Publications by authors named "Bustoros M"
Early therapeutic intervention in high-risk smoldering multiple myeloma (HR-SMM) has shown benefits, however, no studies have assessed whether biochemical progression or response depth predicts long-term outcomes. The single-arm I-PRISM phase II trial (NCT02916771) evaluated ixazomib, lenalidomide, and dexamethasone in 55 patients with HR-SMM. The primary endpoint, median progression-free survival (PFS), was not reached (NR) (95% CI: 57.
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- BCMA-targeting CAR-T cells are now a key treatment for relapsed/refractory multiple myeloma, with patient outcomes linked to T cell expansion post-infusion.
- A study involving 156 patients found that those with higher maximum absolute lymphocyte count (ALCmax) showed significantly improved depth of response and progression-free survival.
- ALCmax over 1.0 × 10^3/μL correlates with better outcomes, while lower counts indicate a higher risk of disease progression, suggesting ALC can serve as an important prognostic marker.
Background: Early therapeutic intervention in high-risk SMM (HR-SMM) has demonstrated benefit in previous studies of lenalidomide with or without dexamethasone. Triplets and quadruplet studies have been examined in this same population. However, to date, none of these studies examined the impact of depth of response on long-term outcomes of participants treated with lenalidomide-based therapy, and whether the use of the 20/2/20 model or the addition of genomic alterations can further define the population that would benefit the most from early therapeutic intervention.
View Article and Find Full Text PDFBiomarkers of Progression and Risk Stratification in Asymptomatic Waldenström Macroglobulinemia.
Hematol Oncol Clin North Am
August 2023
Article Synopsis
- - Waldenström macroglobulinemia is a slow-growing type of cancer that affects B-cells and produces IgM antibodies; it often starts with an asymptomatic phase.
- - Researchers have developed risk models using both specific and general biomarkers to predict how quickly different patients may progress from the asymptomatic stage.
- - Newer models are incorporating continuous variables and genetic alterations, which may enhance the accuracy of risk prediction and improve the management of asymptomatic individuals.
Peripheral blood smear (A) demonstrates increased numbers of plasma cells (representative cells indicated by arrows), (B) demonstrates polytypic nature of plasma cells.
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- Recent research on newly diagnosed multiple myeloma (NDMM) and its early forms, MGUS and smoldering myeloma, has identified high-risk patients likely to progress to more severe illness, termed "progressor" cases.
- Progressor cases show higher mutation rates and specific gene mutations compared to non-progressors, indicating the potential for improved patient identification and intervention strategies.
- In relapsed or refractory multiple myeloma (RRMM), a higher mutational burden and complex genetic changes, like chromosomal alterations, are linked to treatment resistance and worse survival outcomes.
Article Synopsis
- Patients with smoldering multiple myeloma usually wait for their condition to get worse before starting treatment, but treating them early might help them live better.
- A study tested a combination of three medicines (elotuzumab, lenalidomide, and dexamethasone) on patients with a more serious form of the disease and looked at their blood samples to see how their immune cells changed.
- The results showed that early treatment was safe and might help, and how similar a patient’s immune system is to healthy people can help predict how well they will do with the treatment.
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.*
Article Synopsis
- - The study investigates the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in high-risk U.S. populations, particularly focusing on individuals of African descent and those with a family history of related diseases, using advanced mass spectrometry techniques.
- - Out of 7,622 participants screened, 6,305 (83%) were identified as high risk based on their race or family history of hematological conditions, ensuring a diverse representation beyond previous estimates relying on predominantly White populations.
- - The research also highlights the importance of utilizing new screening technology and emphasizes longitudinal follow-up data to better understand the clinical implications of monoclonal gammopathies in these high-risk groups over time.
Regular Aspirin Use and Mortality in Patients with Multiple Myeloma.
Cancer Epidemiol Biomarkers Prev
February 2022
Article Synopsis
- Regular aspirin use has been linked to a reduced risk of developing multiple myeloma, a type of blood cancer, but its impact on survival after diagnosis was previously unclear.* -
- A study analyzing data from 436 multiple myeloma patients found that those who used aspirin post-diagnosis had a significantly lower risk of specific and overall mortality compared to non-users.* -
- The results suggest that aspirin could be a beneficial addition to treatment strategies for improving survival in multiple myeloma patients, prompting further research for confirmation in more comprehensive clinical samples.*
Article Synopsis
- * The 2016 update to the WHO classification of lymphoid neoplasms reflects new insights in clinical and molecular understanding, though there's a lack of imaging information in existing literature.
