Search Results (2,170)

Background: The intersection between oncology and intensive care has shifted from predominantly end-of-life care to a therapeutic bridge that can preserve anticancer trajectories in carefully selected patients. Yet, criteria separating benefit from futility remain fragmented. Objective: This paper seeks to map contemporary evidence (2015–2025) on outcomes after Intensive Care Unit (ICU) admission in adults with cancer and to identify clinical constellations in which ICU-level care still changes prognosis. Methods: PRISMA-ScR scoping review (PCC framework). PubMed search (2015–2025), dual screening, standardized extraction; narrative/thematic synthesis across six clusters (hematologic, solid tumors, sepsis/non-COVID-19 infection, COVID-19/viral pneumonia, novel/targeted-therapy toxicities, end-of-life/aggressive ICU) were used. No meta-analysis given heterogeneity. Results: Seventy-three studies (>170,000 ICU admissions) were included, mostly cohort designs across 27 countries. ICU mortality ranged 8–72% (weighted mean ≈ 41%); hospital ≈ 38%; 90-day ≈ 46%; 1-year ≈ 62%. About one third of ICU survivors resumed systemic therapy. Benefit concentrated in early admissions, single-organ failure, controlled/remission disease, postoperative/elective monitoring, and reversible treatment-related toxicities (e.g., ICI pneumonitis, CAR-T CRS/ICANS). Futility clustered around ≥3 organ supports, RRT > 7 days, refractory/progressive disease, and ECOG ≥ 3. Sepsis outcomes averaged 45–55% ICU mortality but improved with rapid recognition and source control; COVID-19 mortality was particularly high in hematologic malignancies early in the pandemic, with subsequent declines post-vaccination. Conclusions: In modern oncologic practice, ICU care changes prognosis when the acute physiological insult is reversible and cancer control remains plausible; conversely, high organ-support burden and refractory disease define practical futility thresholds. These signals support time-limited ICU trials, earlier ICU involvement for sepsis/irAEs, and embedded palliative care to align intensity with goals. Full article

Background: DDX41 is one of the most frequent adult-onset myeloid neoplasm predisposition gene, yet its biology remains incompletely defined. This study investigated the frequency, spectrum, and clinical characteristics of DDX41 variants in Korean patients with hematologic malignancies, including the patterns of co-occurring somatic variants. Methods: We retrospectively reviewed 716 patients with hematologic malignancies who underwent targeted next-generation sequencing. In patients with germline DDX41 variants, clinicopathologic features, co-occurring variants, variant allele frequency (VAF) distributions, and survival were analyzed. Results:DDX41 variants were identified in 34/716 patients (4.7%), including 33 germline carriers (4.6%), occurring most frequently in AML (6.2%) and MDS (11.1%). Patients with germline DDX41 variants had a median age of 68 years, were predominantly male (69.7%), and commonly had normal karyotypes (72.7%), with similar features in AML and MDS except for lower platelet counts in AML (p = 0.025). The most common germline DDX41 variants were Y259C (20.6%), A500fs (14.7%), E7* (11.8%), V152G (11.8%), and D139G (8.8%), with null variants predominating in AML and missense variants in MDS (p = 0.002). Somatic DDX41 variants occurred in 63.6% of patients with germline DDX41 variants, with R525H being the most frequent (48%), while non-DDX41 somatic variants were detected in 78.8% of patients, most commonly involving ASXL1, DNMT3A, SRSF2, and TET2, which appeared at lower VAFs, suggesting late acquisition. Conclusions: This study demonstrates ethnic-specific DDX41 variant patterns in Korean myeloid neoplasm patients, with biallelic alterations potentially involved in early leukemogenesis. These findings provide further insight into the unique features of DDX41-associated myeloid neoplasms. Full article

