Center Pierre et Marie Curie

mai, Algeria

Center Pierre et Marie Curie

mai, Algeria
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Kharfan-Dabaja M.A.,H. Lee Moffitt Cancer Center and Research Institute | Labopin M.,Acute Leukemia Working Party of EBMT | Bazarbachi A.,American University of Beirut | Hamladji R.M.,Center Pierre et Marie Curie | And 9 more authors.
Bone marrow transplantation | Year: 2014

This retrospective analysis compared two regimens of fludarabine combined with i.v. BU 6.4 mg/kg (FB2) or BU 12.8 mg/kg (FB4) for allografting of AML in first CR. A total of 437 patients (median age: 50 years) were administered FB2 (n = 225, 51%) or FB4 (n = 212, 49%). Median follow-up time was 28 months. Use of FB2 resulted in a longer time to neutrophil engraftment (17 vs 15 days, P < 0.0001) but no difference in incidence of grade II-IV acute (P = 0.54) or chronic GVHD (P = 0.51). In patients < 50 years of age, FB2 was associated with a higher 2-year cumulative incidence of relapse (33 ± 6% vs 20 ± 4%, P = 0.04), but there was no difference in 2-year leukemia-free survival (LFS) (P = 0.45), OS (P = 0.53) or non-relapse mortality (P = 0.17). In recipients ⩾ 50 years of age, FB2 resulted in better 2-year LFS (63 ± 4% vs 42 ± 7%, P = 0.02) and OS (68 ± 4% vs 45 ± 7%, P = 0.006); a lower 2-year non-relapse mortality, albeit not statistically significant (15 ± 3% vs 29 ± 6%, P = 0.06), was observed with FB2. FB2 is an effective and well-tolerated regimen in patients ⩾ 50 years of age and does not compromise survival when used in patients <50 years undergoing allogeneic transplantation for AML in first CR.

Bacigalupo A.,IRCCS AOU San Martino IST | Socie G.,Paris West University Nanterre La Défense | Hamladji R.M.,Center Pierre et Marie Curie | Aljurf M.,King Faisal Specialist Hospital And Research Center | And 11 more authors.
Haematologica | Year: 2015

We have analyzed 1448 patients with acquired aplastic anemia grafted between 2005 and 2009, and compared outcome of identical sibling (n=940) versus unrelated donor (n=508) transplants. When compared to the latter, sibling transplants were less likely to be performed beyond 180 days from diagnosis (39% vs. 85%), to have a cytomegalovirus negative donor/recipient status (15% vs. 23%), to receive antithymocyte globulin in the conditioning (52% vs. 61%), and more frequently received marrow as a stem cell source (60% vs. 52%). Unrelated donor grafts had significantly more acute grade II-IV (25% vs. 13%) and significantly more chronic graft-versus-host disease (26% vs. 14%). In multivariate analysis, the risk of death of unrelated donor grafts was higher, but not significantly higher, compared to a sibling donor (P=0.16). The strongest negative predictor of survival was the use of peripheral blood as a stem cell source (P<0.00001), followed by an interval of diagnosis to transplant of 180 days or more (P=0.0005), patient age 20 years or over (P=0.0005), no antithymocyte globulin in the conditioning (P=0.003), and donor/recipient cytomegalovirus sero-status, other than negative/negative (P=0.04). In conclusion, in multivariate analysis, the outcome of unrelated donor transplants for acquired aplastic anemia, is currently not statistically inferior when compared to sibling transplants, although patients are at greater risk of acute and chronic graft-versus-host disease. The use of peripheral blood grafts remains the strongest negative predictor of survival. ©2015 Ferrata Storti Foundation.

