Search Results (582)

Diffuse large B-cell lymphoma (DLBCL) is a biologically heterogeneous mature B-cell neoplasm whose classification, prognosis, and therapy have been reshaped by advances in genomic, transcriptomic, epigenomic, single-cell, and spatial profiling technologies. This review focuses on how these approaches have refined the molecular landscape of DLBCL, including recurrent chromosomal translocations, tumor-suppressor alterations, oncogenic signaling pathways, and tumor-microenvironment programs. Cell-of-origin (COO) frameworks remain clinically useful. However, contemporary models extend beyond conventional germinal center categories by incorporating probabilistic genetic subtypes, expression-defined high-risk states, and spatially resolved lymphoma-cell and immune-cell ecosystems. These high-resolution methods clarify intratumoral heterogeneity, identify biologically distinct subgroups, and inform prognosis and therapeutic selection. The review also summarizes how tumor-intrinsic biology and the tumor-microenvironment (TME) shape responses to frontline therapy, targeted agents, antibody-drug conjugates, bispecific antibodies, and CD19-directed CAR T-cell therapy. Particular emphasis is placed on product-specific evidence in relapsed/refractory disease, rational sequencing of immunotherapies, and emerging biomarkers such as circulating tumor DNA-based measurable residual disease (ctDNA-MRD). Together, these developments support a shift from COO-centric classification toward dynamic, biology-driven models that incorporate tumor-intrinsic and microenvironmental determinants to guide personalized therapy in DLBCL. Full article

Background: This review aims to provide a comprehensive and practical overview of the evolving role of autologous transplantation in leukaemias, a strategy that was once largely abandoned but has recently regained interest in selected clinical settings. Methods: We reviewed the historical development of autologous transplantation in acute leukaemias, including the early period during which autologous transplantation was considered inferior to allogeneic approaches because of limited graft purification techniques and the inability to induce effective graft-versus-leukaemia (GVL)-like immune responses. We further summarise more recent experimental strategies aimed at improving stem cell purification and enhancing anti-leukaemic immune activity in autologous settings. In addition, we discuss how advances in measurable residual disease (MRD) assessment and molecular risk stratification have contributed to the renewed interest in autologous transplantation in selected subgroups of leukaemia patients. Results: This review identifies clinical situations in which autologous transplantation remains an important therapeutic option, including plasma cell leukaemia, where it continues to represent a standard first-line approach. We also discuss well-defined patient subgroups, particularly selected AML subtypes with intermediate-risk molecular profiles and acute promyelocytic leukaemia (APL) in second remission, in which outcomes following autologous transplantation may be comparable to, or occasionally superior to, those achieved with allogeneic transplantation. In contrast, autologous transplantation currently plays only a limited role in diseases such as chronic lymphocytic leukaemia (CLL) and chronic myeloid leukaemia (CML). Although attempts to induce potent anti-leukaemic immune effects in autologous settings have so far shown limited clinical efficacy, several emerging strategies appear promising and may further expand the role of autologous transplantation, particularly in elderly or frail patients. Discussion: Overall, current molecular and MRD-based risk stratification strategies, together with emerging immunological and graft-manipulation approaches, may redefine the role of autologous transplantation as a personalised therapeutic option in selected subgroups of leukaemia patients. Full article

Pediatric acute myeloid leukemia (AML) is biologically heterogeneous, and genomic profiling increasingly informs risk stratification and treatment. We evaluated the relationship between induction response, genomic risk, transplant allocation, and survival in pediatric AML. We retrospectively analyzed 38 pediatric patients with newly diagnosed AML, treated between 2020 and 2025. Clinical, cytogenetic, molecular, treatment, and outcome data were collected. Genomic alterations were assessed using cytogenetics, fluorescence in situ hybridization (FISH), molecular testing, and next-generation sequencing (NGS). Survival was estimated by Kaplan–Meier analysis, and prognostic factors for event-free survival (EFS) were assessed using univariable Cox regression. This study is exploratory given the limited sample size and should be interpreted accordingly. Complete remission (CR) after the first course of induction was achieved in 25/38 patients (65.8%), partial remission (PR) in 3/38 (7.9%), and refractory disease in 10/38 (26.3%). Twenty-four patients underwent allogeneic hematopoietic stem cell transplantation; 17/24 (70.8%) were alive at last follow-up, with a 2-year overall survival rate of 72.9%. Both induction response and genomic risk stratification showed suggestive associations with outcome; descriptively, induction response showed the strongest prognostic discrimination, with achievement of CR associated with markedly improved survival. High cytogenetic risk and FLT3-ITD were significantly associated with inferior EFS. Post-induction measurable residual disease (MRD) positivity was detected in 16 of 38 patients (42.1%) and was associated with suboptimal induction response; MRD negativity did not uniformly preclude adverse outcomes, particularly in the high-risk genomic subgroup. Genomic profiling refined biological risk and post-remission treatment allocation. Integrated assessment of genomic risk, induction response, and MRD status may improve therapeutic stratification in pediatric AML. Full article

