Publications by authors named "Selina J Chavda"

Introduction: BCL-2 family proteins are important for tumour cell survival and drug resistance in multiple myeloma (MM). Although proteasome inhibitors are effective anti-myeloma drugs, some patients are resistant and almost all eventually relapse. We examined the function of BCL-2 family proteins in stromal-mediated resistance to carfilzomib-induced cytotoxicity in MM cells.

View Article and Find Full Text PDF

Background: Patients with precursors to multiple myeloma are dichotomised as having monoclonal gammopathy of undetermined significance or smouldering multiple myeloma on the basis of monoclonal protein concentrations or bone marrow plasma cell percentage. Current risk stratifications use laboratory measurements at diagnosis and do not incorporate time-varying biomarkers. Our goal was to develop a monoclonal gammopathy of undetermined significance and smouldering multiple myeloma stratification algorithm that utilised accessible, time-varying biomarkers to model risk of progression to multiple myeloma.

View Article and Find Full Text PDF

Patients with multiple myeloma, an incurable malignancy of plasma cells, frequently develop osteolytic bone lesions that severely impact quality of life and clinical outcomes. Eliglustat, a U.S.

View Article and Find Full Text PDF
Article Synopsis
  • The study compares a treatment protocol for multiple myeloma involving carfilzomib without stem cell transplantation to the standard bortezomib protocol followed by stem cell transplant to determine if the new method is equally effective.
  • Conducted in 19 hospitals in the UK, the CARDAMON trial involved 281 patients and focused on key outcomes, including response rates and progression-free survival after treatment.
  • Preliminary findings showed that the trial successfully randomized patients and is designed to assess the safety and efficacy of the new treatment regimen over a two-year period.
View Article and Find Full Text PDF
Article Synopsis
  • Smoldering multiple myeloma (SMM) is an early stage of multiple myeloma (MM) that varies widely in how fast it progresses to active disease.* -
  • Researchers analyzed genetic data from 214 SMM patients and discovered six unique genetic subtypes using advanced clustering techniques.* -
  • Three of these subtypes correlate with a higher risk of developing active MM, suggesting they could improve current methods for assessing patient risk levels in clinical settings.*
View Article and Find Full Text PDF

The benefit of autologous stem cell transplantation (ASCT) in newly diagnosed myeloma patients, apart from supporting high dose chemotherapy, may include effects on T cell function in the bone marrow (BM). We report our exploratory findings on marrow infiltrating T cells early post-ASCT (day+100), examining phenotype and T cell receptor (TCR) repertoire, seeking correlations with timing of relapse. Compared to healthy donors (HD), we observed an increase in regulatory T cells (CD4+FoxP3+, Tregs) with reduction in CD4 T cells, leading to lower CD4:8 ratios.

View Article and Find Full Text PDF

Proteasome inhibitors have been associated with thrombotic microangiopathy (TMA) - a group of disorders characterised by occlusive microvascular thrombosis causing microangiopathic haemolytic anaemia, thrombocytopenia and end-organ damage. To date, carfilzomib-associated TMA has predominantly been described in relapsed/refractory myeloma patients. We report eight patients with newly diagnosed myeloma who experienced TMA events while receiving carfilzomib on the phase II CARDAMON trial.

View Article and Find Full Text PDF

Haematology patients receiving chemo- or immunotherapy are considered to be at greater risk of COVID-19-related morbidity and mortality. We aimed to identify risk factors for COVID-19 severity and assess outcomes in patients where COVID-19 complicated the treatment of their haematological disorder. A retrospective cohort study was conducted in 55 patients with haematological disorders and COVID-19, including 52 with malignancy, two with bone marrow failure and one immune-mediated thrombotic thrombocytopenic purpura (TTP).

View Article and Find Full Text PDF
Article Synopsis
  • Smoldering multiple myeloma (SMM) is a precursor to multiple myeloma (MM) with a significant risk of progression, indicating a need for better risk assessment tools beyond just clinical metrics.
  • Researchers utilized next-generation sequencing on 214 SMM patients and discovered that key genetic alterations linked to progression to MM are usually already present at SMM diagnosis.
  • The study identified specific genetic changes, particularly in certain pathways, as independent risk factors for progression, which were validated in an external cohort, suggesting potential for improved precision in predicting disease evolution from SMM to MM.
View Article and Find Full Text PDF

Purpose: Immune dysregulation is described in multiple myeloma. While preclinical models suggest a role for altered T-cell immunity in disease progression, the contribution of immune dysfunction to clinical outcomes remains unclear. We aimed to characterize marrow-infiltrating T cells in newly diagnosed patients and explore associations with outcomes of first-line therapy.

View Article and Find Full Text PDF