Blood Research最新文献

Background: Inflammation indices are emerging predictors of diseases. Monoclonal gammopathy of undetermined significance (MGUS) is a precancerous state and chronic inflammation may drive MGUS progression. This study aimed to evaluate the association between inflammatory markers and MGUS.

Methods: Data from the National Health and Nutrition Examination Survey (NHANES) III and 1999-2004 were collected from 6,383 participants. MGUS subtypes were identified using immunofixation electrophoresis. Seven inflammatory indices [lymphocyte count (LC), neutrophil count (NC), platelet-neutrophil product (PPN), systemic immune inflammation index (SII), platelet-lymphocyte ratio (PLR), and C-reactive protein (CRP)] were calculated. Weighted multivariate regression and subgroup analyses assessed the relationships, reported as odds ratios (ORs) and 95% confidence intervals (CIs).

Results: Of the 6383 patients included in the study, 157 (2.45%) underwent MGUS. There was a significant correlation trend between ln PPN level and the development of MGUS, especially at low levels (OR: 2.62, 95% CI: 1.54-4.75, p-trend = 0.001), while the correlation between PLR level and MGUS was not obvious. In the subgroup analysis, a significant association between PPN level and MGUS was mainly found in the overall population, female sex, non-Hispanic black, non-hypercholesterolemia, non-type 2 diabetes (T2D), high school education or above, and divorced or widowed; however, there was no significant interaction between PPN level and MGUS in each subgroup.

Conclusion: PPN levels were significantly associated with MGUS development. Our study identified PPN as a novel and convenient inflammatory marker with potential clinical relevance. Although preliminary, the observed associations highlight the need for validation through longitudinal studies before considering their clinical applications.

Purpose: Bruton tyrosine kinase inhibitors (BTKis) are effective and well-tolerated treatments for chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). Here, we describe the clinical characteristics of hepatitis B virus (HBV) reactivation in patients with hematological malignancies treated with BTKis.

Methods: Patients were required to have a pathologically confirmed diagnosis of CLL or MCL, receive at least one cycle of ibrutinib or zanubrutinib, and have either positive hepatitis B surface antigen or hepatitis B core antibody at diagnosis. Patients were excluded if they had received rituximab or obinutuzumab within the previous 12 months.

Results: We identified five patients with CLL and one with MCL who had resolved HBV infections and received BTKis during the study period. None of the patients received anti-HBV prophylaxis after CLL diagnosis. The patient with MCL who received zanubrutinib was confirmed to have HBV reactivation even after prophylactic entecavir administration followed by tenofovir. All five patients with CLL received ibrutinib as second-line therapy. A 62-year-old man died of hepatorenal syndrome associated with HBV reactivation despite entecavir treatment.

Conclusion: To the best of our knowledge, this is the first description of HBV-related death in patients receiving BTKis from HBV-endemic areas, and the first case of HBV reactivation associated with zanubrutinib despite previous entecavir prophylaxis. Further prospective studies are warranted to develop useful guidelines for monitoring HBV DNA and antiviral prophylaxis to prevent HBV reactivation after BTKi therapy.

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 long-term 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 transplantation 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 remission/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.

Purpose: Aging leads to immune dysfunction, including altered T-cell phenotypes such as the CD5^low state. This study investigated how the exon switch regulates CD5 expression in aging in an interleukin-10 (IL-10)-dominated environment and the involvement of CCAAT/enhancer-binding protein beta (CEBP-β) in this process.

Methods: The expression of messenger RNA (mRNA) was analyzed for E1A and E1B in T cells from young and older adults. The effect of IL-10 treatment on the exon switch was assessed by measuring the E1A and E1B mRNA expression in young T cells. MatInspector analysis identified CEBP-β binding sites upstream of E1A and E1B start sites. The effect of IL-10 on CEBP-β isoforms expression was assessed using western blot, and that on CEBP-β binding onto the E1A and E1B upstream was assessed using chromatin immunoprecipitation assays. The short hairpin RNA (shRNA) silencing of CEBP-β was performed to confirm its role in E1A/E1B expression.

Results: Older individuals showed increased E1B and decreased E1A mRNA expression. IL-10 treatment of young T cells persuaded a similar shift. IL-10 changed CEBP-β binding, reducing its association with the E1B upstream region while increasing its binding to E1A. IL-10 also upregulated the liver-enriched inhibitory protein of CEBP-β. shRNA silencing of CEBP-β reduced E1B expression.

Conclusion: IL-10-driven exon switching alters CD5 expression in aged T cells, increasing E1B and decreasing E1A through CEBP-β regulation. These findings reveal a novel mechanism underlying fundamental immune aging and suggest potential targets for immune modulation. These insights may have clinical implications in chronic inflammatory diseases, autoimmune disorders, and cancer therapies.

Purpose: Allogeneic hematopoietic stem cell transplantation remains a curative option for acute leukemia. While an adequate CD34⁺ cell dose is essential for engraftment, the optimal upper threshold in haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) remains unclear.

Methods: We retrospectively analyzed 81 patients with acute leukemia who underwent haplo-PBSCT with reduced-intensity conditioning between 2010 and 2020. Patients were stratified by CD34⁺ cell dose (< 8 × 10⁶/kg vs. ≥ 8 × 10⁶/kg). Clinical outcomes, including overall survival (OS), non-relapse mortality (NRM), graft failure, and graft-versus-host disease (GVHD) incidence, were compared.

Results: A higher CD34⁺ cell dose was associated with inferior OS (P = 0.022) and increased NRM (P = 0.002), despite similar rates of graft failure and acute GVHD. Chronic GVHD was more frequent in the higher dose group, though the difference was not statistically significant. Multivariate Cox analysis confirmed a high CD34⁺ cell dose as an independent predictor of poor OS (HR 2.054, P = 0.031).

Conclusion: These findings suggest that excessively high doses may adversely affect survival by increasing transplant-related toxicity. Graft cell dose should be carefully balanced to optimize outcomes in haplo-PBSCT.

Purpose: Processing methods for hematopoietic stem cells vary significantly across institutions, with no standardized guidelines currently in place. This lack of standardization presents challenges in ensuring consistent quality and outcomes of stem cell transplantation procedures. This study investigated current practices in peripheral blood stem cell (PBSC) processing and storage among transplant centers in Korea to establish a foundation for the development of standardized guidelines.

Methods: A comprehensive questionnaire was distributed to 46 hematopoietic stem cell transplantation centers in Korea, examining five key areas: PBSC collection procedures, use of cryopreservatives, cryopreservation protocols, quality control measures, and thawing protocols.

Results: Analysis of the 29 responses revealed significant variations across different stages of PBSC handling. All centers used controlled-rate freezers, and 92.9% stored cells at temperatures below -150 $_{}^{\circ }C$ . However, other practices varied widely. Additional post-collection processing was performed by 53.8% of respondents. DMSO concentrations ranged from 5 to 15%, with diverse combinations of supplementary media. Notably, 28.6% of patients did not undergo post-thaw quality assessment tests.

Conclusion: This study identified significant heterogeneity in PBSC processing practices across Korean transplant centers. These findings underscore the need for evidence-based standardized guidelines to ensure consistent product quality and improve transplantation outcomes.

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.