Blood Research最新文献

Purpose: Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy with varying prognostic outcomes. This study aimed to observe potential patterns or association between RUNX1 mutations and clinical features of AML patients, including hyperleukocytosis, thrombocytosis, and 12-month survival outcomes.

Methods: A prospective cohort study involving 38 patients diagnosed with de novo AML was conducted at the RSUPN Dr. Cipto Mangunkusumo and Dharmais Cancer Hospital between 2022 and 2023. Patients were followed up for 12 months, and RUNX1 mutations within exons 4, 5, 7, and 8 were detected using polymerase chain reaction (PCR)-Sanger sequencing.

Results: This study found RUNX1 mutations in 18.4% of the patients, predominantly in exons 4 and 5. Significant differences in leukocyte counts were observed between patients with and without RUNX1 mutations (p = 0.004). However, no significant association was observed between RUNX1 mutations and hyperleukocytosis or thrombocytosis. Survival analysis revealed that Individuals with RUNX1 mutations had notably lower survival rates (hazard ratio = 6.024, p = 0.014, 95% CI = 1.436-25.279).

Conclusion: In conclusion, RUNX1 mutations may be associated with poor survival outcomes in Indonesian AML patients. Further studies involving larger cohorts and comprehensive molecular analyses are required to confirm the prognostic significance of these findings.

Purpose: Prevention of vascular events is the main objective in patients with polycythemia vera (PV) or essential thrombocythemia (ET). Carotid ultrasonography (USG) is a safe and noninvasive diagnostic tool that can be used to stratify cardiovascular and stroke risks. In our previous study, carotid plaque burden was significantly higher in patients with PV/ET than in the general population. This study aimed to determine changes in carotid plaques in patients with PV/ET.

Methods: We retrospectively evaluated the medical records of patients with ET/PV who had undergone carotid USG at least twice.

Results: Of the 56 patients, 30 had PV and 26 had ET. The carotid plaque score was increased in the follow-up carotid USG compared with that in the initial carotid USG (3.38 ± 1.47 vs. 3.73 ± 1.46, p = 0.0139). The carotid plaque burden at the time of follow-up carotid USG showed no significant differences in patients with a complete hematologic response (CHR); however, it significantly worsened in patients who failed to achieve CHR.

Conclusion: We confirmed that the carotid plaque burden persisted during follow-up in patients with PV/ET. A CHR may prevent an increase in carotid plaque burden.

Background: Peripheral T-cell lymphomas (PTCLs) are a rare and heterogeneous group of aggressive malignancies. This study aimed to comprehensively analyze patients diagnosed with PTCLs in Korea, evaluating treatment outcomes, including transplantation and long-term survival.

Patients and methods: In this retrospective study, clinical data from the National Health Insurance Service on patients with PTCL were investigated. Most patients diagnosed with mature T-cell lymphomas and natural killer (NK)/T-cell lymphomas between January 2005 and December 2022 in Korea were included. Incidence rates of each subtype and survival outcomes of both treated and untreated patients were analyzed.

Results: A total of 12,573 patients were analyzed. PTCL not otherwise specified (PTCL-NOS) and extranodal NK/T-cell lymphoma were the most frequently diagnosed, followed by angioimmunoblastic T-cell lymphoma (AITL). Compared to the general population, the relative survival rate was highest in anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma. With a median follow-up of 6.7 years, the 3-year and 5-year progression-free survival (PFS) rates among treated patients were 44.0% and 39.5%, while the overall survival (OS) rates were 48.6% and 43.5%, respectively. Kaplan-Meier survival curves indicated that patients who added etoposide to the CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen showed improved PFS and OS. In addition, autologous stem cell transplantation significantly improved PFS and OS, particularly in the PTCL-NOS and AITL subtypes.

Conclusion: Patients who received etoposide-containing CHOP-based regimens had improved treatment outcomes. The survival benefits of consolidative autologous stem cell transplantation (auto-SCT) were evident in PTCL-NOS and AITL.

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.