Bacigalupo A.,IRCCS San Martino IST | Schrezenmeier H.,Institute Klinische und Transfusion Medizin | Tichelli A.,Kantonspital | Locasciulli A.,Ospedale San Camillo | And 10 more authors.
Haematologica | Year: 2012

Background Bone marrow has been shown to be superior to peripheral blood, as a stem cell source, in young patients (<20 years of age) with acquired aplastic anemia undergoing a matched sibling transplant. The aim of this study was to test whether this currently also holds true for older patients with acquired aplastic anemia. Design and Methods We analyzed 1886 patients with acquired aplastic anemia who received a first transplant from a human leukocyte antigen identical sibling between 1999 and 2009, with either bone marrow (n=1163) or peripheral blood (n=723) as the source of stem cells. Results In multivariate Cox analysis negative predictors for survival were: patient's age over 20 years (RR 2.0, P<0.0001), an interval between diagnosis and transplantation of more than 114 days (RR 1.3, P=0.006), no anti-thymocyte globulin in the conditioning (RR 1.6, P=0.0001), a conditioning regimen other than cyclophosphamide (RR=1.3, P=0.008) and the use of peripheral blood as the source of stem cells (RR 1.6, P<0.00001). The survival advantage for recipients of bone marrow rather than peripheral blood was statistically significant in patients aged 1-19 years (90% versus 76% P<0.00001) as well as in patients aged over 20 years (74% versus 64%, P=0.001). The advantage for recipients of bone marrow over peripheral blood was maintained above the age of 50 years (69% versus 39%, P=0.01). Acute and chronic graft-versus-host disease were more frequent in peripheral blood transplants. Major causes of death were graft-versus-host disease (2% versus 6% in bone marrow and peripheral blood recipients, respectively), infections (6% versus 13%), and graft rejection (1.5% versus 2.5%). Conclusions This study shows that bone marrow should be the preferred stem cell source for matched sibling transplants in acquired aplastic anemia, in patients of all age groups. © 2012 Ferrata Storti Foundation.

PubMed | Center Hospitalier Of Bethune, Center Pierre et Marie Curie and Lille University Hospital Center
Type: Journal Article | Journal: Langenbeck's archives of surgery | Year: 2016

Life-threatening postoperative pancreatic fistula (LTPOPF) is the most feared complication after pancreatoduodenectomy (PD). Although completion pancreatectomy (CP) is usually performed when radiological management fails, the associated morbidity and mortality rates remain high. Here, we reviewed pancreas-preserving alternatives to CP.The PubMed database was systematically searched for publications between 1983 and 2014, describing pancreas-preserving surgical treatment of the pancreas remnant (PR) after reintervention in a context of post-PD LTPOPF.A total of 12 articles including 140 patients were reviewed. Six different types of pancreas-preserving treatment were described: external wirsungostomy, simple drainage of the PF, closure of pancreatic stump, internal wirsungostomy, partial CP, and salvage pancreatogastrostomy after major leakage of a pancreatojejunostomy. The overall median survival rate was 75 % but rose to 83 % when patients undergoing only surgical drainage of the fistula were excluded. The median complication rate was 75 %, and the median length of hospital stay was 41.5 days. Further reintervention was required for 25 % of the patients. The median incidence of late diabetes was 22.5 %. The incidence of exocrine insufficiency ranged from 0 to 100 % depending on the intervention.Pancreas-preserving surgical management of the PR after LTPOPF can be performed with acceptable mortality and morbidity. These data suggest that CP should have a more precisely specified role in the management algorithm and should not be performed systematically.

PubMed | Sloan Kettering Cancer Center, University of Science and Technology Houari Boumediene, Center Pierre et Marie Curie and Mustapha Pacha Hospital
Type: Journal Article | Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2016

The role of nitric oxide (NO)() in the development of the metastatic properties of nasopharyngeal carcinoma (NPC) is not fully understood. Previous studies proposed that interleukin-6 (IL-6) would act as regulator of matrix metalloprotease activation in NPC. Recently, we showed that (NO)() was a critical mediator of tumor growth in patients. The aim of this study was to determine the implication of IL-6 in the progression of NPC pathology via metalloprotease (MMP) activation and their possible correlation with (NO)() production. We observed a significant increase in IL-6 and nitrite (NO2 (-)) synthesis in patients (n=17) as well as a strong expression of IL-6 and nitric oxide synthase 2 (NOS2) in the analyzed tumors (n=8). In patients plasma, a negative correlation associated IL-6 with circulating nitrites (r=-0.33). A negative correlation associated the H-scores of these signals in the tumors (r=-0.47). In patients plasma, nitrite synthesis was positively associated with MMP-9 activation (r=0.45), pro-MMP-2 expression (r=0.37), and negatively correlated with MMP-2 activation (r=-0.51). High nitrite levels was associated with better recurrence-free survival (RFS) (p=0.02). Overall, our results suggest that the IL-6/NOS2 inflammatory signals are involved in the regulation of MMP-9- and MMP-2-dependent metastatic activity and that high circulating nitrite levels in NPC patients may constitute a prognostic predictor for survival.