- * This article aims to educate radiologists and other medical professionals on rare B-cell LPD variants, emphasizing their imaging characteristics and key updates from the WHO classification.
Article Synopsis
- The treatment landscape for multiple myeloma is rapidly changing with new agents allowing for minimal residual disease (MRD) negativity to be more achievable across all stages of the disease.
- Advanced technologies like next-generation flow and sequencing are enhancing the detection and monitoring of MRD, while promising liquid biopsy techniques are being developed to deepen our understanding of it.
- Clinicians are increasingly considering MRD status to inform treatment decisions, as ongoing studies highlight its potential importance for improving patient outcomes and guiding future research and clinical trials.
Background: Pregnancy represents a unique challenge for the maternal-fetal immune interface, requiring a balance between immunosuppression, which is essential for the maintenance of a semiallogeneic fetus, and proinflammatory host defense to protect the maternal-fetal interface from invading organisms. Adaptation to repeated inflammatory stimuli (endotoxin tolerance) may be critical in preventing inflammation-induced preterm birth caused by exaggerated maternal inflammatory responses to mild or moderate infections that are common during pregnancy. However, the exact mechanisms contributing to the maintenance of tolerance to repeated infections are not completely understood.
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- Precursor states of Multiple Myeloma (MM) require detailed molecular analysis to improve risk assessment and treatment strategies for patients.
- Single-cell RNA sequencing revealed early immune system changes, including increased NK cell abundance and altered chemokine receptor expression in precursor stages like MGUS and smoldering myeloma (SMM).
- The study identified loss of specific T-cells and dysregulation of MHC class II in monocytes, both contributing to T cell suppression, offering insights for better immune-based patient stratification in MM progression.
Article Synopsis
- Pregnancy in women with essential thrombocythemia (ET) carries a higher risk of complications, as seen in a study of 121 pregnancies among 52 ET women.
- The overall live birth rate was 69%, but nearly half of the women experienced complications, with spontaneous abortion being the most common at 26%.
- Key findings suggest that aspirin use may reduce complications, while a history of pregnancy loss increases them; importantly, women who face complications in one pregnancy have a higher chance of complications in future pregnancies.
Multiple myeloma (MM) is an incurable plasma cell malignancy characterized by clonal proliferation of plasma cells and a heterogenous genomic landscape. Copy number and structural changes due to chromosomal instability (CIN) are common features of MM. In this review, we describe how primary and secondary genetic events caused by CIN can contribute to increased instability across the genome of malignant plasma cells; with a focus on specific driver genomic events, and how they interfere with cell-cycle checkpoints, to prompt accelerated proliferation.
View Article and Find Full Text PDFMultiple myeloma (MM) is a plasma-cell neoplasm that is treated with high-dose chemotherapy, autologous stem cell transplant (ASCT) and long-term immunomodulatory drug (IMiD) maintenance. The presence of somatic mutations in the peripheral blood is termed clonal hematopoiesis of indeterminate potential (CHIP) and is associated with adverse outcomes. Targeted sequencing of the stem cell product from 629 MM patients treated by ASCT at the Dana-Farber Cancer Institute (2003-2011) detects CHIP in 136/629 patients (21.
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- 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.
Article Synopsis
- * Patients with mutated WM face better survival rates compared to those with wild-type WM, who are at higher risk for transformation into more aggressive forms like diffuse large B-cell lymphoma.
- * The understanding of specific mutations has led to targeted drug development for WM, particularly with drugs like BTK inhibitors (e.g., ibrutinib), allowing for more personalized treatment strategies based on mutation status.
Article Synopsis
- Waldenström macroglobulinemia (WM) can develop from an asymptomatic stage known as asymptomatic WM (AWM), and this study investigates the risk of progression from AWM to symptomatic WM among 439 patients.
- The research found that 72% of patients progressed to symptomatic WM over an average of 7.8 years, identifying key predictors of progression such as high immunoglobulin M levels and significant bone marrow infiltration.
- A new risk classification model was developed and validated, categorizing patients into high, intermediate, and low-risk groups for progression, which can help guide patient monitoring and potential early intervention.
Waldenström Macroglobulinemia (WM) is a low-grade B-cell lymphoma characterized by disease progression from IgM MGUS to asymptomatic and then symptomatic disease states. We profiled exosomes from the peripheral blood of patients with WM at different stages (30 smoldering/asymptomatic WM, 44 symptomatic WM samples and 10 healthy controls) to define their role as potential biomarkers of disease progression. In this study, we showed that circulating exosomes and their miRNA content represent unique markers of the tumor and its microenvironment.
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