Blood Research最新文献

Purpose: Minimal residual disease (MRD)-guided therapy is the global standard treatment for pediatric acute lymphoblastic leukemia (ALL). We assessed the impact of MRD-driven intensification along with protocol-defined risk groups in pediatric ALL treatment.

Methods: This retrospective analysis included 209 patients with ALL (treated between January 2013 to June 2023). MRD was assessed using six- to eight-color flow cytometry at the end of each phase before the maintenance phase. Post-induction treatment was determined based on early response, National Cancer Institute risk, and cytogenetics. High-risk (HR) patients followed the Korean HR or CCG-1882 protocols and standard-risk (SR) patients followed the modified COG-AALL0331 protocol. Treatment was intensified if flow-MRD ≥ 0.1% was identified.

Results: Overall, 103 and 106 patients were classified as having SR and HR, respectively. The 5-year overall survival (OS) and event-free survival (EFS) were 92.5% and 84.3%, respectively. Thirty SR and 18 HR patients received intensified chemotherapy. Treatment intensification significantly improved EFS in patients with high MRD (94.2% vs. 75.5%, p = 0.04), particularly in post-induction patients with high MRD (90.0% vs. 19.0%, p = 0.035). The difference in survival between rapid early responder (RER) and slow early responder (SER) groups was eliminated after MRD-based intensification. The implementation rates of treatment intensification varied over time (9.1% before 2015, 28.6% during 2016-2019, and 13.9% during 2020-2023), reflecting improved risk stratification and therapy selection.

Conclusion: MRD-guided therapy intensification markedly improved survival outcomes in patients with pediatric ALL when combined with risk-based protocols, highlighting the importance of MRD monitoring for optimizing risk-adapted treatment strategies.

Purpose: Apixaban is recommended for patients with atrial fibrillation. Although routine monitoring of plasma concentrations is not typically advised, factors such as ethnicity, sex, and comorbidities can influence these levels. Our study analyzed the plasma apixaban concentrations (PAC) in patients to explore whether these levels, along with underlying conditions, offer enhanced insights for risk stratification.

Methods: This study analyzed 49 patients with atrial fibrillation who had been taking apixaban for over a month, examined factor Xa levels within 6 h post-administration, and correlated PAC with clinical characteristics such as age, body weight, estimated glomerular filtration rate (eGFR), presence of heart failure, and bleeding events.

Results: The mean plasma concentration of apixaban in all patients was 160.3 ± 77.5 ng/mL. Those taking apixaban 5 mg twice daily had higher plasma concentrations than those taking 2.5 mg twice daily (191.2 ± 75.3 ng/mL vs. 137.2 ± 72.0 ng/mL, p = 0.014). Among the patients receiving a reduced dose, renal function and heart failure were significantly associated with plasma concentrations. No factors were associated with the plasma concentrations in patients receiving the standard dose. Notably, reduced-dose patients with heart failure had plasma concentrations comparable to those of individuals receiving the standard dose and exhibited a higher incidence of bleeding than the other groups.

Conclusions: PAC measurement revealed that apixaban dosages, classified based on age, body weight, and eGFR, were generally effective. Nonetheless, heart failure may increase plasma levels and correlate with an increased bleeding risk in Korean patients on reduced doses. Therefore, tailoring apixaban prescriptions to account for heart failure and other comorbidities may enhance treatment efficacy.

Purpose: SRY-box transcription factor 4 (SOX4) is a transcription factor involved in early B cell development and has been implicated in various malignancies; however, its role in chronic lymphocytic leukemia (CLL) remains poorly understood. This study investigated the correlation between SOX4 expression and prognostic factors in CLL to determine its relevance to disease progression and clinical outcomes.

Methods: A cohort of patients with CLL with a known immunoglobulin heavy chain variable region (IGHV) mutational status was analyzed for SOX4 expression using quantitative polymerase chain reaction (qPCR). Correlations between SOX4 levels and established prognostic markers including IGHV mutational status, cytogenetic abnormalities, and clinical outcomes were evaluated. Statistical analyses were performed to assess the association between SOX4 expression and patient survival.

Results: Higher SOX4 expression was observed to be significantly associated with unmutated CLL (U-CLL) and adverse prognostic markers, including del(17)(p13). In contrast, lower SOX4 levels were observed in mutated CLL (M-CLL), and cytogenetic abnormalities were noted to be linked to favorable outcomes [del(13)(q21)]. Survival analysis indicated that elevated SOX4 expression was correlated with poor prognosis.

