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Artigues-près-Bordeaux, France

Beldjord K.,University Paris Diderot | Chevret S.,University Paris Diderot | Asnafi V.,University of Paris Descartes | Huguet F.,University Hospital Purpan | And 21 more authors.
Blood | Year: 2014

With intensified pediatric-like therapy and genetic disease dissection, the field of adult acute lymphoblastic leukemia (ALL) has evolved recently. In this new context, we aimed to reassess the value of conventional risk factors with regard to new genetic alterations and early response to therapy, as assessed by immunoglobulin/T-cell receptor minimal residual disease (MRD) levels. The study was performed in 423 younger adults with Philadelphia chromosome-negative ALL in first remission (265 B-cell precursor [BCP] and 158 T-cell ALL), with cumulative incidence of relapse (CIR) as the primary end point. In addition to conventional risk factors, the most frequent currently available genetic alterations were included in the analysis. A higher specific hazard of relapse was independently associated with postinduction MRD level ≥10-4 and unfavorable genetic characteristics (ie, MLL gene rearrangement or focal IKZF1 gene deletion in BCP-ALL and no NOTCH1/FBXW7 mutation and/or N/K-RAS mutation and/or PTEN gene alteration in T-cell ALL). These 2 factors allowed definition of a new risk classification that is strongly associated with higher CIR and shorter relapse-free and overall survival. These results indicate that genetic abnormalities are important predictors of outcomein adult ALL not fully recapitulated by early response to therapy. Patients included in this study were treated in the multicenter GRAALL-2003 and GRAALL-2005 trials. Both trials were registered at http://www.clinicaltrials.gov as #NCT00222027 and #NCT00327678, respectively. © 2014 by The American Society of Hematology.

Perrot A.,University of Lorraine | Luquet I.,University Hospital Robert Debre | Pigneux A.,University Hospital Haut Leveque | Mugneret F.,University Hospital du Bocage | And 16 more authors.
Blood | Year: 2011

The prognosis of acute myeloid leukemia (AML) is very poor in elderly patients, especially in those classically defined as having unfavorable cytogenetics. The recent monosomal karyotype (MK) entity, defined as 2 or more autosomal monosomies or combination of 1 monosomy with structural abnormalities, has been reported to be associated with a worse outcome than the traditional complex karyotype (CK). In this retrospective study of 186 AML patients older than 60 years, the prognostic influence of MK was used to further stratify elderly patients with unfavorable cytogenetics. CK was observed in 129 patients (69%), and 110 exhibited abnormalities according to the definition of MK (59%). MK+ patients had a complete response rate significantly lower than MK- patients: 37% vs 64% (P = .0008), and their 2-year overall survival was also decreased at 7% vs 22% (P < .0001). In multivariate analysis, MK appeared as the major independent prognostic factor related to complete remission achievement (odds ratio = 2.3; 95% confidence interval, 1-5.4, P = .05) and survival (hazard ratio = 1.7; 95% confidence interval, 1.1-2.5, P = .008). In the subgroup of 129 CK+ patients, survival was dramatically decreased for MK+ patients (8% vs 28% at P = .03). These results demonstrate that MK is a major independent factor of very poor prognosis in elderly AML. © 2011 by The American Society of Hematology.

Gronnier C.,Lille University Hospital Center | Gronnier C.,North of France University | Gronnier C.,French Institute of Health and Medical Research | Messager M.,Lille University Hospital Center | And 13 more authors.
Surgery (United States) | Year: 2013

