Publications by authors named "Dima D"

The incidence rate of cutaneous melanoma is on the rise worldwide, due to increased exposure to UV radiation, aging populations, and exposure to teratogen agents. However, diagnosis is more precise, and the increased number of new cases is related to the improved diagnosis tools. Despite better early diagnosis and better therapies, melanoma has remained a significant public health challenge because of its aggressive behavior and high potential for metastasis.

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Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), the asymptomatic precursors to multiple myeloma, affect up to 5% of the population over the age of 40. Bone involvement, a myeloma-defining event, represents a major source of morbidity for patients. Key goals for the management of myeloma precursor conditions include (1) identifying patients at the highest risk for progression to MM with bone involvement and (2) differentiating precursor states from active myeloma requiring treatment.

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Relapse and metastasis are the major challenges that stand in the way of cancer healing and survival, mainly attributed to cancer stem cells (CSCs). Their capabilities of self-renewal and tumorigenic potential leads to treatment resistance development. CSCs function through signaling pathways such as the Wnt/β-catenin cascade.

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Multiple myeloma (MM) is a complex hematological malignancy of clonal plasma cells driven by alterations to the chromosomal material leading to uncontrolled proliferation in the bone marrow. Ethnic and racial disparities persist in the prevalence, diagnosis, management, and outcomes of MM. These disparities are multifaceted and intersect with various factors, including demographics, geography, socioeconomic status, genetics, and access to healthcare.

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Article Synopsis
  • CAR T-cell therapy shows strong initial results for treating relapsed refractory multiple myeloma, but most patients eventually relapse, often within 5 months.
  • In a study of 139 patients who relapsed after CAR T-cell therapy, different salvage therapies were analyzed, revealing that bispecific antibodies, like talquetamab and teclistamab, had the best overall and complete response rates.
  • The presence of extramedullary disease at relapse was linked to poorer outcomes, but bispecific antibodies improved survival rates, suggesting they should be the standard treatment for patients relapsing after CAR T-cell therapy.
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Past studies described occasional patients with myeloid neoplasms (MN) and coexistent large granular lymphocytic leukemia (LGLL) or T-cell clonopathy of unknown significance (TCUS), which may represent expansion of myeloid clonal hematopoiesis (CH) as triggers or targets of clonal cytotoxic T cell reactions. We retrospectively analyzed 349 LGLL/TCUS patients, 672 MN patients, and 1443 CH individuals to establish the incidence, genetic landscape, and clinical phenotypes of CH in LGLL. We identified 8% of cases overlapping with MN, while CH was found in an additional 19% of cases (CH + /LGLL) of which TET2 (23%) and DNMT3A (14%) were the most common.

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Background: Telomere length (TL) has been linked to cognitive function, decline and dementia. This study aimed to explore whether both measured TL and genetic disposition for TL predict dimensions of cognitive performance in a longitudinal sample of older UK adults.

Methods: We analysed data from PROTECT study participants aged ≥50 years without a dementia diagnosis, who had completed longitudinal cognitive testing.

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Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), an uncommon malignancy, was linked to textured breast implants by moderate evidence in 2021. Documenting Romanian cases provides valuable insights into the epidemiology, management, and outcomes, thereby, enhancing global understanding and informing clinical practices. Our objective was to analyze BIA-ALCL cases in Romania, focusing on patient demographics, implant characteristics, clinical presentation, diagnostic methods, treatment, and outcomes.

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  • Castleman disease (CD) is a rare non-cancerous condition that can be unicentric or multicentric (MCD), with MCD leading to serious symptoms due to cytokine issues, particularly involving interleukin-6 (IL-6).
  • This study examined the real-world effectiveness of siltuximab, an anti-IL-6 therapy recommended for idiopathic MCD, in treating patients in Greece and Romania from 2017 to 2022.
  • Out of 48 patients treated, 71.1% had a response to the treatment, with a 3-year survival rate of 74%, but some patients experienced adverse effects like elevated liver enzymes and anxiety.
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  • Ciltacabtagene autoleucel (cilta-cel) CAR-T therapy was approved in 2022 for treating patients with multiple myeloma who have not responded to other treatments.
  • Out of 255 patients, 236 received the therapy, and many of them didn't qualify for earlier trials, but the results were still positive.
  • Most patients experienced some side effects, but many showed good responses to the treatment, with a significant percentage remaining cancer-free after one year.
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: Spontaneous remission of cancer is a rare and poorly understood phenomenon characterized by complete or partial remission of a malignancy in the absence of or with inadequate treatment. The underlying mechanism for such occurrences is poorly understood, however, immune mechanisms seem to play an important role in such cases. In recent years increasingly more data have become available in favor of the clinical benefit of low levels of chimerism in hematologic malignancies.

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  • * Treatment with hypomethylating agents like azacytidine is common, but patient responses vary, necessitating better understanding through genetic and epigenetic analysis, particularly RNA methylation.
  • * Recent research focused on RNA methylation in MDS patients to determine factors that distinguish responders from non-responders to azacytidine, suggesting that analyzing the methylome can provide more accurate prognostic insights for high-grade MDS patients.
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Capillary leak syndrome is a rare complication of cancer, particularly of hematologic malignancies. The syndrome was first described as an idiopathic entity; however, increasingly, more cases are being reported in association with cancers and other conditions. Diagnosis stems from the recognition of the double paradox, consisting of severe generalized oedema and hypotension, accompanied by hallmark laboratory modifications.

