Acute myeloid leukemia (AML) is characterized by the rapid, unchecked clonal proliferation of myeloid precursor cells. It is the most common type of acute leukemia in adults and exhibits significant molecular heterogeneity. FLT3 mutations are among the most common and well-described genetic mutations in AML; they worsen overall survival and increase the relapse rate. Treatment options for FLT3-mutated AML are rapidly expanding, with an increasing number of FLT3 inhibitors being incorporated into treatment regimens. This review provides an overview of the role of FLT3 inhibitors in the current standard of care therapy in both the newly diagnosed and relapsed/refractory settings. Additionally, it highlights the areas of key ongoing investigations in the treatment of FLT3-mutated AML.
Cold agglutinin disease (CAD) is a rare form of autoimmune hemolytic anemia (AIHA) that accounts for approximately 15
Hereditary protein C deficiency, caused by pathogenic variants in the PROC gene, is a known risk factor for venous thrombosis. However, data on PROC variants in Asian populations are limited. This study evaluated the clinical relevance of rs146922325 and its association with thrombotic outcomes in Taiwanese patients. Using genotyping data from a single-nucleotide polymorphism array as part of the Taiwan Precision Medicine Initiative, we conducted a retrospective case–control study that included 805 carriers of the PROC rs146922325 variant and 8,050 age- and sex-matched non-carriers. The baseline characteristics, coagulation profiles, and thrombotic outcomes were systematically compared. Univariable and multivariable logistic regression analyses were performed to assess the association between rs146922325 and venous thrombosis. Sensitivity analyses were conducted by restricting the cohort to warfarin-naïve participants and incident venous thrombosis events occurring after genotyping. Carriers of the rs146922325 T allele exhibited significantly lower protein C levels than non-carriers (71.28
Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common enzymopathy worldwide, poses significant clinical and public health challenges, particularly in malaria-endemic regions. Despite the importance of quantitative G6PD activity assessments, clinically meaningful deficiency thresholds remain difficult to define owing to biological variability related to age, sex, and X-linked inheritance. The adjusted male median (AMM) is a recommended framework for defining 100
Clonal hematopoiesis (CH) is associated with cardiovascular disease (CVD), inflammation, and increased mortality. However, its prevalence and clinical impact in patients with cytopenia and chronic kidney disease (CKD) remain unclear. We conducted a retrospective cohort study of patients with cytopenia and CKD who underwent targeted sequencing to evaluate the association between CH, CKD progression, and overall mortality. A total of 67 patients were included (mean age 75.7 ± 10.5 years; 58.2
Considering the role of circadian clock genes in leukemogenesis through the regulation of cell cycle progression and genomic stability, this study aimed to evaluate the expression of NPAS2, CIPC, BMAL1, and CLOCK in acute myeloid leukemia (AML) and to determine their individual and combined diagnostic performance. In this study, bone marrow (BM) and peripheral blood (PB) samples were obtained from newly diagnosed AML patients and healthy controls under standardized circadian conditions. Gene expression was measured by TaqMan RT-qPCR and normalized to ABL using the 2ΔΔCt method. Diagnostic performance was evaluated by ROC analysis and multivariate logistic regression, and a random forest classifier with SHAP-based feature importance was applied to assess predictive contribution of each gene. PB showed comparable expression levels to paired BM samples, supporting its use as a surrogate tissue for circadian biomarker assessment. All transcripts were significantly downregulated in AML compared with controls (p < 0.001), with NPAS2 showing the most pronounced reduction. NPAS2 exhibited the highest diagnostic performance (AUC = 0.925). The random forest classifier achieved 74
Here, we report a case of TP53-mutated acute myeloid leukemia (AML) with monocytic differentiation that showed striking histiocytoid morphologic transformation following induction chemotherapy. Post-treatment blasts demonstrated significant morphologic overlap with mature malignant histiocytic neoplasms, particularly histiocytic sarcoma subtype, creating a potential diagnostic pitfall. Retained myeloperoxidase expression, together with the absence of cyclin D1 expression, supported a diagnosis of persistent AML rather than divergent histiocytic differentiation.
