Publications by authors named "Willekens C"
Chronic myelomonocytic leukemia (CMML) is a severe myeloid malignancy with limited therapeutic options. Single-cell analysis of clonal architecture demonstrates early clonal dominance with few residual WT hematopoietic stem cells. Circulating myeloid cells of the leukemic clone and the cytokines they produce generate a deleterious inflammatory climate.
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- Circulating proteomes can reveal the body's response to diseases like COVID-19 and treatments like tocilizumab, which is used to mitigate severe symptoms.
- In a study involving 28 hospitalized COVID-19 patients treated with tocilizumab, researchers collected serum samples to analyze changes in protein levels before and after treatment and assessed patient outcomes for 30 days.
- Findings indicated that specific proteins related to the complement system and Fc-epsilon receptor signaling could predict treatment success and mortality, where high complement activation linked to worse outcomes and certain signaling pathways showed lower mortality rates.
Background: Early-phases clinical trials (Phases 1 and 2) have evolved from a traditional assessment of toxicity to an adaptive approach based on patients' medical needs and access to effective new therapies. The global risks, benefits, and relevance of early-phases clinical trials participation for patients with hematological malignancies remain poorly evaluated.
Patients And Methods: All early-phases clinical trials participations for patients with hematological malignancies, from 2008 to 2023, in a tertiary academic center in Europe, were reviewed.
Article Synopsis
- * These mutations vary in their effects based on specific types and can influence treatment efficacy and disease progression; they may not always work as independent prognostic indicators.
- * Research is ongoing into new therapies targeting the RAS pathway, with hope that advances seen in solid tumors will also benefit patients with blood cancers.
Purpose: Follicular lymphoma (FL) is one of the most common lymphoma. Occasionally, FL is associated with tumoral epidural compression and management of these patients remain poorly codified. This study aims to report incidence, clinical characteristics, management and outcomes of patients with FL and tumoral epidural compression.
View Article and Find Full Text PDFHeterozygous mutation targeting proline 95 in Serine/Arginine-rich Splicing Factor 2 (SRSF2) is associated with V617F mutation in Janus Activated Kinase 2 (JAK2) in some myeloproliferative neoplasms (MPNs), most commonly primary myelofibrosis. To explore the interaction of Srsf2 with Jak2, we generated Cre-inducible knock-in mice expressing these mutants under control of the stem cell leukemia (Scl) gene promoter. In transplantation experiments, Srsf2 unexpectedly delayed myelofibrosis induced by Jak2 and decreased TGFβ1 serum level.
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- The SARS-CoV-2 pandemic poses significant risks to immunosuppressed patients with hematological malignancies, leading to higher illness and death rates, even after vaccination.
- Many of these patients showed weak immune responses, particularly low levels of anti-SARS-CoV-2 IgG post-vaccination, prompting the use of monoclonal antibodies for prevention and highlighting the need to study T cell responses more closely.
- In a study of 47 hematological malignancy patients, only a minority developed strong immune responses to the BNT162b2 mRNA vaccine, and the presence of Th1 immune responses was found to be crucial for protection against severe SARS-CoV-2 infection, unlike Th2 responses or IgG
Definition of therapy-related myeloid neoplasms (TRMN) is only based on clinical history of exposure to leukemogenic therapy. No specific molecular classification combining therapy-related acute myeloid leukemia and therapy-related myelodysplastic syndromes has been proposed. We aimed to describe the molecular landscape of TRMN at diagnosis, among 77 patients with previous gynecologic and breast cancer with a dedicated next-generation sequencing panel covering 74 genes.
View Article and Find Full Text PDFThe aim of this study was to characterize a large series of 154 patients with acute promyelocytic leukemia (median age, 53 years; range, 18-90 years) and evaluate real-life outcome after up-front treatment with arsenic trioxide and all-trans retinoic acid. All patients were included in the prospective NAPOLEON registry (NCT02192619) between 2013 and 2019. The acute promyelocytic leukemia was de novo in 91% (n=140) and therapy-related in 9% (n=14); 13% (n=20) of the patients were older than 70 years.
