Search Results (187)

Multiple myeloma (MM) is an incurable malignancy of plasma cells that accounts for 10% of all haematological malignancies diagnosed worldwide. The poor outcome of patients with MM highlights the ongoing need for novel treatment strategies. Ferroptosis is a recently characterised form of non-apoptotic programmed cell death. Phospholipids (PLs) containing polyunsaturated fatty acids (PUFAs) play a crucial role as ferroptosis substrates when oxidised to form toxic lipid reactive oxygen species (ROS). Using a range of scientific techniques, we demonstrate a strong correlation between the PL profile of MM and diffuse large B cell lymphoma (DLBCL) cells with their sensitivity to ferroptosis. Using this PL profiling, we manufacture liposomes that are themselves composed of PL-PUFA ferroptosis substrates relatively deficient in MM cells, with and without the GPX4 inhibitor, RSL3, for investigation of their ferroptosis-inducing potential. PL-PUFAs were more abundant in DLBCL than MM cell lines, consistent with greater ferroptosis sensitivity. In contrast, MM cells generally contained a significantly higher proportion of PLs containing monounsaturated fatty acids. Altering the lipid composition of MM cells through exogenous supplementation with PL-PUFAs induced ferroptosis-mediated cell death and further sensitised these cells to RSL3. Liposomes predominantly comprising PL-PUFAs were subsequently manufactured and loaded with RSL3. Uptake, cytotoxicity and lipid ROS studies demonstrated that these novel liposomes were readily taken up by MM cells. Those containing RSL3 were more effective at inducing ferroptosis than empty liposomes or free RSL3, resulting in IC₅₀ values an average 7.1-fold to 14.5-fold lower than those for free RSL3, from the micromolar to nanomolar range. We provide a better understanding of the mechanisms associated with ferroptosis resistance of MM cells and suggest that strategies such as liposomal delivery of relatively deficient ferroptosis-inducing PL-PUFAs together with other targeted agents could harness ferroptosis for the personalised treatment of MM and other cancers. Full article

Background: Interdigitating dendritic cell sarcoma (IDCS) is a very rare haematologic malignant tumour that arises from antigen-presenting cells. While it primarily affects the lymph nodes, extranodal manifestations have been observed, and there is a slight male predominance. Due to its rarity, diagnosing IDCS can be challenging, as illustrated in our case report of a 61-year-old woman. Methods: In this case presentation, the oncological management of a patient suspected of having malignant melanoma metastasis in the neck lymph nodes is discussed. This includes otorhinolaryngological examinations, fine needle aspiration biopsy, PET CT imaging, and histological analysis with immunohistochemistry. Results: The patient’s medical history included the excision of a pigmented lesion from the left ala of her nose, which was diagnosed as malignant melanoma. After surgical treatment, she experienced a tumour-free period of one year; however, during a follow-up ultrasonography three pathological lymph nodes were detected on the left side of her neck. Initially, a nodal metastasis of melanoma was suspected. Yet, fine needle aspiration cytology revealed myofibroblastic tumour invasion, and a re-biopsy showed no signs of malignancy. To further investigate, PET-CT scans were conducted, and a modified radical neck dissection was performed based on the findings. The histological analysis of the lymph nodes revealed an IDCS, a second independent tumour distinct from the initially diagnosed malignant melanoma, originating from the submandibular, upper jugular, and mid-jugular lymph nodes. Conclusions: This case highlights the diagnostic difficulties associated with IDCS. Initially, the clinical suspicion of malignant melanoma was considered, necessitating further examinations and a multidisciplinary approach to reach a final diagnosis and provide the patient with appropriate treatment. Full article

