Publications by authors named "Mathilde Hunault"
Background: We conducted a randomized controlled trial to compare intermediate doses (IDAC) with high doses of cytarabine (HDAC) as postinduction therapy in patients 18 to 60 years of age with newly diagnosed acute myeloid leukemia (AML). The main objectives were to evaluate noninferiority in overall survival (OS) after IDAC and safety.
Methods: Patients 18 to 60 years of age with newly diagnosed AML, except those with core-binding factor, acute promyelocytic, Philadelphia chromosome-positive, or post-myeloproliferative neoplasm AML, were eligible.
Article Synopsis
- Despite initial treatment with midostaurin (MIDO) and chemotherapy in FLT3-mutated acute myeloid leukemia (AML), many patients face relapses, with complete remission rates around 60-70% and over 40% relapsing.
- A study of 150 patients with refractory/relapsed (R/R) AML revealed that those treated with MIDO showed lower persistence of FLT3-ITD mutations compared to those who did not receive MIDO (68% vs. 87.5%).
- The study found that detecting multiple FLT3-ITD clones at diagnosis related to a higher persistence rate of these mutations at relapse, indicating the need for sensitive techniques in FLT3-
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.
Experts from the European Leukemia Net (ELN) working group for adult acute lymphoblastic leukemia have identified an unmet need for guidance regarding management of adult acute lymphoblastic leukemia (ALL) from diagnosis to aftercare. The group has previously summarized their recommendations regarding diagnostic approaches, prognostic factors, and assessment of ALL. The current recommendation summarizes clinical management.
View Article and Find Full Text PDFWorking groups of the European LeukemiaNet have published several important consensus guidelines. Acute lymphoblastic leukemia (ALL) has many different clinical and biological subgroups and the knowledge on disease biology and therapeutic options is increasing exponentially. The European Working Group for Adult ALL has therefore summarized the current state of the art and provided comprehensive consensus recommendations for diagnostic approaches, biologic and clinical characterization, prognostic factors, and risk stratification as well as definitions of endpoints and outcomes.
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- * In a study of 1091 adult patients, 12.9% had KMT2A-r, with a 5-year relapse rate of 40.7% and overall survival rate of 53.3%. The presence of specific gene alterations like TP53 and IKZF1 correlated with significantly worse outcomes.
- * The analysis showed that measuring minimal residual disease (MRD) using KMT2A markers was more reliable than other methods, indicating that patients responding well early
Tandem duplications (TDs) of the UBTF gene have been recently described as a recurrent alteration in pediatric acute myeloid leukemia (AML). Here, by screening 1946 newly diagnosed adult AML, we found that UBTF-TDs occur in about 3% of patients aged 18-60 years, in a mutually exclusive pattern with other known AML subtype-defining alterations. The characteristics of 59 adults with UBTF-TD AML included young age (median 37 years), low bone marrow (BM) blast infiltration (median 25%), and high rates of WT1 mutations (61%), FLT3-ITDs (51%) and trisomy 8 (29%).
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- Richter syndrome (RS) represents the transformation of chronic lymphocytic leukemia (CLL) into an aggressive form of lymphoma, primarily diffuse large B-cell lymphoma (DLBCL).
- Researchers analyzed 58 primary RS samples using DNA methylation and transcriptome profiling, leading to the identification of epigenetic patterns and a method to assess CLL-RS clonal relationships without the original CLL tumor DNA.
- The study developed classifiers based on DNA and transcriptomic data, revealing a poor-prognosis subset of DLBCL that shares similarities with RS, highlighting the potential to improve prognosis assessment and treatment strategies for affected patients.
Unlabelled: Low hypodiploidy defines a rare subtype of B-cell acute lymphoblastic leukemia (B-ALL) with a dismal outcome. To investigate the genomic basis of low-hypodiploid ALL (LH-ALL) in adults, we analyzed copy-number aberrations, loss of heterozygosity, mutations, and cytogenetics data in a prospective cohort of Philadelphia (Ph)-negative B-ALL patients (n = 591, ages 18-84 years), allowing us to identify 80 LH-ALL cases (14%). Genomic analysis was critical for evidencing low hypodiploidy in many cases missed by cytogenetics.
