Purpose: While TP53 mutations are well known to be associated with adverse prognosis in hematological diseases, their functional impact remains incompletely understood. This study examines the spectrum of TP53 mutations across various hematologic malignancies and evaluates their functional impact. Materials and Methods: Using targeted sequencing panels, we analyzed TP53 mutations in the bone marrow aspiration samples of a retrospective cohort of 856 patients diagnosed with hematologic malignancies. To assess the impact of TP53 mutations, we applied the evolutionary action (EAp53) score and the relative fitness score (RFS), previously proposed functional scoring methods. The effects of variant allele frequency (VAF), disruptive mutations, EAp53 score, and RFS on overall survival (OS) were evaluated. Results: TP53 mutations were associated with inferior OS compared with wildtype TP53 (median OS 10.0 months versus not estimable; hazard ratio (HR) 4.6; p<0.001). In the acute myeloid leukemia, multiple myeloma, and myelodysplastic syndrome subgroups, TP53 mutations had a significant adverse impact on OS. (HRs 3.8, 4.2, 6.0, respectively; p<0.001, p=0.005, p<0.001, respectively). Patients with VAF >50% had significantly poorer OS compared to those with VAF ≤50% (median OS 7.5 months versus 22.8 months; HR 2.2, p=0.016). Moreover, patients in the high-risk RFS group (RFS >0.22) had significantly worse OS compared to those in the low-risk RFS group (RFS ≤0.22) (median OS 5.6 months versus 16.3 months; HR 2.2, p=0.041). However, no significant survival difference was observed between the EAp53 high-risk (>75) and low-risk (≤75) groups, or between patients with disruptive and non-disruptive mutations. Conclusion Our findings highlight VAF and RFS as valuable tools for stratifying TP53-mutant patients into high-risk and low-risk groups.

Purpose: This study evaluates the Korean Cancer Study Group Geriatric Score-7 (KG-7) frailty screening tool’s effectiveness in elderly multiple myeloma (MM) patients to prevent under and overtreatment. Materials and Methods: This prospective pilot cohort study included 100 elderly patients aged 70 and older with newly diagnosed MM who had not undergone transplantation from August 2020 to January 2022. Results: The median age was 77 years, and 73.0% of patients were classified at International Staging System stages 2 or 3. Using a 5-point cutoff on the KG-7 index (non-frail, score ≥ 5; frail, score < 5), 31% were categorized as frail. After a median follow-up of 26.8 months, the 3-year overall survival rate was 73.0%. There was no statistically significant association between any frailty index and the risk of death. However, frail patients defined by the simplified frailty index (hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.09 to 5.95; p=0.030) and by KG-7 (HR, 2.43; 95% CI, 1.03 to 5.86; p=0.043) had a significantly higher risk of grade 3-4 non-hematologic toxicity, whereas the International Myeloma Working Group definition did not. Over a 24-month tracking period, vulnerability as measured by KG-7 either improved or deteriorated. Conclusion The pilot study, which had a limited number of participants, did not demonstrate KG-7’s effectiveness in predicting survival; however, it successfully predicted severe non-hematologic toxicities. We plan to conduct larger studies in elderly MM patients to determine whether KG-7 can help tailor their treatment regimens.

Clonal hematopoiesis (CH), characterized by the expansion of hematopoietic stem and progenitor cells harboring somatic mutations, has emerged as a significant age-related phenomenon with profound implications for human health. While initially recognized in the 1960s, recent technological advances have revealed its complex nature and widespread prevalence, affecting up to 84% of individuals aged ≥ 70 years. The clinical significance of CH extends beyond its well-established role as a precursor to hematological malignancies, encompassing its association with cardiovascular diseases, chronic kidney disease, and other non-malignant disorders. This comprehensive review synthesizes the current understanding of CH, focusing on recent advances in genetic and molecular mechanisms, particularly the roles of commonly mutated genes such as DNMT3A, TET2, and ASXL1. We address the emerging distinction between myeloid and lymphoid CH, their differential impacts on disease progression, and the complex interplay between CH and inflammation. Special attention is given to newly identified genetic determinants of clonal expansion rates and their implications for disease progression. The review also examines the revolutionary concept of passenger-approximated clonal expansion rate and its utility in understanding CH dynamics. Furthermore, we dis‑ cuss therapeutic strategies targeting inflammatory pathways and their potential in mitigating CH-associated compli‑ cations. By integrating recent findings from genetic, molecular, and clinical studies, this review provides a framework for understanding CH as a systemic condition and highlights promising directions for therapeutic interventions.