Background: Colorectal cancer (CRC) is the most common cancer and the leading cause of cancer-related death globally. While survival improved, CRC patients face the risk of subsequent multiple primary cancers (MPCs). This study aimed to determine the incidence and identify risk factors associated with metachronous MPCs among CRC survivors. Methods: A retrospective analysis was performed on adults diagnosed with invasive colorectal adenocarcinoma at Flinders Medical Centre from 2011 to 2024, who had at least 6 months of post-CRC follow-up. Sociodemographic factors, clinical information, tumour characteristics, and treatment types were collected. Cumulative incidence function and sub-distribution hazard models were used to estimate the incidence and identify risk factors of developing MPCs. Results: Of the total 554 eligible study participants, 12% developed MPC, with a median follow-up time of 5 years (interquartile range: 2.8–7.6 years) until the diagnosis of MPC. Gastrointestinal, prostate, and haematological malignancies were the most common types of MPCs identified. The cumulative incidence and standardised incidence ratio (SIR) of an MPC were 20.9% (95% CI: 15.3–25.6) and 1.32 (95% CI: 1.03–1.68), respectively. Male sex, older age (>65 y), early-stage cancer, and loss of mismatch repair (MMR) protein expression were associated with an increased risk of developing MPCs. Conclusions: CRC survivors have a higher risk of developing an MPC compared to the general population. Sex, age, cancer stage, and MMR protein expression are factors associated with MPCs. Therefore, tailored surveillance based on the individual’s risk profile should be considered for timely diagnosis of subsequent cancers to improve long-term outcomes. Full article

Background: Oral mucositis (OM) is a painful inflammation resulting from chemotherapy. It is dependent on factors such as age, gender, chemotherapy regimen, oral health, immunological and nutritional status, and genetics. Objectives: The aim of the study was to conduct a narrative review to compile studies on the contribution of genetic and epigenetic aspects to the pathogenesis of OM in children with haematological malignancies undergoing chemotherapy treatment. Methods: The literature search was performed in Pubmed, Scopus, Web of Science, Cochrane, Lilacs, and grey literature databases covering articles published since 2010. Results: Twenty-two studies investigating polymorphisms and four studies investigating DNA methylation were included. Polymorphisms in the MTHFR, ABCB1, ABCC2, ABCG2, SLCO1B, miR-1206, miR-3683, CAT, and VDR genes were associated as risk factors for OM and polymorphisms in the TYMS and miR-4268 genes were associated as protective factors. With regard to DNA methylation, associations such as protection or susceptibility to OM have not yet been proven. However, studies have shown that DNMT1 methylation and hypomethylation in total DNA and in the TNF-α gene are associated with recovery of the oral mucosa. Conclusions: Genetic variants are associated with OM in various biological pathways, such as folate metabolism, transport proteins, epigenetic machinery, oxidative stress, and vitamin D metabolism. The DNA methylation profile, which is still poorly understood in the pathogenesis of OM, is associated with mucosal recovery (inflammation and epigenetic machinery). Genetic and epigenetic markers may be tools to indicate a patient’s susceptibility to developing OM, and epigenetic markers may be a target for therapies. Full article

Background/Objectives: Prostatic lymphoma is a rare malignant tumour that frequently causes urinary tract obstruction. It is uncommon for patients to present with systemic features or B-symptoms. As a result, it is often diagnosed incidentally during surgical lower urinary tract symptoms (LUTS) treatment. This systematic review aims to identify any common clinical features of prostatic lymphoma diagnosed incidentally during surgical LUTS treatment and summarise disease treatment and outcomes. Methods: The study protocol was registered with Prospective Register of Systematic Reviews (PROSPERO). A search was performed across the following electronic databases: MEDLINE, Embase, Web of Science, and Cochrane Database of Systematic Reviews. Full texts of eligible studies were analysed and data were extracted. The review was performed in accordance with PRISMA guidelines. Results: A total of 24 case reports compromising 25 cases were included. The median (IQR) age was 67 (61–73) years. All patients reported LUTS as their primary complaint, and the median duration of LUTS prior to diagnosis was 17 (4–44) months. Serum prostate-specific antigen (PSA) was normal in 10 cases and prostatomegaly present on imaging in 16 cases. A total of 10 different subtypes of lymphoma were reported. Extra-prostatic involvement was reported in eight patients. Chemotherapy, with or without adjuvant radiotherapy, was the mainstay of lymphoma treatment. The majority of articles reported positive outcomes, with complete remission in 17 cases. Conclusions: Prostatic lymphoma is a difficult clinical diagnosis due to its similar presentation to benign prostatic hyperplasia (BPH). Although rare, prostatic lymphoma may need to be considered as a diagnosis in patients with an atypical presentation of BPH. Prognosis is often favourable after prompt referral to haematology or oncology. Full article