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  • Clinical trials on CAR T-cell therapy for relapsed/refractory multiple myeloma usually exclude patients with AL amyloidosis, leading to a lack of data on its effectiveness for this group.
  • A study reviewed eight patients with both RRMM and AL amyloidosis who underwent standard CAR T-cell therapy, revealing that 75% experienced cytokine release syndrome and low-grade cytopenias were common.
  • The therapy resulted in rapid and significant responses, with a median time to best response of 43 days and a 62.5% rate of achieving a very good partial response or better, indicating that CAR T-cell therapy is feasible and effective for these patients.
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Introduction: Previous studies have shown associations between cognitive function and C-reactive protein (CRP) levels in older adults. Few studies have considered the extent to which a genetic predisposition for higher CRP levels contributes to this association.

Methods: Data was analyzed from 7,817 UK participants aged >50 years as part of the PROTECT study, within which adults without dementia completed a comprehensive neuropsychological battery.

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Humans can recognize and communicate about many actions performed by others. How are actions organized in the mind, and is this organization shared across vision and language? We collected similarity judgments of human actions depicted through naturalistic videos and sentences, and tested four models of action categorization, defining actions at different levels of abstraction ranging from specific (action verb) to broad (action target: whether an action is directed towards an object, another person, or the self). The similarity judgments reflected a shared organization of action representations across videos and sentences, determined mainly by the target of actions, even after accounting for other semantic features.

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Article Synopsis
  • * Results showed that the median relapse-free survival (RFS) was longer for the IO group compared to the TT group, but most patients were alive at the end of the study; however, more patients in the IO group faced severe treatment-related side effects.
  • * The findings suggest that while both therapies can lead to prolonged RFS, TT might have lower tolerance in practice, and there’s a need for further analysis to assess the overall survival benefits over a longer period.
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  • Daratumumab treatment for light chain (AL) amyloidosis can lead to early refractoriness, leaving patients with fewer options if they relapse or respond poorly.
  • This study assessed the effectiveness of venetoclax therapy in AL patients with t(11;14) who had previously failed daratumumab, involving 31 subjects.
  • Results showed a 97% overall hematologic response to venetoclax, with strong organ responses in patients with cardiac (74%) and renal (46%) involvement, indicating promising potential for venetoclax as a salvage therapy after daratumumab failure.
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  • Multiple myeloma (MM) is a cancer of the plasma cells in the bone marrow that leads to symptoms like anemia, renal issues, and fatigue, but currently available treatments often have limited long-term success and frequent relapses occur.* -
  • The development of drug resistance in myeloma cells complicates treatment, making ongoing research into new therapeutic targets and strategies essential for improving patient outcomes.* -
  • This article reviews new and emerging treatment options for MM, organized by specific molecular targets like BCMA and CD38, as well as treatments such as immunomodulatory drugs and NK cell therapy.*
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Current treatment guidelines of myeloma cast nephropathy (MCN) recommend the institution of plasma cell-directed therapy and consideration of therapeutic plasma exchange (TPE), with the goal of rapid reduction of the serum free light chain (sFLC). However, the role of TPE continues to remain a subject of debate. The goal of this retrospective bi-institutional study was to evaluate the clinical outcomes of TPE in combination with systemic therapy.

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BCMA-directed chimeric antigen receptor T-cell (CAR T) therapies, including idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), have transformed the treatment landscape for relapsed-refractory multiple myeloma (RRMM), offering remarkable efficacy with hallmark toxicity risks of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The FDA mandates a 4-week monitoring period at the treatment center as part of a Risk Evaluation and Mitigation Strategy (REMS) to monitor and manage these toxicities, which, while prudent, may add unnecessary challenges related to access and socioeconomic disparities. We sought to assess CRS and ICANS onset and duration, as well as causes of non-relapse mortality (NRM) in real-world BCMA CAR T recipients in order to better inform future changes to the monitoring guidelines for CAR T recipients.

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Idecabtagene vicleucel (Ide-cel) has demonstrated excellent efficacy and durable responses in patients with relapsed/refractory multiple myeloma (RRMM). However, the outcomes with ide-cel in patients with extramedullary disease (EMD) remain incompletely characterized. We included patients with RRMM treated with ide-cel between May 2021 and April 2023 across 11 US academic institutions.

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Idecabtagene vicleucel (ide-cel) has shown impressive efficacy in relapsed/refractory multiple myeloma (RRMM). This study aimed to investigate the impact of absolute lymphocyte count (ALC) on the survival outcomes of RRMM patients treated with standard of care (SOC) ide-cel. Data were collected retrospectively from 11 institutions in the U.

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The presence of extramedullary disease (EMD) has been associated with poor outcomes in patients with relapsed-refractory multiple myeloma (RRMM). Herein, we report the outcomes of RRMM patients who were treated with standard-of-care (SOC) chimeric antigen receptor (CAR) T-cell therapy and had active extraosseous EMD before the infusion. Data were retrospectively collected from patients at three US institutions with the intent to receive SOC CAR T.

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