Publications by authors named "Francois Guilhot"

Article Synopsis
  • * Second-generation TKIs work faster and address resistance mutations but do not improve overall survival compared to imatinib; serious side effects limit their use.
  • * New prognostic tools, like the ELTS-score, highlight that many CML patients may die from causes other than the disease, while ongoing research continues to improve treatment approaches in routine care.
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  • * 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.
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  • 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.
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  • - 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.
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Prognostic scores support clinicians in selecting risk-adjusted treatments and in comparatively assessing different results. For patients with chronic-phase chronic myeloid leukemia (CML), four baseline prognostic scores are commonly used. Our aim was to compare the prognostic performance of the scores and to arrive at an evidence-based score recommendation.

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  • Long-term treatment-free remission (TFR) is a new goal for chronic myeloid leukemia (CML) patients, and dose reductions of tyrosine kinase inhibitors (TKIs) may enhance life quality while minimizing side effects.
  • A study analyzed 77 CML patients who stopped TKIs, focusing on 26 who were on low-dose TKIs before discontinuation, with results showing that low-dose patients had better TFR rates compared to those on full doses.
  • The findings suggest that low-dose TKIs do not negatively affect TFR, but further randomized clinical trials are needed to confirm these results and better understand the potential of TKI dose reductions prior to stopping treatment.*
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Recent clinical findings in patients with chronic myeloid leukemia (CML) suggest that the risk of molecular recurrence after stopping tyrosine kinase inhibitor (TKI) treatment substantially depends on an individual's leukemia-specific immune response. However, it is still not possible to prospectively identify patients that will remain in treatment-free remission (TFR). Here, we used an ordinary differential equation model for CML, which explicitly includes an antileukemic immunologic effect, and applied it to 21 patients with CML for whom time courses had been quantified before and after TKI cessation.

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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.

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  • The study focuses on the immune mechanisms behind treatment-free remission (TFR) in chronic myeloid leukemia (CML), highlighting the lack of defined correlations with CD8(+) T-cell types.
  • Researchers identified a new subset of CD8(+) T-cells called innate CD8(+) T-cells in CML patients who enjoyed TFR for over two years, showing a significant increase in their functionality compared to control and treated patients.
  • The findings suggest a positive relationship between the levels of innate CD8(+) T-cells and natural killer cells, indicating a potential new biomarker profile for successful TFR in CML patients.
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The role of autologous stem cell transplantation (ASCT) in patients with marginal zone lymphoma (MZL) is debatable. This study investigated the outcome and prognostic factors affecting the outcome of patients undergoing ASCT for MZL. Eligible patients had non-transformed nodal, extra-nodal (MALT) or splenic MZL (SMZL), aged ≥18 years, who underwent a first ASCT between1994 and 2013 and were reported to the European Society for Blood and Marrow Transplantation, Fondazione Italiana Linfomi or Gruppo Italiano Trapianto Di Midollo Osseo registries.

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Ponatinib has potent activity against native and mutant BCR-ABL1, including BCR-ABL1 The pivotal phase 2 Ponatinib Ph ALL and CML Evaluation (PACE) trial evaluated efficacy and safety of ponatinib at a starting dose of 45 mg once daily in 449 patients with chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) resistant/intolerant to dasatinib or nilotinib, or with BCR-ABL1 This analysis focuses on chronic-phase CML (CP-CML) patients (n = 270) with 56.8-month median follow-up. Among 267 evaluable patients, 60%, 40%, and 24% achieved major cytogenetic response (MCyR), major molecular response (MMR), and 4.

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  • - SOD2 is important for antioxidant defense, and this study investigates its potential link to genetic instability in Chronic Myeloid Leukemia (CML), specifically how silencing SOD2 affects chromosomal stability in cell lines expressing BCR-ABL mutations.
  • - Researchers found that SOD2 silencing led to significant genetic instability in specific chromosomal regions and observed lower SOD2 mRNA levels in CML patients, correlating with increased disease severity indicators like leukocytosis and Sokal score.
  • - The study suggests that reduced SOD2 expression may contribute to a mutator phenotype in CML patients undergoing Tyrosine Kinase Inhibitor (TKI) therapies, highlighting the need for further research into
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We investigated factors that physicians consider of most importance in the selection of second line tyrosine kinase inhibitors treatments (TKIs) in chronic myeloid leukemia patients (CML).

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Despite persistence of leukemic stem cells, patients with chronic myeloid leukemia who achieve and maintain deep molecular responses may successfully stop the tyrosine kinase inhibitor imatinib. However, questions remain unanswered regarding the biological basis of molecular relapse after imatinib cessation. In IMMUNOSTIM, we monitored 51 patients from the French Stop IMatinib trial for peripheral blood T cells and natural killer cells.

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Imatinib has revolutionized the treatment and prognosis of chronic myeloid leukemia (CML) with survival rates now approaching those of the age-matched healthy population. To be able to discontinue tyrosine kinase inhibitor (TKI) treatment, it is necessary to develop complementary therapies to target minimal residual disease. Recent findings by a number of investigators in both CML mouse models and CML patients offer evidence that many factors in the leukemic microenvironment can collectively contribute to immune escape, including expansion of myeloid-derived suppressor cells, programmed death-1/programmed death-1 ligand interactions resulting in T-cell impairment, expression of soluble suppressive factors such as soluble CD25, and down-regulation of MHC molecules by CML cells.

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Background: In the adult population with newly diagnosed chronic myeloid leukemia (CML), variant translocations are usually not considered to be impairing the prognosis, whereas some additional cytogenetic abnormalities (ACAs) are associated with a negative impact on survival. Because of the rarity of CML in the pediatric population, such abnormalities have not been investigated in a large group of children with CML.

Methods: The prognostic relevance of variant t(9;22) and ACAs at diagnosis was assessed in 301 children with CML in the chronic phase who were enrolled in the International Registry for Chronic Myeloid Leukemia in Children and Adolescents.

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Age is a well-known factor in solid tumours linked to lower adherence to guidelines. Scarce data exist for haematologic malignancies such as multiple myeloma (MM). The aim of the study was to investigate the relationships among age, adherence to guidelines in MM, and overall survival (OS).

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Background: Imatinib, a selective BCR-ABL1 kinase inhibitor, improved the prognosis for patients with chronic myeloid leukemia (CML). We conducted efficacy and safety analyses on the basis of more than 10 years of follow-up in patients with CML who were treated with imatinib as initial therapy.

Methods: In this open-label, multicenter trial with crossover design, we randomly assigned patients with newly diagnosed CML in the chronic phase to receive either imatinib or interferon alfa plus cytarabine.

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Article Synopsis
  • Researchers discovered a new type of NK-like CD8(+) T cells in humans, which are potent in fighting off infections and tumors, similar to invariant natural killer T (iNKT) cells.
  • In patients with chronic myeloid leukemia (CML), these innate CD8(+) T cells were found to be significantly reduced and functionally impaired, showing a loss of their natural ability to fight disease.
  • Patients achieving complete remission through treatment showed some recovery in the number and function of these innate CD8(+) T cells, highlighting a potential link between these cells and the effectiveness of iNKT cells in immune responses.
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