Background/Objectives: Patients with haematological malignancies less frequently receive specialist palliative care, although they may have unmet needs for symptom control and alleviating psychosocial and existential burdens. The ‘Surprise’ Question, ‘Would you be surprised if this patient died in the next 12 months?’, helps physicians to identify patients who may benefit from palliative care. We tested the influencing factors of the feasibility of the ‘Surprise’ Question in haemato-oncology outpatients. Methods: We performed a prospective cohort study comparing patients with solid tumours and haematological malignancies. All the patients in the haemato-oncology outpatient clinics of a German university hospital were screened by haemato-oncologists using the ‘Surprise’ Question. Results: A survival analysis was performed on 672 patients (76% with haematological malignancies) at 3 and 12 months. Within one year, 110 patients (16%) died. Of these, 30/52 (58%) were patients with solid tumours, but only 12/53 (23%) patients with haematological malignancies were identified in advance by the ‘Surprise’ Question, which reflects ambiguous test sensitivity. A substantial part of the haematology patients in their last year of life were not identified (77%). The match between the survival estimates and actual outcomes was fair (Cohen’s kappa 0.37). The proximity from prediction to event and the estimating physician rather than patient characteristics influenced the accuracy of the instrument. Conclusions: For the first time, the feasibility of the ‘Surprise’ Question in haematology outpatients was proven. Factors that would improve haemato-oncologists’ clinical intuition should be further explored to facilitate timely conversations about issues important to patients nearing the end of life. Full article

Monoclonal antibodies (mAbs) targeting various pathways in cancer therapy play crucial roles in enhancing the immune system’s ability to recognise and eliminate tumour cells. These therapies are designed to either block inhibitory immune checkpoint pathways or to target specific tumour cell markers for direct destruction. Additionally, mAbs can modulate the tumour microenvironment, enhance antibody-dependent cellular cytotoxicity, and inhibit angiogenesis, further amplifying their therapeutic impact. Below is a summary of monoclonal antibodies targeting key pathways, along with their indications and mechanisms of action, which are reviewed based on therapeutic mechanisms. Full article

B-cell lymphoma-2 (Bcl-2) family proteins are fundamental regulators of intrinsic cell apoptosis, and overexpression of apoptotic proteins (Bcl-2 and Mcl-1) is a characteristic of many haematological malignancies. Thus, it is necessary to discover novel inhibitors to treat leukemia. In the current study, we synthesized a series of quercetagetin derivatives (compounds 2a–2t, 3a–3j and 4a–4g) and evaluated their anticancer activities on four leukemia cells (U937, K562, K562R and KG-1). Among those synthesized derivatives, compounds 2a exhibited the best antiproliferative activity (IC₅₀ = 0.276, 0.159, 0.312 and 0.271 µM to U937, K562, K562R and KG-1, respectively). In addition, 2a induced apoptosis in K562 and markedly arrested the cell cycle G2/M phase of K562. The Western blot assay showed that 2a is a potential inhibitor that can effectively suppress the expression of Bcl-2 and Mcl-1. The molecular docking study predicted that 2a had firm interactions with the active pockets of Bcl-2 and Mcl-1. Finally, in silico pharmacokinetic evaluation of 2a indicated its potential as an anti-leukemia drug lead in the future. Full article

