Juliette Lambert's research while affiliated with Centre Hospitalier de Versailles and other places

Publications (29)

Article
DDX41 germline mutations (DDX41MutGL) are the most common genetic predisposition to myelodysplastic syndrome and acute myeloid leukemia (AML). Recent reports suggest that DDX41MutGL myeloid malignancies could be considered as a distinct entity, even if their specific presentation and outcome remain to be defined. We described here the clinical and...
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The independent prognostic impact of specific dysplastic features in acute myeloid leukemia (AML) remains controversial and may vary between genomic subtypes. We apply a machine learning framework to dissect the relative contribution of centrally reviewed dysplastic features and oncogenetics in 190 patients with de novo AML treated in ALFA clinical...
Article
Introduction Based on the results of the ALFA-0701 trial (Castaigne et al. Lancet 2012), the addition of fractionated doses of the anti-CD33 antibody drug conjugate gemtuzumab ozogamicin (GO, Mylotarg®) to conventional chemotherapy has been approved in 2017 for frontline treatment of adults with CD33-positive acute myeloid leukemia (AML). Prolonged...
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Introduction: In 2010 the French Health Agency opened a compassionate patient named program of gemtuzumab ozogamicin (GO, Mylotarg®) in relapsed/refractory (R/R) patients with acute myeloid leukemia (AML). Of note, since 2012, it was recommended to use GO at the dose of 3 or 6 mg/m 2 in addition to chemotherapy. We conducted a retrospective trial (...
Article
Background: The WHO 2016 classification identifies myeloid malignancies with germline predisposition as a distinct subgroup (Arber DA et al., Blood 2016). We and other reported mutations of the DEAD-box RNA helicase 41 gene (g DDX41m) as the most common predisposition to MDS/AML (Sébert et al., Blood 2019). Relatively good outcomes have been sugges...
Article
WT1 overexpression is frequently identified in acute myeloid leukemia (AML) and has been reported as a potential marker for measurable residual disease (MRD) monitoring. Here, we evaluated the value of post-induction WT1 MRD level as a prognostic factor, as well as the interaction between post-induction WT1 MRD response and the effect of allogeneic...
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Myelofibrosis (MF) are a non-BCR-ABL myeloproliferative neoplasms (NMPs) associated with poor outcomes. Current treatment has little effect on the natural history of the disease. MF results from complex interactions between 1) the malignant clone, 2) an inflammatory context, and 3) remodeling of the bone marrow (BM) microenvironment. Each of these...
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IDH inhibitors are effective in AML, and trials evaluating frontline combinations with intensive chemotherapy (IC) are ongoing. Data on the prognostic significance of co-occurring genetic alterations and allogeneic hematopoietic stem cell transplantation (HSCT) are conflicting in each IDH-mutated subgroup treated by IC, while this information is im...
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The phase 3 ALFA-0701 trial demonstrated improved outcomes with fractionated-dose gemtuzumab ozogamicin (GO) combined with standard chemotherapy vs. standard chemotherapy alone in adults with de novo acute myeloid leukemia (AML). We examined post-transplant outcomes and occurrence of hepatic veno-occlusive disease/sinusoidal obstruction syndrome (V...
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Advances in transcriptomics have improved our understanding of leukemic development and helped to enhance the stratification of patients. The tendency of transcriptomic studies to combine AML samples, regardless of cytogenetic abnormalities, could lead to bias in differential gene expression analysis because of the differential representation of AM...
Article
A multistage model instructed by a large dataset (knowledge bank [KB] algorithm) has recently been developed to improve outcome prediction and tailor therapeutic decision, including hematopoietic stem cell transplantation (HSCT) in AML. We assessed the performance of the KB in guiding HSCT decision in first complete remission (CR1) in 656 AML patie...
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Gemtuzumab ozogamicin (GO, Mylotarg®) consists of a humanized CD33-targeted antibody-drug conjugated to a calicheamicin derivative. Growing evidence of GO efficacy in acute myeloid leukemia (AML), demonstrated by improved outcomes in CD33-positive AML patients across phase I to III clinical trials, led to the Food and Drug Administration (FDA) appr...
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In this study, we aimed to refine prognostication of older with acute myeloid leukemia (AML) after intensive chemotherapy. Five hundred and nine patients aged 60 years or older (median age, 68 years) were prospectively enrolled in the intensive Acute Leukemia French Association (ALFA)-1200 trial between 2012 and 2016, and 471 patient samples were s...
