International Journal of Hematology最新文献

Evidence regarding the efficacy and safety of DeVIC (dexamethasone, etoposide, ifosfamide, and carboplatin) therapy for relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) is critically lacking. This retrospective study analyzed 78 patients with r/r DLBCL who received DeVIC therapy at a single institution. The overall response rate was 37.2%, comprising 21.8% complete and 15.4% partial responses. A total of 15 (19.2%) patients proceeded to transplantation or cellular therapy. The 3-year overall survival and progression-free survival were 28.2 and 18.0%, respectively. Multivariable analyses identified refractoriness to prior therapy and elevated serum lactate dehydrogenase (LDH) levels as significant predictors of poor response and survival. Decision tree models confirmed these findings, revealing that relapsed cases with low LDH had the most favorable outcomes. Hematological toxicities were frequent, with febrile neutropenia in 52.6% and infection-related mortality in 3.8% of patients. Those with central nervous system involvement had a dismal prognosis, underscoring the need for novel therapeutic approaches. These findings highlight the potential role of DeVIC therapy in selected patients with r/r DLBCL and provide insights into optimizing bridging strategies and subsequent immunocellular therapies.

Recent therapeutic advances, including immunomodulatory drugs, proteasome inhibitors, monoclonal antibodies, bispecific antibodies, and chimeric antigen receptor-T-cell therapies, have transformed the treatment landscape of multiple myeloma (MM). Beyond direct cytotoxicity, these agents profoundly reshape the bone marrow immune microenvironment, which plays a decisive role in disease initiation, progression, and therapeutic response. MM cells thrive within this specialized niche by recruiting and reprogramming regulatory T cells, myeloid-derived suppressor cells, dendritic cells, and macrophages to suppress antitumor immunity while simultaneously driving functional exhaustion of effector T cells and impairing natural killer cell cytotoxicity. Accumulating evidence demonstrates that these immune alterations emerge even at precursor stages, such as monoclonal gammopathy of undetermined significance and smoldering MM, progressively intensifying disease evolution. In this review, we synthesize recent insights into immune cell dynamics during MM progression, highlighting both regulatory and effector compartments. We further discuss how contemporary therapies modulate these immune interactions, underscoring their dual roles in fostering immune activation while, at times, sustaining immunosuppressive pathways. A comprehensive understanding of the immune landscape in MM will be critical to optimizing existing treatments, overcoming therapeutic resistance, and guiding the development of next-generation immunotherapies.

Chronic graft-versus-host disease (cGVHD) is a leading cause of late morbidity and mortality after allogeneic hematopoietic cell transplantation. Corticosteroids remain the standard first-line therapy; however, many patients develop steroid-refractory or steroid-dependent disease, underscoring the need for more effective and better-tolerated treatments. Ruxolitinib has emerged as the most evidence-supported option for steroid-refractory cGVHD, with the phase 3 REACH3 trial demonstrating higher response rates, durable disease control, and clinically meaningful improvements in symptom burden compared with best available therapy. Belumosudil and axatilimab have also shown encouraging efficacy and safety in heavily pretreated populations. The addition of novel agents to standard corticosteroid-based therapy has been explored in clinical trials. Interest in combination strategies, such as ruxolitinib with extracorporeal photopheresis or belumosudil, is increasing, though prospective studies are required to define their role. Key challenges include optimizing long-term safety, mitigating infectious complications, and preserving the graft-versus-leukemia effect. This review summarizes current therapeutic strategies and discusses evolving treatment algorithms, emphasizing practical considerations in therapy selection. Approaches targeting specific pathogenic mechanisms, combining agents with distinct mechanisms of action, and incorporating biomarker-driven strategies are expected to further improve outcomes and quality of life for patients with cGVHD.