View Article and Find Full Text PDFRetrospective, real-life study of venetoclax plus azacitidine or low-dose cytarabine in French patients with acute myeloid leukemia ineligible for intensive chemotherapy.
Cancer Med
March 2023
Background: Recently, the combination of venetoclax plus a hypomethylating agent (HMA; azacitidine ordecitabine) or low-dose cytarabine (LDAC) showed promise in Phase III trials in previously untreated AML. In France at the time of this study, venetoclax was not yet approved for AML and there were therefore no formal usage recommendations. Here we report the first study in a French cohort that assessed venetoclax in combination with existing treatments for AML under real-life conditions.
View Article and Find Full Text PDFFrugal alignment-free identification of FLT3-internal tandem duplications with FiLT3r.
BMC Bioinformatics
October 2022
Article Synopsis
- FLT3-ITDs are important markers for assessing risk in acute myeloid leukemia (AML), and a new algorithm called FiLT3r has been developed to efficiently identify and quantify these markers using high-throughput sequencing (HTS) data without the need for alignment.
- FiLT3r focuses on specific k-mers from FLT3 exons 14 and 15, and tests showed it outperformed existing software and the gold standard method in accuracy, achieving no false positives or negatives in a study involving 185 AML patients.
- The algorithm is resource-efficient, and its results were confirmed using public RNA-Seq data; FiLT3r is available for free
Article Synopsis
- The treatment of AML with unfavorable cytogenetics remains difficult, prompting a study on the effects of fish oil emulsion (FO) combined with a specific chemotherapy regimen (3+7).
- Thirty patients participated, showing that FO increased EPA and DHA levels significantly, but it didn't affect the chemotherapy drugs' pharmacokinetics.
- The study found a complete response rate of 77%, similar to previous trials, indicating that adding FO to the treatment doesn't significantly improve outcomes for high-risk AML patients.
Article Synopsis
- The study investigates B-cell acute lymphoblastic leukemia (B-ALL) in adults to identify new genetic drivers behind the disease through RNA sequencing and whole-genome analyses, revealing a novel subtype with a distinct gene expression.
- This new subtype features unique genomic microdeletions, leading to a fusion of UBTF and ATXN7L3 genes, as well as deregulation of the CDX2 gene due to enhancer hijacking mechanisms.
- Patients with this subtype (CDX2/UBTF ALL) are typically younger, predominantly female, exhibit poor treatment responses, and have a higher risk of disease relapse compared to other B-ALL patients.
High tumor burden before blinatumomab has a negative impact on the outcome of adult patients with B-cell precursor acute lymphoblastic leukemia. A real-world study by the GRAALL.
Haematologica
September 2022
Article Synopsis
- Blinatumomab is a bispecific T-cell engager used for treating B-cell precursor acute lymphoblastic leukemia (B-ALL) in patients who have minimal residual disease (MRD) or are in relapse, with a study analyzing 73 patients receiving this treatment.
- The results showed that high pre-treatment MRD levels correlated with poorer outcomes, specifically shorter relapse-free survival and overall survival rates.
- The study suggests that understanding tumor burden prior to treatment could lead to more personalized strategies for managing relapsed patients, highlighting the importance of MRD levels in treatment planning.
DNA methylation, a major biological process regulating the transcription, contributes to the pathophysiology of hematologic malignancies, and hypomethylating agents are commonly used to treat myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML). In these diseases, bone marrow mesenchymal stromal cells (MSCs) play a key supportive role through the production of various signals and interactions. The DNA methylation status of MSCs, likely to reflect their functionality, might be relevant to understand their contribution to the pathophysiology of these diseases.