Background: Oculopharyngodistal myopathy (OPDM) is a rare disorder with progressive ptosis, ophthalmoplegia, and oral incompetence, which pose challenges to management. While surgical interventions for blepharoptosis have been reported, addressing concurrent facial muscle weakness remains a significant challenge in comprehensive disease management. Case: A 59-year-old woman with OPDM exhibited severe ptosis and oral incompetence. Despite undergoing prior cosmetic interventions, these symptoms had progressively worsened over 10 years. Preoperative evaluation revealed complete ptosis with a margin reflex distance 1 (MRD-1) of 0 mm and preserved Bell’s phenomenon. A two-stage reconstruction using fascia lata grafting corrected ptosis with a frontalis sling and restored oral competence with U-shaped grafts anchored to the zygomatic arches. Results: At 3 years and 6 months postoperatively, eyelid elevation had improved without corneal exposure, and oral competence was restored, resolving drooling. Conclusions: Semi-dynamic reconstruction using fascia lata grafting effectively addresses ptosis and oral incompetence in OPDM, improving visual and swallowing functions and enhancing quality of life. Full article

Background/Objectives: Long non-coding RNAs (lncRNAs) have been identified as potential biomarkers for cancer diagnosis and prognosis. In the present study, we proposed the analysis of four lncRNAs as a diagnostic support candidate for the follow-up of leukemia patients. The aim of this study was to characterize the expression of BALR6, LINC-PINT, MEG3, and ZEB1-AS1 in patients with B-cell acute lymphoblastic leukemia (B-ALL) at diagnosis and at the end of remission induction therapy. Methods: B-ALL diagnosis and MRD assessment were performed by flow cytometry, while lncRNA expression levels were quantified using TaqMan probe-based assays. Results: Fifteen pediatric patients with B-ALL were followed longitudinally. MRD evaluation identified seven refractory and eight remitted patients. Significant expression changes were observed for MEG3 in remitted patients and for BALR6 and LINC-PINT in refractory patients. No statistically significant differences were detected for ZEB1-AS1. Conclusions: Changes in MEG3, LINC-PINT, and BALR6 lncRNA expression are associated with treatment response and MRD status in pediatric B-ALL, supporting their potential role as complementary biomarkers to conventional MRD monitoring. Full article

Background/Objectives: Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer with a 40% recurrence rate. However, reliable biomarkers for early recurrence detection or treatment guidance are lacking, especially for virus-negative tumors. Circulating tumor DNA (ctDNA), a fragment of tumor-derived cell-free DNA in blood, has emerged across multiple cancers as a minimally invasive precision biomarker to detect minimal residual disease (MRD); predict recurrence; and monitor treatment response. This review’s objective was to summarize recent advances in ctDNA as a tool for therapeutic decision-making in MCC, contextualized by findings in other malignancies. Methods: A comprehensive literature review was performed, focusing on studies published between 2016 and 2026 that evaluate ctDNA in MCC and other cancers. Key prospective trials, observational studies, and case reports were identified through PubMed and relevant conference proceedings. Data on ctDNA assay methods (tumor-informed vs. tumor-agnostic), clinical sensitivity, lead time for recurrence detection, and predictive value for therapy response were extracted and synthesized. Results: Across cancers such as colorectal, lung, and melanoma, ctDNA positivity after curative treatment predicts relapse months in advance of imaging and can guide adjuvant therapy decisions. In MCC, recent studies demonstrate that ctDNA levels correlate with MCC tumor burden and exhibit high sensitivity and specificity for clinically evident disease. Stage I-III MCC patients who were ctDNA-positive within four months of treatment had a 7.4-fold higher recurrence risk within the subsequent 12–18 months of follow-up. Serial ctDNA monitoring may enable earlier intervention in otherwise asymptomatic ctDNA-positive MCC cases, helping distinguish responders from non-responders. Conclusions: ctDNA is an emerging precision biomarker that offers significant prognostic and surveillance utility in MCC. It enables earlier detection of recurrence, potentially allowing treatment to begin before clinical disease manifests. It also helps stratify patients by risk and treatment response, informing personalized surveillance intensity and therapeutic choices. Integrating ctDNA monitoring into MCC management could improve outcomes by guiding timely interventions, although prospective trials are needed to confirm that ctDNA-guided decisions translate to improved patient survival. Formal cost-effectiveness analyses have not yet been conducted and represent an important area for future investigation. Full article

