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Le Touquet – Paris-Plage, France

Brands-Nijenhuis A.V.M.,Catharina Ziekenhuis Eindhoven | Labopin M.,EBMT Data Office Paris | Schouten H.C.,Maastricht University | Volin L.,University of Helsinki | And 9 more authors.

Despite the overall benefit from allogeneic hematopoietic stem cell transplantation observed in patients with poor cytogenetic risk acute myeloid leukemia in first complete remission, the precise effect of this procedure for different poor-risk subtypes has not been fully analyzed. This retrospective analysis was performed to investigate whether allogeneic hematopoietic stem cell transplantation performed in first complete remission in patients with monosomal karyotype can overcome the adverse prognosis associated with these patients. Of the 4635 patients included in the study, 189 (4%) harbored a monosomal karyotype. The presence of a monosomal karyotype was associated with a worse outcome, with an inferior leukemia-free survival and overall survival (5-year leukemia-free survival and overall survival: 24±3% and 26±3% vs. 53±1% and 57±1% in monosomal-karyotype and non-monosomal-karyotype, respectively; P<0.0001) and higher relapse risk after transplantation (cumulative incidence of relapse at 5 years: 56±4% in monosomal-karyotype vs. 28±1% in nonmonosomal-karyotype; P<0.0001). The adverse negative impact of monosomal karyotype cytogenetics was confirmed in the entire cohort in a multivariate analysis [Hazard Ratio (HR): 1.88, 95% Confidence Interval (CI):1.29-2.73, P=0.001 for relapse incidence; HR:1.71, 95%CI:1.27-2.32, P<0.0001 for leukemia-free survival; HR:1.81, 95%CI:1.32-2.48, P=0.0002 for overall survival], and was independent of the presence of other poor-risk cytogenetic subtypes. In summary, monosomal karyotype arises as a strong negative prognostic feature in acute myeloid leukemia also in patients who undergo allogeneic hematopoietic stem cell transplantation in first complete remission, stressing the need to develop additional pre-and post-transplantation strategies aimed at improving overall results. Nonetheless, allogeneic hematopoietic stem cell transplantation in early phase is currently the best therapy for this very poor-risk acute myeloid leukemia subtype. © 2016 Ferrata Storti Foundation. Source

Panaccione R.,University of Calgary | Higgins P.D.R.,University of Michigan | Vermeire S.,University Hospital Gasthuisberg | Gassull M.,Health science Research Institute | And 22 more authors.
American Journal of Gastroenterology

The advent of biological therapy has revolutionized inflammatory bowel disease (IBD) care. Nonetheless, not all patients require biological therapy. Selection of patients depends on clinical characteristics, previous response to other medical therapy, and comorbid conditions. Availability, reimbursement guidelines, and patient preferences guide the choice of first-line biological therapy for luminal Crohn's disease (CD). Infliximab (IFX) has the most extensive clinical trial data, but other biological agents (adalimumab (ADA), certolizumab pegol (CZP), and natalizumab (NAT)) appear to have similar benefits in CD. Steroid-refractory, steroid-dependent, or complex fistulizing CD are indications for starting biological therapy, after surgical drainage of any sepsis. For fistulizing CD, the efficacy of IFX for inducing fistula closure is best documented. Unique risks of NAT account for its labeling as a second-line biological agent in some countries. Patients who respond to induction therapy benefit from systematic re-treatment. The combination of IFX with azathioprine is better than monotherapy for induction of remission and mucosal healing up to 1 year in patients who are nave to both agents. Whether this applies to other agents remains unknown. IFX is also effective for treatment-refractory, moderate, or severely active ulcerative colitis. Patients who have a diminished or loss of response to anti-tumor necrosis factor (TNF) therapy may respond to dose adjustment of the same agent or switching to another agent. Careful consideration should be given to the reasons for loss of response. There are insufficient data to make recommendations on when to stop anti-TNF therapy. Preliminary evidence suggests that a substantial proportion of patients in clinical remission for 1 year, without signs of active inflammation can remain in remission after stopping treatment. © 2011 by the American College of Gastroenterology. Source

Terry S.,French Institute of Health and Medical Research | Terry S.,University Paris Est Creteil | Terry S.,University Pierre and Marie Curie | Nicolaiew N.,French Institute of Health and Medical Research | And 16 more authors.

