Publications by authors named "Bris Y"
Int J Lab Hematol
February 2025
Article Synopsis
- VEXAS syndrome, identified in 2020, is caused by mutations in the UBA1 gene and shows a variety of clinical and hematological features, making it challenging to distinguish from other inflammatory conditions. !*
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- This study collected a dataset of 9,514 images of polymorphonuclear cells (PMNs) and used a convolutional neural network (CNN) to automate the detection of specific dysplastic features unique to VEXAS, achieving a high level of accuracy (AUC of 0.85-0.97). !*
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- Results indicate that automated analysis can effectively support hematologists in identifying potential VEXAS cases, suggesting a screening score for UBA1 mutational
Article Synopsis
- - A study reported on five patients with myeloid neoplasms who experienced liver complications, with liver biopsies showing that their liver sinusoids were blocked by platelet clumps and evidence of extramedullary hematopoiesis.
- - The group included four men and one woman, ages 50 to 82, diagnosed with various haematological disorders, such as myeloproliferative neoplasms and chronic myelomonocytic leukaemia.
- - All patients had severe liver issues, leading to different causes of death within 2 to 23 months post-biopsy, including acute myeloblastic leukaemia and portal hypertension, suggesting that microthromboses could lead to liver complications
Rheumatology (Oxford)
February 2024
Article Synopsis
- VEXAS is a newly identified syndrome linked to mutations in the UBA1 gene, which may lead to an increased risk of disseminated non-tuberculous mycobacterial infections (NTMi), despite not being officially recognized as a cause of acquired immunodeficiency.
- In a study of 10 VEXAS patients, two were found with Mycobacterium avium, alongside a review of 20 cases of disseminated NTMi over 13 years, highlighting common conditions among the patients.
- The findings suggest that VEXAS patients may have a higher susceptibility to NTMi due to issues with their immune response, specifically monocytic dysfunction, and emphasize the need for vigilant diagnosis of opportunistic infections before adjusting
Article Synopsis
- The presence of donor Vγ9Vδ2 T-cells after haploidentical hematopoietic stem cell transplant (h-HSCT) is linked to better disease-free survival, as these cells can target tumor cells without triggering severe side effects.
- A clinical study assessed the safety of generating these T-cells by combining zoledronic acid (ZA) with interleukin-2 (IL-2), showing that the procedure is safe and successfully increases T-cell numbers in patients.
- The study's outcomes suggest potential for further research into using this immunotherapy to reduce relapse rates after h-HSCT, indicating that more extensive trials may come next.
Article Synopsis
- Researchers used CRISPR/Cas9 to create TP53-/- clones from human myeloma cell lines to study p53-dependent gene expression, identifying a functional score based on 13 genes downregulated when p53 is silenced.
- This score can differentiate myeloma cells based on TP53 status, predict patient survival, and identifies patients with complete TP53 inactivation.
- The study found that the p53-regulated gene BAX impacts myeloma cell sensitivity to specific treatments, and combining MCL1 and BCL2 inhibitors may provide better treatment options for patients with TP53 inactivation.
EClinicalMedicine
October 2023
Article Synopsis
- In acute myeloid leukaemia (AML), interleukin-6 (IL-6) is linked to chemotherapy resistance and worse patient outcomes, prompting researchers to explore tocilizumab, an anti-IL-6 receptor monoclonal antibody, as a potential treatment in combination with standard chemotherapy.
- A phase 1 trial at Nantes University Hospital tested three escalating doses of tocilizumab in adults with newly diagnosed or relapsed AML, aiming to determine the maximum tolerated dose (MTD) while monitoring safety and treatment responses.
- Of the 12 patients treated, no significant toxicities related to tocilizumab were observed, nine out of ten evaluable patients had a positive response to the treatment, indicating
Hemasphere
September 2023
Article Synopsis
- - The study evaluated the effectiveness and costs of next-generation sequencing (NGS) in treating various hematological cancers in both pediatric and adult patients, collecting data from 26 laboratories with differing practices.
- - Results showed that NGS influenced treatment management for 73.4% of cases, particularly providing prognostic information and aiding treatment adaptations, though about 18.9% of prescriptions had no immediate impact on therapy.
- - The average cost for NGS samples was 191 €, with variations based on the type of panel used, highlighting the need for clear discussions about precision medicine's effects on patient care and financial implications.
Article Synopsis
- * Researchers used genomic and RNA-sequencing analyses to find that subclones of resistant cancer cells develop mutations (like CARD11) that enable them to evade the therapies by enhancing specific survival genes, contributing to treatment resistance.
- * They proposed a new approach that targets MALT1, a key partner in the resistance pathway, which shows potential for overcoming resistance and improving treatment outcomes in MCL, even in the presence of resistance mutations.
Lancet Haematol
July 2023
Article Synopsis
- CPX-351, a drug combining cytarabine and daunorubicin, shows better results than traditional treatments for secondary acute myeloid leukemia and is being tested for its safety and efficacy in related blood disorders.
