Search Results (2,344)

Background: Lenalidomide maintenance after autologous stem cell transplantation (ASCT) improves progression-free survival (PFS) and overall survival (OS) in multiple myeloma; however, these benefits are attenuated in high-risk multiple myeloma (HRMM). No standard post-transplant maintenance strategy is established for HRMM, and some centers employ doublet maintenance with bortezomib plus lenalidomide (VR). We evaluated outcomes with VR versus lenalidomide alone (R) in HRMM. Methods: We conducted a multicenter retrospective study through the US Myeloma Innovations Research Collaborative (USMIRC), including adults with HRMM who received R or VR maintenance following ASCT between January 2009 and January 2024. HRMM was defined by del(17p), t(4;14), t(14;16), or t(14;20), with or without 1q gain. PFS and OS were estimated using Kaplan–Meier methods. Median follow-up was 91 months. Baseline characteristics, induction regimens, and post-transplant response depth were well balanced between the groups. Median PFS was 51 months (95% CI, 20–NR) with VR and 36 months (95% CI, 31–56) with R (p > 0.05). Median OS was 103 months (95% CI, 90–NR) and 110 months (95% CI, 94–NR), respectively (p > 0.05). VR was associated with numerically longer PFS, although the difference was not statistically significant. No treatment-related mortality occurred within 100 days post-ASCT. Conclusions: In this multicenter real-world analysis of HRMM, VR maintenance did not result in statistically significant improvements in PFS or OS compared with lenalidomide alone. These findings underscore the need for prospective, risk-adapted trials incorporating novel maintenance strategies, including CD38- and BCMA-directed therapies, in high-risk disease. Full article

Background/Objectives: 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is used in oncology but has limited specificity due to uptake in infectious and inflammatory conditions. This study evaluated the diagnostic value of 18F-FDG PET/CT in patients with infectious, inflammatory, and malignant lesions and its role in guiding histopathological biopsy decisions in an infectious disease setting. Methods: A retrospective cohort study included 186 adult patients who underwent 18F-FDG PET/CT between 2018 and 2023 for diagnostic evaluation at a tertiary care hospital. Clinical indications were fever of unknown origin (FUO), inflammation of unknown origin (IUO), lymphadenopathy of unknown origin, and suspected solid mass. Diagnostic yield, biopsy decisions, and factors associated with biopsy were analyzed. Results: The diagnostic yield of 18F-FDG PET/CT was 58.6%, with higher in malignant conditions (hematologic malignancy 85.7%, solid organ malignancy 88.9%) and lower in autoimmune/inflammatory diseases (20.8%) and mycobacterial infections. PET/CT showed moderate sensitivity (59.8%) and high specificity (98.7%) for infection detection, improving to 67.8% sensitivity after excluding mycobacterial infections. Biopsy was performed more in patients with lymphadenopathy, higher SUVmax (>7.4), and PET/CT findings not suggestive of infection. Analysis identified lymphadenopathy (aOR = 2.77), PET/CT not suggestive of infection (aOR = 4.73), and SUVmax > 7.4 (aOR = 4.98) as predictors of biopsy. Conclusions: 18F-FDG PET/CT provides moderate diagnostic value across infectious, inflammatory, and malignant diseases and guides biopsies effectively, particularly in patients with lymphadenopathy, elevated SUVmax, and non-infectious findings. Its limited performance in mycobacterial and autoimmune diseases requires cautious interpretation. Overall, 18F-FDG PET/CT supports clinical decisions in complex diagnostic scenarios. Full article