PubMed | Hospital Universitario La Paz, Beilinson Hospital, Institute Paoli Calmettes, Centro Unico Regionale Trapianti and 8 more.
Type: Journal Article | Journal: Journal of hematology & oncology | Year: 2017

The impact of the use of anti-thymocyte globulin (ATG) in allogeneic stem cell transplantation performed with HLA-identical sibling donors following fludarabine and 4days intravenous busulfan myeloablative conditioning regimen has been poorly explored.We retrospectively analyzed 566 patients who underwent a first HLA-identical allogeneic stem cell transplantation with this conditioning regimen for acute myeloid leukemia in first complete remission between 2006 and 2013 and compared the outcomes of 145 (25.6%) patients who received ATG (ATG group) to 421 (74.4%) who did not (no-ATG group). The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate.Patients in the ATG group were older, received more frequently peripheral blood stem cell grafts from older donors, and were transplanted more recently. With a median follow-up of 19months, patients in the ATG group had reduced 2-year cumulative incidence of chronic graft-versus-host disease (GVHD) (31 vs. 52%, p=0.0002) and of its extensive form (8 vs. 26%, p<0.0001) but similar relapse incidence (22 vs. 27%, p=0.23) leading to improved GVHD and relapse-free survival (GRFS) (60 vs. 40%, p=0.0001). In multivariate analyses, the addition of ATG was independently associated with lower chronic GVHD (HR=0.46, p=0.0001), improved leukemia-free survival (HR=0.67, p=0.027), overall survival (HR=0.65, p=0.027), and GRFS (HR=0.51, p=410These results suggest that the use of ATG with fludarabine and 4days intravenous busulfan followed by HLA-identical sibling donor allogeneic stem cell transplantation for acute myeloid leukemia improves overall transplant outcomes due to reduced incidence of chronic GVHD without increased relapse risk.

Arias-Pulido H.,University of New Mexico | Royce M.,University of New Mexico | Gong Y.,University of Houston | Joste N.,University of New Mexico | And 7 more authors.
Breast Cancer Research and Treatment | Year: 2010

GPR30 is a novel G protein-coupled estrogen receptor (ER) associated with metastases in breast cancer (BC) and poor survival in endometrial and ovarian tumors. The association of GPR30 expression with inflammatory breast cancer (IBC), an aggressive and commonly hormone-independent form of BC, has not been studied. GPR30, ER, progesterone receptor (PR), epidermal growth factor receptor (EGFR), and HER-2 expression were assessed by immunohistochemistry (and FISH for HER-2) in 88 primary IBCs. GPR30 expression was correlated with patient overall survival (OS), disease-free survival (DFS), pathologic variables, and other biomarkers. GPR30 expression was found in 69% of IBC cases. ER, PR, HER-2, and EGFR were found in 43, 35, 39, and 34% of IBC cases, respectively. GPR30 expression correlated inversely with ER expression (P = 0.02). Co-expression of ER and GPR30 was found in 24% of IBC samples; 19% expressed only ER and 46% expressed only GPR30. Univariate analysis showed no association between GPR30 expression and OS or DFS. However, co-expression of ER and GPR30 was associated with improved OS (P < 0.03) and marginally with DFS (P < 0.06); the absence of both ER and GPR30 was associated with worse OS and DFS (P = 0.03 for both). Multivariate analysis identified ER as an independent prognostic factor of OS (P = 0.008) and DFS (P = 0.02). The majority of IBC tumors are GPR30-positive, suggesting that estrogen signaling may be active in ER-negative IBC patients. These findings suggest potential new therapeutic targets for IBC such as novel endocrine agents or direct modulation of GPR30. © 2009 Springer Science+Business Media, LLC.