View Article and Find Full Text PDFBackground: Three different scoring systems have been developed to assess pre-transplant comorbidity in allogeneic hematopoietic stem cell transplantation (Allo-HSCT): the Hematopoietic Cell Transplantation-Specific Comorbidity Index, the Comorbidity/Age index, and the Augmented Comorbidity/Age index. All were devised to predict overall survival (OS) and disease-free survival (DFS) survivals and non-relapse mortality (NRM) in patients receiving HLA-matched Allo-HSCT, but their performance has scarcely been studied in the haploidentical Allo-HSCT setting with post-transplant cyclophosphamide, a procedure in constant expansion worldwide.
Methods: To address this issue, their impact on survivals and NRM was examined in a cohort of 223 patients treated with haploidentical Allo-HSCT in four different centers.
Article Synopsis
- Ischemic stroke can occur in patients with clonal hypereosinophilic syndrome caused by the FIP1L1-PDGFRA fusion, which is responsive to the drug imatinib.
- A study analyzed 16 male patients with a history of ischemic stroke and eosinophilia, finding a high incidence of bilateral infarctions and a significant proportion of strokes with unclear causes.
- Treatment with imatinib showed promising results, with a low recurrence rate of strokes over a median follow-up period of 4.5 years, suggesting that this syndrome should be considered in unexplained stroke cases.
Early Post-Transplantation Serum Ferritin Level Predicts Survival in Recipients of Haploidentical Stem Cell Transplantation Using Post-Transplantation Cyclophosphamide as Graft-versus-Host Disease Prophylaxis.
Transplant Cell Ther
October 2021
The negative impact of high serum ferritin level (SFL) before and after allogeneic hematopoietic cell transplantation (allo-HSCT) on outcomes is well recognized. However, it is poorly documented in adults undergoing haploidentical HSCT (haplo-HSCT) with post-transplantation cyclophosphamide (PTCY) for hematologic malignancies. The main objective was to assess the impact of pretransplantation and post-transplantation SFL on overall survival (OS), disease-free survival (DFS), and nonrelapse mortality (NRM) in patients undergoing haplo-HSCT with PTCY.
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- Immunoglobulin replacement therapy is often recommended for severe hypogammaglobulinemia in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT), but its link to increased infection risk remains unconfirmed.
- A study involving 76 allo-HSCT patients found no significant difference in gamma globulin levels between those who had infections and those who did not during the first 100 days post-transplant.
- The findings suggest that humoral deficiency has a limited role in immune deficiency during this period, raising questions about the necessity of immunoglobulin replacement therapy.
Objectives: The impact of conventional treatment for acute myeloid leukemia (AML) on the nutritional, cognitive, and functional status of elderly patients is seldom studied. This assessment was performed in the context of the LAMSA 2007 trial.
Methods: The trial enrolled 424 patients with de novo AML.
Autologous hematopoietic stem cell transplantation (ASCT) is curative for a proportion of patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL). However, there is a small group of patients with high-risk of relapse after ASCT that might benefit from other approaches. We conducted a retrospective analysis on 126 patients treated with tandem ASCT-reduced intensity conditioning (RIC)-allogeneic-SCT and reported to the EBMT registry to analyze the efficacy and safety of this approach.
View Article and Find Full Text PDFWe previously reported the benefit of lomustine addition to conventional chemotherapy in older acute myeloid leukemias with nonadverse chromosomal aberrations in the LAM-SA 2007 randomized clinical trial (NCT00590837). A molecular analysis of 52 genes performed in 330 patients included in this trial, 163 patients being treated with lomustine in combination with idarubicin and cytarabine and 167 without lomustine, identified 1088 mutations with an average of 3.3 mutations per patient.
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- FIP1L1-PDGFRA-positive myeloid neoplasm with eosinophilia (F/P+ MN-eo) is a rare condition with limited epidemiological data; a retrospective study analyzed 151 patients in France from 2003-2019.
- Imatinib mesylate (IM) is very effective, with 98% of treated patients achieving complete hematologic and molecular responses; however, a significant percentage of patients relapsed after stopping IM.
- Factors such as the timing of IM initiation and duration of treatment were identified as independent predictors of relapse, suggesting that early and prolonged treatment may help reduce the chances of relapse.