TP53-mutated myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) comprise a distinct subgroup of myeloid neoplasms with unique biological and clinical features. The molecular alterations linked to TP53 mutations drive genomic instability and treatment resistance and ultimately lead to poor survival outcomes. The disease biology is further shaped by alterations in immune response within the bone marrow microenvironment and significant changes in cellular metabolism. Conventional treatments, including chemotherapy and hypomethylating agents +/− venetoclax, offer limited benefit, with high relapse rates and short remissions. Allogeneic bone marrow transplantation is the only curative approach, but the vast majority of patients relapse. Novel therapeutic approaches—ranging from p53 reactivation strategies to immunotherapy and targeted inhibition of specific signaling pathways—are under active investigation. Our review summarizes current knowledge on the molecular pathogenesis, prognostic implications, and therapeutic landscape of TP53-mutated MDS/AML and discusses ongoing challenges and opportunities for improving patient outcomes. Full article

Background/Objectives: Janus kinase 2 (JAK2) is a pivotal signaling protein implicated in various hematological malignancies and inflammatory disorders, making it a compelling target for therapeutic intervention. Methods: In this study, we employed an integrative computational approach combining ligand-based screening, pharmacophore modeling, molecular docking, molecular dynamics (MD) simulations, and MM/PBSA free energy calculations to identify JAK2 inhibitors from the ChEMBL database. A comprehensive virtual screening of over 1,900,000 compounds was conducted using Tanimoto similarity and a validated pharmacophore model, resulting in the identification of 39 structurally promising candidates. Docking analyses prioritized compounds with favorable interaction energies, while MD simulations over 100 ns assessed the dynamic behavior and binding stability of top hits. Results: Four compounds, CHEMBL4169802, CHEMBL4162254, CHEMBL4286867, and CHEMBL2208033, exhibited consistently superior performance, forming stable hydrogen bonds, favorable RMSD profiles (≤0.5 nm), and strong binding interactions, including salt bridges. Notably, the binding free energies revealed ΔG values as low as −29.91 kcal/mol, surpassing that of the reference inhibitor, momelotinib (−24.17 kcal/mol). Conclusions: Among these, CHEMBL4169802 emerged as the most promising candidate due to its synergistic electrostatic and hydrophobic interactions. Collectively, our results highlight these compounds as probable, JAK2-selective inhibitors with strong potential for further biological validation and optimization. Full article

Polyomaviruses (BKPyV and JCPyV) and herpesviruses (EBV, CMV) usually infect people during childhood, and may be associated, in some clinical states, with immunocompromised individuals. The aim of this study was to investigate the occurrence and coexistence of polyomavirus (BKPyV and JCPyV) and herpesvirus (CMV and EBV) DNAemia in pediatric hematology/oncology patients, including HCT recipients, and to assess the clinical relevance of polyomaviruses DNAemia. Whole blood samples of 99 children (including 71 patients undergoing HCT) were analyzed for the DNA of the herpes- and polyomaviruses. Co-existence of herpesvirus DNAemia was checked for the patients and clinically analyzed in detail, especially for those positive for BKPyV DNA. BKPyV DNAemia was detected in 15 (15.2%) patients, with viral loads ranging from 1.2 × 10³–1.7 × 10⁷ DNA IU/mL. No JCPyV DNA was detected in any of the samples. Coinfections with EBV or CMV DNAemia were observed in a subset of BKPyV-positive patients. BKPyV DNAemia was more frequent among children with leukemia and in those undergoing HCT. Our findings highlight the clinical associations between BKPyV and herpesvirus DNAemia in immunocompromised pediatric patients. Routine BKPyV DNA monitoring, alongside standard herpesvirus screening, may provide clinically valuable insights in high-risk pediatric cohorts, particularly those with hematologic malignancies and post-HCT status. Full article

