Publications by authors named "Laurence Legros"
Article Synopsis
- A new community of heads of haematology departments has been formed to provide mutual support in response to challenges within the French hospital system.
- An inaugural seminar held in January 2023 laid the groundwork for this initiative, fostering connections and collaboration among participants.
- The community expanded in January 2024, involving a wider group of department heads, enhancing teamwork and resource-sharing to improve hospital management and operations.
Article Synopsis
- Mutations in a protein called calreticulin (mutCALR) cause blood disorders known as myeloproliferative neoplasms (MPNs), but there aren’t any treatments specifically targeting this mutation.
- A new antibody called INCA033989 can specifically attack cells with the mutCALR mutation, stopping them from growing and causing problems.
- In tests on mice, INCA033989 not only prevented issues like high blood cell counts but also showed it could help treat the disease without harming normal blood cell production.
Article Synopsis
- Chronic myeloid leukemia (CML) is treated with special pills called tyrosine kinase inhibitors, and one of them is called bosutinib.
- Bosutinib is used to help adult patients with CML, either as a first treatment or if other treatments haven't worked.
- Doctors found that bosutinib can cause side effects like stomach problems and liver issues, so a group of experts made guidelines to help manage these side effects and keep patients safe while they are being treated.
Article Synopsis
- The French hospital system is facing a crisis due to staff shortages, prompting department heads to seek collaborative solutions for maintaining patient care.
- A two-day seminar was held for fourteen hematology department heads, focusing on sharing experiences and fostering a community aimed at improving their hospitals.
- The participants expressed interest in expanding collaboration through regular seminars for department heads across various specialties, aligning with public service strategies to strengthen hospital departments and inspire broader change in the health system.
Article Synopsis
- Accelerated phase chronic myeloid leukemia (AP-CML) has a poorer prognosis than chronic phase (CP-CML), prompting researchers to test second-generation tyrosine kinase inhibitors (TKI2) as an initial treatment due to their reduced toxicity.
- In a study of 69 newly diagnosed patients with AP-CML, various health parameters were measured, revealing worse conditions in those with hematologic AP compared to cytogenetically defined AP.
- Regardless of the type of TKI2 treatment used, the patients achieved similar rates of clinical response and overall survival, suggesting that TKI2 can effectively manage AP-CML and mitigate the challenges associated with its advanced disease phase.
Efficacy and safety of nilotinib in chronic myeloid leukaemia patients who failed to achieve a treatment-free remission period after imatinib discontinuation: Results of the French Nilo post-STIM study.
Br J Haematol
June 2023
Article Synopsis
- Molecular recurrence (MRec) affects about 50% of chronic myeloid leukaemia (CML) patients who stop taking tyrosine kinase inhibitors (TKI) and occurs despite achieving sustained deep molecular responses.
- In a study involving 31 patients, 23 who switched to nilotinib (300 mg twice daily) maintained their molecular response for an average of 22 months, while seven experienced serious side effects leading to treatment discontinuation.
- The study found that 59.1% of patients remained treatment-free and maintained molecular response 24 months after stopping nilotinib, and 42.1% maintained it at 48 months, indicating promising results
Purpose: This manuscript reports on the occurrence of early and frequent erythrocytosis in advanced hepatocellular carcinoma (HCC) patients treated with lenvatinib.
Methods: A cohort of 23 patients with advanced HCC, treated with this antiangiogenic drug for at least one month, was retrospectively analyzed.
Results: These patients (82.
Background & Aims: In CML, Leukemic Stem Cells (LSCs) that are insensitive to Tyrosine Kinase Inhibitors are responsible for leukemia maintenance and relapses upon TKI treatment arrest. We previously showed that downregulation of the BMI1 polycomb protein that is crucial for stem/progenitor cells self-renewal induced a CCNG2/dependent proliferation arrest leading to elimination of Chronic Myeloid Leukemia (CML) cells. Unfortunately, as of today, pharmacological inhibition of BMI1 has not made its way to the clinic.
View Article and Find Full Text PDFThis study evaluated the performances of immunoassays (LFIA and ELISA) designed for SARS-CoV-2 Antigen (Ag)-detection in nasopharyngeal (NP) and serum samples in comparison to RT-PCR. NP samples from patients with respiratory symptoms (183 RT-PCR-positive and 74 RT-PCR-negative samples) were collected from March to April and November to December 2020. Seroconversion and antigen dynamics were assessed by symptom onset and day of RT-PCR diagnosis.
View Article and Find Full Text PDFDasatinib plus Peg-Interferon alpha 2b combination in newly diagnosed chronic phase chronic myeloid leukaemia: Results of a multicenter phase 2 study (DASA-PegIFN study).
Br J Haematol
January 2023
Article Synopsis
- * A total of 79 patients participated, and the primary goal was to assess the cumulative molecular response rates over 12 months, with results showing significant rates of deep molecular response at 5 years.
- * While grade 3 neutropenia was common, it didn't lead to severe infections, and most patients continued the Peg-IFN treatment for a substantial time, resulting in notable molecular response rates after 12 and 24 months.
Article Synopsis
- * A total of 133 patients were assessed, and of the 86 who were identified as underdosed, those in the TDM group had higher imatinib levels and a significantly better major molecular response (MMR) at 12 months (67% for TDM vs. 39% for control).