The treatment landscape for severe aplastic anemia (SAA) has undergone a significant paradigm shift with the integration of thrombopoietin receptor agonists (TPO-RAs) into standard immunosuppressive therapy (IST). However, clinical practice in Korea is shaped by a distinct regulatory and therapeutic environment characterized by the exclusive availability of rabbit antithymocyte globulin (rabbit ATG) and restrictive reimbursement policies governing TPO-RA use. This expert consensus statement provides a systematic framework and age-stratified treatment algorithms tailored to Korea-specific constraints. For treatment-naïve patients with SAA who are not candidates for immediate hematopoietic stem cell transplantation, a combination of rabbit ATG-based IST and TPO-RA is recommended as the first-line strategy. While eltrombopag is supported by robust global data, the panel emphasized the clinical utility of romiplostim in the Korean setting, given its established evidence in rabbit ATG-based regimens and the limited approved dosing of eltrombopag in Korea relative to pivotal global trials. The consensus also provides practical guidance on TPO-RA initiation, retreatment, and switching in refractory or relapsed disease, while emphasizing careful evaluation of clonal evolution in patients with insufficient response or newly emerging hematologic abnormalities, regardless of the specific TPO-RA used. Ultimately, these recommendations aim to standardize SAA management in Korea, optimize patient outcomes, and support future policy refinements to better align domestic practices with evolving global evidence.
Primary cutaneous γδ T-cell lymphoma (PCGDTCL) is a rare cutaneous T-cell lymphoma defined by γδ T-cell receptor expression and a cytotoxic phenotype. It has historically been considered highly aggressive, with median survival of 15–30 months and no standardized treatment due to its rarity. However, emerging reports describe subsets with relatively indolent behavior. We report a 20-year single-institution experience to better define the clinical spectrum and therapeutic implications of PCGDTCL. Patients diagnosed with PCGDTCL at Samsung Medical Center between January 2005 and September 2025 were retrospectively reviewed. Clinical, pathologic, and immunophenotypic features were collected and confirmed by hematopathology review. Pathologic features were visualized using heatmaps, and treatment courses were visualized using swimmer plots. Tumor response was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Six patients were identified (median age 57 years). All presented with cutaneous lesions, ranging from localized solitary lesions to multifocal cutaneous involvement. ^18F-fluorodeoxyglucose positron emission tomography (FDG-PET) demonstrated heterogeneous metabolic activity, with maximum standardized uptake values (SUVmax) ranging from absent uptake to 8.9. Immunophenotyping showed uniform CD3 positivity, T-cell receptor γδ expression, βF1 negativity, and variable CD4, CD8, and CD56 expression. First-line therapies included observation, corticosteroids, CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), and GDP (gemcitabine, dexamethasone, cisplatin). Durable complete remissions occurred with CHOP and GDP. One patient experienced multiple relapses, later developed clinicopathologic features resembling mycosis fungoides, and survived for 13 years. PCGDTCL appears to show broader clinical and therapeutic heterogeneity than historically appreciated. Durable responses in selected patients suggest that treatment responsiveness may vary across the disease spectrum.
Combination therapy with novel agents is the standard initial treatment for transplant-eligible patients with newly diagnosed multiple myeloma. However, the benefit of additional induction therapy for insufficient response remains unclear. This multicenter prospective study investigated response-adapted intensification with lenalidomide and dexamethasone (LenDex) after cyclophosphamide, bortezomib, and dexamethasone (CyBorD) in patients who did not achieve a very good partial response (VGPR) or better, followed by autologous stem cell transplantation (ASCT) and lenalidomide maintenance. Sixty-three patients were enrolled at 10 centers between March 2014 and December 2017. Of the 63 patients, 44 underwent ASCT. Six patients (9.5
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the BCR::ABL1 fusion oncogene. Asciminib, a first-in-class STAMP (Specifically Targeting the ABL Myristoyl Pocket) inhibitor, represents a novel therapeutic approach distinct from conventional ATP-competitive tyrosine kinase inhibitors (TKIs). This systematic review evaluated the efficacy and safety of asciminib as first-line therapy in patients with newly diagnosed chronic-phase CML. We conducted a comprehensive systematic review following PRISMA guidelines. Electronic searches were performed in PubMed, Embase, the Cochrane Library, and clinical trial registries through December 2025. Eligible studies included randomized controlled trials, prospective cohort studies, and compassionate use programs evaluating asciminib as first-line therapy in adult patients with chronic-phase CML. Primary outcomes included molecular response rates (major molecular response [MMR], MR4, and MR4.5), whereas secondary outcomes included safety profiles and treatment discontinuation rates. The systematic review identified eight eligible studies comprising more than 500 patients. In the pivotal ASC4FIRST phase 3 trial (n = 405), asciminib demonstrated superior efficacy compared with investigator-selected TKIs. At 96 weeks, MMR rates were 74.1
The optimal treatment strategy for patients aged 65–75 years with multiple myeloma (MM) remains undefined, as most clinical trials involving transplant-eligible patients have excluded this subgroup. We investigated the real-world treatment patterns, outcomes, and clinical impact of autologous stem cell transplantation (ASCT) and quadruplet therapy in this population. We retrospectively analyzed 561 patients aged 65–75 years with newly diagnosed MM treated between 2015 and 2023 at two tertiary centers. Patients were stratified by age (< 70 vs. ≥ 70 years) and ASCT status. The use of quadruplet regimens and ASCT has increased markedly since 2021. Among patients aged 65–69 years, ASCT was associated with improved progression-free survival (PFS) (hazard ratio [HR], 0.37; 95