Conclusion: SOX4 expression stratifies CLL subtypes and aligns with established prognostic markers. High SOX4 levels are associated with aggressive disease phenotypes, whereas low SOX4 expression is associated with better clinical outcomes. These findings indicate that SOX4 may serve as a potential biomarker for disease classification and risk stratification. Further studies are required to elucidate the biological significance of this phenomenon.

Epstein-Barr virus (EBV)-associated lymphomas can, on rare occasions, involve body cavities, making effusion cytology an important diagnostic tool. This mini-review explores the spectrum of EBV-related lymphomas that may be detected in serous fluids, including EBV-positive nodal T/NK-cell lymphoma (EBV + nT/NKCL), extranodal NK/T-cell lymphoma, primary effusion lymphoma, EBV-positive diffuse large B-cell lymphoma, and classic Hodgkin lymphoma. We present an index case of EBV + nT/NKCL with lymphomatous pleural effusion and discuss the cytologic features, differential diagnoses, and role of ancillary studies such as immunocytochemistry, EBER in situ hybridization, and molecular assays. Accurate diagnosis requires the integration of cytomorphologic, immunophenotypic, and molecular findings with clinical information to establish a definitive diagnosis and distinguish these aggressive lymphomas from reactive and non-hematologic mimics.

Purpose: Central nervous system (CNS) relapse is associated with poor survival, and remains an unmet challenge in patients with diffuse large B-cell lymphoma (DLBCL). Identifying patients at high risk of CNS relapse and offering prophylactic treatment could improve patient prognosis.

Methods: Here, we studied 234 patients with DLBCL using open patient-level clinical and sequencing data to explore risk factors for CNS relapse. Patients were divided into Cohort A (CNS involvement at baseline), Cohort B (CNS recurrence), and Cohort C (patients without secondary CNS involvement and with a follow-up interval > 3 years). We investigated the risk factors for CNS relapse in Cohorts B + C.

Results: Genetic alterations with statistical significance, determined by univariate analysis, and an incidence rate ≥ 5%, together with clinical factors, correlated with CNS relapse risk in a multivariate analysis. Multivariate logistic regression analysis revealed that concomitant MYD88 L265P and CDKN2A loss (p = 0.012), TET2 mutation (p = 0.037), ARID1A mutation (p = 0.010), and INO80 (p = 0.002) were independently correlated with a high risk of CNS relapse after adjusting for the IPI risk groups, B symptom and cell of origin (COO). The classifier that integrated genomic risk factors was superior in predicting CNS relapse (area under the receiver operating characteristic curve [AUROC]: 0.91) compared with the IPI (AUROC: 0.77, p < 0.001) or IPI in combination with COO classifiers (AUROC: 0.81, p = 0.013).

Conclusion: This study identified several genomic alterations as risk factors for CNS relapse.

Older patients with classic Hodgkin lymphoma (HL) often experience poor outcomes due to age-related comorbidities and treatment-related toxicity. Comprehensive geriatric assessment and supportive care measures, including pre-phase corticosteroids, growth factor prophylaxis, and organ function monitoring, are essential for optimizing treatment tolerance in this vulnerable patient population. Recent phase III trial (S1826) demonstrated that nivolumab plus doxorubicin, vinblastine, and dacarbazine (Nivo + AVD) significantly improves progression-free survival and is better tolerated than brentuximab vedotin (BV) + AVD, particularly in patients over 60 years of age. Given its efficacy and reduced toxicity, Nivo + AVD is likely to become a key treatment option for fit older patients with HL. For frail patients, chemo-free approaches with BV and checkpoint inhibitors remain viable alternatives. Future research should refine fitness-based treatment strategies, integrate novel agents, and enhance supportive care to improve outcomes and minimize treatment-related toxicity in this population.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important treatment option for hematologic diseases. However, limited studies have evaluated the prognosis of patients receiving single human leukocyte antigen (HLA) mismatched unrelated donor allo-HSCT (HLA 9/10 MMUD-HSCT) compared to those receiving fully matched unrelated donor allo-HSCT (10/10 MUD-HSCT). This study retrospectively analyzed 126 cases of unrelated donor allo-HSCT (URD-HSCT) at our center, in which anti-human thymocyte globulin (ATG, 7.5 mg/kg) was used as a graft-versus-host disease (GVHD) prophylaxis strategy. The MUD-HSCT group had a significantly lower incidence of grade II-IV acute GVHD (13.89% vs. 35.19% in the MMUD-HSCT group, p = 0.005). In contrast, the incidence of moderate-to-severe chronic GVHD (cGVHD) did not differ significantly between the two groups (16.67% vs. 29.63%, p = 0.083). The median follow-up time was 16.98 months (range: 7.88-38.55). There were no significant differences between the two groups in the 1-year cumulative incidence of relapse (CIR) (p = 0.707), 3-year CIR (p = 0.764), 1-year disease-free survival (DFS) (p = 0.954), 3-year DFS (p = 0.888), 1-year overall survival (OS) (p = 0.611), 3-year OS (p = 0.796), 3-year non-relapse mortality (NRM) (p = 0.711), or GVHD-free relapse-free survival (GRFS) (p = 0.546). The estimated median OS and DFS times were not reached in either group. In conclusion, under an ATG-based GVHD prophylaxis regimen, HLA 9/10 MMUD-HSCT is a viable alternative donor option, offering comparable clinical outcomes to those of fully matched unrelated donor HSCT.

