Current Issue

  • REVIEW 2024-02-13

    0 867 141
    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.

  • RESEARCH 2024-02-19

    0 547 92

    Adding MYC/BCL2 double expression to NCCN-IPI may not improve prognostic value to an acceptable level

    Naree Warnnissorn, Nonglak Kanitsap, Pimjai Niparuck, Paisarn Boonsakan, Prapasri Kulalert, Wasithep Limvorapitak, Lantarima Bhoopat, Supawee Saengboon, Chinnawut Suriyonplengsaeng, Pichika Chantrathammachart, Teeraya Puavilai and Suporn Chuncharunee

    Blood Res (2024) 59:2
    Abstract

    Abstract : Background MYC/BCL2 double expression (DE) is associated with poor prognosis in patients with diffuse large B-cell lymphoma (DLBCL) receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). This study aimed to determine whether the addition of DE to the National Comprehensive Cancer Network Internal Prognostic Index (NCCN-IPI) could improve the prediction of disease progression in patients with DLBCL treated with R-CHOP.
    Methods This confirmatory prognostic factor study retrospectively recruited patients with newly diagnosed DLBCL between January 1, 2014, and January 31, 2018, at Ramathibodi Hospital (RA) and Thammasat University Hospital (TU). The follow-up period ended on July 1, 2022. Tumors expressing MYC ≥ 40% and BCL2 ≥ 50% were classified as DE. We calculated the hazard ratios (HR) for progression-free survival (PFS) from the date of diagnosis to refractory disease, relapse, or death. Discrimination of the 5-year prediction was based on Cox models using Harrell’s concordance index (c-index).
    Results A total of 111 patients had DE (39%), NCCN-IPI (8%), and disease progression (46%). The NCCN-IPI adjusted HR of DE was 1.6 (95% confidence interval [CI]: 0.9–2.8; P = 0.117). The baseline NCCN-IPI c-index was 0.63. Adding DE to the NCCN-IPI slightly increased Harrell’s concordance index (c-index) to 0.66 (P = 0.119).
    Conclusions Adding DE to the NCCN-IPI may not improve the prognostic value to an acceptable level in resource-limited settings. Multiple independent confirmatory studies from a large cohort of lymphoma registries have provided additional evidence for the clinical utility of DE.

  • RESEARCH 2024-02-19

    0 481 105

    Real-world incidence and risk factors of bortezomib-related cardiovascular adverse events in patients with multiple myeloma

    Bitna Jang, Jonghyun Jeong, Kyu‑Nam Heo, Youngil Koh and Ju‑Yeun Lee

    Blood Res (2024) 59:3
    Abstract

    Abstract : Background Although most studies on the cardiovascular toxicity of proteasome inhibitors have focused on carfilzomib, the risk of cardiotoxicity associated with bortezomib remains controversial. This study aimed to evaluate the incidence and risk factors of cardiovascular adverse events (CVAEs) associated with bortezomib in patients with multiple myeloma in a real-world setting.
    Methods This cross-sectional study included patients who were treated with bortezomib at a tertiary hospital in South Korea. CVAEs, defined as hypertension, arrhythmia, heart failure, myocardial infarction, pulmonary arterial hypertension, angina, and venous thromboembolism, were detected using cardiac markers, ECG, echocardiography, medications, or documentation by clinicians. The patients were observed for at least 6 months and up to 2 years after starting bortezomib administration.
    Results Among the 395 patients, 20.8% experienced CVAEs of any grade, and 14.7% experienced severe adverse events. The median onset time for any CVAE was 101.5 days (IQR, 42–182 days), and new-onset/worsened hypertension was the most prevalent CVAE. The risk of CVAEs increased in patients with a body mass index lower than 18.5 (adjusted HR (aHR) 3.50, 95% confidence interval (CI) 1.05-11.72), light chain (1.80, 1.04-3.13), and IgD (4.63, 1.06-20.20) as the multiple myeloma subtype, baseline stroke (4.52, 1.59-12.80), and hypertension (1.99, 1.23-3.23). However, CVAEs did not significantly affect the 2-year overall survival and progression-free survival.
    Conclusion Approximately 15% of the Korean patients treated with bortezomib experienced severe CVAEs. Thus, patients, especially those with identified risk factors, should be closely monitored for CVAE symptoms during bortezomib treatment.