- * TDM proved to be a feasible approach that not only heightened drug levels but also maintained a positive impact on treatment outcomes for up to three years.
Article Synopsis
- Myeloproliferative neoplasms (MPNs) are rare in individuals under 25, and a study examined 444 such patients over a median follow-up of 9.7 years across 38 centers globally.
- The study found that 11.1% had a history of thrombosis, with higher risks associated with the JAK2V617F mutation and hyperviscosity symptoms, while new thrombotic and hemorrhagic events occurred at significant rates.
- It highlighted that disease transformation, particularly to myelofibrosis, was common, with splenomegaly identified as a new risk factor, indicating a need for updated management guidelines for young MPN patients.
Article Synopsis
- Discontinuing tyrosine kinase inhibitors in chronic phase chronic myeloid leukemia (CML) is feasible, but more research is needed on factors that predict recurrence after stopping treatment and the long-term effects of treatment-free remission (TFR).
- In a study updating data from the STIM2 trial, 199 patients were analyzed, showing a significant percentage (43.4%) achieved TFR at 5 years, but many experienced a loss of major molecular response over time.
- The timing of molecular recurrence varied, with most recurrences occurring within the first 6 months after stopping treatment, and certain factors such as treatment duration and molecular response levels were linked to recurrence within the first 24 months but not later.
Article Synopsis
- Dasatinib, a medication for chronic myeloid leukaemia (CML), was studied for its potential to cause pleural effusion (fluid buildup in the lungs) in patients taking it.
- A clinical trial was conducted with patients taking 100 mg of dasatinib, assessing whether therapeutic drug monitoring (TDM) could reduce significant side effects by comparing a dose-reduction strategy with standard care.
- Although the main goal of reducing adverse events wasn't achieved due to early complications, TDM significantly lowered the incidence of pleural effusion in the long run while maintaining similar molecular responses across treatment groups.
Numerous combinations of signaling pathway blockades in association with tyrosine kinase inhibitor (TKI) treatment have been proposed for eradicating leukemic stem cells (LSCs) in chronic myeloid leukemia (CML), but none are currently clinically available. Because targeting protein kinase Cδ (PKCδ) was demonstrated to eliminate cancer stem cells (CSCs) in solid tumors, we evaluated the efficacy of PKCδ inhibition in combination with TKIs for CML cells. We observed that inhibition of PKCδ by a pharmacological inhibitor, by gene silencing, or by using K562 CML cells expressing dominant-negative (DN) or constitutively active (CA) PKCδ isoforms clearly points to PKCδ as a regulator of the expression of the stemness regulator BMI1.
View Article and Find Full Text PDFLong-term outcome of imatinib 400 mg compared to imatinib 600 mg or imatinib 400 mg daily in combination with cytarabine or pegylated interferon alpha 2a for chronic myeloid leukaemia: results from the French SPIRIT phase III randomised trial.
Leukemia
August 2021
Article Synopsis
- - The SPIRIT trial is a long-term study that compares the effectiveness of various treatments for chronic-phase chronic myeloid leukaemia (CML), involving 787 patients followed for an average of 13.5 years.
- - Overall and progression-free survival rates after 15 years were similar across four treatment groups, ranging from 80% to 87%, suggesting comparable effectiveness of different combinations.
- - The combination of imatinib with pegylated interferon alpha2a resulted in significantly better molecular response rates compared to imatinib alone, although toxicity led to treatment cessation for some patients.
Article Synopsis
- The study aimed to assess how common the V617F JAK2 mutation is in patients with thrombosis who do not show other signs of myeloproliferative neoplasm (MPN) over a 10-year period.
- Out of 340 patients analyzed, only 9 (2.65%) were found to have the JAK2 mutation, with the four patients showing higher allele burdens later diagnosed with MPN.
- Key risk factors linked to the JAK2 mutation included older age, higher platelet count, elevated C-reactive protein levels, and particularly splenomegaly, which was associated with a significantly increased likelihood of having the mutation.
Evaluation of Residual Disease and TKI Duration Are Critical Predictive Factors for Molecular Recurrence after Stopping Imatinib First-line in Chronic Phase CML Patients.
Clin Cancer Res
November 2019
Purpose: Tyrosine kinase inhibitor (TKI) discontinuation is an emerging goal in chronic myelogenous leukemia (CML) management and several studies have demonstrated the feasibility of safely stopping imatinib. A sustained deep molecular response on long-term TKI is critical prior to attempting treatment-free remission. Reproducible results from several studies reported recently, failed to identify robust and reproducible predictive factors for the selection of the best candidates for successful TKI cessation.
View Article and Find Full Text PDFThe effectiveness of tyrosine kinase inhibitors (TKIs) has made it possible to consider treatment discontinuation in chronic myeloid leukaemia (CML) patients that achieve an excellent response. However, a few of the patients included in the Europe Stop Tyrosine Kinase Inhibitors (EURO-SKI) trial reported musculoskeletal pain shortly after stopping TKIs, considered as a withdrawal syndrome (WS). To identify factors that may predispose to TKI WS, we analysed the pharmacovigilance declarations for the 6 months after stopping TKIs in a large cohort of CML (n = 427) that combined the French patients included in the STop IMatinib 2 (STIM2; n = 224) and EURO-SKI (n = 203) trials.
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