Cytomegalovirus (CMV) infection remains a major complication in recipients of hematopoietic stem cell transplantation (HSCT) and contributes significantly to morbidity and mortality. Effective CMV prevention and management are essential for improving transplant outcomes. Preventive strategies include antiviral prophylaxis and preemptive treatments (PET). Letermovir, a terminase complex inhibitor, has become the standard of care for primary prophylaxis in CMV-seropositive recipients because of its efficacy and favorable safety profile. PET involves regular monitoring of CMV DNAemia via polymerase chain reaction (PCR) and initiation of antiviral therapy, most commonly ganciclovir or valganciclovir, upon detection of early viral reactivation. Refractory or resistant CMV infections present a significant therapeutic challenge and often require switching to a different antiviral class while awaiting genotypic resistance testing. Maribavir, a UL97 kinase inhibitor, has demonstrated superior efficacy and improved tolerability compared to conventional therapies in the phase 3 SOLSTICE trial, making it a promising therapy for refractory or resistant CMV. Optimal CMV management requires a risk-adapted, individualized approach that integrates prophylaxis, early detection, and timely intervention to reduce CMV-related complications.

Cell-based artificial platelet production has made remarkable progress over the past three decades, driven by the need for safe and stable platelet sources in the face of donor limitations and transfusion-related risks. This review provides a chronological overview of the evolution of in vitro platelet production from various cell sources (CD34+ hematopoietic stem cells, embryonic stem cells, induced pluripotent stem cells (iPSCs), and others) and highlights key advances in the field. We outline developments from the foundational experiments of the 1990s, through the introduction of iPSCs in the mid-2000s, to the adoption of three-dimensional culture and bioreactor technologies in the late 2010s and the emergence of clinical trials in the 2020s. In addition, we discuss future perspectives, including the role of advanced gene editing and scalable biomanufacturing technologies in accelerating clinical translation. This comprehensive review underscores the promise of artificial platelet production technologies for clinical applications and discusses the remaining challenges, such as scalability, cost-effectiveness, and regulatory hurdles. The recent completion of the first human clinical trials using iPSC-derived platelets marks a significant milestone, pointing to a future in which patient-specific or human leukocyte antigen-universal platelets may be transformed into transfusion medicine and regenerative therapies.

Purpose: Neutropenia is a hematologic condition characterized by an absolute neutrophil count < 1500/μL, associated with increased infection risk. This review aimed to provide an updated overview of the classification, pathophysiology, etiology, diagnosis, and management of neutropenia in congenital and acquired forms.

Methods: We conducted a comprehensive literature review of various causes of neutropenia, including genetic syndromes, autoimmune disorders, infections, and drug-induced mechanisms. Emphasis was placed on clinical manifestations, underlying mechanisms, diagnostic algorithms, and therapeutic approaches, including recent advances in molecular diagnostics and biologic therapies.

Results: Neutropenia can result from decreased neutrophil production, immune-mediated destruction, or abnormal distribution. Congenital neutropenia is often linked to mutations in genes such as ELANE, HAX1, and SBDS. Acquired neutropenia can be caused by chemotherapy, infections, autoimmune diseases, or nutritional deficiencies. Diagnostic evaluation requires a stepwise approach incorporating clinical history, blood counts, peripheral smear, bone marrow biopsy, and molecular or serologic testing. Treatment depends on the etiology and severity and includes granulocyte colony-stimulating factor, immunosuppressants, antimicrobial prophylaxis, and hematopoietic stem cell transplantation in selected cases.

Conclusion: Neutropenia is a multifactorial disorder requiring individualized evaluation and management. Advances in genetic and immunological diagnostics combined with targeted therapies have improved risk stratification and outcomes. Early recognition and a multidisciplinary approach are essential to reduce infection-related morbidity and prevent progression to hematologic malignancies in high-risk patients.