  • RESEARCH 2024-02-19

    0 314 89

    Upregulation of lnc-FOXD2-AS1, CDC45, and CDK1 in patients with primary non-M3 AML is associated with a worse prognosis

    Saba Manoochehrabadi, Morteza Talebi, Hossein Pashaiefar, Soudeh Ghafouri‑Fard, Mohammad Vaezi, Mir Davood Omrani and Mohammad Ahmadvand

    Blood Res (2024) 59:4
    Abstract

    Abstract : Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy with an unfavorable outcome. The present research aimed to identify novel biological targets for AML diagnosis and treatment. In this study, we performed an in-silico method to identify antisense RNAs (AS-RNAs) and their related co-expression genes. GSE68172 was selected from the AML database of the Gene Expression Omnibus and compared using the GEO2R tool to find DEGs. Antisense RNAs were selected from all the genes that had significant expression and a survival plot was drawn for them in the GEPIA database, FOXD2-AS1 was chosen for further investigation based on predetermined criteria (logFC ≥|1| and P < 0.05) and its noteworthy association between elevated expression level and a marked reduction in the overall survival (OS) in patients diagnosed with AML. The GEPIA database was utilized to investigate FOXD2-AS1-related co-expression and similar genes. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and gene ontology (GO) function analysis of the mentioned gene lists were performed using the DAVID database. The protein–protein interaction (PPI) network was then constructed using the STRING database. Hub genes were screened using Cytoscape software. Pearson correlation analysis was conducted using the GEPIA database to explore the relationship between FOXD2-AS1 and the hub genes. The transcription of the selected coding and non-coding genes, including FOXD2-AS1, CDC45, CDC20, CDK1, and CCNB1, was validated in 150 samples, including 100 primary AML non-M3 blood samples and 50 granulocyte colony stimulating factor (G-CSF)-mobilized healthy donors, using quantitative Real-Time PCR (qRT-PCR). qRT-PCR results displayed significant upregulation of lnc-FOXD2-AS1, CDC45, and CDK1 in primary AML non-M3 blood samples compared to healthy blood samples (P = 0.0032, P = 0.0078, and P = 0.0117, respectively). The expression levels of CDC20 and CCNB1 were not statistically different between the two sets of samples (P = 0.8315 and P = 0.2788, respectively). We identified that AML patients with upregulation of FOXD2-AS1, CDK1, and CDC45 had shorter overall survival (OS) and Relapse-free survival (RFS) compared those with low expression of FOXD2-AS1, CDK1, and CDC45. Furthermore, the receiver operating characteristic (ROC) curve showed the potential biomarkers of lnc -FOXD2-AS1, CDC45, and CDK1 in primary AML non-M3 blood samples. This research proposed that the dysregulation of lnc-FOXD2-AS1, CDC45, and CDK1 can contribute to both disease state and diagnosis as well as treatment. The present study proposes the future evolution of the functional role of lnc-FOXD2-AS1, CDC45, and CDK1 in AML development.

  • IMAGE 2024-02-26

    0 283 62

    Peripheral T-cell lymphoma, NOS in bone marrow and heart

    Hye Won Lee and Ja Young Lee

    Blood Res (2024) 59:5
  • RESEARCH 2024-02-26

    0 338 78

    Comparable outcomes with low‑dose and standard‑dose horse anti‑thymocyte globulin in the treatment of severe aplastic anemia

    Arihant Jain, Aditya Jandial, Thenmozhi Mani, Kamal Kishore, Charanpreet Singh, Deepesh Lad, Gaurav Prakash, Alka Khadwal, Reena Das, Neelam Varma, Subhash Varma and Pankaj Malhotra

    Blood Res (2024) 59:6
    Abstract

    Abstract : Background The standard dose (SD) of horse anti-thymocyte globulin (hATG) ATGAM (Pfizer, USA) or its biosimilar thymogam (Bharat Serum, India) for the treatment of Aplastic Anemia (AA) is 40 mg/kg/day for 4 days in combination with cyclosporine. Data on the impact of hATG dose on long-term outcomes are limited. Here, we describe our comparative experience using 25 mg/kg/day (low-dose [LD]) hATG for 4 days with SD for the treatment of AA.
    Methods We retrospectively studied patients with AA (age > 12 years) who received two doses of hATG combined with cyclosporine. Among 93 AA patients who received hATG, 62 (66.7%) and 31 (33.3%) patients received LD and SD hATG with cyclosporine, respectively. Among these,seventeen(18.2%) patients also received eltrombopag with hATG and cyclosporine. Overall response rates [complete response (CR) and partial response (PR)] of LD and SD hATG groups at 3 months (50% vs. 48.4%; p = 0.88), 6 months (63.8% vs. 71.4%; p = 0.67), and 12 months (69.6% vs. 79.2%; p = 0.167) were comparable. The mean (Standard Deviation) 5-year Kaplan–Meier estimate of overall survival and event-free survival was 82.1 (4.6)% and 70.9 (5.5)% for the study population. The mean (standard deviation) 5-year Kaplan–Meier estimate of overall survival and event-free survival of those who received LD hATG versus SD hATG dose was 82.9 (5·3)% versus 74.8 (10·3)% (P = 0·439), and 75.2 (6.2)% versus 61.4(11.2)% (P = 0·441).
    Conclusion Our study revealed that the response rates of patients with AA and LD were similar to those of patients with SD to hATG combined with cyclosporine in a real-world setting.