The management of acute myeloid leukemia (AML) remains characterized by high relapse rates despite advances in induction and consolidation therapy. Relapse prevention represents a major unmet need, particularly in patients ineligible for allogeneic hematopoietic stem cell transplantation (allo-HSCT) or at high risk of post-transplant recurrence. This review examines current evidence supporting maintenance strategies following intensive chemotherapy or allo-HSCT, with emphasis on measurable residual disease (MRD)-guided approaches and targeted therapies. We summarize data from randomized and phase II/III trials evaluating hypomethylating agents, FLT3 inhibitors, IDH inhibitors, and immunotherapeutic strategies in post-remission settings. Oral azacitidine (CC-486) demonstrated overall survival benefit in older patients in first complete remission who were not transplant candidates, establishing a standard of care in this population. In FLT3-mutated AML, post-transplant maintenance with sorafenib and gilteritinib reduces relapse risk, with emerging evidence supporting MRD as a predictive biomarker for benefit. Other targeted agents and immunotherapies have shown promising early-phase results, although confirmatory data are limited. Ongoing phase III studies will clarify optimal patient selection, treatment duration, and integration with transplantation, aiming to transform post-remission management from passive surveillance to precision-based relapse prevention. Full article

Mg–Y–Zn alloys have attracted considerable attention for lightweight structural applications; however, the influence of extrusion temperature on microstructural evolution and the underlying mechanisms governing strength–ductility synergy remains insufficiently understood. In this study, a novel YZG921 (Mg–9Y–1.8Zn–1.2Gd–0.5Zr–0.3Ca, wt.%) alloy was fabricated by hot extrusion at temperatures ranging from 480 to 520 °C. The microstructure, mechanical properties, and deformation behavior were systematically investigated using SEM, TEM, EBSD, in situ EBSD, and slip-trace analysis. The results show that extrusion temperature significantly affects the evolution of secondary phases, grain size, and texture intensity. At 500 °C, an 18R-LPSO phase was formed, accompanied by a more homogeneous distribution of secondary phases and the finest grain structure (~3.8 μm), whereas the average grain size remained close to 10 μm for the alloys extruded at 480 °C and 520 °C. Meanwhile, the maximum basal texture intensity decreased from 4.16 to 4.79 m.r.d. to 2.18–2.58 m.r.d. Mechanical testing revealed that the alloy extruded at 500 °C exhibited the optimum strength–ductility balance, with an ultimate tensile strength of 498.4 MPa and an elongation of 13.8%. In situ EBSD analysis showed that the fraction of low-angle grain boundaries increased from ~7% to 43% during tensile deformation, while the average KAM value increased from ~0.5° to 0.88°. Slip-trace analysis further demonstrated that plastic deformation was predominantly governed by basal slip, accounting for approximately 84.2% of the activated slip systems. The superior mechanical performance achieved at 500 °C is attributed to the synergistic effects of grain refinement, LPSO and second-phase strengthening, texture weakening, and sustained strain hardening. These findings provide insights into microstructure–property relationships and offer guidance for the optimization of thermomechanical processing parameters in Mg–Y–Zn alloys. Full article

The influence of double continuous cold rolling followed by annealing on the texture evolution and mechanical properties of a commercial low-carbon ferritic steel was investigated. Ultrathin sheets (final thickness 0.22 mm) were produced through a two-stage cold rolling process with intermediate and final annealing at 690 °C for 35 s, followed by light temper rolling at 100 °C for 20 s. Texture evolution was characterized using Electron Backscatter Diffraction (EBSD) with Orientation Imaging Microscopy (OIM), producing pole figures and orientation distribution functions (ODFs). Mechanical properties were evaluated through Vickers microhardness and ultimate tensile strength measurements obtained from three independent locations per sample. Quantitative ODF analysis (φ₂ = 45°) revealed that γ-fiber ({111}//ND) intensity increased after each cold reduction stage and decreased after annealing due to recrystallization. The α-fiber (110/RD) and cube components (001//RD) showed a slight increase after annealing. The final ultrathin sheet exhibited moderate γ-fiber intensity (≈3 M.R.D), low Vickers microhardness (100–150 HV), and tensile strength (400–450 MPa). These results demonstrate controlled evolution of texture and microstructure during double cold rolling and annealing, providing a basis for future studies on forming-related behavior without directly assessing formability. Full article

