an important cellular immunotherapy platform with the potential to broaden immunotherapeutic applications beyond lymphoid malignancies.

  • Review Article2023-04-30

    3 2634 562

    Transfusion support in hematopoietic stem cell transplantation

    Dong Wook Jekarl, Jae Kwon Kim, Jay Ho Han, Howon Lee, Jaeeun Yoo, Jihyang Lim, Yonggoo Kim

    Blood Res 2023; 58(S1): S1-S7
    Abstract

    Abstract : Transfusion support for hematopoietic stem cell transplantation (HSCT) is an essential part of supportive care, and compatible blood should be transfused into recipients. As leukocyte antigen (HLA) matching is considered first and as the blood group does not impede HSCT, major, minor, bidirectional, and RhD incompatibilities occur that might hinder transfusion and cause adverse events. Leukocyte reduction in blood products is frequently used, and irradiation should be performed for blood products, except for plasma. To mitigate incompatibility and adverse events, local transfusion guidelines, hospital transfusion committees, and patient management should be considered.

  • Review Article2023-04-30

    0 1504 201

    Transfusion thresholds: the need for a patient-centered approach in hematologic disorders that require chronic transfusion therapy

    Han Joo Kim, Sang-Hyun Hwang, Heung-Bum Oh, Dae-Hyun Ko

    Blood Res 2023; 58(S1): S8-S10
    Abstract

    Abstract : Transfusion is an essential life-sustaining treatment for many patients. However, unnecessary transfusion has been reported to be related to worse patient outcomes. Further, owing to the recent pandemic, blood supply has been more challenging to maintain. Many studies have been conducted to elucidate the optimal transfusion threshold for many clinical conditions, and most suggested that a restrictive transfusion strategy has advantages over a liberal transfusion strategy. Hematologic disorders, which require chronic transfusion in many cases, have not been the main subjects of such studies, and only little evidence is available regarding the optimal transfusion threshold in these patients. According to several recent studies, a liberal transfusion strategy is preferable for patients with hematologic disorders due to their quality of life. A patient-centered approach is needed for proper management of hematologic disorders.

  • Review Article2023-04-30

    6 2570 485

    Practical issues in CAR T-cell therapy

    Ja Min Byun

    Blood Res 2023; 58(S1): S11-S12

    Abstract : Chimeric antigen receptor (CAR) T-cell therapy presents a revolutionary advancement in personalized cancer treatment. During the production process, the patient's own T-cells are genetically engineered to express a synthetic receptor that binds to a tumor antigen. CAR T-cells are then expanded for clinical use and infused back into the patient's body to attack cancer cells. Although CAR T-cell therapy is considered a major breakthrough in cancer immunotherapy, it is not without limitations. In this review, we discuss the barriers to effective CAR T-cell therapy in Korea.

  • Review Article2023-04-30

    1 2740 767

    Novel therapeutics for myelofibrosis

    Sung-Eun Lee

    Blood Res 2023; 58(S1): S13-S19
    Abstract

    Abstract : Myelofibrosis (MF) includes primary MF, post-essential thrombocythemia MF, and post-polycythemia vera MF. MF is a progressive myeloid neoplasm characterized by ineffective clonal hematopoiesis, extramedullary hematopoiesis, a reactive bone marrow environment resulting in reticulin deposition and fibrosis, and a propensity for leukemia transformation. The identification of driver mutations in JAK2, CALR, and MPL has contributed to a better understanding of disease pathogenesis and has led to the development of MF-specific therapies, such as JAK2 inhibitors. Despite the fact that ruxolitinib and fedratinib have been clinically developed and approved, their use is limited due to adverse effects such as anemia and thrombocytopenia. Recently, pacritinib has been approved for a group of thrombocytopenic patients with significant unmet clinical needs. In symptomatic and anemic patients with prior JAK inhibitor exposure, momelotinib was superior to danazol in preventing exacerbation of anemia and in controlling MF-associated signs and symptoms, such as spleen size. Although the development of JAK inhibitors is remarkable, modifying the natural course of the disease remains a priority. Therefore, many novel treatments are currently under clinical development. Agents targeting bromodomain and extra-terminal protein, anti-apoptotic protein Bcl-xL, and phosphatidylinositol-3-kinase delta have been studied in combination with JAK inhibitors. These combinations have been employed in both the frontline and “add-on” approaches. In addition, several agents are being studied as monotherapies for ruxolitinib-resistant or -ineligible patients. We reviewed several new MF treatments in the advanced stages of clinical development and treatment options for cytopenic patients.