  • IMAGE 2024-02-28

    0 195 90

    Gaucher or pseudo-Gaucher cells

    Gurpreet Kaur, Ankur Ahuja, Ganesh Kumar Vishwananthan and Arijit Sen

    Blood Res (2024) 59:7
  • RESEARCH 2024-03-01

    0 450 98

    Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) gene polymorphisms in a cohort of Egyptian patients with immune thrombocytopenia (ITP)

    Doaa Mohamed El Demerdash , Maha Mohamed Saber, Alia Ayad, Kareeman Gomaa and Mohamed Abdelkader Morad

    Blood Res (2024) 59:8
    Abstract

    Abstract : Background Immune thrombocytopenia (ITP) is characterized by immune response dysregulations. Cytotoxic T lymphocyte‐associated antigen‐4 (CTLA‐4) plays a central role in immune checkpoint pathways and preventing autoimmune diseases by regulating immune tolerance. We aimed to explore the potential association between CTLA-4 gene polymorphisms and ITP as well as study their impact on the response to therapy.
    Methods We investigated two CTLA-4 single‐nucleotide polymorphisms (SNPs; rs: 231775 and rs: 3087243) using real-time PCR as well as the plasma levels of CTLA-4 by ELISA in 88 patients with ITP and 44 healthy participants (HC).
    Results CTLA-4 (rs: 3087243) A > G polymorphism analysis showed most HC had the homozygous AA genotype, which was statistically significant compared to patients with ITP. Plasma levels of CTLA4 were statistically lower in patients with acute ITP. There was no correlation between CTLA-4 (rs: 231775 and rs: 3087243) A/G SNPs were not correlated to the response to all lines of therapy assessed (corticosteroids, thrombopoietin receptor agonists, splenectomy, and rituximab).
    Conclusion CTLA-4 CT 60 A/G may affect the susceptibility of ITP, but both CTLA-4 + 49 A/G and CT60 A/G did not impact the response of patients with ITP to different lines of therapy.

  • RESEARCH 2024-03-04

    0 460 66

    Impact of CYP1A1 variants on the risk of acute lymphoblastic leukemia: evidence from an updated meta-analysis

    Imen Frikha, Rim Frikha, Moez Medhaffer, Hanen Charfi, Fatma Turki and Moez Elloumi

    Blood Res (2024) 59:9
    Abstract

    Abstract : Objective Our study aimed to investigate the association between cytochrome P450 1A1 (CYP1A1) polymorphisms (T3801C and A2455G) and acute lymphoblastic leukemia (ALL) risk, considering genetic models and ethnicity.
    Materials and methods PubMed, Embase, Web of Knowledge, Scopus, and the Cochrane electronic databases were searched using combinations of keywords related to CYP1A1 polymorphisms and the risk of ALL. Studies retrieved from the database searches underwent screening based on strict inclusion and exclusion criteria.
    Results In total, 2822 cases and 4252 controls, as well as 1636 cases and 2674 controls of the C3801T and A2455G variants of CYP1A1, respectively, were included in this meta-analysis. The T3801C polymorphism of CYP1A1 significantly increases the risk of ALL, particularly those observed in Asian and Hispanic populations, independent of age. Similarly, the A2455G polymorphism of CYP1A1 plays a significant role in the susceptibility to ALL in all genetic models, except the heterozygous form. This association was observed mainly in mixed populations and in both children and adults (except in the heterozygous model).
    Conclusion Our comprehensive analysis indicates that the T3801 and A2455G polymorphisms of CYP1A1 may increase the risk of ALL depending on ethnicity. Therefore, both variants should be considered promising biomarkers for ALL risk. Further large-scale investigations are necessary to assess other factors, such as gene-gene or gene-environment interactions.

