Leukemia & Lymphoma最新文献

Hyperhomocysteinemia and oxidative stress are increasingly recognized in pediatric malignancies, but their interplay remains unclear. We evaluated homocysteine metabolism, vitamin cofactor status, and oxidative stress in 90 children with newly diagnosed lymphoma before chemotherapy. Plasma homocysteine, folate, vitamins B₁₂ and B₆, and oxidative stress markers (8-OHdG, nitrotyrosine, protein carbonyls, NO, iNOS) were measured, alongside MTHFR C677T genotyping. Hyperhomocysteinemia (>15 μmol/L) was present in 96% (n = 87), with low folate (median 2.6 ng/mL) and B₁₂ deficiency (B₁₂<200 pg/mL in 84%, n = 76). Homocysteine correlated inversely with folate and B₆, and positively with 8-OHdG (p < 0.05). MTHFR 677CT carriers had markedly elevated nitrotyrosine and higher 8-OHdG (p < 0.05), independent of homocysteine levels. In multivariate analysis, the T-allele predicted nitrotyrosine (p < 0.05), while homocysteine did not. These findings demonstrate profound disruption of one-carbon metabolism and oxidative stress in pediatric lymphoma at diagnosis, with genetic and micronutrient factors modulating the oxidative burden, emphasizing the value of early metabolic assessment.

Acute lymphoblastic leukemia (ALL) is among the most curable pediatric cancers, yet relapse involving the central nervous system (CNS) remains a major therapeutic obstacle. In this prospective cohort, 97 children (aged 1.1-18.2 years) experiencing their first CNS relapse were enrolled in the ALL-IC REL study. Relapses were classified as isolated CNS (i-CNS, n = 43) or combined CNS (c-CNS, n = 54), and patients received treatment through standard- or high-risk regimens, encompassing chemotherapy, cranial irradiation, and allogeneic stem cell transplantation. The estimated 2-year event-free survival was 40.0%, and overall survival 49.4%, closely matching outcomes reported internationally. Survival rates were comparable across i-CNS and c-CNS relapses, while induction failure occurred more frequently in c-CNS. Multivariable analysis identified female sex, T-cell phenotype, and very early relapse as independent predictors of poor prognosis. These results underscore the critical necessity for risk-adapted therapy techniques and the incorporation of innovative medicines into forthcoming procedures.

Acute myeloid leukemia (AML) cells depend on nicotinamide adenine dinucleotide (NAD⁺) biosynthesis via nicotinamide phosphoribosyltransferase (NAMPT) for survival. Single-cell RNA sequencing revealed robust NAMPT expression across diverse AML subtypes. Proteomic profiling showed that NAMPT inhibition with KPT-9274 induced adaptive upregulation of BCL2, an anti-apoptotic protein, highlighting a survival mechanism. BH3 profiling confirmed that AML cells hierarchically depend on BCL2, followed by MCL1 and BCLxL, for survival. Combining KPT9274 with the BCL2 inhibitor venetoclax synergistically enhanced mitochondrial dysfunction, cytochrome C release, and apoptotic death in AML blasts. Additionally, NAMPT inhibition reduced PARP activity and impaired DNA repair pathways, sensitizing AML cells to cytarabine and hypomethylating agents. Together, these results demonstrate that NAMPT inhibition both potentiates venetoclax activity and enhances the cytotoxic effects of standard chemotherapies by targeting metabolic and DNA repair vulnerabilities. These findings provide strong preclinical support for evaluating NAMPT and BCL2 dual inhibition strategies in future AML clinical trials.

Treatment of mantle cell lymphoma (MCL) is evolving rapidly. In the front-line setting important recent developments include (1) approval of the BTK inhibitor (BTKi) acalabrutinib in combination with the chemoimmunotherapy, (2) evidence that the BTKi ibrutinib given with induction chemotherapies and during maintenance phase is highly effective, (3) BTKi without chemotherapy has produced promising results, (4) BCL2 inhibitor venetoclax and BTKi can be combined to effectively treat high risk MCL with TP53 alterations, and (5) consolidation with autologous stem cell transplant (ASCT) may not provide additional efficacy benefit for patients who have received highly effective first-line treatments but may be associated with substantial toxicities. These results support a concerted effort to bring BTKi to the first-line treatment of MCL. This review focuses on key clinical trials that provide the above insights and provides a succinct review of relevant historical regimens to guide oncologists in the management of untreated MCL.