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- * Analysis found significant changes in 77 metabolites (like amino acids and sugars) in critical COVID-19 patients compared to those with mild symptoms.
- * Among moderately ill patients treated with tocilizumab, only 10 metabolites differed in those who improved versus those who worsened, with high levels of anthranilic acid linked to poor outcomes, suggesting potential therapeutic targets for treatment.
Objectives: To evaluate the efficacy and tolerability of an attenuated immunochemotherapy regimen based on cytarabine, etoposide and dexamethasone plus rituximab (R-mini-CYVE) in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL).
Methods: We included pretreated adult patients with B-cell NHL who were ineligible for high-dose immunochemotherapy (HDT). Cytarabine and etoposide were given at four different dose levels, depending on the patient's frailty.
Article Synopsis
- - Systemic inflammatory and autoimmune diseases can occur alongside myelodysplastic syndromes, and current treatments like steroids and biologics are not very effective due to their low response rates and side effects.
- - This study treated three patients with myelodysplastic syndromes and autoimmune disorders using low doses of IL-2, aiming to stimulate regulatory T-cells and reduce reliance on steroids.
- - Results showed clinical improvement and a reduction in steroid use for 2 out of 3 patients, with no serious side effects or disease progression, indicating potential for further research on IL-2 in this context.
Article Synopsis
- Iadademstat is a new, powerful drug targeting LSD1 that shows promise in treating patients with relapsed/refractory acute myeloid leukemia (R/R AML) based on earlier studies.
- The study involved a phase I trial with 27 patients to assess the drug's safety, how it's processed in the body (pharmacokinetics), and its initial effectiveness, with a recommended dose determined at 140 µg/m/d.
- Results indicated that most side effects were manageable, and some patients showed reduced leukemia cells and signs of differentiation, leading to one case of complete remission, with further studies planned to explore combination treatments.
Isocitrate dehydrogenase 1 () and 2 () mutations in Myeloid Neoplams (MNs) exhibit DNA hypermethylation 2-hydroxyglutarate (2HG) over-production. Clinical impact of azacitidine (AZA) remains inconsistent in -mutated MNs and the potential of serum 2HG as a suitable marker of response to AZA is unknown. To address these questions, we retrospectively analyzed 93 MNs patients (78 AML, 11 MDS, 4 CMML) with / mutations treated with AZA.
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- * Key factors affecting mortality included age over 70, smoking, metastatic disease, and a poor Eastern Cooperative Oncology Group score, with the latter being the strongest predictor.
- * Treatments like immunotherapy and targeted therapy did not worsen outcomes; however, biomarkers like C-reactive protein and D-dimer levels indicated increased risks, while COVID-19 management led to delays and changes in cancer treatments for many patients.
Induction chemotherapy (7 + 3 regimen) remains the gold standard for patients with acute myeloid leukemia (AML) but is responsible for gut damage leading to several complications such as bloodstream infection (BSI). We aimed to investigate the impact of induction chemotherapy on the intestinal barrier of patients with AML and in wild-type mice. Next, we assessed the potential benefit of strengthening the mucosal barrier in transgenic mice releasing a recombinant protein able to reinforce the mucus layer (Tg222).
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- Blood myeloid cells show dysregulation in COVID-19, with changes in monocyte and neutrophil populations linked to disease severity.
- In severe cases, there's a notable decrease in non-classical CD14CD16 monocytes and an accumulation of HLA-DR classical monocytes, along with high levels of calprotectin.
- The findings suggest that measuring calprotectin levels and non-classical monocyte frequencies could help predict which COVID-19 patients are at higher risk for severe illness, indicating a need for further study.
Background: High-dose cyclophosphamide to treat solid refractory tumors demonstrated meaningful activity, while data to treat lymphoma remain scarce. This study aims to assess high-dose cyclophosphamide to treat relapsed or refractory lymphoma.
Methods: A phase II study included adult patients with relapsed or refractory B-cell non-Hodgkin's lymphoma, previously treated by ≥2 prior lines with no other available option of therapy.