Author
Jacques Delaunay
Other affiliations: Centre national de la recherche scientifique, University of Toulouse
Bio: Jacques Delaunay is an academic researcher from French Institute of Health and Medical Research. The author has contributed to research in topics: Transplantation & Population. The author has an hindex of 30, co-authored 171 publications receiving 3770 citations. Previous affiliations of Jacques Delaunay include Centre national de la recherche scientifique & University of Toulouse.
Papers published on a yearly basis
Papers
More filters
TL;DR: Gemtuzumab ozogamicin can be safely added to conventional induction therapy and provides a significant survival benefit for patients without adverse cytogenetic characteristics, and its licence status might need to be reviewed.
Abstract: Summary Background Gemtuzumab ozogamicin was the first example of antibody-directed chemotherapy in cancer, and was developed for acute myeloid leukaemia. However, randomised trials in which it was combined with standard induction chemotherapy in adults have produced conflicting results. We did a meta-analysis of individual patient data to assess the efficacy of adding gemtuzumab ozogamicin to induction chemotherapy in adult patients with acute myeloid leukaemia. Methods We searched PubMed for reports of randomised controlled trials published in any language up to May 1, 2013, that included an assessment of gemtuzumab ozogamicin given to adults (aged 15 years and older) in conjunction with the first course of intensive induction chemotherapy for acute myeloid leukaemia (excluding acute promyelocytic leukaemia) compared with chemotherapy alone. Published data were supplemented with additional data obtained by contacting individual trialists. The primary endpoint of interest was overall survival. We used standard meta-analytic techniques, with an assumption-free (or fixed-effect) method. We also did exploratory stratified analyses to investigate whether any baseline features predicted a greater or lesser benefit from gemtuzumab ozogamicin. Findings We obtained data from five randomised controlled trials (3325 patients); all trials were centrally randomised and open label, with overall survival as the primary endpoint. The addition of gemtuzumab ozogamicin did not increase the proportion of patients achieving complete remission with or without complete peripheral count recovery (odds ratio [OR] 0·91, 95% CI 0·77–1·07; p=0·3). However, the addition of gemtuzumab ozogamicin significantly reduced the risk of relapse (OR 0·81, 0·73–0·90; p=0·0001), and improved overall survival at 5 years (OR 0·90, 0·82–0·98; p=0·01). At 6 years, the absolute survival benefit was especially apparent in patients with favourable cytogenetic characteristics (20·7%; OR 0·47, 0·31–0·73; p=0·0006), but was also seen in those with intermediate characteristics (5·7%; OR 0·84, 0·75–0·95; p=0·005). Patients with adverse cytogenetic characteristics did not benefit (2·2%; OR 0·99, 0·83–1·18; p=0·9). Doses of 3 mg/m 2 were associated with fewer early deaths than doses of 6 mg/m 2 , with equal efficacy. Interpretation Gemtuzumab ozogamicin can be safely added to conventional induction therapy and provides a significant survival benefit for patients without adverse cytogenetic characteristics. These data suggest that the use of gemtuzumab ozogamicin should be reassessed and its licence status might need to be reviewed. Funding None.
485 citations
TL;DR: Routine tests can identify subgroups of patients with distinct prognosis with AZA treatment, and achievement of hematological improvement in patients who did not obtain complete or partial remission was associated with improved OS.
352 citations
TL;DR: It is suggested that MRD, rather than gene mutations, should be used for future treatment stratifications in CBF-AML patients, as the sole prognostic factor in multivariate analysis.
296 citations
TL;DR: Interestingly, advanced age was associated with a trend for more frequent additional chromosome abnormalities and predictive of higher cumulative incidence of relapse rather than death in first CR, markedly contrast with those reported in patients with t(8;21) AML in whom WBC, and not age, was the main high-risk factor for relapse, DFS, and survival.
183 citations
TL;DR: The data support a potential role of lenalidomide in higher-risk MDS with isolated del 5q and suggest a positive prognosis for patients with hematologic response.