Immunotherapy with immune checkpoint inhibitors (ICIs) has represented a major breakthrough in the treatment of multiple solid and hematological malignancies, significantly improving survival and tumor control. However, the blockade of immune regulatory pathways such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) is associated with the development of immune-related adverse events, among which immune-mediated colitis (IMC) constitutes one of the most relevant gastrointestinal complications due to its frequency, potential severity, and impact on the continuation of oncologic treatment. IMC typically presents with diarrhea, abdominal pain, and gastrointestinal bleeding, and may progress to severe, life-threatening forms. Its incidence varies according to the type of ICI, and is higher with CTLA-4 inhibitors and particularly elevated with combination therapies. The pathophysiology is complex and multifactorial, involving dysregulated activation of proinflammatory T lymphocytes, impairment of immune regulatory mechanisms, disruption of the intestinal epithelial barrier, and a key modulatory role of the gut microbiota. Diagnosis requires a high index of clinical suspicion and relies on endoscopy with biopsies, given the poor correlation between clinical severity and endoscopic or histological findings. Fecal biomarkers, such as calprotectin and lactoferrin, are useful for risk stratification and disease monitoring. Treatment is based on a stepwise immunosuppressive approach, with corticosteroids as first-line therapy and biologic agents such as infliximab or vedolizumab in refractory cases. Emerging strategies, including fecal microbiota transplantation, offer new therapeutic perspectives. This article provides a comprehensive review of the current evidence on the epidemiology, pathophysiology, diagnosis, and management of IMC, as well as future challenges and opportunities in its clinical management. Full article

Cancer-associated thrombosis (CAT) is a major cause of morbidity and mortality in oncology, arising from complex interactions between tumor biology, host factors, and anticancer therapies. Growing evidence indicates that biological sex and gender-related factors modulate both thrombotic risk and clinical expression of venous thromboembolism (VTE) in patients with cancer. In this narrative review, we summarize current epidemiological, biological, and clinical data on sex- and gender-related differences in CAT across solid and hematologic malignancies. Men generally exhibit a higher overall incidence of VTE, whereas women may experience earlier, treatment-associated thrombotic events, with variability according to cancer type, stage, and therapy. Biological factors linked to coagulation and inflammation differ between sexes and may contribute to these patterns, although mechanistic evidence remains incomplete. Sex-related disparities also emerge in treatment-associated complications, including bleeding risk and abnormal uterine bleeding in anticoagulated women of reproductive age. In contrast, evidence for sex differences in oncohematology-associated thrombosis is limited and inconsistent. Gender-related inequalities in clinical trial participation further constrain the interpretation of available data. Overall, current evidence supports sex as a clinically relevant modifier of CAT risk, underscoring the need for systematic sex- and gender-informed research, to improve mechanistic understanding, and sex-stratified reporting to advance precision medicine in thrombosis and oncology. Full article

This narrative review provides a comprehensive synthesis of patients with cancer disproportionately affected by vaccine-preventable infectious diseases due to malignancy-related immune dysfunction and treatment-induced immunosuppression. Vaccination represents a cornerstone of supportive care in oncology; however, vaccine uptake remains suboptimal and immune responses are frequently attenuated, particularly in patients with hematological malignancies and those receiving highly immunosuppressive therapies. This review provides a comprehensive synthesis of current evidence on vaccine immunogenicity, clinical effectiveness, and safety in oncology patients. We discuss immunological mechanisms underlying impaired vaccine responses, summarize evidence for major vaccines recommended in oncology practice, and address key clinical challenges such as timing relative to anticancer therapies, heterogeneity of immune responses, and vaccine hesitancy. An extended discussion highlights emerging strategies, including booster dosing, adjuvanted vaccines, and personalized vaccination approaches. Finally, future perspectives are outlined to improve integration of vaccination into routine oncology care. Full article