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Acute myeloid leukemia (AML) is a highly heterogeneous disease characterized by miscellaneous genetic background and response to chemotherapy. While molecular aberrations are routinely used to stratify AML patients into prognostic subgroups when receiving standard chemotherapy, the predictive value of the genetic background and co-occurring mutatio...
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Background : Point mutations in isocitrate dehydrogenase (IDH) genes are seen in 20% of adult patients (pts) with acute myeloid leukemia (AML). Prognostic significance of each IDH1/2 mutation (mut) analyzed with co-occurring mutations treated with intensive chemotherapy (IC) remains inconsistent, particularly with the advent of IDH inhibitors. Furt...
Article
Background High-resolution sequencing has improved prognostication of AML. A multistage model (MM), based on a knowledge bank (KB) of 1540 patients (pts) treated between 2004 and 2010, has been set up to improve outcome prediction and tailor therapeutic decision, including SCT (Gerstung, Nat Genet 2017). Validation of overall survival (OS) predicti...
Article
Introduction: The randomized phase 3 ALFA-0701 study demonstrated improved outcomes with the addition of gemtuzumab ozogamicin (GO) to standard 7+3 chemotherapy in patients with de novo acute myeloid leukemia (AML; Castaigne et al, Lancet 2012). 85 of 271 patients in the study received hematopoietic stem cell transplantation (HSCT) at any time duri...
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The randomized, phase 3 ALFA-0701 trial showed that a reduced and fractionated dose of gemtuzumab ozogamicin added to standard front-line chemotherapy significantly improves event-free survival in adults with de novo acute myeloid leukemia. Here we report an independent review of event-free survival, final overall survival, and additional safety re...
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Aims: We sought to assess whether global longitudinal strain (GLS) measured early during treatment with anthracyclines (at a cumulative dose of 150 mg/m(2)) can predict subsequent alterations in left ventricular ejection fraction. Methods and results: Eighty-six patients with Hodgkin's disease, non-Hodgkin's lymphoma, or acute leukaemia and rece...
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OBJECTIVE Invasive aspergillosis (IA) is a rare but severe infection caused by Aspergillus spp. that often develops in immunocompromised patients. Lethality remains high in this population. Therefore, preventive strategies are of key importance. The impact of a mobile air decontamination system (Plasmair, AirInSpace, Montigny-le-Bretonneux, France...
Article
Full-text available
We analysed the prognostic significance of minimal residual disease (MRD) level in adult patients with acute myeloid leukemia (AML) treated in the randomized gemtuzumab ozogamicin (GO) ALFA-0701 trial. Levels of WT1 and NPM1 gene transcripts were assessed using cDNA-based real-time quantitative PCR in 183 patients with WT1 overexpression and in 77...
Article
659 Background NPM1 mutations and WT1 expression are frequently identified in acute myeloid leukemia (AML). Both markers have been reported as suitable molecular target for minimal residual disease (MRD) monitoring. Recently, Gemtuzumab Ozogamicin (GO) has been shown to improve event free survival and overall survival in adult AML. Aims To follow...

Citations

... Accumulating evidence suggests DDX41 plays a critical role in the STING-TBK1-IRF3-type I IFN signaling pathway (Parvatiyar Article ll OPEN ACCESS et al., 2012;Soponpong et al., 2018;Ma et al., 2018;Stavrou et al., 2018;Zhang et al., 2013;Hu et al., 2020); however, other groups found that knockdown of DDX41 has little effect on IFN-b induction in response to DNA stimulation or DNA virus infection (Abe et al., 2013;Sun et al., 2013). In addition to its role in innate immunity, both germline and acquired somatic mutations of DDX41 have been associated with myelodysplastic syndromes (MDSs) and/or acute myeloid leukemia (AML) (Cardoso et al., 2016;Ding et al., 2012;Abou Dalle et al., 2019;Hosono, 2019;Kim et al., 2020;Qu et al., 2020;Bannon et al., 2020;Choi et al., 2021;Fazio et al., 2021;Singhal et al., 2021;Goyal et al., 2021;Polprasert et al., 2020;Li et al., 2021;Yang et al., 2021;Alkhateeb et al., 2021;Churpek and Smith-Simmer, 1993;Duployez et al., 2022), chronic myeloid leukemia (CML) (Goyal et al., 2021), acute erythroid leukemia (AEL) (Iacobucci et al., 2019), and other hematolymphoid malignancies (Goyal et al., 2021;Singhal et al., 2021;Choi et al., 2021). The most frequently identified somatic mutation is c.1574G>A, p.R525H (Yoneyama-Hirozane et al., 2017;Lewinsohn et al., 2016;Polprasert et al., 2015;Singhal et al., 2021), which is confined to a highly conserved region of DDX41 and is thought to contribute to nucleotide coordination (Li et al., 2016). ...