Data of cardiovascular health and its impact in acute lymphoblastic leukemia (ALL) is limited. We analyzed 164 patients with newly diagnosed ALL (median age 35 years) undergoing intensive chemotherapy to assess baseline cardiovascular risk and cardiac biomarkers impact on outcomes. Most common comorbidities were overweight/obesity (55.5%), smoking (27%), diabetes (15%), and hypertension (13%). Elevated hs-TnI and BNP were found in 8% and 32%, respectively. Using the HFA-ICOS tool, 70% of patients were classified with low-risk for cardiovascular toxicity, while the remaining comprised the moderate- and high-risk. Overall survival (OS) was better in the low-risk group (29 vs 10 months, p < 0.0001). Patients with moderate-high HFA-ICOS cardiac risk had higher induction-related mortality (HR 2.26, 95% CI 1.01-5.07; p = 0.048). Baseline biomarkers were associated with induction mortality and shorter OS. Baseline cardiovascular risk and cardiac biomarkers have prognostic impact on ALL patients. Preventive cardiovascular strategies may contribute to improved outcomes in this population.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome marked by defective cytotoxic lymphocyte function. While its immunologic features are recognized, the contribution of immunothrombosis is less defined. We analyzed plasma from 12 HLH patients with viral, lymphomatous, and autoimmune etiologies. Hallmark features included hyperferritinemia, cytopenias, hypertriglyceridemia, elevated sIL-2Rα, and acute-phase reactants. Cytokine profiling showed high IL-6, IL-8, IL-10, TNF-α, CRP, and IL-18, with variable IFN-γ. Coagulation studies revealed compensated DIC, elevated FVIIa/antithrombin complexes, and microparticle-bound tissue factor, implying in extrinsic pathway activation. Thrombomodulin shedding and reduced Protein S indicated impaired protein C anticoagulant function. The fibrinolytic system is impaired based on high levels of PAI-1/tPA, and complement activation with consumption of C3. Endothelial dysfunction was evidenced by elevated sVCAM-1, sICAM-1, angiopoietin-2, and decreased ADAMTS13. Elevated plasma SVEP-1 and immunohistochemical evidence of pS6 supported mTORC1 activation in histiocytes. In conclusion, HLH is more accurately described as a "cytokine storm" with pronounced immunothrombosis. The interplay between these 2 processes through multiple, redundant, and reciprocal mechanisms may represent a unifying pathway in HLH pathogenesis and reveal novel therapeutic targets.

Gene expression profiling (GEP)-based cell-of-origin (COO) classification is the gold standard for molecular subtyping of diffuse large B-cell lymphoma (DLBCL). However, the consistency of COO classification over time, particularly in relapsed or refractory (R/R) settings, remains insufficiently validated. In this longitudinal study, we assessed the stability and reproducibility of COO classification using the NanoString Lymph2Cx assay in paired primary and relapse samples from 84 patients with R/R LBCL. Of these, 90.2% were classified as either activated B-cell-like (ABC) or germinal center B-cell-like (GCB). COO inconsistencies were observed in 18 patients, with four patients showing a shift between ABC and GCB subtypes. While the Lymph2Cx assay demonstrates utility in COO determination, our findings raise important questions regarding the biological and clinical implications of COO shifts. Further investigation is needed to understand the mechanisms behind this instability and to refine the role of COO assessment in guiding therapeutic strategies for R/R LBCL.

Leukemia is a blood cancer caused by the abnormal multiplication of immature white blood cells and is the 11th most prevalent cancer worldwide. Early and accurate leukemia diagnosis is critically important because it directly influences treatment decisions and patient outcomes. Delayed or inaccurate diagnosis leads to disease progression, a higher risk of life-threatening infections, and poorer survival rates. Conventional detection techniques, including manual microscopic analysis and complete blood count tests, are time-consuming, less reliable, and require medical experts. Accurate and timely detection improves treatment outcomes and increases survival chances. Various artificial intelligence approaches have been implemented for leukemia detection and offer satisfactory results. This study presents a systematic review of artificial intelligence-based approaches used in leukemia diagnosis. It includes an analysis of image acquisition methods such as peripheral blood smear microscopy, flow cytometry, bone marrow biopsy imaging, and advanced imaging techniques. Preprocessing steps such as noise removal, artifact removal, and image enhancement methods that improve image contrast and quality are discussed. The review provides an overview of segmentation techniques, from conventional clustering algorithms to deep learning frameworks. It also examines machine learning and deep learning models used in leukemia classification, highlighting their merits and challenges while identifying existing issues and potential future directions.

The risk factors and prognostic impact of extramedullary involvement (EMI) before and after allogeneic hematopoietic stem-cell transplantation (allo-HSCT) in t(8;21)(q22;q22) acute myeloid leukemia (AML) remain inconclusive. We performed a multicenter retrospective study including 560 t(8;21) AML patients from 15 Chinese hematology centers. KIT mutations were more frequently observed in patients with EMI at diagnosis. EMI at diagnosis was not an independent risk factor for overall survival (OS) after adjustment for KIT mutations. The 3-year post-transplant OS rates between isolated extramedullary relapse (EMR) and bone marrow relapse after allo-HSCT were comparable. Chronic graft-versus-host disease (cGVHD) was associated with increased incidence of isolated EMR (HR = 2.33, p = 0.048). Pre- and post-transplant minimal residual disease (MRD), measured by RUNX1-RUNX1T1 transcript levels, showed no significant association with isolated EMR. In conclusion, EMI at diagnosis may not significantly impact survival in t(8;21) AML. For patients with cGVHD after allo-HSCT, EMR should be monitored.