Blood Research最新文献

Patients with acute leukemia, particularly those undergoing allogeneic hematopoietic stem cell transplantation, are at a high risk of contracting invasive fungal infections (IFIs). These IFIs substantially increase morbidity and mortality. Over the past decade, the paradigm of IFI management has shifted markedly, with an increased emphasis on prevention and treatment. Expanded use of antifungal agents and advances in novel therapies have prolonged survival in patients with hematologic malignancies. This progress also allows subsequent lines of chemotherapy to be administered while maintaining antifungal therapy once IFIs are controlled. However, these shifts have introduced new challenges, including a rising incidence of breakthrough infections despite prophylaxis, the emergence of infections caused by rare fungi, and growing concerns regarding azole resistance. Although Aspergillus species remain the predominant pathogens, infections by uncommon molds and yeasts are increasingly encountered. This phenomenon complicates the diagnosis and necessitates diagnostic tools beyond galactomannan testing alone. Integration of novel biomarkers and antifungal susceptibility testing is essential for timely and accurate diagnosis. Current guidelines provide relatively well-defined recommendations for the definitive management of invasive aspergillosis, candidiasis, and mucormycosis. Individualized care and multidisciplinary collaboration are essential to optimize patient outcomes. In addition to prevention, diagnosis, and treatment, a deeper understanding of host immunity and its interactions with IFIs is critical for improving patient outcomes and guiding the next generation of management strategies.

Purpose: To evaluate the feasibility and safety of prophylactic donor lymphocyte infusion (DLI) following allogeneic hematopoietic stem cell transplantation (HSCT) to improve survival outcomes in pediatric patients with acute leukemia (AL).

Methods: Children with AL who received prophylactic DLI transfusion after allogeneic HSCT between October 2015 and October 2024 were retrospectively analyzed.

Results: In total, 101 pediatric patients with AL were enrolled in this study, comprising 42 acute lymphoblastic leukemia, 54 acute myeloid leukemia, and five mixed-phenotype acute leukemia cases. The median age at transplantation was 7.52 ± 3.98 years. The median time from HSCT to first DLI was 306.26 days (range 51.00-1016.00). Patients received a median cumulative dose of 5.00 × 10⁷/kg (0.50-36.20). Post-DLI GVHD occurred in 46.53% of cases. Most events were mild; severe GVHD occurred in only five cases. After prophylactic DLI transfusion, the 5-year overall survival (OS) and event-free survival (EFS) rates were 88.74% ± 3.70% and 79.66% ± 4.92%, respectively. The difference of the OS and EFS in patients with GVHD and without GVHD after prophylactic DLI transfusion were not statistically significant (χ² = 0.39, P = 0.53 and χ² = 0.98, P = 0.32). Cumulative DLI dose > 4.75 × 10⁷/kg was associated with favorable prognosis (Area under the curve 0.67, 95% confidence interval 0.50-0.83, P = 0.03).

Conclusion: Prophylactic DLI transfusion following allogeneic HSCT remains a safe and effective treatment for pediatric patients with AL and can reduce post-transplant relapse and improve long-term survival.

Background: Fatigue significantly affects health-related quality of life (HRQoL) in patients with immune thrombocytopenia (ITP). However, the interplay between fatigue and cytokines in ITP remains poorly understood.

Methods: This study included 100 patients with persistent or chronic ITP who had not received ITP-directed therapy in the previous 8 weeks and 50 age-matched healthy controls. Fatigue and HRQoL were assessed using the Functional Assessment of the Chronic Illness Therapy (FACIT) scale. Concurrently, plasma levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12, IL-17, and interferon-gamma (IFN-γ) were measured via enzyme-linked immunosorbent assay (ELISA).

Results: ITP patients had significantly lower total FACIT scores [median 146 (range 59-160]) and fatigue subscale scores [median 45 (range 9-52]) than controls [155 (149-159) and 49 (44-52), respectively; both p < 0.001]. IL-12 levels were significantly elevated in patients (313.2 vs. 95.5 pg/mL; p < 0.001) and showed a significant negative correlation with FACIT scores (Spearman's ρ = -0.272, p = 0.007). Multivariate analysis revealed that female sex, longer disease duration among patients with chronic ITP (> 24 months), and elevated IL-12 levels were independently associated with greater fatigue and poorer HRQoL.

Conclusions: ITP is associated with significant fatigue and HRQoL impairment, with IL-12 emerging as a potential immunological marker linked to this symptom burden.

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, 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 withdrew 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.

