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.

Recent developments in the treatment of lower-risk myelodysplastic syndromes have focused on improving anemia management, which remains a major clinical challenge. Erythropoiesis-stimulating agents (ESAs) and lenalidomide are the standard therapies; however, their effectiveness is limited by resistance and patient selection criteria. Luspatercept, a transforming growth factor-beta superfamily ligand trap, has shown improved transfusion independence and is now considered a frontline option for a broader group of patients. Clinical trials have indicated that luspatercept provides a sustained response in several cases. Imetelstat, a telomerase inhibitor, offers an alternative for patients who do not respond to ESAs and has been shown to reduce the clonal mutation burden, suggesting possible disease-modifying effects. However, unresolved issues remain, such as the lack of predictive biomarkers to guide therapy selection, uncertainty about the optimal sequencing or combination of available treatments, and the fact that most patients eventually progress to higher-risk disease. Additionally, the real-world use of these new agents remains limited in some regions owing to issues with local introduction and reimbursement. This review summarizes recent clinical data on luspatercept and imetelstat, highlights their current limitations, and discusses areas for future research based on recent trial outcomes and evolving clinical practices.

Purpose: Brentuximab vedotin (BV)-based combinations have shown promising results in patients with relapsed or refractory Hodgkin’s lymphoma (RRHL) in Western countries. We conducted a phase II study to further define the role of BV-based salvage therapy in transplant-eligible patients with RRHL in Korea. Methods: Transplant-eligible patients with RRHL were recruited to receive two cycles of BV (1.8 mg/kg) plus DHAP (cisplatin 100 mg/m2 , cytarabine 2 g/m2/sup> , and dexamethasone 40 mg). Autologous stem cells were collected from non-progressive patients who received one more cycle of BV-DHAP. After three cycles, the responding patients underwent autologous stem cell transplantation (ASCT). The primary endpoint was a complete metabolic response (CMR) rate after two cycles of BV-DHAP. Results: Between April 2022 and August 2024, seven lymphoma cases were recruited. Owing to slow accrual, the study was terminated early. Their median age was 30 years (range, 24–62 years). All patients received at least two cycles of BV-DHAP; the overall response rate (ORR) was 100%, and four patients showed CMR (57%). One patient with‑ drew consent after the second cycle, and the other six patients received one more cycle of BV-DHAP, resulting in five patients achieving CMR (71%). One patient failed to receive ASCT, and all five patients who received ASCT achieved post-transplant CMR with a 80% complete response (CR) over a 12-month duration. Thrombocytopenia was the most common grade 3 or higher grade hematologic adverse events (n = 5). Grade 2 nausea occurred in three patients.Three patients experienced dose reduction, and four patients experienced treatment delays. Conclusions Despite its encouraging early efficacy, the administration of BV-DHAP in Korean patients with RRHL requires careful monitoring due to toxicity concerns.

Purpose: To compare the hematologic response to ropeginterferon alfa-2b versus available therapies in patients with hydroxyurea-resistant or intolerant polycythemia vera (HU-R/I PV) using propensity-matched real-world data. Methods: This retrospective propensity-matched cohort study compared a single-arm clinical trial cohort with a historical control cohort from five Korean institutions. We included 36 HU-R/I patients from a prospective phase II trial (PV IIT, registration number KCT0006138) and 81 matched historical controls. Propensity score matching and weighted analyses balanced the baseline characteristics (age, sex, disease duration, hematologic parameters, and HU status).The primary endpoint was a complete hematologic response (CHR) at 48 weeks. Results: At 48 weeks, ropeginterferon alfa-2b achieved significantly higher CHR rates (52%; 95% confidence interval [CI]: 35–70%) than historical controls (15%; 95% CI: 8–27%; odds ratio 0.15; 95% CI: 0.07–0.33; p < 0.0001). This superiority remained consistent across various matching ratios and weighted analyses. Subgroup analyses showed higher response rates to ropeginterferon alfa-2b, regardless of HU status (resistant vs. intolerant), age (< 60 vs. ≥ 60 years), or disease duration (< 5 vs. ≥ 5 years). In the control group, the most common regimen was a combination of HU and phlebotomy (53%) with limited use of ruxolitinib (5.5%). Analyses confirmed robustness with no significant baseline imbalances after matching. Conclusion Ropeginterferon alfa-2b demonstrated superior early hematologic efficacy compared with conventional salvage therapies in Korean patients with HU-R/I PV. Extended follow-up is warranted to assess the long-term clinical benefits.

Myelodysplastic syndrome (MDS) is a heterogeneous disorder with diverse prognoses influenced by cytopenias, genetic variants, and myeloblast proportions in the bone marrow. Accurate prognosis prediction and tailored treatment plans are essential. The International Prognostic Scoring System-Molecular (IPSS-M), which additionally reflects the impact of MDS-related genetic mutations to the clinical and laboratory information, is anticipated to offer superior prognostic accuracy compared to existing systems like the Revised International Prognostic Scoring System (IPSS-R). Despite its statistical complexity, its web-based calculation and ease of discussing results with patients using intuitive data sets provide notable advantages. Progress in MDS treatment, exemplified by effective anemia correction with an erythropoiesis-maturation agent in SF3B1-mutated cases and efforts to refine poor prognoses in TP53-mutated cases, reflects the evolving landscape of genetic-based interventions in MDS. Advancements in genetic diagnostic technology, combined with enhanced knowledge of the bone marrow niche, are anticipated to lead to significant improvement in MDS treatment outcomes in the future.