Chronic lymphocytic leukaemia (CLL) is a haematological malignancy primarily affecting older adults, characterised by the proliferation of functionally impaired B lymphocytes with abnormal expression of CD5, a typical T cell marker. The current study investigates the expression of cytotoxicity-related receptors (CD16, CD56, CD57, CD69) and a checkpoint (LAG-3) on γδ T cells in CLL patients. Sixty-nine treatment-naive CLL patients and fourteen healthy controls were recruited. Flow cytometry analysis revealed that the CLL patients had higher expressions of CD56 and LAG-3 and lower CD16 on their γδ T cells compared to the healthy controls. Subgroup analysis showed that ZAP-70-negative patients exhibited increased CD69, while CD38-negative patients showed higher CD16 expression. Additionally, CD16 expression was inversely correlated with serum LDH levels, a marker of disease progression. Bioinformatic analysis of the LAG-3 ligand mRNA in a CLL dataset indicated higher expression of HLA-DQA2 and HLA-DRB5 in patients with unmutated IGVH. Our findings highlight the altered expression of key cytotoxicity markers on γδ T cells in CLL, suggesting their potential role in disease progression and as a therapeutic target. In particular, the use of anti-LAG-3 antibodies seems promising. Full article

Background and Objectives: Gallbladder cancer (GBC) is a biologically aggressive malignancy characterised by poor survival outcomes often attributed to delayed diagnosis due to nonspecific clinical presentations. Paraneoplastic syndromes (PNSs), atypical symptoms caused by cancer itself, may serve as valuable indicators for timely diagnosis, particularly in malignancies with nonspecific features. Understanding the manifestations of PNSs in GBC is, therefore, critical. This systematic review collates case studies documenting the association of PNS with GBC, including subsequent management and clinical outcomes. Materials and Methods: A comprehensive search of PubMed, Embase, CINAHL, Web of Science, and Cochrane Library databases yielded 49 relevant articles. Upon searching other information sources, two more relevant articles were identified via citation sources. Results: The paraneoplastic syndromes were classified according to haematological (leukocytosis), dermatological (inflammatory myositis like dermatomyositis and polymyositis, acanthosis nigricans, Sweet’s syndrome, exfoliative dermatitis), neurological, metabolic (hypercalcemia, hyponatremia), and others (chorea). The analysis included the age, sex, and country of origin of the patient, as well as the time of PNS diagnosis relative to GBC diagnosis. Furthermore, common presenting complaints, investigations, and effectiveness of treatment modalities using survival time were assessed. Conclusions: While PNS management can offer some benefits, oncologic outcomes of GBC are largely poor. The majority of PNS in GBC are reported in advanced stages, and, hence, PNS has a minimal role in early diagnosis. PNS management can improve a patient’s quality of life, and thus recognition and treatment are important considerations in the holistic management of GBC patients. Full article

Background/Objectives: Although the benefits of low-germ diets for patients are increasingly being questioned, their application in practice is widespread. The aim of this review is to summarise the current data and evaluate the effectiveness of the neutropenic diet (ND) in adult haemato-oncological patients to provide a basis for practical guidelines. Methods: A systematic search was conducted in four electronic databases (Medline (Ovid), CINAHL (EBSCO), EMBASE (Ovid) and Cochrane CENTRAL) to identify English and German randomised controlled trials (RCTs) concerning the effectiveness of an ND in adult haematological patients. The main endpoints were fever and systemic infections, gastrointestinal (GI) infections, mortality, nutritional status and hospitalisation length. Results: A total of five RCTs with 510 adult patients were included in this systematic review. All patients received high-dose chemotherapy in order to treat haemato-oncological malignancies. None of the analysed endpoints showed a significant advantage of the ND compared to the control group. Conclusions: An ND does not have a beneficial effect on infection rates, GI health, mortality or hospitalisation length for haemato-oncological patients. On the contrary, an ND tends to negatively affect the patient’s nutritional status; therefore, an adaption in clinical routine should take place. Full article

Haematological malignancies comprise a diverse group of life-threatening systemic diseases, including leukaemia, lymphoma, and multiple myeloma. Currently available therapies, including chemotherapy, immunotherapy, and CAR-T cells, are often associated with important side effects and with the development of drug resistance and, consequently, disease relapse. In the last decades, it was largely demonstrated that the tumor microenvironment significantly affects cancer cell proliferation and tumor response to treatment. The development of biomimetic, in vitro models may promote the investigation of the interactions between cancer cells and the tumor microenvironment and may help to better understand the mechanisms leading to drug resistance. Although advanced in vitro models have been largely explored in the field of solid tumors, due to the complex nature of the blood cancer tumor microenvironment, the mimicking of haematological malignancies mostly relies on simpler systems, often limited to two-dimensional cell culture, which intrinsically excludes the microenvironmental niche, or to ethically debated animal models. This review aims at reporting an updated overview of state-of-the-art hematological malignancies 3D in vitro models, emphasizing the key features and limitations of existing systems to inspire further research in this underexplored field. Full article