Background: Patients with hematologic malignancy (HM) experience high symptom burden (SB) and diminished quality of life (QOL). While early palliative care (EPC) benefits solid tumors, its impact in HM remains uncertain. Objectives: To systematically review the effects of EPC on patient-centered outcomes in individuals with HM. Methods: MEDLINE, Web of Science, Cochrane Library, and Scopus were searched for English-language articles published between 2020 and 2024. Eligible studies included adults with advanced HM receiving EPC compared with usual care, reporting outcomes on SB, QOL, place of death (POD), healthcare costs (HCCs), or healthcare utilization (HCU). All original study designs were considered. Critical appraisal was performed, and results were synthesized narratively. The review was registered in PROSPERO (CRD420251019687). Results: Twelve studies were included, most of high quality (n = 10) and mainly conducted in America and Europe. Collectively, they enrolled 42,053 participants, largely with advanced disease, poor performance status, or limited prognosis. EPC consistently improved SB, particularly pain, appetite, and functional well-being, although results for anxiety and depression were inconsistent. Findings for QOL were mixed. EPC was associated with higher likelihood of home or hospice death. One study demonstrated substantial cost savings with home-based EPC. Across several studies, EPC was linked to lower HCU, including fewer transfusions, reduced chemotherapy near the end-of-life, and fewer aggressive interventions, hospitalizations, and intensive care admissions. Conclusions: EPC improves SB, influences POD, and reduces HCCs and HCU in HM. Evidence for QOL and psychological outcomes remains inconclusive. Further high-quality research is required to consolidate these findings. Full article

Background: Leukemia comprises heterogeneous hematologic malignancies, and whether circulating metabolites contribute causally to subtype-specific risk remains uncertain. Objectives: The aim of this study was to assess the causal effects of plasma metabolites for acute myeloid leukemia (AML), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL). Methods: A two-sample Mendelian randomization (MR) using summary-level genome-wide association study statistics was conducted. For each metabolite, a single variant showing the strongest association with the metabolite that had the largest variance explained (R²) among the independent genome-wide significant (p < 5 × 10⁻⁸) SNPs assigned to effector genes was selected as sentinel. Multiple comparisons using Bonferroni correction (0.05/83 = 6.02 × 10⁻⁴) were applied to minimize the risk of obtaining false positive results. Results: Totally, 83 metabolites and metabolite ratios were analyzed for AML, CML, ALL, and CLL. Lithocholate sulfate (1), instrumented by the rs10425975 variant in the SULT2A1 gene, was significantly associated with an increased risk of CLL (OR = 2.19; 95% CI: 1.45–3.31; p = 2 × 10⁻⁴). An additional 17 metabolite-leukemia associations showed suggestive evidence of significance. Approximately 300 drug entries linked to candidate metabolites were curated to provide a basis for mechanistic follow-up. Conclusions: Our MR result supports a causal link between higher genetically proxied lithocholate sulfate (1) and increased CLL risk. The discovery of these “metabolite-gene-drug” relationships suggests a central role in leukemia pathogenesis and warrants further functional investigation for their therapeutic potential. Full article

Background: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, yet diagnosis still relies primarily on invasive bone-marrow procedures and advanced laboratory assays. Non-invasive, rapid, and cost-effective tools remain an unmet need. Fourier-transform infrared (FTIR) spectroscopy has shown promise for detecting cancer-associated biochemical changes in biofluids and cells. Methods: Serum from pediatric ALL patients and controls (n = 103; ALL = 45, controls = 58: healthy = 14, hematology controls = 44 with anemia, thrombocytopenia, leukopenia, and pancytopenia) was analyzed using FTIR. Spectra (800–1800, 2800–3500 cm⁻¹) were preprocessed with baseline correction, derivative filtering, and normalization. Group differences were assessed statistically, and logistic regression with stratified 10-fold cross-validation was applied; Receiver operating characteristic (ROC)\precision–recall (PR) analyses were based on out-of-fold predictions. Results: Distinct spectral alterations were observed between ALL and controls. Leukemia samples showed higher amide I (~1640 cm⁻¹) and amide II (~1545 cm⁻¹) absorbance, lower lipid-related bands (~1450, ~2920 cm⁻¹), and increased nucleic-acid–associated signals (~1080 cm⁻¹). Differences were significant (q < 0.05) with moderate effect sizes. Logistic regression achieved area under the curve (AUC) ≈ 0.80 with sensitivity ~0.73–0.84 across practical decision thresholds (0.50 → 0.30) and higher recall attainable at the expense of specificity. Principal component analysis (PCA)\hierarchical cluster analysis (HCA) indicated partial but consistent group separation, aligning with supervised performance. Conclusions: Serum FTIR spectroscopy shows promise for distinguishing pediatric ALL from controls by reflecting disease-related metabolic changes. The technique is rapid, label-free, and requires only small serum volumes. Our findings represent proof-of-concept, and validation in larger, multi-center studies is needed before clinical implementation can be considered. Full article

