Nabih Azar
University of Paris
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Publication
Featured researches published by Nabih Azar.
Journal of Clinical Oncology | 2001
Carole Soussain; Florence Suzan; Khê Hoang-Xuan; Nathalie Cassoux; Vincent Levy; Nabih Azar; Coralie Belanger; Eddine Achour; Vincent Ribrag; Sophie Gerber; Jean-Yves Delattre; and Véronique Leblond
PURPOSE To assess the feasibility and efficacy of intensive chemotherapy with hematopoietic stem-cell rescue (IC + HCR) in patients with refractory or recurrent primary CNS lymphoma (PCNSL) or intraocular lymphoma (IOL). PATIENTS AND METHODS IC consisted of thiotepa 250 mg/m(2)/d days -9 through -7, busulfan 10 mg/kg (total dose) days -6 through -4, and cyclophosphamide 60 mg/kg/d days -3 and -2. Intravenous clonazepam 2 mg/d was given prophylactically from the day before initiation of busulfan therapy to the day after completion of busulfan therapy. Patients with refractory or recurrent PCNSL underwent IC + HCR only if they were chemosensitive to two cycles of salvage treatment with cytarabine (2 g/m(2)/d days 2 through 5 and 50 mg/m(2)/d days 1 through 5 in a 12-hour infusion) and etoposide (VP-16; 200 mg/m(2)/d days 2 through 5) (CYVE). Patients with IOL refractory to high-dose methotrexate (MTX) and cytarabine entered the IC + HCR program directly. RESULTS Twenty-two patients (10 with relapses, 12 with refractory disease) were enrolled. Twenty patients entered the IC + HCR program: twelve entered after CYVE treatment, seven entered directly, and one had previously been retreated with high-dose MTX. Before IC, eight patients were in complete remission (CR), four were in partial remission (PR), one had stable disease, and seven had refractory disease. After IC + HCR, 16 patients entered CR, two remained in PR, one had stable disease, and one had disease progression. Fourteen patients remained alive (median follow-up time, 41.5 months). The overall probability of survival at 3 years was 63.7%. After IC, that probability was 60% and the 3-year probability of event-free survival was 53%. Seven patients had neurologic adverse events during the entire procedure. CONCLUSION IC + HCR proved feasible and effective in patients with refractory or recurrent PCNSL or IOL. The entire procedure seemed to be most toxic in patients > or = 60 years. A prospective multicenter study is ongoing.
Science Translational Medicine | 2010
Sébastien Maury; François M. Lemoine; Yosr Hicheri; Michelle Rosenzwajg; Cécile Badoual; Mustapha Cherai; Jean-Louis Beaumont; Nabih Azar; Nathalie Dhedin; Anne Sirvent; Agnès Buzyn; Marie-Thérèse Rubio; Stéphane Vigouroux; Olivier Montagne; Dominique Bories; Françoise Roudot-Thoraval; Jean-Paul Vernant; Catherine Cordonnier; David Klatzmann; José L. Cohen
Immunological effects of donor lymphocyte infusion for treatment of recurrent malignancy after allogeneic hematopoietic cell transplantation can be enhanced by depleting T regulatory cells in the infused cells and in the recipient. Regulatory T Cells Interfere with Graft-Versus-Tumor Effects Patients search for organ donors who are close genetic matches to avoid immune reactions. But sometimes a little immune activation is a good thing. Hematopoietic stem cells in the form of bone marrow are often used to treat blood cancers, and the donated cells not only engraft in bone to provide a source of healthy blood cells but also contain T cells that attack and destroy any remaining cancerous cells. This graft-versus-tumor effect is also harnessed when such patients suffer a relapse and donor T cells are infused into the patient. These infusions often fail to quell the malignancy, however. The reason for failure, Maury et al. have now shown, is that the donor cells can often include regulatory T cells (Tregs), a class of T cells that dampens the immune response. Removing these cells before the infusion markedly improved the graft-versus-tumor effect and the patients’ survival. The beneficial graft-versus-tumor effect of transplantation can be accompanied by the not-so-desirable graft-versus-host disease. Like the transplanted T cells that perceive cancer cells as foreign, T cells can also attack the host’s skin, liver, intestinal lining, and other internal organs—a condition that is serious but can be treated. The authors of this study used the presence of graft-versus-host disease as a sign that there were active, functioning T cells that also provided graft-versus-tumor effects. They treated 17 patients with relapsed blood cancer who had previously received an infusion of lymphocytes