Clonal hematopoiesis (CH), characterized by the expansion of hematopoietic stem and progenitor cells harboring somatic mutations, has emerged as a significant age-related phenomenon with profound implications for human health. While initially recognized in the 1960s, recent technological advances have revealed its complex nature and widespread prevalence, affecting up to 84% of individuals aged ≥ 70 years. The clinical significance of CH extends beyond its well-established role as a precursor to hematological malignancies, encompassing its association with cardiovascular diseases, chronic kidney disease, and other non-malignant disorders. This comprehensive review synthesizes the current understanding of CH, focusing on recent advances in genetic and molecular mechanisms, particularly the roles of commonly mutated genes such as DNMT3A, TET2, and ASXL1. We address the emerging distinction between myeloid and lymphoid CH, their differential impacts on disease progression, and the complex interplay between CH and inflammation. Special attention is given to newly identified genetic determinants of clonal expansion rates and their implications for disease progression. The review also examines the revolutionary concept of passenger-approximated clonal expansion rate and its utility in understanding CH dynamics. Furthermore, we dis‑ cuss therapeutic strategies targeting inflammatory pathways and their potential in mitigating CH-associated compli‑ cations. By integrating recent findings from genetic, molecular, and clinical studies, this review provides a framework for understanding CH as a systemic condition and highlights promising directions for therapeutic interventions.

Clonal hematopoiesis (CH), characterized by the expansion of hematopoietic stem and progenitor cells harboring somatic mutations, has emerged as a significant age-related phenomenon with profound implications for human health. While initially recognized in the 1960s, recent technological advances have revealed its complex nature and widespread prevalence, affecting up to 84% of individuals aged ≥ 70 years. The clinical significance of CH extends beyond its well-established role as a precursor to hematological malignancies, encompassing its association with cardiovascular diseases, chronic kidney disease, and other non-malignant disorders. This comprehensive review synthesizes the current understanding of CH, focusing on recent advances in genetic and molecular mechanisms, particularly the roles of commonly mutated genes such as DNMT3A, TET2, and ASXL1. We address the emerging distinction between myeloid and lymphoid CH, their differential impacts on disease progression, and the complex interplay between CH and inflammation. Special attention is given to newly identified genetic determinants of clonal expansion rates and their implications for disease progression. The review also examines the revolutionary concept of passenger-approximated clonal expansion rate and its utility in understanding CH dynamics. Furthermore, we dis‑ cuss therapeutic strategies targeting inflammatory pathways and their potential in mitigating CH-associated compli‑ cations. By integrating recent findings from genetic, molecular, and clinical studies, this review provides a framework for understanding CH as a systemic condition and highlights promising directions for therapeutic interventions.

Purpose: Stem cell transplantation (SCT) has historically played a major role in the long-term remission of mantle cell lymphoma (MCL), an incurable hematological malignancy. Using data from the Korean Society of Bone and Marrow Transplantation registry, we retrospectively analyzed the role of autologous (auto) and allogeneic (allo) SCT in longterm MCL survival. Methods: This study analyzed data from 188 patients (age ≥ 19 years at the time of transplantation) who underwent a transplant for MCL from 2011 to 2020. Progression-free survival (PFS) was defined as the time from transplantation to disease progression, relapse, or death from any cause. Overall survival (OS) was defined as the time from transplan‑ tation to death from any cause or the last follow-up. Results: In total, 109 patients underwent consolidative SCT after first-line chemotherapy. The 3-year PFS and OS rates were 65.4% and 78.5%, respectively, in the auto-SCT group, and 66.7% and 71.4%, respectively, in the allo-SCT group. The PFS and OS did not differ significantly between the auto- and allo-SCT groups. As part of salvage treatment, 52 patients with relapsed or refractory disease underwent auto- or allo-SCT. Patients who underwent auto-SCT with complete remis‑ sion/partial remission status reported better outcomes. In patients with refractory status, allogeneic transplantation using human leukocyte antigen (HLA) fully matched donors was a significantly favorable factor for PFS and OS. Conclusion The long-term survival of patients who underwent consolidative transplantation was similar to that reported in previous studies. Auto-SCT may be beneficial in patients who respond to salvage therapy, whereas allo-SCT with HLA-matched donors may be an alternative for patients with refractory disease. 