Background: Haematological malignancies and their treatment regimens often lead to various complications that impair patients’ physical functioning. This study aimed to assess the level of physical activity and exercise capacity in patients with haematological malignancies who were qualified for haematopoietic stem cell transplantation (HSCT). Methods: A prospective, single-centre study was conducted on patients with haematological malignancies qualified for HSCT (study group, n = 103) and a cohort of healthy volunteers (reference group, n = 100). The assessment protocol included the International Physical Activity Questionnaire (IPAQ) and the 6-Minute Walk Test (6MWT). Results: The median age was 57 years in the study group and 56 years in the reference group. In the IPAQ assessment, at least 50% of the study group reported no engagement in moderate or intense physical activity. In the 6MWT, the study group demonstrated a significantly shorter walking distance compared to the reference group (p < 0.0001). Factors such as group membership (study vs. reference group), age, gender, and body mass index (BMI) were found to have a significant impact on 6MWT performance. No significant differences were observed in IPAQ or 6MWT results among subgroups within the study group when categorized by diagnosis. Conclusions: Patients with haematological malignancies who qualified for HSCT often show physical activity levels below recommended standards, which can negatively impact their ability to endure physical exertion. Insufficient activity prior to transplantation may contribute to reduced exercise capacity. Therefore, prehabilitation programmes aimed at improving physical activity and structured exercise should be an integral part of their care. Full article

Acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL) remain significant challenges in haematological oncology. This review examines the pathophysiology, classification, and risk stratification of these aggressive malignancies, emphasising their impact on treatment strategies and prognosis. We discuss current standard-of-care treatments, including chemotherapy regimens and targeted therapies, while addressing the associated adverse effects and hypersensitivity reactions. Delving into the metabolic characteristics and vulnerabilities of leukaemia cells, the review highlights the key differences between lymphoid and myeloid leukaemia and how metabolic insights can be utilised for therapeutic purposes, with special focus on asparaginase therapy and its potential for improvement in both ALL and AML treatment. The review conveys the importance of personalised medicine approaches based on individual metabolic profiles and the challenges posed by metabolic heterogeneity and plasticity in leukaemia cells. Combining molecular and metabolic profiling can enhance and refine treatment strategies for acute leukaemia, potentially improving patient outcomes and quality of life. However, integrating these into routine clinical practice requires overcoming various practical, technical, and logistical issues. Full article

The advent of chimeric antigen receptor (CAR)-T cells has recently changed the prognosis of relapsing/refractory diffuse large B-cell lymphomas, showing response rates as high as 60 to 80%. Common toxicities reported in the pivotal clinical trials include the cytokine release syndrome (CRS) and the Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS), a stereotyped encephalopathy related to myeloid cell activation and blood–brain barrier dysfunction, presenting with a distinctive cascade of dysgraphia, aphasia, disorientation, attention deficits, vigilance impairment, motor symptoms, seizures, and diffuse brain oedema. The tremendous oncological efficacy of CAR-T cells observed in systemic B-cell malignancies is leading to their growing use in patients with primary or secondary central nervous system (CNS) lymphomas and in patients with solid tumours, including several CNS cancers. Early studies conducted in adult and paediatric patients with solid CNS tumours reported a distinct profile of neurotoxicity referred to as Tumour inflammation-associated neurotoxicity (TIAN), corresponding to local inflammation at the tumour site manifesting with focal neurological deficits or mechanical complications (e.g., obstructive hydrocephalus). The present review summarises available data on the efficacy and safety of CAR-T cells for solid and haematological CNS malignancies, emphasising known and emerging phenotypes, ongoing challenges, and future perspectives. Full article