Background: Patients with systemic autoimmune diseases (SAID) are at a higher risk of developing neoplasms, such as solid tumors and hematologic malignancies. Chronic stimulation of the immune system and some treatments for these diseases increase the risk of developing solid tumors. Also, it is known that patients with SAID are usually excluded from clinical trials, but immune checkpoint inhibitors (ICI) are still used in these patients in everyday practice. Objectives: The objective of this article is to review the most up-to-date and robust literature on the use of ICI in patients with SAID for the treatment of solid tumors to obtain information on the efficacy and safety of these drugs in this subgroup of patients. Methods: A literature review was performed through international databases that included PubMed, Medline, Scopus, and Google Scholar. Articles about the use of ICI for solid tumors in patients with SAID were included; the types of articles included were retrospective studies, systematic reviews, and meta-analyses. A summarized descriptive analysis was performed about the efficacy and safety of ICI treatment for the main solid tumors (lung, melanoma, and other cutaneous malignancies, as well as renal and urothelial carcinoma). Conclusions: In general, it seems that ICI treatment is safe in patients with asymptomatic SAID. Close follow-up with a multidisciplinary team should be performed when ICI therapy is prescribed. A substitution of selective immunosuppressants (SIM) in place of nonselective immunosuppressants (NSIM) in asymptomatic patients is recommended before the initiation of ICI. Full article

Pre-B-cell leukemia factor 1 (PBX1) is a transcription factor that plays a significant role in various physiological, developmental, and oncogenic processes in humans. The mechanisms and interactions of PBX1 in both solid and hematologic malignancies remain significant areas of study. It was initially found in pre-B-cell acute lymphoblastic leukemia as a result of the chromosomal translocation t(1;19). Over the years, its role in other blood neoplasms has been studied. PBX1 and its variant E2A::PBX1 regulate gene expression that influences cell proliferation and differentiation in hematopoietic lineages. Their interaction with oncogenic partners results in abnormal gene regulation and tumorigenesis. Research has predominantly focused on the role of these factors in leukemias and plasma cell neoplasms, whereas other hematologic neoplasms have been largely overlooked. The potential application of PBX1 as a prognostic and predictive biomarker has recently gained attention. However, further research is needed to fully understand its complex role and how it can be targeted for therapeutic purposes. This review summarizes current knowledge on PBX1’s role in the growth of both mature and immature hematologic neoplasms. Moreover, it focuses on its prospective use as a therapeutic target and to predict prognosis, especially for aggressive neoplasms that do not respond to current therapeutic approaches. Full article

Background and clinical significance: Lymphedema is a relatively common clinical manifestation in patients and has a broad differential diagnosis, the main concern being the exclusion of malignancy. However, a rare constellation of lymphedema with systemic features and no underlying malignancy is yellow nail syndrome (YNS). YNS is a lymphatic abnormality, characterized by a triad of yellow nails, primary lymphedema and respiratory manifestations. Case presentation: Here, we report a 74-year-old male patient who presented to us with massive chylous ascites, cough, yellow nails and recurrent bilateral leg edema. During the last 10 years, he had thrice undergone thoracocentesis, which revealed chylous pleural effusion, although there was no documented diagnosis of yellow nail syndrome. We pursued a thorough work-up to rule out underlying cirrhosis and malignancy (the main causes of chylous ascites). There are only few cases of yellow nail syndrome reported in the literature with chylous ascites as a manifestation of YNS. Conclusions: The co-existence of chylous ascites with the classical triad of pleural effusion, lymphedema and yellow nail changes in the same patient has to be included in the diagnostic process to differentiate this entity from liver cirrhosis and solid or hematological cancer. Full article

