Publications by authors named "Eric Hermet"

Disease relapse remains the first cause of mortality of hematological malignancies after allogeneic hematopoietic stem cell transplantation (allo-HCT) for acute myeloid and lymphoid leukemia (AML and ALL) and for myelodysplastic syndroms (MDS). More and more patients are eligible for allo-HCT over the years and for many of them, only reduced intensity conditioning is possible, which is associated with a higher risk of relapse. Knowledge and biotechnology allow us to better identify diseases at very high risk of relapse and to measure residual disease before allo-HCT.

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Background: In the era of targeted therapies, the influence of aging on cancer management varies from one patient to another. Assessing individual frailty using geriatric tools has its limitations, and is not appropriate for all patients especially the youngest one. Thus, assessing the complementary value of a potential biomarker of individual aging is a promising field of investigation.

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Article Synopsis
  • In chronic myeloid leukemia, predicting stable treatment-free remission (TFR) after stopping tyrosine kinase inhibitors (TKIs) is difficult, especially using early molecular indicators.
  • A study involving 408 patients compared various predictive tools, including the EUTOS long-term survival score, BCR::ABL1 transcript halving time, and residual disease measurements at months 3 and 6.
  • While months 3 and 6 residual disease showed good predictive performance, particularly month 6, no early indicators effectively forecasted the TKI discontinuation criteria or TFR maintenance, indicating additional factors may be at play.
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From COVID pandemic spread until now, many HSCT unrelated donor registries recommend as a precaution a systematic COVID-19 testing for all donors during the precollection time. Literature is quite poor to support this systematic attitude. We report one sibling allogeneic HSCT which we proceeded despite a positive COVID test on related asymptomatic donor and summarize the all seven cases reported until now.

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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.
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  • Guidelines for managing chronic phase-chronic myeloid leukemia (CML) primarily rely on clinical trial data, but real-world data can enhance these recommendations, as seen in the French CML Observatory database study involving 646 patients.!
  • The analysis revealed that patients receiving second-generation tyrosine kinase inhibitors (2G-TKIs) achieve faster major molecular responses (MMR) and highlighted that being female and having residual disease at 6 months predicts better deep molecular response (DMR).!
  • Although 30% of patients qualified to stop treatment after 5 years, only 38% actually did, with a notable relapse rate of 31.5% among those who discontinued; early withdrawal is linked to higher
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  • Accumulation of nilotinib in target cells is crucial for effective targeted therapy in Chronic Phase-Chronic Myeloid Leukaemia (CP-CML), where response to treatment varies widely among patients.
  • A study using flow cytometry revealed that a significant portion of CP-CML cells, including 13.3% of mature polymorphonuclear cells and 40% of immature CD34 cells, did not retain detectable levels of nilotinib, impacting its efficacy.
  • The research indicated that the level of nilotinib in cells correlates with disease burden and early treatment response, highlighting the importance of understanding individual and intra-clonal differences in drug accumulation for better patient outcomes.
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Clonal chromosome abnormalities in Philadelphia-negative cells could concern chronic myeloid leukemia patients treated by tyrosine kinase inhibitors. The European LeukemiaNet distinguishes -7/del(7q) abnormalities as a "warning". However, the impact of clonal chromosome abnormalities, and specifically those of -7/del(7q), in Philadelphia-negative cells on clinical outcomes is unclear and based on case-reports showing morphological dysplasia and increased risk of acute myeloid leukemia, suggesting the coexistence of chronic myeloid leukemia and high-risk myelodysplastic syndrome.

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Article Synopsis
  • * A second allo-HSCT can be a good treatment option, particularly for patients with favorable conditions like good performance status and low co-morbidity scores.
  • * Recommendations include using matched related donors for better outcomes and immunoablative regimens in cases of graft dysfunction; switching donors may also be a viable option if there's no graft-versus-host disease.
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  • Ponatinib shows promise for treating chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) patients who didn't respond to other therapies, but it has notable toxicity risks.
  • A national observational study tracked 48 CML patients with a median follow-up of over 26 months, revealing overall survival rates and major molecular response rates comparable to earlier clinical trials.
  • The study also highlighted an increased rate of cardiovascular issues among patients taking ponatinib, leading to recommendations for better management of cardiovascular risks and careful patient selection.
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Despite the high efficiency of tyrosine kinase inhibitors (TKI), some patients with chronic myeloid leukemia (CML) will display residual disease that can become resistant to treatment, indicating intraclonal heterogeneity in chronic-phase CML (CP-CML). To determine the basis of this heterogeneity, we conducted the first exhaustive characterization of the DNA methylation pattern of sorted CP-CML CD34 CD15 (immature) and CD34 CD15 (mature) cells at diagnosis (prior to any treatment) and compared it to that of CD34 CD15 and CD34 CD15 cells isolated from healthy donors (HD). In both cell types, we identified several hundreds of differentially methylated regions (DMRs) showing DNA methylation changes between CP-CML and HD samples, with only a subset of them in common between CD34 CD15 and CD34 CD15 cells.