Myelodysplastic syndrome (MDS) is a heterogeneous disorder with diverse prognoses influenced by cytopenias, genetic variants, and myeloblast proportions in the bone marrow. Accurate prognosis prediction and tailored treatment plans are essential. The International Prognostic Scoring System-Molecular (IPSS-M), which additionally reflects the impact of MDS-related genetic mutations to the clinical and laboratory information, is anticipated to offer superior prognostic accuracy compared to existing systems like the Revised International Prognostic Scoring System (IPSS-R). Despite its statistical complexity, its web-based calculation and ease of discussing results with patients using intuitive data sets provide notable advantages. Progress in MDS treatment, exemplified by effective anemia correction with an erythropoiesis-maturation agent in SF3B1-mutated cases and efforts to refine poor prognoses in TP53-mutated cases, reflects the evolving landscape of genetic-based interventions in MDS. Advancements in genetic diagnostic technology, combined with enhanced knowledge of the bone marrow niche, are anticipated to lead to significant improvement in MDS treatment outcomes in the future.

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.

Myelodysplastic syndrome (MDS) is a heterogeneous disorder with diverse prognoses influenced by cytopenias, genetic variants, and myeloblast proportions in the bone marrow. Accurate prognosis prediction and tailored treatment plans are essential. The International Prognostic Scoring System-Molecular (IPSS-M), which additionally reflects the impact of MDS-related genetic mutations to the clinical and laboratory information, is anticipated to offer superior prognostic accuracy compared to existing systems like the Revised International Prognostic Scoring System (IPSS-R). Despite its statistical complexity, its web-based calculation and ease of discussing results with patients using intuitive data sets provide notable advantages. Progress in MDS treatment, exemplified by effective anemia correction with an erythropoiesis-maturation agent in SF3B1-mutated cases and efforts to refine poor prognoses in TP53-mutated cases, reflects the evolving landscape of genetic-based interventions in MDS. Advancements in genetic diagnostic technology, combined with enhanced knowledge of the bone marrow niche, are anticipated to lead to significant improvement in MDS treatment outcomes in the future.

Background: Previous studies have suggested that patients with polycythemia vera (PV) who exhibit hydroxyurea-resistance (HU-R) and -intolerance (HU-I) may have distinct characteristics and clinical outcomes. However, to date, no studies have reported a comparison between these two groups or assessed prognostic factors in these patients. Methods: The objective of this study was to evaluate clinical outcomes and identify prognostic factors among PV patients with HU-R or HU-I. We conducted a review of PV patients who received frontline treatment with HU from nine centers and identified 90 patients with HU-R or HU-I. Results: The cumulative incidence of thrombosis after 7 years of HU-R/I was 21.4%, and the incidence of disease progression was 22.5%. Comparing the HU-R and HU-I groups, the HU-R group had a significantly higher rate of disease progression (36.7% vs. 0.56%, P = 0.009), while there was no significant difference in thrombosis incidence (19.0% vs. 22.9%, P = 0.463). Multivariate analysis revealed that HU-R was an independent prognostic factor for progression-free survival (hazard ratio, 6.27, 95% confidence interval, 1.83–21.47, P = 0.003).Additionally, higher lactate dehydrogenase levels, multiple cardiovascular risk factors, and prior thrombosis were identified as unfavorable predictors of overall survival. Conclusion These findings suggest that patients with HU-R face a higher risk of hematological transformation, but have a comparable risk of thrombosis to patients with HU intolerance. These distinctions should guide decisions on second-line treatment options and clinical trials involving these patients.

Background: The efficacy and safety of direct oral anticoagulants (DOACs) versus warfarin in patients with antiphospholipid syndrome-associated venous thromboembolism (APS-VTE) remain uncertain. We aimed to evaluate efficacy and safety of DOACs in patients with APSVTE. Methods: Using the Korean Health Insurance Review and Assessment Service database, we retrospectively identified all APS-VTE cases. We examined the VTE recurrence, arterial thrombosis, death and bleeding in patients who received DOACs compared with warfarin for therapeutic anticoagulation. Results: Of all the VTE cases (n = 84,916) detected between 2014 and 2018, patients with APS-VTE (n = 410) accounted for 0.48%. Most patients with APS-VTE (73%) were aged < 60 years. The recurrent VTE occurred in 8 of 209 patients (3.8%) who received DOACs and in 7 of 201 (3.5%) who received warfarin (relative risk [RR], 1.099; 95% confidence interval [CI], 0.41–2.98; P = 1.000). The arterial thrombosis (ATE) occurred in 8 of 209 patients (3.8%) who received DOAC and in 20 of 201 (10%) who received warfarin (RR, 0.385; 95% CI, 0.17–0.85; P = 0.024). The composite outcomes of VTE recurrence, ATE, or mortality were significantly lower in patients (9.1%) on DOAC than in those (16.3%) on warfarin (RR, 0.537; 95% CI, 0.32–0.91; P = 0.028). The bleeding outcome occurred in 7 of 209 (3.4%) patients in the DOACs group and 7 of 201 (3.5%) patients in the warfarin group (RR, 0.96; 95% CI, 0.34–2.69; P = 0.840). Conclusion In patients with APS-VTE, DOACs group showed comparable rates of recurrent VTE, bleeding, and deaths, but a significantly lower incidence of ATE and composite outcomes compared with the warfarin group in Korea.