Acute myeloid leukemia (AML) is a molecularly diverse hematologic malignancy, with clinical outcomes driven by patient fitness, disease biology, and the depth of remission. Over the past decade, the increasing use of molecular studies has enabled genotype-directed therapy and accelerated the incorporation of targeted agents into both intensive and lower-intensity treatment regimens. FLT3 inhibitors are now well established across a wide disease spectrum, including frontline settings, relapsed/refractory disease, and post–allogeneic hematopoietic cell transplantation maintenance, with emerging evidence supporting measurable residual disease (MRD)-adapted maintenance approaches. IDH1/2 inhibitors offer therapy for specific molecular subsets, particularly in older or unfit patients, and are increasingly being evaluated in doublet and triplet combinations. Venetoclax-based regimens have become a cornerstone for older or unfit patients with AML and are being optimized through response-adapted dosing and careful partner selection to mitigate cytopenias while deepening remission. Menin inhibitors represent a major therapeutic advance for KMT2A-rearranged and NPM1-mutated AML and are rapidly moving into combination and earlier-line treatment strategies. In parallel, immune and cellular therapies, including antibody–drug conjugates, immune checkpoint modulation, bispecific engagers, and chimeric antigen receptor T-cell and chimeric antigen receptor natural killer constructs, are under investigation, although durable, practice-changing benefits outside select settings remain limited to date. This review synthesizes pivotal clinical data and translational principles informing emerging targeted, immune-based, and cellular strategies in AML, with an emphasis on remission depth, MRD-driven decision-making, and relapse prevention.
To translate, culturally adapt, and evaluate the reliability and construct validity of the Korean version of the Haemophilia Activities List (HAL) in adult patients with hemophilia. This cross-sectional validation study included adult patients with hemophilia A and B. The HAL was translated into Korean using a standardized forward–backward translation process according to international guidelines. The participants completed the Korean HAL, the EuroQol Five-Dimension Five-Level Questionnaire (EQ-5D-5L), and the Routine Assessment of Patient Index Data 3 (RAPID3) questionnaire. Internal consistency was assessed using Cronbach’s alpha, test–retest reliability was assessed using intraclass correlation coefficients (ICCs), and construct validity was assessed using Spearman’s correlation analysis. A total of 87 adult patients completed the questionnaire. The mean age was 37 years (range, 18–62 years), and most participants had severe hemophilia. The Korean HAL demonstrated high internal consistency, with a Cronbach’s alpha coefficient of 0.97 for the total score and domain-specific values ranging from 0.78 to 0.95. The test–retest reliability was excellent, with an overall ICC of 0.95. Construct validity was supported by strong correlations between the HAL and EQ-5D-5L overall scores (r = 0.78, p < 0.01) and strong correlations with RAPID3 physical function scores (r = -0.82, p < 0.01). The Korean version of the HAL demonstrated excellent reliability and good construct validity in adult patients with hemophilia. These findings support the use of the Korean HAL as a reliable and culturally appropriate patient-reported outcome measure to assess functional limitations in clinical practice and research.
Abstract Chimeric antigen receptor (CAR) T-cell therapy is an established treatment for relapsed or refractory B-cell malignancies. Despite therapeutic success, infectious complications remain a major contributor to non-relapsed morbidity and mortality. The risk of infection reflects a prolonged and multifactorial state of immunosuppression resulting from lymphodepleting chemotherapy, treatment-related cytopenia, sustained CD4+ T-cell lymphopenia, B-cell aplasia with hypogammaglobulinemia, and the use of corticosteroids or cytokine-directed therapies for the management of immune effector cell-associated toxicities (i.e., cytokine-release syndrome and immune effector cell–associated neurotoxicity). The spectrum of infections has evolved over time. Bacterial infections are observed most frequently in the early post-infusion period, whereas viral and opportunistic infections become more prominent later, particularly in patients with delayed immune recovery. Infection risk is also influenced by the underlying malignancy, prior exposure to treatment, and the type of CAR T-cell product used. For example, BCMA-directed CAR T-cell therapy has been associated with a higher infection burden, likely related to profound plasma cell depletion and sustained impairment of humoral immunity. Preventing infections in this setting requires a structured and individualized approach. Common strategies include antiviral and Pneumocystis jirovecii pneumonia prophylaxis, the selective use of antibacterial and antifungal prophylaxis during periods of severe or prolonged cytopenia, immunoglobulin replacement in patients with clinically significant hypogammaglobulinemia, and vaccination schedules guided by immune recovery. Therefore, coordinated and risk-adapted prevention is essential to minimize infectious complications and to improve long-term outcomes after CAR-T cell therapy. This review summarizes the current evidence and major recommendations of international guidelines to provide an updated overview of infection mechanisms, risk stratification, and preventive strategies for patients receiving CAR T-cell therapy.