  • IMAGE 2024-03-06

    0 380 62

    Acute erythroid leukemia leading to the diagnosis of Schwachman-Diamond syndrome

    Bernhard Strasser, Sebastian Mustafa, Josef Tomasits and Alexander Haushofer

    Blood Res (2024) 59:10
  • REVIEW 2024-03-06

    1 477 77
    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.

  • REVIEW 2024-03-08

    0 427 109
    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.

  • IMAGE 2024-03-25

    0 132 68
  • REVIEW 2024-04-12

    0 125 41

    Transfusion-transmitted infections

    Han Joo Kim and Dae‑Hyun Ko

    Blood Res (2024) 59:14
    Abstract

    Abstract : The risk of transfusion-transmitted infection (TTI) has always existed because transfused blood products are biological materials derived from humans. To prevent TTIs, screening strategies have been developed for various infectious diseases, such as hepatitis B virus, hepatitis C virus, and human immunodeficiency virus, contributing significantly to reducing TTI globally. Nevertheless, septic transfusion reactions (STRs) due to bacterial contamination remain an unresolved issue. Various infectious diseases can be transmitted through blood products, and preventive and selective screening strategies have been applied across different regions. Although multiple strategies, including culture-based and rapid detection kit-based methods, have been introduced to overcome STRs, complete prevention has not yet been achieved. Recently, pathogen inactivation methods have been developed to eliminate non-specific organisms rather than screening specific organisms. This approach is anticipated to contribute significantly to diminishing the risk of TTIs in the future.

  • REVIEW 2024-04-15

    0 146 62

    What is new in acute myeloid leukemia classification?

    Hee Sue Park

    Blood Res (2024) 59:15
    Abstract

    Abstract : Recently, the International Consensus Classification (ICC) and the 5th edition of the World Health Organization classification (WHO2022) introduced diagnostically similar yet distinct approaches, which has resulted in practical confusion. This review compares these classification systems for acute myeloid leukemia (AML), building up on the revised 4th edition of WHO (WHO2016). Both classifications retain recurrent genetic abnormalities as a primary consideration. However, they differ in terms of blast threshold. The ICC mandates a minimum of 10% blasts in the bone marrow or peripheral blood, whereas the WHO2022 does not specify a blast cut-off. AML with BCR::ABL1 requires > 20% blast count in both classifications. In WHO2022, AML with CEBPA mutation requires > 20% blasts. TP53 mutation, a new entity is exclusive to ICC, diagnosed with > 20% blasts and variant allele frequency > 10%. AML with myelodysplasia-related changes is defined by cytogenetic or gene mutation-based criteria, not morphological dysplasia. Eight genes were common to both groups: ASXL1, BCOR, EZH2, SF3B1, SRSF2, STAG2, U2AF1, and ZRSR2. An additional gene, RUNX1, was included in the ICC classification. AML cases defined by differentiation (WHO2022) and AML not otherwise specified (ICC) are categorized as lacking specific defining genetic abnormalities, WHO2022 labels this as a myeloid neoplasm post cytotoxic therapy (MN-pCT), described as an appendix after specific diagnosis. Similarly, in ICC, it can be described as “therapy-related”, without a separate AML category.

  • RESEARCH 2024-04-16

    1 86 51

    Abnormal frequency of the memory B cell subsets and plasmablasts in patients with congenital severe hemophilia A: correlation with “Inhibitor” formation

    Omid Reza Zekavat, Yasaman Movahednezhad, Amin Shahsavani, Sezaneh Haghpanah, Negin Shokrgozar, Hossein Golmoghaddam, Mehdi Kalani, Mohammad Reza Bordbar and Nargess Arandi

    Blood Res (2024) 59:16
    Abstract

    Abstract : Background Development of antibodies against infused Factor VIII (FVIII) or "inhibitors" represents a major challenge following FVIII replacement therapy in patients with hemophilia A (HA). Recent studies have shown that certain cellular compartments of the immune system contribute to the production of such antibodies. Herein, we determined the frequency of class-switched CD19+IgDCD27+/non-class-switched CD19+IgD+CD27+ memory B cell subsets and CD19+CD27hiCD38hi plasmablasts in patients with severe HA and their association with the development of inhibitors in these patients.
    Methods This cross-sectional case–control study enrolled 32 patients with severe HA, including 8 with and 24 without inhibitors, and 24 healthy individuals. The frequencies of the memory B cell subsets and plasmablasts were determined using flow cytometry.
    Results The frequency of CD19+IgD+CD27+ non-class-switched memory B cells was significantly lower in patients with HA (including both patients with and without inhibitors) than in healthy controls. The percentages of both CD19+IgDCD27+ class-switched and CD19+IgD+CD27+ non-class-switched memory B cells did not differ significantly between patients with and without inhibitors. HA patients with inhibitors had significantly higher proportions of CD19+CD27hiCD38hi plasmablasts than the control group as well as the inhibitor (-) ones. No significant correlation was observed between the inhibitor levels with the percentages of memory B cell subsets and plasmablasts.
    Conclusion This study is the first to demonstrate a dysregulated proportion of CD19+IgD+CD27+ non-class-switched memory B cells and CD19+CD27hiCD38hi plasmablasts in patients with severe HA. Therefore, strategies targeting memory B-cell/plasmablast differentiation may have promising outcomes in the management of inhibitor formation in patients with severe HA.