and had neither clinical manifestations of graft-versus-host disease nor control of their malignancy. After receiving a new infusion of lymphocytes from which the Tregs had been removed, two of the patients developed graft-versus-host disease for the first time in their transplant history. Hypothesizing that this low rate of response was a result of Treg cells present in the recipient, they treated four of the patients who needed more infusions with the same Treg-depleted cells but now infused them immediately after recipient Tregs were eliminated with lymphopdepletive chemotherapy. These four patients, all of whom had Hodgkin’s lymphoma, reacted to the infused cells by developing graft-versus-host disease, a sign that the infused cells were likely attacking the tumor cells as well. When the whole group was assessed 1 year after treatment, the patients who had experienced a graft-versus-host reaction after cell infusion were found to have survived longer, likely a result of successful immune control of the cancer cells by the infused Treg-depleted lymphocytes. This preliminary study shows that depleting donor lymphocytes of inhibitory regulatory T cells can be a safe and effective way to free active T cells from inhibition so that they can fight cancer cells in the recipient. Further studies are needed, but this seemingly inappropriate encouragement of immune reactions in transplant recipients may prove a boon to patients with blood cancers. Donor T cells play a pivotal role in the graft-versus-tumor effect after allogeneic hematopoietic stem cell transplantation. Regulatory T cells (Tregs) may reduce alloreactivity, the major component of the graft-versus-tumor effect. In the setting of donor lymphocyte infusion after hematopoietic stem cell transplantation, we postulated that Treg depletion could improve alloreactivity and likewise the graft-versus-tumor effect of donor T cells. The safety and efficacy of Treg-depleted donor lymphocyte infusion was studied in 17 adult patients with malignancy relapse after hematopoietic stem cell transplantation. All but one had previously failed to respond to at least one standard donor lymphocyte infusion, and none had experienced graft-versus-host disease. Two of the 17 patients developed graft-versus-host disease after their first Treg-depleted donor lymphocyte infusion and experienced a long-term remission of their malignancy. Four of the 15 patients who did not respond after a first Treg-depleted donor lymphocyte infusion received a second Treg-depleted donor lymphocyte infusion combined with lymphodepleting chemotherapy aimed to also eliminate recipient Tregs. All four developed acute-like graft-versus-host disease that was associated with a partial or complete and durable remission. In the whole cohort, graft-versus-host disease induction through Treg depletion was associated with improved survival. These results suggest that Treg-depleted donor lymphocyte infusion is a safe, feasible approach that induces graft-versus-host or graft-versus-tumor effects in alloreactivity-resistant patients. In patients not responding to this approach, the combination of chemotherapy-induced lymphodepletion of the recipient synergizes with the effect of Treg-depleted donor lymphocyte infusion. These findings offer a rational therapeutic approach for cancer cellular immunotherapy.
The Lancet | 2000
Jean Gabarre; Nabih Azar; Brigitte Autran; Christine Katlama; Véronique Leblond
We describe the results of autologous haematopoietic stem-cell transplantation in eight patients with HIV-1-associated lymphoma. Collection and grafting of stem cells is feasible and this treatment seems appropriate in chemotherapy-sensitive HIV-1-associated lymphoma.
Transfusion | 2011
Stéphanie Nguyen; Vivien Béziat; Françoise Norol; Madalina Uzunov; Hélène Trébéden-Nègre; Nabih Azar; Ali Boudifa; Dominique Bories; Patrice Debré; Jean-Paul Vernant; Vincent Vieillard; Nathalie Dhedin
BACKGROUND: Allogeneic donor natural killer (NK)‐cell infusion (NK‐DLI) is a promising immunotherapy for patients with hematologic disorders.
Transfusion | 2010
Hélène Trébeden-Nègre; Michelle Rosenzwajg; Marie-Laure Tanguy; François Lefrère; Nabih Azar; Farhad Heshmati; Ramdane Belhocine; Jean-Paul Vernant; David Klatzmann; Françoise Norol
BACKGROUND: Some patients demonstrate delayed recoveries after autologous hematopoietic stem cell transplantation despite infusion of an adequate number of CD34+ cells/kg and clinically stable status. Factors considered being possible predictors of this outcome in this context were explored.