Interferons (IFNs) are pleiotropic cytokines involved in antiviral defense, immune regulation, and tumor suppression. In myeloproliferative neoplasms (MPNs) and related disorders—including classical BCR, ABL1-negative MPNs, chronic myeloid leukemia (CML), and rarer entities such as chronic neutrophilic leukemia and hypereosinophilic syndromes—disease pathogenesis arises from a spectrum of somatic and structural genetic abnormalities and chronic inflammation, in which IFNs play a paradoxical role. They contribute to disease pathogenesis by promoting abnormal hematopoiesis and immune dysregulation, while also representing a therapeutic option capable of inducing hematologic and molecular remissions. This review outlines the biology and classification of IFNs, focusing on their signaling pathways and downstream effects in both normal and malignant hematopoiesis. We discuss the dual impact of IFN signaling on hematopoietic stem cells, including induction of proliferation, senescence, apoptosis, and DNA damage, and how these mechanisms may both sustain clonal evolution and facilitate disease control. Clinical data supporting the efficacy and safety of IFN-α, particularly pegylated formulations, in polycythemia vera, essential thrombocythemia, myelofibrosis, and chronic myeloid leukemia are reviewed, along with insights into next-generation IFNs and combination therapies. Understanding the dichotomous effects of IFNs in MPNs not only clarifies their role in disease biology but also informs their optimal use in clinical practice. This duality highlights the need for personalized approaches to IFN-based therapies. Full article

Background: The American Society of Clinical Oncology (ASCO) established recommendations for palliative care (PC), and they still remain the most trusted source overall. The standard published by C. Earle (defined in solid tumors) for referral to PC is > 55%. However, these rates remain unclear in general onco-hematology. Our referral rate reaches 60%; while it meets the standard, there are significant differences between ST and HM. Several authors have already pointed out these discrepancies. Arguing in some cases its possible relationship with the different behavior of professionals with different pathologies. Objective: The primary objective of this work is to understand the role that PC plays in onco-hematology and to determine the profile of patients referred to PC. Therefore, the article aims to establish some recommendations related to the results of prevalent characteristics. Methods: The Mortality Subcommittee (MS) includes and registers in a database all cancer patients who died in hospital undergoing systemic anticancer therapy (SACT) in their last 30 days of life (SACT ≤ 30 d). PC, in turn, works on relieving symptoms related to the disease and the patient. To understand the impact of PC in the MS database patients, we reviewed the literature for symptoms related to palliative care activity. Subsequently, we selected some signs and symptoms, by consensus with our PC specialists, in order to add them to the MS database and register them retrospectively. We measured the percentage of patients who registered these symptoms based on the data found in their electronic records. The results include the comparison by group: between patients referred or not to the PC program (PCP), and between the pathologies ST and HM. We used the programming language R (version 4.2) in our statistical analysis, including the “compareGroups” package (version 4.6), applying the pertinent tests based on the distribution of the data. Results: We completed the records on the 1681 patients from the period 2020–2023. 59.4% were men, the average age was 65.5 years, and 73.5% had ST and 26.5% had HM. Patients with lung cancer predominate (28.5%), with 71% of them being in the stage IV, followed by leukemia (9.76%). 60% are in progression of their disease, and 77% have advanced disease (AD). The average therapeutic aggressiveness indicators were SACT < 30 d: 38.9% (ST: 33.4%; HM: 70.97%); SACT < 14 d: 16.36% (ST: 13.76%; HM: 31.56%); the change in therapeutic regimen was 22% (ST: 20.8%; HM: 25.1%). The referral rate to PCP was 59.7% (ST: 68.2% and HM: 36.3%). Late referral (PCP ≤3 days before death) occurred in 29.2% of all patients, being 29% for ST cases and 30.4% for HM cases. Regarding the recording of signs and symptoms: psycho-emotional and analgesia regimens (including opioids) are better recorded in the PCP group (p < 0.001); the more physical symptoms (dyspnea, bleeding, infections, and severe symptoms) do not present statistically significant differences, although the severe symptoms in the PCP group are more disabling (cerebral involvement, spinal cord compression, vertebral crushing). The number of bags of blood products transfused is significantly lower in the PCP group (average 6.9 vs. 12.7). The total number of symptom variables with significant statistical differences was 13 for ST and 8 for HM. Conclusions: In this cohort, patients visited by PC had a better record of psycho-emotional symptoms. We consider that patients who are in any of the following situations should be referred to PC: initial diagnosis of stage IV lung cancer, leukemia; patients with advanced disease; presence of pain requiring opioids; psychoemotional symptoms; need for >7 to 15 transfusions of blood products and, if there are disabling symptoms. PC improves professional interest in the psycho-emotional and fragility situation of these patients. According to our data (in terms of the number of variables with significant differences by pathology group), we observed that hematologists tend to take on palliative tasks more frequently than their oncologist peers, who delegate them to PC in order to have more time dedicated to their specific field. Full article