Background In view of the marked molecular heterogeneity of prostate cancer (PCa), clinical and pathologic parameters alone may be unreliable for predicting disease outcomes after surgical intervention. The development of biomarkers may be helpful to estimate tumor heterogeneity and stratify patients in terms of their risk of progression. Levels of v-ets avian erythroblastosis virus E26 oncogene homolog (ERG), trefoil factor 3 (TFF3), and serine peptidase inhibitor, Kazal type 1 (SPINK1) are commonly elevated in PCa, but it is unclear whether the evaluation of these 3 markers can help to discriminate patients who will have different clinical outcomes. The authors investigated whether assessment of ERG, TFF3, and SPINK1 expression could help to define clinically relevant, distinct subsets of patients with PCa. Methods The cohort consisted of 279 men with PCa who underwent radical prostatectomy at Henri Mondor Hospital. Expression levels of ERG, TFF3, and SPINK1 were evaluated immunohistochemically in the prostatectomy specimens. Potential associations of ERG, TFF3, and SPINK1 with age, prostate-specific antigen (PSA), tumor stage, Gleason score, and biochemical recurrence, defined by PSA failure, were investigated. Results Although prognostic significance was not observed for ERG or TFF3, an exclusive pattern of expression was demonstrated for TFF3 and ERG. SPINK1 expression was observed exclusively in a subgroup of cancers that expressed TFF3 (41 of 175 tumors). Moreover, SPINK1 positivity was identified as predictive of biochemical recurrence in univariate (P = .0009) and multivariate (P = .0003) analyses. Conclusion The current results suggest that ERG and TFF3 characterize 2 distinct subsets of PCa, with a more aggressive subgroup of TFF3-expressing tumors that express SPINK1. Together, these findings support a rationale of screening for these biomarkers for prognostic purposes and molecular subtyping of the disease. Cancer 2015;121:1422-1430. © 2015 American Cancer Society. Source

Giebel S.,Center of Oncology of Poland | Labopin M.,Hospital Saint Antoine | Labopin M.,University Pierre and Marie Curie | Labopin M.,French Institute of Health and Medical Research | And 11 more authors.
European Journal of Cancer

Background Outcome of Philadelphia-positive acute lymphoblastic leukaemia (Ph+ ALL) improved significantly with the introduction of tyrosine kinase inhibitors (TKIs). Autologous stem cell transplantation (ASCT) has never been considered a standard of care in this setting. The aim of our study was to analyse if results of ASCT improved in the era of TKIs. Patients and Methods One-hundred and seventy-seven adults with Ph+ ALL treated with ASCT in first complete remission were analysed for the impact of year of transplantation on outcome. Additional analysis was performed including 32 patients for whom detailed data on the use of TKIs and the status of minimal residual disease were collected. Results The probability of the overall survival (OS) at 3 years increased from 16% for transplants performed between 1996 and 2001 to 48% between 2002 and 2006 and 57% between 2007 and 2010 (P <.0001). Leukaemia-free survival (LFS) was 11%, 39% and 52%, respectively (P <.0001). Relapse incidence decreased from 70% to 45% and 45% (P =.01), respectively, while non-relapse mortality was 19%, 15% and 3% (P =.08). In a multivariate analysis, year of ASCT was the only independent factor influencing the risk of treatment failure (hazard ratio (HR) = 0.37; P <.001). In a subgroup of 22 patients actually treated with TKIs and being in complete molecular remission at the time of ASCT, the LFS rate at 3 years was 65%. Conclusions Results of ASCT for Ph+ ALL improved significantly over time. Prospective, innovative studies are needed to verify the role of ASCT in this patient setting. © 2013 Elsevier Ltd. All rights reserved. Source

Schmidt-Hieber M.,HELIOS Clinic Berlin Buch | Schmidt-Hieber M.,Charite - Medical University of Berlin | Labopin M.,European Group for Blood and Marrow Transplantation Acute Leukemia Working Party Office | Labopin M.,University Pierre and Marie Curie | And 16 more authors.

We analyzed the prognostic impact of donor and recipient cytomegalovirus (CMV) serostatus in 16628 de novo acute leukemia patients after allogeneic stem cell transplantation (allo-SCT). Compared with CMV-seronegative recipients who underwent allograft from a CMV-seronegative donor, cases of CMV seropositivity of the donor and/or the recipient showed a significantly decreased 2-year leukemia-free survival (44% vs 49%, P Source

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