To describe the post-transplant outcomes in patients with myelofibrosis stratified by the Dynamic International Prognostic Scoring System (DIPSS) risk at transplantation, and to identify clinical factors associated with overall survival (OS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively analyzed the data of 42 patients with myelofibrosis who underwent allo-HSCT at Samsung Medical Center between 2014 and 2023. OS was estimated using the Kaplan–Meier method and compared using the log-rank test. Exploratory Cox proportional-hazard regression analyses were performed to assess independent associations with OS. At transplantation, 28 patients (66.7
Abstract Background Gilteritinib is an established FLT3 inhibitor used to treat patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) harboring FLT3 mutations. Prior studies have predominantly evaluated gilteritinib as a posttransplant maintenance therapy in patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) in complete remission. Nonetheless, evidence remains limited for patients who receive gilteritinib as salvage therapy in a relapsed or refractory setting, proceed to allo-HSCT, and subsequently continue gilteritinib maintenance. This real-world study aimed to address this knowledge gap in an Asian cohort. Method and Result Patients with FLT3-mutated R/R AML received gilteritinib before transplantation, and those achieving engraftment without grade ≥ 2 acute graft-versus-host disease were offered posttransplant maintenance between days 30 and 90. The cohort (median age, 48 years; 92.0% FLT3-ITD) achieved a complete response (CR) rate of 76.2%. At a median follow-up of 46.2 months, gilteritinib maintenance therapy was associated with longer relapse-free and overall survival and a significantly lower 1-year cumulative incidence of relapse. Exploratory measurable residual disease (MRD) subgroup analyses suggested a numerically greater survival difference in patients without flow cytometry-detectable MRD before or after transplantation; however, the findings are limited by the small sample size and lack of FLT3-targeted next-generation sequencing-based MRD assessment. Conclusion Gilteritinib was generally well-tolerated, with no observed increase in cytomegalovirus (CMV)-related or graft-versus-host complications. This study provides real-world evidence in a clinically relevant scenario and supports the use of gilteritinib maintenance in patients with FLT3-mutated AML who undergo transplantation during R/R disease.
Abstract Purpose An immune-mediated pathogenesis has been postulated for aplastic anemia (AA), and impaired Tregs and other immune abnormalities have been identified in patients with AA. However, the process by which abnormal immunity specifically damages hematopoietic stem cells (HSCs) remains unclear. We conducted primary clinical studies to investigate whether the depletion of HSCs in AA could be attributed to the collapse of immune privilege (IP) afforded by regulatory T cells (Tregs). Methods The distribution of Tregs in the bone marrow of children with AA, myelodysplastic syndrome (MDS), and control participants was separately detected by immunohistochemistry. T-helper 1 (Th1), T-helper 2 (Th2), and T-helper 17 (Th17) cells, cytokines, and HSCs in the bone marrow of the AA and control groups were examined using flow cytometry. Results Patients with AA showed significantly lower FoxP3 + /CD4 + ratios (AA vs. normal: 18.09% ± 5.38% vs. 21.72% ± 4.21%, P = 0.014; AA vs. MDS: 18.09% ± 5.38% vs. 22.63% ± 5.98%, P = 0.030) and reduced Treg counts (AA vs. normal: 4.07 ± 1.41 vs. 5.25 ± 1.86 cells/HP, P = 0.014; AA vs. MDS: 4.07 ± 1.41 vs. 5.30 ± 1.49 cells/HP, P = 0.024) near the endosteum. The bone marrow in patients with AA exhibited Th1 dominance (AA vs. normal: 39.80% ± 5.20% vs. 22.1% ± 2.9% in controls, P < 0.001) and Th2 reduction (AA vs. normal: 59.20% ± 5.30% vs. 77.20% ± 2.60%, P < 0.001), indicating IP dysfunction. Significant elevation of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-17 levels was observed in the bone marrow of patients with AA. Long-term (LT)-HSCs were severely depleted in patients with AA (AA vs. normal: 0.13% vs. 1.22%, P = 0.035), with moderate reduction in short-term (ST)-HSCs. Conclusions Patients with AA showed endosteal Treg reduction, Th1 dominance, elevated proinflammatory cytokine levels, and severe LT-HSC depletion, linking bone marrow IP dysfunction to HSC damage. These findings provide a mechanistic explanation for the specific loss of HSCs in AA and highlight the IP niche as a therapeutic target.