TC2 titanium alloy (Ti-4Al-1.5Mn, wt.%) is a near-α titanium alloy with promising aerospace and biomedical applications, but its limited room temperature ductility and strong texture sensitivity hinder the fabrication of high-performance sheets. In this study, the effects of hot rolling at 830 °C and 930 °C on the microstructure, macro-texture, mechanical properties, and fracture behavior of TC2 alloy were investigated. Compared with the 830 °C rolled sample, the 930 °C rolled sample exhibited finer primary α grains, a higher volume fraction of fine and dispersed secondary α_s phase, and more uniform Mn distribution, while both samples retained an α + β phase constitution. Texture and ODF (orientation distribution function) analyses revealed that increasing the rolling temperature reduced the maximum intensity of the (0001) pole figure from 6.68 to 5.23 m.r.d. (multiples of a random distribution) and increased that of the (10-10) pole figure to 9.62 m.r.d., indicating weakened basal texture, enhanced prismatic texture, and more dispersed orientation distribution. Consequently, although the tensile strength slightly decreased to approximately 730 MPa, the elongation increased from approximately 24% to 28%. The finer and denser dimples observed after 930 °C rolling further confirmed improved plastic deformation coordination. Full article

Measurable residual disease (MRD) in acute myeloid leukemia (AML) is monitored through detection of leukemia-associated phenotypic protein markers (LAPMs) in bone marrow aspirates, hindering disease real-time monitoring. We explored peripheral blood (PB), extracellular vesicle (EV)-based methods for MRD monitoring. To confirm that LAPMs are present in AML-derived EVs, EVs were isolated from OCI-AML3 cells by differential centrifugation and characterized according to their size (nanoparticle tracking analysis), morphology (transmission electron microscopy) and protein cargo (proteomic analysis and Western blot). CD14 and CD33 were detected in OCI-AML3 cells and their released EVs. To select a method to isolate EVs from the PB of AML patients, three techniques were tested: size exclusion chromatography followed by ultrafiltration (SEC-UF), Total Exosome Isolation Kit (Invitrogen) and Exo-spin™ Exosome Purification Kit (Cell Guidance Systems). SEC-UF allowed EV isolation with higher purity and less aggregates than the other techniques. LAPMs were detected in those EVs, but their presence depended on the isolation method. Finally, EVs from seven AML patients’ plasma were isolated by SEC-UF. LAPMs were identified in paired samples at diagnosis and remission, with differential expression throughout disease evolution. This proof-of-concept study highlights the possibility of real-time MRD monitoring through LAPMs’ analysis in AML patient’s circulating EVs. Full article

Acute myeloid leukemia (AML) is a genetically and clinically heterogeneous hematologic malignancy in which intensive induction chemotherapy remains the standard therapeutic platform for medically fit adults. In recent years, however, the frontline treatment paradigm has progressively evolved from a purely cytotoxic approach toward a biologically informed strategy. This shift has been driven by the identification of recurrent molecular alterations—particularly FLT3 and IDH1/2 mutations—as well as renewed interest in antibody-based therapies and the growing recognition that relapse, resistance, and measurable residual disease (MRD) are shaped by clonal architecture rather than blast burden alone. This review examines the development of targeted therapies combined with intensive chemotherapy in AML. We discuss the biological rationale for combination approaches and summarize the key clinical studies that have defined current practice, including trials evaluating FLT3 inhibitors, gemtuzumab ozogamicin, IDH inhibitors, and venetoclax-based strategies. We also address the role of targeted therapy across different treatment phases, including induction, consolidation, and post-remission settings, and analyze emerging data regarding MRD-guided treatment strategies, mechanisms of resistance, and integration with allogeneic hematopoietic stem cell transplantation. The integration of targeted agents with intensive chemotherapy is reshaping frontline AML therapy and represents a critical step toward precision medicine. While genotype-directed strategies—such as FLT3 inhibition—have already demonstrated survival benefit, optimal patient selection, treatment sequencing, and duration remain areas of active investigation. Future progress will likely depend on MRD-driven treatment adaptation, improved understanding of clonal evolution, and the development of rational multi-agent combinations capable of achieving deeper and more durable remissions. Full article