143 citations
Cited by
More filters
University of Ulm1, Fred Hutchinson Cancer Research Center2, King's College London3, University of Rome Tor Vergata4, University of Münster5, Brigham and Women's Hospital6, University of Chicago7, Memorial Sloan Kettering Cancer Center8, Leipzig University9, VU University Amsterdam10, University of Valencia11, National Taiwan University12, Alfred Hospital13, Monash University14, Erasmus University Medical Center15, Ohio State University16
TL;DR: An international panel to provide updated evidence- and expert opinion-based recommendations for diagnosis and management of acute myeloid leukemia in adults includes a revised version of the ELN genetic categories, a proposal for a response category based on MRD status, and criteria for progressive disease.
4,066 citations
University of Ulm1, University of Rome Tor Vergata2, Fred Hutchinson Cancer Research Center3, University of Münster4, University of Wales5, University of Chicago6, Nagoya University7, Leipzig University8, VU University Medical Center9, Northwestern University10, Erasmus University Medical Center11, Ohio State University12
TL;DR: An international expert panel is provided to provide updated evidence- and expert opinion-based recommendations for the diagnosis and management of AML, that contain both minimal requirements for general practice as well as standards for clinical trials.
3,000 citations
TL;DR: Genotypes defined by the mutational status of NPM1, FLT3, CEBPA, MLL, and MLL are associated with the outcome of treatment for patients with cytogenetically normal AML.
Abstract: Background Mutations occur in several genes in cytogenetically normal acute myeloid leukemia (AML) cells: the nucleophosmin gene (NPM1), the fms-related tyrosine kinase 3 gene (FLT3), the CCAAT/enhancer binding protein α gene (CEPBA), the myeloid–lymphoid or mixed-lineage leukemia gene (MLL), and the neuroblastoma RAS viral oncogene homolog (NRAS). We evaluated the associations of these mutations with clinical outcomes in patients. Methods We compared the mutational status of the NPM1, FLT3, CEBPA, MLL, and NRAS genes in leukemia cells with the clinical outcome in 872 adults younger than 60 years of age with cytogenetically normal AML. Patients had been entered into one of four trials of therapy for AML. In each study, patients with an HLA-matched related donor were assigned to undergo stem-cell transplantation. Results A total of 53% of patients had NPM1 mutations, 31% had FLT3 internal tandem duplications (ITDs), 11% had FLT3 tyrosine kinase–domain mutations, 13% had CEBPA mutations, 7% had MLL partial ...
1,538 citations
TL;DR: Whereas significant progress has been made in the treatment of younger adults, the prospects for elderly patients have remained dismal, with median survival times of only a few months, current efforts in clinical research focus on the assessment of targeted therapies.
1,232 citations
University of Texas MD Anderson Cancer Center1, Medical University of Lublin2, Medical University of Łódź3, Wrocław Medical University4, Masaryk University5, National Taiwan University6, University of Toronto7, Charles University in Prague8, Chang Gung University9, Autonomous University of Barcelona10, University of Nantes11, Royal North Shore Hospital12
TL;DR: In older patients with AML, decitabine improved response rates compared with standard therapies without major differences in safety, and an unplanned survival analysis showed a benefit for decit abine, which was not observed at the time of the primary analysis.
Abstract: Purpose This multicenter, randomized, open-label, phase III trial compared the efficacy and safety of decitabine with treatment choice (TC) in older patients with newly diagnosed acute myeloid leukemia (AML) and poor- or intermediate-risk cytogenetics. Patients and Methods Patients (N = 485) age ≥ 65 years were randomly assigned 1:1 to receive decitabine 20 mg/m2 per day as a 1-hour intravenous infusion for five consecutive days every 4 weeks or TC (supportive care or cytarabine 20 mg/m2 per day as a subcutaneous injection for 10 consecutive days every 4 weeks). The primary end point was overall survival (OS); the secondary end point was the complete remission (CR) rate plus the CR rate without platelet recovery (CRp). Adverse events (AEs) were recorded. Results The primary analysis with 396 deaths (81.6%) showed a nonsignificant increase in median OS with decitabine (7.7 months; 95% CI, 6.2 to 9.2) versus TC (5.0 months; 95% CI, 4.3 to 6.3; P = .108; hazard ratio [HR], 0.85; 95% CI, 0.69 to 1.04). An unp...
942 citations