Background and Objectives: Idiopathic inflammatory myopathies (IIMs) are rare autoimmune diseases with extra-muscular manifestations. A firm association with malignancy, mainly observed in dermatomyositis (DM) is well established and several predictors of malignancy were previously published. However, given the low prevalence of IIMs, large population-based studies are scarce, hindering a comprehensive understanding of site-specific cancer patterns and risk factors. This study aimed to evaluate malignancy patterns and predictors, in a large, diverse cohort of patients with DM and PM. Materials and Methods: This retrospective cohort study used the Clalit Health Services electronic database, including 1557 DM patients and 528 PM patients diagnosed between 2002 and 2018, along with age-, sex-, and residence-matched controls at a 1:5 ratio. The incidence and risk of malignancies were assessed using Cox proportional hazards models, and predictors of solid and hematologic malignancies within the PM/DM cohort were analyzed using adjusted logistic regression. Results: In our cohort, DM was associated with an increased risk of both solid and hematologic malignancies (HR 1.89, 95%CI 1.47–2.41), whereas in PM the association was less pronounced and limited to solid malignancies (HR 1.50, 95%CI 1.06–2.11). In DM, higher risks were observed for breast cancer (HR 1.86) and chronic leukemia (HR 5.02). Across both subtypes, older age at diagnosis, the presence of specific autoantibodies were associated with increased malignancy risk. Significant markers included antiphospholipid antibodies (OR 2.28), lupus anticoagulant (OR 2.29), anti-Mi2 (OR 2.09), any of the antinuclear antibodies (OR 2.37), and individually anti-RNP/Sm (OR 1.70), anti-Ro/La (OR 1.79), anti-Scl-70 (OR 1.60), and anti-DNA (OR 1.97). Conclusions: Our study demonstrates an increased risk of malignancy in both DM and PM, with the relationship being stronger and broader in DM, involving both solid and hematologic cancers. Older age at diagnosis, and a distinct serological profile, particularly antiphospholipid antibodies and various antinuclear antibodies, identify patients at highest risk, warranting heightened clinical vigilance. Full article

Hematopoietic stem cells (HSCs) are essential for lifelong blood production and immune homeostasis. However, aging induces functional declines in HSCs, leading to hematological disorders, immune dysfunction, and increased susceptibility to malignancies. This review explores the biological underpinnings of HSC aging, highlighting the intrinsic and extrinsic factors that drive this process. We discuss the molecular and cellular mechanisms contributing to HSC aging, including genetic instability, epigenetic alterations, metabolic shifts, and inflammation signaling. Additionally, we examine the role of the bone marrow microenvironment in modulating HSC aging, emphasizing the impact of niche interactions, stromal cell dysfunction, and extracellular matrix remodeling. To advance our understanding of HSC aging, pluripotent stem cell differentiation platforms provide a valuable tool for modeling aged HSC phenotypes and identifying potential therapeutic targets. We review current strategies for HSC rejuvenation, including metabolic reprogramming, epigenetic modifications, pharmacological interventions, and niche-targeted approaches, aiming to restore HSC function and improve regenerative potential. Finally, we present emerging perspectives on the clinical implications of HSC aging, discussing potential translational strategies for combating age-associated hematopoietic decline. By integrating insights from stem cell biology, aging research, and regenerative medicine, this review provides a comprehensive overview of HSC aging and its therapeutic potential. Addressing these challenges will be critical for developing interventions that promote hematopoietic health and improve outcomes in aging populations. Full article