... B-cell depleting therapies such as anti-CD20 antibody agents are known to reduce vaccine efficacy. 18,20,29 In our study of myeloid malignancies, seroconversion rates after vaccination were comparable to healthy individuals. Therefore, patients with myeloid malignancies may have less diseaserelated immune dysfunction than patients with lymphoid malignancies. ...
... PPARγ beneficially regulates the expression of numerous OA mediators, balances oxidative stress by directly transactivating antioxidant enzymes (33, 42), and inhibits inflammatory gene expression through several mechanisms. For example, PPARγcan modulate p38 mitogenactivated protein kinase activity (22), trap p300, a critical protein acetyltransferase for gene transcription (25) and form complexes with AP-1 and NF-κB family members to interrupt their functionalities (10), which reportedly account for the IL-1β inhibition and the anti-OA activities of a number of OA-protective agents, such as abietic acid, oridonin (18,20) and pioglitazone class PPARγ agonists (4,23,25). We further demonstrate that by several studies (6,44,51). ...
... 31 The full prognostic impact of IDH1/2 mutations has been incompletely resolved, and likely depends on the constellations of other synchronous mutational events. 32 These mutations are enriched in cytogenetically normal AML. A 2010 retrospective analysis of patients with IDH1/2-mutated AML receiving various investigative protocols across the CALGB trial portfolio concluded that the patients with IDH2 R172 mutations were mutually exclusive with NPM1 mutations and had particularly poor outcomes characterized by relatively high rates of induction failures. ...
... Interestingly, no differences were observed in post-transplant survival outcomes, although GO did improve OS in patients not receiving HCT. The lack of outcome difference may be due to 97% of patients who received GO ≥ 2 months before HCT [69]. Nevertheless, the study indicated that GO was indeed safe for use prior to HCT. ...
... However, highly sensitive NGS techniques for monitoring NPM1 MRD have become available [92][93][94]. Digital droplet PCR may be an alternative, even for assessing rare NPM1 mutations [95]. ...
... 17 ), APS 37 , 3-Gene 38 and CODEG22 (ref. 39 )), we found convergence across all four scores, wherein patients with high scores, indicative of adverse prognosis, had high Quiescent LSPC abundance and low GMP-like abundance (Extended Data Fig. 5h,i). Finally, unbiased analysis of associations between the expression of individual genes and patient survival outcomes revealed that genes associated with shorter survival were enriched for HSC-specific programs, whereas genes associated with longer survival were enriched for GMP-specific programs (Extended Data Fig. 5j). ...
... While chemotherapy kills leukemia cells, it often results in serious side effects to the patients and drug resistance of the leukemia cells. Although hematopoietic stem cell transplantation can alleviate or even cure AML with complex karyotype, its limited source restricts its wide application in clinical settings (Fenwarth et al., 2021). Therefore, finding a more effective and readily available treatment for AML is of the utmost importance. ...
... Higher expression level of P-gp, encoded by ABCB1, constitutes a poor prognostic factor related to overall survival and event-free survival [94,95]. In addition, CD33 expression was inversely correlated with P-gp drug efflux activity [95]. ...
... A multicentre prospective Phase 2 study also reported benefit with overall survival at 2 years of 40% (12). Studies comparing RIC transplant with standard chemotherapy in this age group are however lacking although recently the ALFA-1200 trial reported benefit in high-risk older patients only (13) The NCRI AML16 trial for patients with AML and high grade myelodysplastic syndrome (>10% blasts) over the age of 60 years permitted RIC transplant in CR1 for patients with a suitably matched sibling or unrelated donor if they lacked favourable risk cytogenetics. Here we report on a comparison of RIC transplant with chemotherapy in older patients fit for intensive chemotherapy. ...