Background: Acquired epidermodysplasia verruciformis (AEV) is a rare cutaneous disorder arising in immunocompromised individuals. AEV is characterized by flat-topped, wart-like, or hypopigmented lesions predominantly on sun-exposed areas. Unlike classic genetic EV, AEV develops in the absence of germline mutations or family history. AEV most commonly arises in patients receiving iatrogenic immunosuppressive therapy for organ transplantation, autoimmune disease, or hematologic disorders. Methods: A comprehensive literature review was conducted via the PubMed database. Case reports and case series studies describing AEV in transplant and non-transplant iatrogenic immunosuppression were identified through a literature search. There were no restrictions on language or publication year. The last search was conducted in July 2025. Reports were analyzed for patient demographics, immunosuppressive agents, HPV subtypes, clinical and histopathologic features, and treatment outcomes. Results: AEV occurs across a broad spectrum of immunosuppressive therapies, including calcineurin inhibitors, antimetabolites, biologics, tyrosine kinase inhibitors, and cytotoxic chemotherapy. β-HPV subtypes, most commonly HPV 5 and 8, drive lesion formation in the context of impaired cell-mediated immunity. Histopathology demonstrates keratinocyte vacuolization, acanthosis, and perinuclear halos. Lesions may persist despite immunosuppressive adjustment, due to viral latency and incomplete immune reconstitution. Treatment strategies are varied and include topical retinoids, immune response modifiers, systemic retinoids, and HPV vaccination, and have variable efficacy. AEV carries an elevated risk of cutaneous squamous cell carcinoma, particularly in transplant recipients, and highlights the need for proactive dermatologic management. Conclusions: AEV represents a clinically significant consequence of immunosuppression mediated by β-HPV. Early recognition, monitoring for malignant transformation, and individualized multimodal therapy are critical. Future studies should evaluate targeted interventions to enhance antiviral immunity and establish standardized treatment guidelines. Full article

Background/Objectives: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma and remains incurable in approximately 30–40% of patients despite advances in immunochemotherapy. Although gene expression profiling has improved risk stratification, there is an ongoing need for non-invasive, cost-effective, and clinically practical biomarkers to identify patients at high risk of treatment resistance or relapse (R/R). Systemic inflammation plays a pivotal role in DLBCL pathogenesis, impacting both tumor progression and treatment response. The C-reactive protein–albumin–lymphocyte (CALLY) index, integrating markers of inflammation, nutritional status, and immune competence, has demonstrated prognostic relevance in solid tumors; however, its relevance in hematologic malignancies remains unexplored. Methods: We retrospectively analyzed 180 adults with newly diagnosed DLBCL, NOS (not otherwise specified) who received frontline rituximab-based immunochemotherapy (R-CHOP or CHOP-like regimens) between January 2014 and December 2019 at three tertiary centers in Serbia. The median age was 67 years (IQR 59–73), and 56.1% were female. Receiver operating characteristic (ROC) analysis determined 6.5 as the optimal CALLY index cut-off (AUC 0.744, 95% CI 0.670–0.817; p < 0.001). Results: A low CALLY index (<6.5) was significantly associated with adverse clinical features, including anemia, elevated lactate dehydrogenase and β2-microglobulin, poor ECOG performance status, bulky disease, advanced stage, and unfavorable IPI, R-IPI, and NCCN-IPI scores (all p < 0.001). In contrast, no associations were observed with tumor subtype, immunophenotype, or comorbidities. Furthermore, patients with CALLY <6.5 showed lower overall response rates to treatment (59.6% vs. 85.5%, p < 0.001) and higher relapse rates (21.0% vs. 6.2%, p = 0.014). They also experienced reduced 3- and 5-year overall survival (OS) and event-free survival (EFS) (all p < 0.001). In multivariate analysis, a low CALLY index independently predicted poorer OS (HR 2.04, 95% CI 1.13–3.67; p = 0.017) and EFS (HR 1.89, 95% CI 1.13–3.14; p = 0.015). In addition, it independently identified patients at risk of relapsed/refractory (R/R) disease (OR 2.50, 95% CI 1.02–10.10; p = 0.04), outperforming standard prognostic indices. Conclusions: The CALLY index is a simple, low-cost, and widely accessible biomarker that independently predicts prognosis in DLBCL, NOS. It outperforms standard indices in identifying R/R cases. The CALLY index may enhance risk stratification and guide individualized treatment strategies. Full article