Multiple myeloma (MM), a hematological malignancy, is characterized by malignant plasma cell proliferation in the bone marrow. Recent treatment advances have significantly improved patient outcomes associated with MM.In this study, we aimed to develop comprehensive, evidence-based guidelines for the diagnosis, prognosis, and treat‑ ment of MM. We identified 12 key clinical questions essential for MM management, guiding the extensive literature review and meta-analysis of the study. Our guidelines provide evidence-based recommendations by integrating patient preferences with survey data. These recommendations include current and emerging diagnostic tools, thera‑ peutic agents, and treatment strategies. By prioritizing a patient-centered approach and rigorous data analysis, these guidelines were developed to enhance MM management, both in Korea and globally.

Background: There is limited data regarding the clinical outcomes of clonal hematopoiesis of indeterminate potential (CHIP) in patients with chronic obstructive pulmonary disease (COPD). This study aimed to evaluate the clinical significance of CHIP as a COPD biomarker. Methods: This retrospective study was conducted on patients with COPD who were enrolled prospectively in the Seoul National University Hospital Airway Registry from January 2013 to December 2019 and underwent pulmonary function and blood tests. We evaluated the CHIP score according to smoking status and severity of airflow obstruction. Results: We analyzed next-generation sequencing data to detect CHIP in 125 patients with COPD. Current smokers had a higher prevalence of CHIP in combination of DNMT3A, TET2, and PPM1D (DTP), DNA methyltransferase 3 alpha (DNMT3A), and protein phosphatase, Mg2+/Mn2+ dependent 1D (PPM1D) genes than in never- or ex-smokers. CHIP of DTP and DNMT3A genes was significantly associated with current smokers (adjusted odds ratio [aOR], 2.80; 95% confidence interval [CI], 1.01 to 7.79) (aOR, 4.03; 95% CI, 1.09 to 14.0). Patients with moderate-to-severe airflow obstruction had a higher prevalence of CHIP in most of the explored genes than those with mild obstruction, although the difference was not statistically significant. CHIP in ASXL transcriptional regulator 1 (ASXL1) genes was significantly associated with history of mild, severe, and total acute exacerbation. Conclusion Given that CHIP in specific genes was significantly associated with current smoking status and acute exacerbation, CHIP can be considered as a candidate biomarker for COPD patients.

Background: Although most studies on the cardiovascular toxicity of proteasome inhibitors have focused on carfil‑ zomib, 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 hyperten‑ sion 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 bort‑ ezomib treatment.

Purpose: Despite the recent success of Bruton’s tyrosine kinase (BTK) inhibitors for the treatment of Waldenstrom macroglobulinemia (WM), their indefinite treatment duration ultimately tantamount to substantial financial and emotional burden. On the other hand, fixed duration of proteasome inhibitors (PI) have shown rapid and reasonable response in WM treatment. Despite the well-known synergism between PI and immunomodulatory drugs (IMiD), there is no trials evaluating such combination in WM. Materials and Methods: Based on above, we designed this phase II study to investigate the efficacy and safety of 6 cycles of 28-day bortezomib-thalidomide-dexamethasone (VTD) regimen for treatment-naïve WM. Results: A total of 15 patients were enrolled: major response rate was 64.3%, and overall response rate was 78.6%. During the median follow-up of 41 months, median progression-free survival (PFS) was 13 months and overall survival 40 months. For responders, median duration of response was 13 months and median PFS 19 months. The most common adverse event (AE) of any grade was constipation (57.1%). The most common grade ≥ 3 AE was anemia (21.4%). Conclusion All in all, we hereby provide proof-of-concept that PI + IMiD may be an attractive backbone for fixed duration treatment. It should be noted that granting the same level of access to newer drugs globally is virtually impossible. Thus efforts to develop regimens using readily available drugs to yield similar or adequate treatment outcomes should not be disregarded. In this sense, we believe our study holds its place for its novelty and eloquently addresses achieving the daunting societal quest of health equity.