Background: The Blood Cancer Network Ireland and National Cancer Registry Ireland worked to create an Enhanced Blood Cancer Outcomes Registry (EBCOR). Enhanced data in acute myeloid leukaemia (AML) included an extensive data dictionary, bespoke software and longitudinal follow-up.
Aims: To demonstrate the utility of the database, we applied the data to examine a clinically relevant question: Charlson comorbidity index (CCI) usefulness in predicting AML patients' survival.
Multiple Myeloma (MM) is an incurable haematological malignancy caused by uncontrolled growth of plasma cells. MM pathogenesis is attributed to crosstalk between plasma cells and the bone marrow microenvironment, where extracellular vesicles (EVs) play a role. In this study, EVs secreted from a panel of MM cell lines were isolated from conditioned media by ultracentrifugation and fluorescently stained EVs were co-cultured with THP-1 monocyte cells.
View Article and Find Full Text PDFThis paper describes a machine learning (ML) decision support system to provide a list of chemotherapeutics that individual multiple myeloma (MM) patients are sensitive/resistant to, based on their proteomic profile. The methodology used in this study involved understanding the parameter space and selecting the dominant features (proteomics data), identifying patterns of proteomic profiles and their association to the recommended treatments, and defining the decision support system of personalized treatment as a classification problem. During the data analysis, we compared several ML algorithms, such as linear regression, Random Forest, and support vector machines, to classify patients as sensitive/resistant to therapeutics.
View Article and Find Full Text PDFTo improve the outcomes of patients with the otherwise incurable hematologic malignancy of multiple myeloma (MM), a key paradigm includes initial treatment to establish disease control rapidly followed by maintenance therapy to ensure durability of response with manageable toxicity. However, patients' prognosis worsens after relapse, and the disease burden and drug toxicities are generally more challenging with subsequent lines of therapy. It is therefore particularly important that patients with newly diagnosed multiple myeloma (NDMM) receive optimal frontline therapy.
View Article and Find Full Text PDFMultiple myeloma (MM) is an incurable haematological malignancy of plasma cells in the bone marrow. In rare cases, an aggressive form of MM called extramedullary multiple myeloma (EMM) develops, where myeloma cells enter the bloodstream and colonise distal organs or soft tissues. This variant is associated with refractoriness to conventional therapies and a short overall survival.
View Article and Find Full Text PDFThere are limited prospective data on lenalidomide, subcutaneous bortezomib, and dexamethasone (RsqVd) in transplant-eligible/transplant-ineligible patients with newly diagnosed multiple myeloma. Reliable biomarkers for efficacy and toxicity are required to better tailor therapy. Two parallel studies were conducted by Cancer Trials Ireland (CTI; NCT02219178) and the Dana-Farber Cancer Institute (DFCI; NCT02441686).
View Article and Find Full Text PDFWe aimed to use SARS-CoV-2 antibody tests to assess the asymptomatic seroprevalence of individuals in high-risk hospital cohorts who's previous COVID-19 exposure is unknown; staff, and patients requiring haemodialysis or chemotherapy after the first wave. In a single Center, study participants had five SARS-CoV-2 antibody tests done simultaneously; one rapid diagnostic test (RDT) (Superbio Colloidal Gold IgM/IgG), and four laboratory tests (Roche Elecsys® Anti-SARS-CoV-2 IgG [RE], Abbott Architect i2000SR IgG [AAr], Abbott Alinity IgG [AAl], and Abbott Architect IgM CMIA). To determine seroprevalence, only positive test results on laboratory assay were considered true positives.
View Article and Find Full Text PDFDespite several new therapeutic options, multiple myeloma (MM) patients experience multiple relapses and inevitably become refractory to treatment. Insights into drug resistance mechanisms may lead to the development of novel treatment strategies. The S100 family is comprised of 21 calcium binding protein members with 17 S100 genes located in the 1q21 region, which is commonly amplified in MM.
View Article and Find Full Text PDFSince the emergence of high-throughput proteomic techniques and advances in clinical technologies, there has been a steady rise in the number of cancer-associated diagnostic, prognostic, and predictive biomarkers being identified and translated into clinical use. The characterisation of biofluids has become a core objective for many proteomic researchers in order to detect disease-associated protein biomarkers in a minimally invasive manner. The proteomes of biofluids, including serum, saliva, cerebrospinal fluid, and urine, are highly dynamic with protein abundance fluctuating depending on the physiological and/or pathophysiological context.