Acute Lymphoblastic Leukemia (ALL) is a heterogeneous hematological malignancy in which disease progression and response to therapy are influenced by a complex network of molecular alterations, interactions with the bone marrow microenvironment, and epigenetic modulation mechanisms. Crosstalk between oncogenic, inflammatory, and immunoregulatory signaling pathways, together with epigenetic modifications, contributes to the maintenance of leukemic survival and the development of therapeutic resistance. This review analyzes the role of cytokines and chemokines such as IL-6, TNF-α, and CXCL12, which act as biological biomarkers and key mediators of leukemia niche remodeling, and the main signaling pathways involved in ALL, such as Wnt/β-catenin, JAK/STAT, PI3K/AKT/mTOR, Notch, and BCR, highlighting their functional interconnection with the tumor microenvironment. The role of epigenetics in modulating the dialogue between leukemia cells and stromal components is also discussed. Epigenetic programs govern leukemia’s dependence on stromal support, inflammatory and niche-derived signals, as well as the microenvironment signaling pathways. Overall, targeting leukemia-niche interactions is a crucial strategy for improving outcomes in ALL and to identify potential molecular vulnerabilities, also for developing new therapeutic approaches for the treatment of the disease. Full article

Background/Objectives: Calprotectin (CLP), a calcium-binding protein complex released predominantly from neutrophils and monocytes, plays a key role in the inflammatory response. Increased levels of CLP have been reported in various inflammatory and malignant conditions. This study aimed to evaluate serum CLP concentrations and their associations with hematological and biochemical parameters in patients with lung cancer. Methods: This prospective observational study included newly diagnosed lung cancer patients and a healthy control group. Demographic data, routine laboratory parameters, CLP levels, and inflammatory indices including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune–inflammation index (SII), systemic inflammation response index (SIRI), and pan-immune–inflammation value (PIV) were recorded. Comparisons were made between groups and across tumor molecular profile, cancer stages, and metastasis status. Correlation and ROC analyses were performed. Results: Serum CLP levels were significantly higher in the lung cancer group compared with healthy controls (p < 0.001). Among molecular subgroups, patients with positive molecular testing had significantly elevated CLP levels compared with negative and untested groups (p = 0.025). CLP did not differ significantly across cancer stages or metastasis status (p > 0.05). CLP showed a positive correlation with the SIRI (r = 0.323; p = 0.004) and PIV (r = 0.395; p < 0.001). ROC analysis revealed that CLP demonstrated good diagnostic performance for lung cancer, with an AUC of 0.930 (95% CI: 0.849–0.976), sensitivity of 79.5%, and specificity of 92.3%. Among inflammatory indices, PIV (AUC = 0.863) and SIRI (AUC = 0.810) also showed high diagnostic accuracy. Conclusions: CLP levels are significantly elevated in lung cancer and show strong discriminative ability, outperforming commonly used inflammatory indices. Although CLP is not specific to lung cancer, it may serve as a supportive, noninvasive biomarker reflecting inflammatory burden when interpreted alongside clinical evaluation, imaging findings, and other laboratory parameters. Full article

Invasive infections attributed to rare yeasts are increasingly recognized and often exhibit resistance to echinocandins or fluconazole. Despite geographical variability, epidemiological data from Greece are limited. To bridge this gap, we conducted a 15-year retrospective study of rare yeast fungaemia at a tertiary teaching hospital in Athens. All microbiologically confirmed cases in hospitalized patients (2010–2024) were included. Demographic and clinical data were retrieved from medical records. Incidence was calculated per 1000 admissions and 10,000 bed days. Isolates were identified using Vitek 2 and, when available, further characterized by MALDI-TOF MS and tested for antifungal susceptibility based on EUCAST guidelines. A total of 29 episodes (3% of all fungaemias) were identified, with an incidence of 0.04/1000 admissions and 0.09/10,000 bed days. Hematological malignancies (31%) were the most common underlying condition. All patients had central venous catheters and were receiving antibiotics; 38% were non-neutropenic/non-immunosuppressed. The most frequently isolated species were Rhodotorula mucilaginosa (41%), Saccharomyces cerevisiae (31%) and Trichosporon asahii (21%), with single cases of Apiotrichum loubieri and Magnusiomyces capitatus. Amphotericin B exhibited good in vitro activity against all species; echinocandins were active only against S. cerevisiae, and azole activity was species dependent. The median time from hospital admission to fungaemia onset was 27 days; one-third of cases were breakthrough infections, and in 19%, diagnosis was established post-mortem. Despite antifungal therapy, crude mortality was 53%. Although infrequent, rare yeast fungaemia at our centre was associated with high breakthrough rates and substantial mortality. Regional epidemiological insight and heightened clinical awareness are key to optimizing outcomes. Full article