Arias-Pulido H.,University of New Mexico | Chaher N.,Center Pierre et Marie Curie | Gong Y.,University of Houston | Qualls C.,University of New Mexico | And 2 more authors.
BMC Cancer | Year: 2012

Background: Inflammatory breast cancer (IBC) is a highly angiogenic disease; thus, antiangiogenic therapy should result in a clinical response. However, clinical trials have demonstrated only modest responses, and the reasons for these outcomes remain unknown. Therefore, the purpose of this retrospective study was to determine the prognostic value of protein levels of vascular endothelial growth factor (VEGF-A), one of the main targets of antiangiogenic therapy, and its receptors (VEGF-R1 and -R2) in IBC tumor specimens.Patients and Methods: Specimens from IBC and normal breast tissues were obtained from Algerian patients. Tumor epithelial and stromal staining of VEGF-A, VEGF-R1, and VEGF-R2 was evaluated by immunohistochemical analysis in tumors and normal breast tissues; this expression was correlated with clinicopathological variables and breast cancer-specific survival (BCSS) and disease-free survival (DFS) duration.Results: From a set of 117 IBC samples, we evaluated 103 ductal IBC tissues and 25 normal specimens. Significantly lower epithelial VEGF-A immunostaining was found in IBC tumor cells than in normal breast tissues (P <0.01), cytoplasmic VEGF-R1 and nuclear VEGF-R2 levels were slightly higher, and cytoplasmic VEGF-R2 levels were significantly higher (P = 0.04). Sixty-two percent of IBC tumors had high stromal VEGF-A expression. In univariate analysis, stromal VEGF-A levels predicted BCSS and DFS in IBC patients with estrogen receptor-positive (P <0.01 for both), progesterone receptor-positive (P = 0.04 and P = 0.03), HER2+ (P = 0.04 and P = 0.03), and lymph node involvement (P <0.01 for both). Strikingly, in a multivariate analysis, tumor stromal VEGF-A was identified as an independent predictor of poor BCSS (hazard ratio [HR]: 5.0; 95% CI: 2.0-12.3; P <0.01) and DFS (HR: 4.2; 95% CI: 1.7-10.3; P <0.01).Conclusions: To our knowledge, this is the first study to demonstrate that tumor stromal VEGF-A expression is a valuable prognostic indicator of BCSS and DFS at diagnosis and can therefore be used to stratify IBC patients into low-risk and high-risk groups for death and relapses. High levels of tumor stromal VEGF-A may be useful for identifying IBC patients who will benefit from anti-angiogenic treatment. © 2012 Arias-Pulido et al.; licensee BioMed Central Ltd.

Chaher N.,Center Pierre et Marie Curie | Arias-Pulido H.,University of New Mexico | Terki N.,Center Pierre et Marie Curie | Qualls C.,University of New Mexico | And 4 more authors.
Breast Cancer Research and Treatment | Year: 2012

Inflammatory breast cancer (IBC) shows a high incidence in Tunisia and Egypt but epidemiological and molecular characteristics have not been described in Algeria. We compared 117 IBC and 59 non-IBC locally advanced breast cancers (LABC), for estrogen and progesterone receptors, HER2, and EGFR protein expression by immunohistochemistry, and HER2 gene amplification by chromogenic in situ hybridization. Demographic, clinico-pathological, and molecular variables were compared with chi-square and Fisher's exact tests to test for significance (P < 0.05, two-tailed). Overall survival (OS) and disease-free survival (DFS) were plotted using Kaplan-Meier curves and compared using the log-rank test. Tumor emboli were detected in 77% of IBC. Palpable masses were found in all LABC but only in 32% of IBC (P < 0.001). Recurrences were higher in LABC than in IBC (48 vs. 35%; P = 0.14) but OS was worse in IBC (68 vs. 71%; P = 0.06). There were no significant differences between IBC and LABC by demographics or by clinico-pathological parameters. The majority of IBC and LABC tumors were luminal A (62 and 64%), followed by basal (∼18%, each), triple negative (∼18%, each), and HER2+ (∼10%, each) subtypes. In multivariate analyses, grade was associated with worse OS (P = 0.04), and DFS (P < 0.001) in IBC; chemo- and radio-therapy were associated with improved OS and DFS, respectively (P < 0.05 for each) in LABC. In conclusion, IBC in Algeria shows similar characteristics to IBC described for Egypt and Tunisia with subtle molecular differences. Current therapeutic treatments were not very effective in this population and new approaches are much needed. © 2011 Springer Science+Business Media, LLC.

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