  • REVIEW 2024-05-07

    0 121 31
    Abstract

    Abstract : Histiocytic and dendritic cell neoplasms comprise diverse tumors originating from the mononuclear phagocytic system, which includes monocytes, macrophages, and dendritic cells. The 5th edition of the World Health Organization (WHO) classification updating the categorization of these tumors, reflecting a deeper understanding of their pathogenesis.
    In this updated classification system, tumors are categorized as Langerhans cell and other dendritic cell neoplasms, histiocyte/macrophage neoplasms, and plasmacytoid dendritic cell neoplasms. Follicular dendritic cell neoplasms are classified as mesenchymal dendritic cell neoplasms within the stroma-derived neoplasms of lymphoid tissues.
    Each subtype of histiocytic and dendritic cell neoplasms exhibits distinct morphological characteristics. They also show a characteristic immunophenotypic profile marked by various markers such as CD1a, CD207/langerin, S100, CD68, CD163, CD4, CD123, CD21, CD23, CD35, and ALK, and hematolymphoid markers such as CD45 and CD43. In situ hybridization for EBV-encoded small RNA (EBER) identifies a particular subtype. Immunoprofiling plays a critical role in determining the cell of origin and identifying the specific subtype of tumors. There are frequent genomic alterations in these neoplasms, especially in the mitogen-activated protein kinase pathway, including BRAF (notably BRAF V600E), MAP2K1, KRAS, and NRAS mutations, and ALK gene translocation.
    This review aims to offer a comprehensive and updated overview of histiocytic and dendritic cell neoplasms, focusing on their ontogeny, morphological aspects, immunophenotypic profiles, and molecular genetics. This comprehensive approach is essential for accurately differentiating and classifying neoplasms according to the updated WHO classification.

  • RESEARCH 2024-05-14

    0 29 10

    Assessment of the phenotypic severity of hemophilia A: using rotational thromboelastometry (ROTEM) and APTT‑clot waveform analysis

    Deepika Gupta, Vandana Arya, Jasmita Dass, Nitin Gupta, Manas Kalra, Anupam Sachdeva and Jyoti Kotwal

    Blood Res (2024) 59:19
    Abstract

    Abstract : Background Hemophilia A (HA) is an X-linked inherited bleeding disorder caused by reduced factor VIII (FVIII) levels. Approximately 10–15% of patients with severe HA (SHA) do not present with the anticipated bleeding pattern. Here, we assessed the phenotypic severity of hemophilia A using rotational thromboelastometry (ROTEM) and activated partial thromboplastin time-clot waveform analysis (APTT-CWA).
    Methods Patients diagnosed with hemophilia A were enrolled. Clinical phenotype assignment was performed according to the published literature, and patients were classified into four phenotypic subgroups. The whole blood sample was first run on ROTEM in INTEM mode using platelet-poor plasma, APTT was run, and the APTT-CWA graph was simultaneously recorded.
    Results A total of 66 patients were recruited for this study. Statistically significant differences were observed between the four phenotypically categorized groups using ROTEM and APTT-CWA. On comparing patients with mild/moderate-to-severe phenotypes (Group II) with SHA without inhibitors (Group IV), no significant difference was found for all parameters of ROTEM or APTT-CWA. The MCF, MA30, MAXV, and Alpha angle values using ROTEM were found to be the lowest in patients with SHA with inhibitors, which helped differentiate them from those with SHA without inhibitors. However, these two groups could not be differentiated using the APTT-CWA parameters.
    Conclusion ROTEM can be used to distinguish patients with SHA with inhibitors from those with SHA without inhibitors using a combination of parameters with high sensitivity and specificity. However, APTT-CWA cannot be used to differentiate these patient groups.

  • CORRECTION ARTICLE 2024-05-27

    0 4 3
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