Allogeneic hematopoietic stem cell transplantation (HSCT) is a medical procedure to treat hematologic malignancies and restore bone marrow function. However, this approach may lead to graft-versus-host disease (GvHD), a major cause of mortality and morbidity after allogeneic HSCT. Some studies have suggested the involvement of gut microbiota in the development and prognosis of GvHD. In this context, the main objective of this study was to compare the fecal microbiome composition and short-chain profile of pediatric patients who underwent successful HSCT, developed GvHD or died. The bacterial composition was analyzed using 16S rRNA gene sequencing, while short-chain fatty acids (SCFAs) were quantified by gas chromatography. Fecal samples at engraftment were mainly characterized by a loss of bacterial diversity, a depletion of sequences belonging to the genus Blautia and significantly lower concentrations of fecal butyrate and acetate compared with those obtained before HSCT and 100 days after HSCT. Our findings confirm that children experiencing GvHD after HSCT have distinct gut microbiota and SCFA profiles, which might contribute to developing new microbiota-targeted strategies for GvHD prevention during HSCT procedures. Full article

Background and Objectives: Procalcitonin (PCT) is widely used to support the diagnosis of bacterial infection and sepsis, yet clinically relevant elevations also occur in multiple non-infectious conditions. This systematic review aimed to synthesize human evidence on non-infectious causes of elevated PCT and to summarize proposed pathophysiological mechanisms, with the goal of supporting context-based interpretation in clinical practice. Materials and Methods: A systematic search of PubMed/MEDLINE, Embase, Web of Science, and Scopus was performed from inception to 31 July 2025. Human studies published in English reporting quantitative PCT values in non-infectious contexts were eligible (observational studies, clinical trials, and case series with ≥5 patients). Results: Seventy-six unique studies were included. Evidence was organized across systemic inflammatory responses, cardiovascular pathology, nephrological disorders and renal replacement therapy, pulmonary diseases, gastrointestinal and hepatopancreatic diseases, autoimmune and rheumatologic conditions, neurologic and ophthalmologic conditions, onco-hematologic disorders, surgery, traumatology and transplanted patients. Across conditions, non-infectious PCT elevations were variable and frequently overlapped with ranges reported in bacterial infection, particularly in settings characterized by severe sterile inflammation and tissue injury (e.g., major surgery, trauma, shock, pancreatitis, and burns), as well as in selected malignancies with tumor-associated PCT production. Conclusions: Elevated PCT is not synonymous with bacterial infection. Interpretation should emphasize clinical context, timing, and serial trends rather than isolated thresholds, especially in high-acuity settings with strong non-infectious inflammatory stimuli. Standardized reporting of assays and sampling time points and condition-specific kinetic data are needed to refine diagnostic and stewardship algorithms. Full article