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The French society of bone marrow transplantation and cell therapy (SFGM-TC) organizes annually workshops in the attempt to harmonize clinical practices between different francophone transplantation center. Here, we report our recommendations regarding the management of Epstein Barr virus reactivation and lymphoproliferative disorders, cytomegalovirus (CMV) and human herpes virus 6 (HHV6) after allogeneic stem cell transplantation.

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To understand the complex interactions between hematopoietic stem cells and the bone marrow niche, a human experimental model is needed. Our hypothesis is that hematons are an appropriate ex vivo model of human bone marrow. We analyzed the hierarchical hematopoietic cell content and the tissue organization of single hematons from healthy donors.

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Introduction: Malnutrition is common after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and is a well-known prognostic factor for survival. The nutritional status of patients in a long term after allo-HSCT is less well documented. The main objective of this study was to evaluate the prevalence of malnutrition in adult patients who underwent allo-HSCT more than one year ago.

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Allogeneic hematopoietic cell transplantation (allo-HCT) is indicated for patients with relapsed or refractory Hodgkin lymphoma (HL). Although long-term disease control can be achieved, relapse is still frequent. The programmed cell death protein 1 (PD-1) pathway-blocking antibody nivolumab has shown substantial therapeutic activity and an acceptable safety profile in patients with relapsed or refractory HL who did not receive allo-HCT.

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To harmonize clinical practice in hematopoietic stem cell transplantation, the Francophone Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the sixth annual series of workshops which brought together practitioners from all member centers and took place in September 2015 in Lille. The main aim of this session was to describe the impact, evaluation and treatment of post-transplant iron overload.

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Reduced intensity conditioning for allogeneic hematopoietic stem cell transplantation (allo-HSCT) is often proposed for patients with comorbidities. To enhance engraftment and limit graft-versus-host disease (GVHD), antithymoglobulin (ATG) is usually used. However, the dose needed remains unclear unlike myeloablative conditioning.

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Tyrosine kinase inhibitors targeting the BCR-ABL oncoprotein represent an outstanding progress in chronic myeloid leukemia and long-term progression-free survival has become a reality for a majority of patients. However, tyrosine kinase inhibitors may at best chronicize rather than cure the disease thus current recommendation is to pursue treatment indefinitely. As a consequence, high quality treatment and care must integrate optimal disease control and treatment tolerability.

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Background: Nilotinib is now recommended for patients with newly diagnosed chronic myeloid leukaemia in chronic phase and leads to important rates of molecular response 4·5 log (MR(4·5)), allowing the prospect of therapy cessation. However, most patients do not reach this criterion and nilotinib is taken for lengthy periods, resulting in chronic or late-onset adverse events. Nilotinib combined with interferon might further increase rates of MR(4·5), avoid late side-effects, and allow therapy cessation.

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Background: Myeloablative allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a major procedure usually accompanied by multifactorial malnutrition, prompting the recommendation of systematic artificial nutritional support. Parenteral nutrition (PN) is usually administered during allo-HSCT, essentially for practical reasons. Recently published data suggest that enteral nutrition (EN), given as systematic artificial nutrition support, could decrease grade III-IV graft-versus-host disease (GVHD) and infectious events, which are associated with early toxicity after allo-HSCT and then have an impact on early transplant-related mortality (D100 mortality).

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We investigated Syk as a potential marker of CML progression. We observed a significant over-expression of Syk mRNA and constitutive phosphorylation of Syk Y348 in blast cells from six AP or BP-CML, but not in 15 CML in chronic phase. We could follow in vivo the recurrence of pSyk(348) throughout blast cell escape, despite observing storage of dasatinib in blast cells.

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Allogeneic hematopoietic stem cell transplantation is mainly indicated in bone marrow dysfunction related to blood diseases, but also in some rare diseases (adrenoleucodystrophy, mitochondrial neurogastrointestinal encephalomyopathy or MNGIE...

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