Review Highlights

  • Review Article2023-04-30

    1 1380 319

    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

    0 687 120

    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

    1 1289 307

    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

    0 1545 508

    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

    1 1186 428

    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

    2 1574 417

    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.

  • Review Article2023-04-30

    1 997 268

    Prognostication in myeloproliferative neoplasms, including mutational abnormalities

    Junshik Hong

    Blood Res 2023; 58(S1): S37-S45
    Abstract

    Abstract : Increasing knowledge of the molecular features of myeloproliferative neoplasms (MPNs) is being combined with existing prognostic models based on clinical, laboratory, and cytogenetic information. Mutation-enhanced international prognostic systems (MIPSS) for polycythemia vera (PV) and essential thrombocythemia (ET) have improved prognostic assessments. In the case of overt primary myelofibrosis (PMF), the MIPSS70 and its later revisions (MIPSS70+ and MIPSS70+ version 2.0) effectively predicted the overall survival (OS) of patients. Because post-PV and post-ET myelofibrosis have different biological and clinical courses compared to overt PMF, the myelofibrosis secondary to PV and ET-prognostic model was developed. Although these molecular-inspired prognostic models need to be further validated in future studies, they are expected to improve the prognostic power in patients with MPNs in the molecular era. Efforts are being made to predict survival after the use of specific drugs or allogeneic hematopoietic stem cell transplantation. These treatment outcome prediction models enable the establishment of personalized treatment strategies, thereby improving the OS of patients with MPNs.

  • Review Article2023-04-30

    0 925 288

    Current status of red blood cell manufacturing in 3D culture and bioreactors

    Soonho Kweon, Suyeon Kim, Eun Jung Baek

    Blood Res 2023; 58(S1): S46-S51
    Abstract

    Abstract : Owing to donor-related issues, blood shortages and transfusion-related adverse reactions have become global issues of grave concern. In vitro manufactured red blood cells (RBCs) are promising substitutes for blood donation. In the United Kingdom, a clinical trial for allogeneic mini transfusion of cultured RBCs derived from primary hematopoietic stem cells has recently begun. However, current production quantities are limited and need improved before clinical use. New methods to enhance manufacturing efficiencies have been explored, including different cell sources, bioreactors, and 3-dimensional (3D) materials; however, further research is required. In this review, we discuss various cell sources for blood cell production, recent advances in bioreactor manufacturing processes, and the clinical applications of cultured blood.

  • Review Article2023-04-30

    0 1409 375

    T-large granular lymphocytic leukemia

    Sang Hyuk Park, Yoo Jin Lee, Youjin Kim, Hyun-Ki Kim, Ji-Hun Lim, Jae-Cheol Jo

    Blood Res 2023; 58(S1): S52-S57

    Abstract : T-cell large granular lymphocyte (T-LGL) leukemia is characterized by clonal expansion of cytotoxic T cells resulting in cytopenia. The proliferation of clonal LGLs is caused by prolonged antigenic stimulation, which leads to apoptotic dysregulation owing mainly to the constitutive activation of survival pathways, notably the JAK/STAT pathway. Understanding how leukemic T-LGL persists can aid in the development of future immunosuppressive therapies. In this review, we summarize the diagnosis and current standard of therapy for T-LGL leukemia, as well as recent advances in clinical trials.

  • Review Article2023-04-30

    1 1494 441

    Treatment-free remission after discontinuation of imatinib, dasatinib, and nilotinib in patients with chronic myeloid leukemia

    Jae Joon Han

    Blood Res 2023; 58(S1): S58-S65
    Abstract

    Abstract : Patients with chronic myeloid leukemia (CML) in the chronic phase receiving tyrosine kinase inhibitor (TKI) therapy are expected to have long-term survival outcomes comparable to those of the general population. Many clinical trials have confirmed that some patients sustain molecular responses without continuing TKI therapy. Treatment-free remission (TFR) is a new goal in treating chronic CML. The safety and outcome of TFR were studied in clinical trials after discontinuing imatinib or the second-generation TKIs dasatinib or nilotinib. TFR was safe in approximately 50% of patients who achieved a deep molecular response to TKI therapy. Patients who relapsed after discontinuing TKI responded immediately to the reintroduction of TKI. The mechanism by which TFR increases the success rate still needs to be understood. The hypothesis that the modulation of immune function and targeting of leukemic stem cells could improve the TFR is under investigation. Despite the remaining questions, the TFR has become a routine consideration for clinicians in the practice of molecular remission in patients with CML.

Blood Res
Sep 30, 2023 Vol.58 No.3, pp. 125~164

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pISSN 2287-979X
eISSN 2288-0011
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