Leukemia & Lymphoma最新文献

Radiotherapy (RT) is increasingly used as bridging therapy before CD19-targeted CAR-T infusion in large B-cell lymphoma, but its clinical role remains uncertain. We conducted a systematic review and meta-analysis of 16 studies involving 488 patients with large B-cell non-Hodgkin lymphoma who received bridging RT. Pooled estimates showed an overall response rate (ORR) of 74.6% and complete response (CR) rate of 55%. The 1-year progression-free survival (PFS) and overall survival (OS) rates were 57.7% and 72.1%, respectively. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 76.8% and 36.9% of patients, with grade ≥3 events in 6.7% and 19.1%, respectively. Compared with systemic bridging, RT was associated with superior survival, while outcomes were comparable to non-bridging cohorts. These findings suggest that bridging RT is a feasible, well-tolerated, and potentially advantageous in selected patients undergoing CAR-T therapy.

Unlike the well-recognized two-fold higher incidence rate and an earlier age of onset of MM among African Americans (AA) compared to European Americans (EA) in the United States, findings on racial disparities in survival outcomes of MM are inconclusive, ranging from worse survival, to no difference, to better overall survival in AA patients than EA patients. The clinical outcomes for patients with MM depend on a complex interplay of factors including age, disease severity, cytogenetics, treatment modalities, biological features of the responsible clone, and non-biological factors such as treatment utilization and access to care. This review focuses on genetic and molecular heterogeneity of the disease biology and characteristics among MM patients from different populations. The review discusses possible determinants of racial and ethnic disparities in the outcomes of MM and considers potential strategies to address them with an ultimate goal of decreasing MM health disparities.

Despite initiatives to enhance diversity in clinical trials (CTs), disparities persist in hematologic malignancy (HM) studies. We reviewed 1,230 US-based phase II-III HM CTs (2000-2023) including 149,434 participants and compared enrollment to SEER benchmarks. Race was reported in 59% of trials and ethnicity in 40%, with significant improvement over time. Trials initiated in 2016 or later were more likely to report race (OR 36.3) and ethnicity (OR 8.0) than those before 2008. Compared with NIH-sponsored studies, institutional (OR 0.34) and industry trials (OR 0.52) had lower odds of reporting demographics. Black and Hispanic individuals were consistently underrepresented, most notably in multiple myeloma (7.0% vs. 20.0% expected) and acute lymphoblastic leukemia (21.5% vs. 36.9% expected). NIH-funded trials enrolled more Black participants than other sponsor types. These findings emphasize the need for enforceable mandates on race and ethnicity reporting, as well as representation targets, to ensure equitable access and generalizability.

Random skin biopsy (RSB) is essential for diagnosing intravascular large B-cell lymphoma (IVLBCL), but previous clinical prediction models have shown limited performance. This study developed and internally validated predictive models for RSB positivity using data from a single center with 181 Japanese patients who underwent RSB and positron emission tomography-computed tomography (PET-CT) between 2006 and 2024. Three models were evaluated: clinical (lactate dehydrogenase [LDH] and hypoxia), PET-CT (maximum standardized uptake values [SUVmax] of the lymph nodes, lungs, and adrenal glands), and combined (LDH and SUVmax of the lymph nodes, lungs, and nose). The combined model showed superior discriminative power compared to the clinical model. All models demonstrated good calibration. Decision curve analysis revealed higher net benefits for PET-CT and combined models. These findings suggest incorporating PET-CT improves patient selection for RSB in the diagnosis of IVLBCL, and external validation in larger cohorts is needed.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma with high mortality. Ferroptosis, an iron-dependent form of programmed cell death, has potential in cancer therapy. This study investigates the role of miR-22-3p in regulating ferroptosis in DLBCL through the SIRT1/P53 pathway. Bioinformatics analysis identified key microRNAs and target genes associated with ferroptosis. Dual-luciferase assays confirmed the interaction between miR-22-3p and its target genes, while qPCR and Western blot demonstrated its regulatory effects on the SIRT1/P53 axis. Immuno-precipitation revealed the interaction between SIRT1 and P53. MiR-22-3p expression was found to be downregulated in DLBCL patients. MiR-22-3p mimic promoted apoptosis and inhibited proliferation and invasion of DLBCL cells. Knockdown of SIRT1 disrupted mitochondrial morphology, and miR-22-3p was shown to trigger ferroptosis via the SIRT1/P53 pathway.

This bi-institutional retrospective cohort study evaluated whole-body diffusion-weighted MRI (WB DW-MRI) for myeloma response assessment and its concordance with bone marrow minimal residual disease (MRD) testing. Among 53 patients, 49.1% achieved imaging complete response (imaging-CR; defined as no active focal lesions or diffuse infiltration) on post-treatment WB DW-MRI, while 33.96% showed multiple active focal lesions, 7.5% had a single active lesion, and 5.7% demonstrated persistent diffuse infiltration. Patients achieving imaging-CR demonstrated superior progression-free survival compared to non-CR patients (median not reached vs 43.3 months respectively; p = 0.025). Notably, only slight concordance was observed between bone marrow MRD (at 10^-5 sensitivity) and imaging (Cohen's kappa coefficient = 0.197). Importantly, 38.5% of MRD-negative patients with persistent imaging abnormalities progressed during follow-up, whereas PET/CT-based CR showed no prognostic impact. This study establishes WB DW-MRI as a feasible response assessment tool in myeloma with significant prognostic value in the context of modern therapies.

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.