Background: Although the signet ring cell histologic subtype (SRC) is an independent predictor of poor prognosis in advanced gastric adenocarcinomas (GA), its prognostic value in early GA remains highly controversial. The aim of the study was to evaluate the prognostic impact of SRC in mucosal and submucosal GAs. Methods: Based on a multicenter cohort of 3,010 patients operated on for GA between January 1997 and January 2010, patients with pTis or pT1 tumors were extracted and analyzed comparatively between the SRC and non-SRC groups. The primary objective was to compare the 5-year survival rate between groups. Results: Among 421 patients with a pTis or pT1 tumor, 104 (25%) were SRC and 317 (75%) were non-SRC. Demographic variables were comparable between groups, except median age, which was less in the SRC group (59.6 vs 68.8 years; P <.001). Submucosal involvement was more frequent in the SRC group (94% vs 85%; P =.043), whereas lymph node involvement and number of invaded nodes were comparable between the 2 groups. When comparing SRC and non-SRC, recurrence rates (6% vs 9%; P =.223) and sites of recurrence were similar. The 5-year overall survival benefit in SRC patients (85% vs 76%, respectively; P =.035), was not evident when considering exclusively disease-specific survival or in multivariable analysis. Conclusion: Contrary to more advanced GA, SRC morphologic subtype is not a negative prognostic factor in early GA. Better survival identified in some reports may be related to the younger age in SRC patients. © 2013 Mosby, Inc. All rights reserved.

Rollin A.,Toulouse University Hospital Center | Rollin A.,Institute National Of La Sante Et Of La Recherche Medicale Umr 1027 | Maury P.,Toulouse University Hospital Center | Bongard V.,Toulouse University Hospital Center | And 10 more authors.
American Journal of Cardiology | Year: 2012

Early repolarization pattern (ERP) has recently been associated with idiopathic ventricular fibrillation and with cardiovascular mortality in the general population. We aimed to identify electrocardiographic tools to differentiate the "malignant" form of ERP from benign ERP in a population-based study. We retrospectively assessed the prevalence of ERP by recording electrocardiograms in 1,161 southwestern French subjects 35 to 64 years old. ERP was defined by an elevation of the J point <1 mm in 2 consecutive leads excluding leads V1 through V3. We categorized ERP as notching or slurring pattern as located in inferior and/or lateral leads and measured the J-point elevation amplitude. ST segment after ERP was categorized as ascendant or horizontal/nonascendant and T waves as negative or positive. Association of ERP with all-cause and cardiovascular mortalities was assessed by adjusted Cox proportional hazard models. ERP was found in 157 subjects (13.3%). During a mean follow-up of 14.2 ± 2 years, 77 subjects died (6.6%), of whom 24 (2.1%) died from cardiovascular causes. Subjects with ERP had an increased hazard ratios for all-cause mortality (2.45, 95% confidence interval [CI] 1.44 to 4.15, p = 0.001) and cardiovascular mortality (5.60, 95% CI 2.27 to 11.8, p = 0.001). The highest risk was found for notching ERP and ERP with a nonascendant/horizontal ST segment, yielding when associated increased hazard ratios of 3.84 (95% CI 2.14 to 6.92, p = 0.001) and 8.75 (95% CI 3.48 to 22.0, p = 0.001) for all-cause and cardiovascular mortalities, respectively. Conversely, a slurring ERP or ascendant ST segment was not associated with increased mortality. ERP localization, J-point elevation amplitude, or T-wave morphology did not distinguish benign from malignant forms of ERP. In conclusion, ERP with notching pattern and horizontal/descendant ST segments was associated with the highest risk of all-cause and cardiovascular deaths. These electrocardiographic patterns may be used for risk stratification in subjects with ERP. © 2012 Elsevier Inc. All rights reserved.

Guy J.,University Hospital of Dijon | Antony-Debre I.,University Hospital Henri Mondor | Benayoun E.,University Hospital Henri Mondor | Arnoux I.,University Hospital La Timone | And 8 more authors.
British Journal of Haematology | Year: 2013

The World Health Organization 2008 Classification emphasizes myeloperoxidase (MPO) detection as sufficient for assigning a blast population to the myeloid lineage. Published MPO positivity thresholds are 10% for flow cytometry (FCM) but 3% for cytochemistry. Here we re-evaluated the FCM-MPO threshold by comparing retrospectively 128 acute lymphoblastic leukaemias and 75 acute myeloid leukaemias without maturation, all assessed by benzidine-based cytochemistry. A 13% threshold was found to be relevant using an isotype control as background-reference (sensitivity 95·1%, specificity 91·7%). Residual normal lymphocytes proved to be an advantageous alternative reference, a threshold of 28% yielding improved 97·4% sensitivity and 96·1% specificity. © 2013 John Wiley & Sons Ltd.

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