- A phase 2 trial included patients with higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia, focusing on those in their first-line treatment, while a second cohort was halted due to low patient enrollment.
- The trial's results indicated a strong response rate, with 87% of participants showing improvement after treatment with CPX-351, backed by data collected from 31 patients during the study period.
Article Synopsis
- Immunotherapy that uses the body's immune system is becoming popular in treating blood cancers like mantle cell lymphoma (MCL), but there's little understanding of immune cell behavior in MCL patients' lymph nodes and bone marrow.
- The study utilized a technique called RT-MLPA to analyze gene expression in MCL patients at diagnosis and relapse, focusing on immune-related genes to gain insights into tumor aggressiveness and immune response.
- Results showed that aggressive MCL forms had increased macrophage-related gene expression but lower T-cell markers, which could help differentiate between patient groups and guide personalized treatment approaches.
Bone Marrow Transplant
September 2022
Article Synopsis
- Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) can fail due to disease relapse in patients with high-risk myeloid malignancies, with CD34 cells in bone marrow possibly being either malignant recipient cells or donor cells signaling recovery.
- A study of 261 Allo-HSCT recipients analyzed donor/recipient chimerism in BM CD34 sorted cells, finding that thresholds of 98% donor cells in peripheral blood and 90% in BM-CD34SC could predict relapse.
- Machine learning was used to confirm that mixed chimerism in BM-CD34SC is a strong predictor of relapse, significantly affecting disease-free and overall survival, highlighting its potential for guiding preemptive treatment strategies
Article Synopsis
- DDX41 germline mutations are a common cause of a type of cancer called myelodysplastic syndrome and acute myeloid leukemia (AML).
- In a study of 191 patients with these mutations, it was found that most were older men with specific characteristics like low white blood cell counts and fewer genetic changes.
- Patients with these mutations had higher chances of getting better with treatment (94% complete remission) and lived longer compared to those without the mutation, but their chances of relapse became similar after a few years.
Haematologica
December 2022
Article Synopsis
- Aggressive B-cell malignancies like mantle cell lymphoma (MCL) depend on their microenvironment, and understanding these interactions can improve treatments.
- A transcriptomic analysis compared circulating MCL cells to those in lymph nodes, revealing that interleukin-32 beta (IL32β) is secreted in a microenvironment-dependent manner and is linked to tumor survival.
- The study found that IL32β influences monocyte polarization into MCL-associated macrophages, promoting tumor support, and showed that inhibiting the NIK/alternative-NFkB pathway can disrupt this survival mechanism.
Transplant Cell Ther
October 2021
Article Synopsis
- High-risk patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) often relapse after allogeneic stem cell transplants, prompting the study of post-transplant maintenance therapies like low-dose azacitidine (AZA) and donor lymphocyte infusion (DLI).
- A retrospective analysis of 77 high-risk AML/MDS patients who underwent maintenance therapy showed that 47% completed 12 cycles of AZA and 79% received at least one DLI, with a 25% relapse rate observed within 24 months.
- The study reported overall survival and progression-free survival rates at 24 months of 70.8% and 68.3%, respectively, along with incidence
Hum Vaccin Immunother
October 2021
Article Synopsis
- This study evaluated the feasibility of a vaccine using dendritic cells pulsed with leukemic apoptotic corpses in elderly patients with acute myeloid leukemia (AML) who were in remission.
- Five patients received a series of five doses of the vaccine, which were administered both subcutaneously and intra-dermally.
- No serious side effects were reported, leading to the conclusion that larger studies are needed to determine the effectiveness of this vaccine in both older and younger AML patients.
Article Synopsis
- The study looked at how different gene mutations affect the health of people with myelofibrosis, a type of blood disease.
- Researchers analyzed 479 patients and grouped them based on specific mutations to see how these groups relate to worsening conditions or death.
- They found that mutations in certain genes like TP53 and high-risk genes made it more likely for patients to get worse or die, while a mutation in the ASXL1 gene alone didn’t have a significant negative impact.
Article Synopsis
- * It focuses specifically on two cytokines: Fms-like tyrosine kinase 3 ligand (FL) and interleukin-6 (IL-6), measuring their levels during initial intensive treatment.
- * A new risk stratification model is proposed based on the cytokine levels, identifying three risk groups (high, intermediate, favorable) that could improve predictions of survival compared to existing classifications.
Article Synopsis
- The study focuses on the effects of acute graft versus host disease (GVHD) on survival in patients undergoing haploidentical allogeneic stem-cell transplants using peripheral blood stem-cells, supplemented with post-transplant cyclophosphamide.
- It includes data from 131 patients, mainly treated for myeloid malignancies, and shows a significant occurrence of GVHD, particularly grade 2-4 within the first 100 days.
- Importantly, having grade 2 acute GVHD is linked to improved survival rates, leading to a recommendation for further research into GVHD prevention strategies in haplo-transplants combining anti-thymoglobulin and post-transplant cyclophosph