Therapy for chronic lymphocytic leukemia (CLL) has evolved dramatically with the introduction of targeted agents, particularly Bruton tyrosine kinase inhibitors (BTKis) and BCL2 inhibitors (BCL2is). This review summarizes contemporary frontline and relapsed/refractory treatment strategies, with an emphasis on molecular risk stratification, combination and triplet regimens, measurable residual disease (MRD)–guided therapy, and time-limited approaches. We further examine how genomic complexity, prior therapies, and sociodemographic factors influence disease progression, treatment resistance, and clinical outcomes. Full article

Background: Pancreatic ductal adenocarcinoma (PDAC) exhibits high post-resection relapse and early systemic dissemination rates. The level of circulating tumor cells (CTCs) correlates with early metastatic failure, motivating CTC interception strategies. Methods: In this hypothesis-driven review, we synthesized the contemporary evidence on PDAC staging and therapy, CTC detection (including portal versus peripheral sampling), and circulating tumor DNA (ctDNA)-based minimal residual disease (MRD), and evaluated the translational rationale for CTC-targeted adoptive immunotherapy focusing on CEACAM6 and CAR-T cells. Results: Prospective studies report higher portal versus peripheral CTC yields and stronger associations with relapse; tumor-informed ctDNA positivity in peri-operative and surveillance windows predicts shorter disease-free survival. CEACAM6 is overexpressed in PDAC and linked to invasion and metastasis, supporting antigen selection. However, target overexpression alone does not establish clinical suitability for adoptive cell transfer. Consequently, its therapeutic implementation must contend with assay heterogeneity, on-target/off-tumor risks, and the lack of interventional outcome data in PDAC, all of which remain key hurdles. Conclusions: CTC-targeting is biologically plausible and operationally measurable in PDAC. Consequently, a CEACAM6-directed CAR-T approach is proposed as a potential strategy for the interception of minimal residual disease (MRD). Randomized and biomarker-selected trials with composite MRD-clearance endpoints (CTC < LOQ and ctDNA-negative) may be justified to validate this interventional hypothesis. Full article

Relapse remains the leading cause of treatment failure following hematopoietic cell transplantation (HCT) for hematologic malignancies. Circulating tumor DNA (ctDNA) has emerged as a promising minimally invasive biomarker for measurable residual disease (MRD) assessment and early relapse detection; however, the prognostic significance of ctDNA in the post-transplant setting has not been comprehensively synthesized. We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines and registered the protocol in PROSPERO (CRD420261392100). PubMed, Embase, Web of Science, EBSCO, Cochrane CENTRAL, and supplementary sources were searched through November 2025. Eligible studies evaluated tumor-specific ctDNA or tumor-informed/tumor-associated cfDNA in patients undergoing allogeneic or autologous HCT for hematologic malignancies. Random-effects meta-analyses were performed for relapse/progression, overall survival (OS), and relapse-free/progression-free survival (RFS/PFS). Studies evaluating total cfDNA quantity, methylation-based cfDNA profiling, cfRNA, or chimerism-only monitoring were synthesized narratively. Ten observational cohort studies comprising 883 patients met inclusion criteria. Across acute leukemias, lymphomas, multiple myeloma, and myelodysplastic syndromes, ctDNA/cfDNA positivity was consistently associated with adverse outcomes. The pooled hazard ratio (HR) for relapse or disease progression was 12.57 (95% CI: 4.59–34.46; p < 0.001), while pooled HRs were 7.45 (95% CI: 4.11–13.48; p < 0.001) for OS and 4.46 (95% CI: 2.22–8.97; p < 0.001) for RFS/PFS. Although statistical heterogeneity was low, interpretation was limited by the relatively small number of studies contributing to each pooled endpoint. Narrative evidence additionally suggested that broader circulating nucleic acid approaches may provide complementary information regarding graft-versus-host disease, infection, and other post-transplant complications. Tumor-specific ctDNA positivity is consistently associated with increased relapse risk and inferior survival outcomes following HCT. These findings support further investigation of ctDNA-based MRD monitoring as a promising non-invasive biomarker for post-transplant molecular surveillance and risk stratification. However, prospective multicenter validation studies, assay standardization, and ctDNA-guided interventional trials remain necessary before routine clinical implementation can be recommended. Full article