  • Review Article2023-04-30

    3 1921 680

    Management of adverse events in young adults and children with acute B-cell lymphoblastic leukemia receiving anti-CD19 chimeric antigen receptor (CAR) T-cell therapy

    Jae Won Yoo

    Blood Res 2023; 58(S1): S20-S28
    Abstract

    Abstract : With impressive clinical advancements in immune effector cell therapies targeting CD19, chimeric antigen receptor (CAR) T-cell therapy has emerged as a new paradigm for treating relapsed/refractory B-cell malignancies. Currently, three second-generation CAR T-cell therapies have been approved, of which only tisagenlecleucel (tisa-cel) is approved for treating children and young adults with B-cell acute lymphoblastic leukemia (ALL) with durable remission rates of approximately 60‒90%. Although CAR T-cell therapies are considered to treat refractory B-ALL, they are associated with unique toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The severity of CAR T-cell therapy toxicities can vary according to several clinical factors. In rare cases, severe CRS can progress to a fulminant hyperinflammatory syndrome known as hemophagocytic lymphohistiocytosis, which has a poor prognosis. The first-line treatments for CRS/ICANS include tocilizumab and corticosteroids. When severe CAR T-cell toxicity is resistant to first-line treatment, an additional approach is required to manage the persistent inflammation. In addition to CRS/ICANS, CAR T-cell therapy can cause early and delayed hematological toxicity, which can predispose patients to severe infections. The use of growth factors and anti-infective prophylaxis should follow institutional guidelines according to patient-specific risk factors. This review provides a thorough summary of updated practical recommendations for managing acute and delayed adverse effects following anti-CD19 CAR T-cell therapy in adults and children.

  • Review Article2023-04-30

    4 2459 726

    Asciminib: the first-in-class allosteric inhibitor of BCR::ABL1 kinase

    Eun-Ji Choi

    Blood Res 2023; 58(S1): S29-S36
    Abstract

    Abstract : The prognosis of patients with chronic phase (CP) chronic myeloid leukemia (CML) has significantly improved due to the development of potent BCR::ABL1 tyrosine kinase inhibitors (TKIs). However, approximately 15‒20% of patients ultimately experience treatment failure due to resistance or intolerance to TKI therapy. As the prognosis of patients in whom multiple TKIs fail remains poor, an optimal therapeutic approach is required to treat the condition. Asciminib, an allosteric inhibitor that targets ABL1 myristoyl pocket, has been approved by the Food and Drug Administration for use in patients with CP-CML resistant or intolerant to ≥2 prior TKIs or those with T315I mutation. In a phase 1 trial, asciminib monotherapy showed a relatively favorable safety profile and potent efficacy in patients with and without the T315I mutation. In a subsequent phase 3 trial, asciminib treatment was associated with a significantly higher major molecular response rate and lower discontinuation rate than bosutinib in patients with CP-CML for whom two previous TKIs failed. Several clinical trials are being performed in various clinical settings to evaluate the role of asciminib as a frontline treatment for newly diagnosed CP-CML, either as a single agent or in combination with other TKIs as a second-line or additive treatment to improve treatment-free or deep remission. This review summarizes the incidence, available therapies, and outcomes of patients with CP-CML who experienced treatment failure, the mechanism of action, preclinical and clinical data, and ongoing trials for asciminib.

Blood Res
Volume 59 2024

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pISSN 2287-979X
eISSN 2288-0011
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