Although chimeric antigen receptor (CAR)-T cell therapies are highly effective for B-cell lymphoma, they frequently cause cytokine release syndrome (CRS). High-grade CRS is serious and may require intensive care, yet reliable early predictive markers remain elusive. To identify risk factors for high-grade CRS, we retrospectively analyzed B-cell lymphoma patients who received CD19 CAR-T cell therapy. Of 106 patients analyzed, CRS occurred in 93 (88%), Grade ≥ 2 CRS in 28 (26%), and Grade ≥ 3 CRS in 6 (6%). Reticulocyte counts at infusion were significantly lower in patients who developed Grade ≥ 2 CRS (1.85 vs. 2.80 × 10⁴/µL, p = 0.02). Multivariate analysis identified low reticulocyte count (< 15,000/µL; HR 2.21; 95% CI 1.01-4.86; p = 0.048), high metabolic tumor volume (> 100 mL), and use of axicabtagene ciloleucel as independent risk factors for Grade ≥ 2 CRS. Stratification by the reticulocyte cutoff showed higher 30-day cumulative incidence of CRS in patients with low counts, for both Grade ≥ 2 (42.9% vs. 19.7%, p = 0.012) and Grade ≥ 3 CRS (17.9% vs. 1.3%, p < 0.001). KyoTox-CRS, a risk-scoring system integrating these factors, effectively stratified these CRS risks. Early prediction of high-grade CRS based on the reticulocyte count at infusion may help to guide optimal risk-based management of CAR-T cell therapy.

Venetoclax (VEN) has emerged as a frontline therapy for older adults with acute myeloid leukemia (AML), yet its advantages over intensive chemotherapy (IC) remain uncertain. This single-center retrospective study compared the efficacy and safety of VEN-based regimens (n = 35) with IC (n = 54) in newly diagnosed patients with AML aged ≥ 65 years. No significant differences were found in the primary endpoints of median event-free survival (190.0 vs. 84.5 days, p = 0.20) or median overall survival (324 vs. 273 days, p = 0.30). However, the VEN group demonstrated a significantly higher overall response rate (71% vs. 48%, p = 0.03) and a more favorable safety profile. Notably, 30-day mortality was 0% in the VEN group compared to 16.7% in the IC group. Rates of Grade ≥ 3 cytopenias and febrile neutropenia were also significantly lower in the VEN group. These findings suggest that VEN-based regimens offer comparable survival with improved response rates and reduced early mortality, supporting their use as an effective and safer alternative to IC even for some IC-eligible older adults with AML, though these conclusions are drawn from a single-center, retrospective study.

Iron absorption after the administration of oral iron preparations following a meal is generally reduced compared with fasting. The aim of this study was to investigate the effect of food on iron absorption following ferric citrate hydrate administration in patients with iron deficiency anemia. A randomized, open-label, two-cohort, two-period, single-dose crossover study was conducted to assess the effect of food on iron absorption when 500 mg ferric citrate hydrate (approximately 120 mg of ferric iron) was administered under fasted and fed (immediately after a meal) conditions. Twelve patients aged 20-45 years with iron deficiency anemia (hemoglobin: male 8.0-13.0 g/dL, female 8.0-12.0 g/dL; serum ferritin < 12 ng/mL; transferrin saturation ≤ 16%), participated. The maximum serum iron concentration change was defined as ΔC_max, and the area under the serum iron concentration change versus time curve from baseline to 24 h after administration as ΔAUC_0-24. Serum iron levels increased regardless of fasting or fed conditions, and the ΔC_max and ΔAUC_0-24 values were 39% and 29% higher, respectively, under fed versus fasting conditions. No adverse events were reported. In conclusion, food had no notable effect on iron absorption following ferric citrate hydrate administration in patients with iron deficiency anemia.

SF3B1 mutations are among the most common splicing factor mutations in myeloid malignancies, yet the mechanisms linking aberrant splicing to metabolic phenotypes remain incompletely understood. We previously demonstrated that SF3B1 mutations cause nonsense-mediated decay of BRD9, a core component of the non-canonical BAF chromatin remodeling complex. Here, we investigated how the SF3B1-BRD9 pathway contributes to metabolic reprogramming in hematopoietic cells. Using BRD9-depleted murine models and analyses of SF3B1-mutated samples, we found that BRD9 depletion markedly upregulates ALOX5, which plays a key role in lipid peroxidation, particularly by oxidizing polyunsaturated fatty acids. BRD9 and ALOX5 expressions are negatively correlated, and the presence of SF3B1 mutations is associated with ALOX5 upregulation in AML datasets. Notably, transcriptomic analysis demonstrated preferential upregulation of ALOX5 in mature myeloid lineages rather than stem/progenitor fractions. Mechanistically, integrated RNA-seq/ChIP-seq and Hi-C analyses revealed that BRD9 loss enhances CTCF occupancy at the ALOX5 locus boundary, enabling aberrant chromatin loop formation that drives transcriptional activation. These events increase lipid peroxidation and ferroptosis susceptibility in hematopoietic cells as evidenced by enhanced BODIPY-C11 oxidation and erastin sensitivity. Our findings reveal a spliceosome-to-chromatin-to-metabolism pathway in which SF3B1 mutations promote ferroptosis through BRD9-mediated chromatin dysregulation, highlighting the previously unrecognized metabolic rewiring in myeloid malignancies.