Chemoimmunotherapy (CIT) combines anti-CD20 monoclonal antibodies with chemotherapy and has long been the standard first-line treatment for follicular lymphoma (FL). However, a significant subset of patients, particularly those who experience disease progression within 24 months (POD24), continue to experience poor long-term outcomes. Conventional salvage therapies offer limited benefits for high-risk individuals, highlighting the urgent need for novel treatment strategies. T-cell redirecting therapies, including chimeric antigen receptor (CAR) T-cell products and bispecific antibodies (BsAbs), have emerged as effective options in the relapsed/refractory (R/R) setting, demonstrating high response rates and durable remissions, even among patients with POD24 or refractory disease. Although CAR T-cell therapies are associated with deeper and more sustained responses, they also have higher toxicity and greater logistical complexity. In contrast, BsAbs such as mosunetuzumab and epcoritamab offer favorable safety profiles, off-the-shelf availability, and the potential for outpatient administration. Ongoing clinical trials are actively investigating the integration of BsAbs into earlier lines of therapy, including frontline settings, with encouraging results. However, in Korea, access to CAR T-cell therapies and BsAbs remains limited to clinical trials, highlighting the need for broader clinical availability. Ultimately, treatment selection and sequencing should be personalized based on patient comorbidities, prior therapies, tumor biology, and urgency of disease control. As the treatment landscape continues to evolve, immunotherapeutic modalities are expected to play a central role in improving the outcomes of patients with FL.

β-Thalassemia is characterized by defective β-globin synthesis and chronic transfusion dependence. Beyond anemia and iron overload, patients with β-thalassemia display heightened susceptibility to infections. Neutrophil granulocytes (NGs) are crucial innate immune cells that protect against bacteria through phagocytosis, degranulation, generation of reactive oxygen species (ROS), and neutrophil extracellular trap (NET) formation. Neutrophils in patients with thalassemia exhibit impaired functions, including defective chemotaxis, reduced phagocytic killing, attenuated respiratory burst, and abnormal NET formation. Chronic immune activation and iron overload, with consequent oxidative stress, are key contributors to these defects. Iron accumulation leads to excess free iron and heme, catalyzing ROS production that damages neutrophil membranes and enzymes and induces heme oxygenase-1 (HO-1), which suppresses immune responses. Neutrophils from patients with thalassemia often show an immature phenotype and increased apoptosis, further compromising innate immunity. A growing body of evidence confirms that systemic iron overload is inversely correlated with neutrophil bactericidal activity. These neutrophil defects contribute to the high risk of infection in thalassemia. Therapeutic strategies such as intensive iron chelation, antioxidants, and modulation of the HO-1 pathway hold promise for restoring neutrophil function. A deeper understanding of these mechanisms may guide the development of new interventions to reduce infectious complications and improve patient outcomes.

Purpose: Achieving high-quality immune reconstitution (IR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is directly associated with the patient's ability to resist infections, prevent tumor relapses, and suppress graft-versus-host disease (GVHD). The status of CD4 + T cells is critical for reconstituting adaptive immunity after transplantation; however, the patterns of reconstitution and their influencing factors remain unclear.

Methods: This retrospective cohort study involved 164 patients who underwent myeloablative allo-HSCT from April 2016 to May 2023. Based on the early post-transplantation CD4 + T cell counts, the cohort was divided into two groups: 73 patients with high-quality IR (HIR) and 34 patients with low-quality IR (LIR). LIR was associated with an increased risk of Epstein-Barr virus (EBV) reactivation following transplantation. Plasma EBV viral load was monitored weekly using quantitative PCR for the first 100 days post-transplantation.

Results: The LIR group had a higher viral load at the time of the first EBV reactivation and a significantly earlier first reactivation compared to the HIR group. No significant differences were observed in overall survival, GVHD incidence, or relapse rates between the groups. A CD4 + T cell count of < 60 cells/μL within 30 days post-transplantation was associated with a higher incidence of EBV viremia compared to the control group.

Conclusion: These findings suggest that early CD4 + T cell counts may serve as a predictive marker for post-transplant EBV infection.

The phosphatidylinositol-3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway and microRNA (miRNA) regulation have been implicated in the initiation and progression of acute leukemia. Despite significant progress in the understanding of leukemogenic mechanisms, current therapies remain limited by relapse, drug resistance, and poor long-term survival, underscoring the need for novel targeted strategies. This review provides the current evidence regarding the molecular interplay between PI3K/AKT/mTOR signaling and miRNA dysregulation in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). We highlight key oncogenic and tumor-suppressive miRNAs, discuss their regulatory impact on critical genes (PIK3CA, AKT1, PTEN, and FMS-like tyrosine kinase 3 [FLT3]), and evaluate therapeutic approaches, including PI3K/AKT inhibitors and miRNA-based interventions. Furthermore, we identified existing controversies, methodological limitations, and unresolved research gaps. Finally, we emphasize the translational potential of miRNA-targeted therapies and pathway-specific inhibitors, providing insights into their integration into personalized treatment strategies for acute leukemia.