Background: Acalabrutinib is a selective Bruton tyrosine kinase inhibitor widely used for chronic lymphocytic leukemia and mantle cell lymphoma. Real-world safety evidence from Latin America remains limited, which restricts local benchmarking and pharmacovigilance planning. In this study we aimed to assess exposure-adjusted adverse events in routine care in Mexico. Methods: We analyzed postmarketing surveillance datasets and spontaneous reports from March 2020 to August 2024, classifying events with MedDRA and summarizing seriousness, severity, and incidence per 100 patient-years. Results: A total of 266 patients were registered; 193 had evaluable exposure and safety data, contributing 242.73 patient-years. The overall adverse event incidence was 24.71 per 100 patient-years. Twenty-eight individual case safety reports documented 60 events. Forty-four events were serious. Among 33 events with reported severity, 14 were severe, 14 moderate, and five mild. Frequently affected system organ classes were blood and lymphatic, vascular, and infections. Seven deaths were reported; most were associated with COVID-19 complications or disease progression. Conclusions: The adverse event profile observed aligns with published trial experience and supports the tolerability of acalabrutinib in Mexican practice. These country-level, exposure-adjusted estimates provide actionable context for clinicians, institutional pharmacists and pharmacovigilance teams and point to the value of strengthening report completeness to improve signal detection in routine oncology care. Full article

Primary central nervous system lymphoma (PCNSL) is an aggressive malignancy for which early management decisions frequently occur within neurosurgical workflows prior to oncologic treatment. In this retrospective single-center study, we aimed to explore whether early neurosurgical workflow characteristics are associated with survival outcomes in patients with PCNSL. Consecutive adult patients diagnosed with PCNSL between 2012 and 2022 were included, and the variables of interest comprised pre-biopsy corticosteroid exposure, the interval between diagnostic magnetic resonance imaging (MRI) and stereotactic biopsy, and the time from biopsy to initiation of high-dose methotrexate–based induction therapy. All patients were treated under a standardized hematology protocol to limit systemic treatment heterogeneity. Overall survival (OS) and progression-free survival (PFS) were calculated from the date of diagnostic biopsy, and survival analyses were performed using Kaplan–Meier methods and log-rank testing. Twenty-nine patients met the inclusion criteria. Median OS and PFS were not reached in steroid-naïve patients, whereas pre-biopsy corticosteroid exposure was associated with consistently shorter survival trajectories, with a clear separation of the survival curves, despite conventional statistical significance not being reached. Similarly, median OS and PFS were not reached in patients undergoing biopsy within 7 days of MRI, and an MRI-to-biopsy interval exceeding 7 days demonstrated an unfavorable survival trajectory compared with earlier biopsy; biopsy-to-induction timing did not show a measurable association with early survival outcomes. Established prognostic stratification using Memorial Sloan–Kettering Cancer Center classes showed expected survival discrimination within the cohort, supporting internal validity. Given the limited sample size and retrospective design, all findings should be interpreted as exploratory associations rather than evidence of causality. These results suggest that early neurosurgical workflow characteristics, particularly empiric pre-biopsy corticosteroids avoidance and diagnostic delay minimization, may be associated with early survival trajectories in PCNSL and warrant further evaluation in larger prospective studies. Full article

Acute myeloid leukemia (AML) is a biologically heterogeneous hematologic malignancy arising from the oncogenic transformation of hematopoietic stem and progenitor cells, resulting in clonal expansion and progressive subclonal diversification. Although considerable advances have deepened our understanding of AML pathogenesis, major challenges persist, particularly regarding relapses and therapeutic resistance. In recent years, exosomes—extracellular vesicles of 30–150 nm in diameter of endosomal origin—have emerged as critical mediators of intercellular communication within the AML tumor microenvironment. These vesicles transport a diverse cargo of proteins, metabolites, and nucleic acids, including mRNA, non-coding RNA species, and DNA, which is selectively packaged during their biogenesis. Circulating exosomes have garnered attention as promising liquid biomarkers for diagnosis, prognosis, and monitoring minimal residual disease, while also representing potential therapeutic targets or delivery platforms. Nonetheless, significant knowledge gaps remain regarding the mechanisms governing exosome biogenesis, cargo selection, and the functional impact on leukemia progression and immune modulation. This review focuses on the role of exosomes in acute myeloid leukemia, with an emphasis on the molecular mechanisms underlying their involvement in pathogenesis, tumor communication, and resistance to therapies, as well as their potential as diagnostic biomarkers. Full article