Background: von Willebrand disease (VWD) is a hereditary bleeding disorder caused by quantitative or qualitative deficiencies in von Willebrand factor (VWF). Our previous studies demonstrated that emicizumab, a bispecific monoclonal antibody that mimics activated factor VIII (FVIII) cofactor activity, enhances thrombus formation under high-shear conditions in whole blood from patients with VWD (PwVWD). However, its effect on plasma coagulation potential remains unclear.

Aim: To evaluate the coagulation-enhancing effect of emicizumab in plasma samples from PwVWD using global coagulation assays.

Methods: Plasma samples from PwVWD (type 1, n = 4; type 2, n = 9; type 3, n = 3) were spiked with emicizumab (50 or 100 µg/mL), recombinant VWF (rVWF; 2.4 U/mL), or plasma-derived FVIII/VWF concentrate (pd-FVIII/VWF; 1/2.4 U/mL). Coagulation potential was assessed using clot waveform analysis (Ad|min1|) and thrombin generation assay (Peak-Th).

Results: Emicizumab dose-dependently increased Ad|min1| in all type 1 VWD samples and improved Peak-Th in two cases. In type 2 VWD, Ad|min1| increased in all samples, while Peak-Th improved in six cases. In type 3 VWD, emicizumab increased both parameters in all cases.

Conclusion: Emicizumab enhanced ex vivo coagulation potential in plasma samples from PwVWD across all subtypes, supporting its potential as a therapeutic option.

Azacitidine (AZA) monotherapy demonstrates efficacy for post-transplant maintenance in patients with high-risk myeloid malignancies. However, no study has directly compared combination regimens. In this retrospective cohort study, 59 patients (AML = 56, MDS = 3) received AZA-based maintenance post-allogeneic hematopoietic stem cell transplantation (allo-HSCT), as monotherapy (n = 33), AZA plus interferon-α (IFN-α) (n = 15), or AZA plus targeted agents (n = 11). At the median 31-month follow-up, the overall relapse rate was 10.2% (6/59), with comparable rates across groups (AZA: 9.1%, AZA + IFN-α: 13.3%, AZA + targeted: 9.1%) (P = 0.850). Three 3-year relapse-free survival (89.4%; 95%CI 84.7-94.1%) and overall survival (84.4%; 95%CI 78.9-89.9%) rates did not differ significantly between monotherapy and combination regimens (RFS P = 0.975; OS P = 0.770). Overall adverse event rates showed no statistical difference (P > 0.05), although febrile reactions were more common with IFN-α combination regimens (P < 0.001). These findings demonstrate that AZA monotherapy has non-inferior efficacy compared with combination regimens and has a favorable toxicity profile, establishing it as a viable backbone for maintenance therapy in MRD-negative patients. Biomarker-driven combinations warrant prospective validation.

Hematopoietic stem cell transplantation (HSCT) recipients are highly susceptible to viral infections, many of which are missed by conventional diagnostic tests owing to limited coverage and slow turnaround times. This single-center, prospective observational study evaluated a rapid multiplex PCR (mPCR) assay to detect 13 DNA viruses for diagnosis and management of post-HSCT viral infections. Between December 2020 and March 2025, 63 HSCT recipients with suspected viral infections underwent mPCR testing of blood (n = 51) or cerebrospinal fluid (CSF) (n = 12) in parallel with standard diagnostics. The mPCR results were reported within 24 h and integrated into clinical decision-making. The etiology was identified in 44 of 51 (86%) blood samples (30 infections) and 9 of 12 (75%) CSF samples (5 infections). mPCR provided the sole etiological diagnosis in 19 of 63 (30%) episodes: 15 of 51 (29%) blood and 4 of 12 (33%) CSF samples. mPCR enabled targeted treatment in 15 of 63 (24%) episodes: 11 of 51 (22%) blood and 4 of 12 (33%) CSF samples. Unexpected infections, such as varicella-zoster virus meningitis and human herpesvirus 7 encephalitis, were identified only by mPCR. Rapid mPCR provided timely, actionable diagnosis and directly influenced the clinical management of post-HSCT patients.