View Article and Find Full Text PDFWith the introduction of novel therapeutic agents, survival in Multiple Myeloma (MM) has increased in recent years. However, drug-resistant clones inevitably arise and lead to disease progression and death. The current International Myeloma Working Group response criteria are broad and make it difficult to clearly designate resistant and responsive patients thereby hampering proteo-genomic analysis for informative biomarkers for sensitivity.
View Article and Find Full Text PDFPost-translational modifications (PTMs) add a layer of complexity to the proteome through the addition of biochemical moieties to specific residues of proteins, altering their structure, function and/or localization. Mass spectrometry (MS)-based techniques are at the forefront of PTM analysis due to their ability to detect large numbers of modified proteins with a high level of sensitivity and specificity. The low stoichiometry of modified peptides means fractionation and enrichment techniques are often performed prior to MS to improve detection yields.
View Article and Find Full Text PDFWe report a case of 33-year-old female with underlying genetic susceptibility for familial porphyria cutanea tarda due to novel variant (c.636 + 2 dupT) unmasked by transient exposure to supraphysiological oestrogen concentrations following a single cycle of successful controlled ovarian stimulation for oocyte retrieval. Use of oral oestrogen in the form of oral contraceptive pills and hormone replacement therapy has been well known to trigger active porphyria cutanea tarda phenotype in susceptible women.
View Article and Find Full Text PDFMultiple Myeloma (MM), the second most common lymphoid cancer worldwide, is characterised by the uninhibited proliferation of terminally differentiated B-lymphocytes. Leading to The diagnosis typically requires the presence of a monoclonal protein (M protein) and the demonstration of CRAB features (hypercalcemia, renal impairment, anaemia and bone lesions). MM is considered incurable as, due to serial clonal evolution, the vast majority of patients succumb to treatment-refractory disease.
View Article and Find Full Text PDFInnate drug sensitivity in healthy cells aids identification of lineage specific anti-cancer therapies and reveals off-target effects. To characterize the diversity in drug responses in the major hematopoietic cell types, we simultaneously assessed their sensitivity to 71 small molecules utilizing a multi-parametric flow cytometry assay and mapped their proteomic and basal signaling profiles. Unsupervised hierarchical clustering identified distinct drug responses in healthy cell subsets based on their cellular lineage.
View Article and Find Full Text PDFBackground: As lenalidomide becomes increasingly established for upfront treatment of multiple myeloma, patients refractory to this drug represent a population with an unmet need. The combination of pomalidomide, bortezomib, and dexamethasone has shown promising results in phase 1/2 trials of patients with relapsed or refractory multiple myeloma. We aimed to assess the efficacy and safety of this triplet regimen in patients with relapsed or refractory multiple myeloma who previously received lenalidomide.
View Article and Find Full Text PDFMultiple myeloma, an incurable malignancy of the plasma cells in the bone marrow, has a complex pathogenesis due to clonal heterogeneity. Over the years, many clinical trials and researches have led to the development of effective myeloma treatments, resulting in survival prolongation. Molecular prognostic markers for risk-stratification to predict survival, and predictive markers for treatment response are being extensively explored.
View Article and Find Full Text PDFDespite significant advances in cancer diagnostics and therapeutics the majority of cancer unfortunately remains incurable, which has led to continued research to better understand its exceptionally diverse biology. As a result of genomic instability, cancer cells typically have elevated proteotoxic stress. Recent appreciation of this functional link between the two secondary hallmarks of cancer: aneuploidy (oxidative stress) and proteotoxic stress, has therefore led to the development of new anticancer therapies targeting this emerging "Achilles heel" of malignancy.
View Article and Find Full Text PDFIn multiple myeloma (MM), maintenance therapy is a longer, less intensive treatment course than initial therapy that is administered postinduction to delay disease progression. Maintenance and continuous therapy have been shown to suppress minimal residual disease and deepen and prolong responses, with the goal of improving progression-free survival and overall survival. Areas covered: In this review, we have summarized current clinical trial data on maintenance and continuous therapy in newly diagnosed MM and relapsed/refractory MM (RRMM), focusing on lenalidomide and bortezomib.
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