Leukemia | 2014
Sébastien Maury; Michelle Rosenzwajg; Redjoul R; Marcais A; Aliénor Xhaard; Mustapha Cherai; Cabanne L; Guillaume Churlaud; Felipe Suarez; Socié G; Gregoire L; Debbache K; Claude Bernard; Jean-Louis Beaumont; Nabih Azar; Olivier Boyer; Roudot-Thoraval F; José L. Cohen; Catherine Cordonnier; François M. Lemoine; David Klatzmann
Lymphodepletion followed by infusion of suicide gene-transduced donor lymphocytes to safely enhance their antitumor effect: a phase I/II study
Haematologica | 2015
Magali Le Garff-Tavernier; Linda Herbi; Christophe de Romeuf; Nabih Azar; Damien Roos-Weil; Patrick Bonnemye; Rémi Urbain; Véronique Leblond; Hélène Merle-Béral; Vincent Vieillard
Waldenstrom macroglobulinemia (WM) is a rare form of lymphoma characterized by an infiltration of lymphoplasmacytic cells in bone marrow and immunoglobulin M monoclonal gammopathy.[1][1] Despite the introduction of several therapeutic approaches, WM remains incurable.[2][2] Therefore, a better
British Journal of Haematology | 2012
Alexa S. Green; Sophie Grabar; Micheline Tulliez; Sophie Park; Chadi Al-Nawakil; Nicolas Chapuis; Nathalie Jacque; Lise Willems; Nabih Azar; Norbert Ifrah; Francois Dreyfus; Catherine Lacombe; Patrick Mayeux; Didier Bouscary; Jerome Tamburini
phopshatidylserine exposure, which may be reached only during acute crisis and not in patients undergoing RCE as a preventive therapy. In conclusion, using a triple Annexin V/CD41/GPA staining that enabled us to detect and quantify both platelets-derived and erythrocytes-derived MPs in the same sample, we confirmed that the MPs from both origins are clearly increased in SCD patients. Moreover, we observed a selective reduction in the number of erythrocytes-derived MPs after RCE, while the number of platelets-derived MPs and total MPs remained unchanged. This selective reduction of erythrocytes-derived MPs could contribute to the benefit of this procedure as a prevention of stroke in SCD patients.
Journal of Clinical Apheresis | 2018
Nabih Azar; Maya Ouzegdouh; Sylvain Choquet; Véronique Leblond
Plerixafor (Mozobil) in combination with granulocyte colony‐stimulating factor (G‐CSF) has shown to increase mobilization of peripheral blood stem cells (PBSC) as compared to G‐CSF alone in patients undergoing autologous stem cell transplantation (ASCT). However, up to 25% of patients treated with G‐CSF alone still fail mobilization. Adding plerixafor to poor mobilizers allows to rescue these patients from mobilization failure and to reduce the number of apheresis sessions. The goal of this retrospective study was to capture the impact of plerixafor on treatment outcome and on apheresis department efficiency. The latter was measured in terms of time‐slots lost, that is, the number of apheresis sessions scheduled but not carried out due to poor mobilization, and the number of elective apheresis sessions performed for patients undergoing extracorporeal photopheresis (ECP). Hospital records of patients treated before and after introduction of plerixafor were collected and analyzed. With plerixafor, the mobilization failure rate dropped from 12% to 4% and the mean number of time‐slots lost per patient dropped from 1.39 to 0.89. Additional drug costs due to plerixafor were partially balanced by a reduction in apheresis sessions, resulting in an additional cost of 759€ per ASCT candidate. More importantly, with the use of plerixafor, the availability of time‐slots turned from erratic to predictable such that freed capacity could be dedicated to other apheresis procedures. As a result, the number of ECP sessions increased from 0 in 2005 to 685 sessions in 2014.
Haematologica | 2018
Meriem Ladli; Cyrielle Richard; Lilia Cantero Aguilar; Sarah Ducamp; Sabrina Bondu; Pierre Sujobert; Jerome Tamburini; Catherine Lacombe; Nabih Azar; Marc Foretz; Yael Zermati; Patrick Mayeux; Benoit Viollet; Frédérique Verdier
AMP-activated protein kinase (AMPK) is a heterotrimeric complex containing α, β, and γ subunits involved in maintaining integrity and survival of murine red blood cells. Indeed, Ampk α1−/−, Ampk β1−/− and Ampk γ1−/− mice develop hemolytic anemia and the plasma membrane of their red blood cells shows elasticity defects. The membrane composition evolves continuously along erythropoiesis and during red blood cell maturation; defects due to the absence of Ampk could be initiated during erythropoiesis. We, therefore, studied the role of AMPK during human erythropoiesis. Our data show that AMPK activation had two distinct phases in primary erythroblasts. The phosphorylation of AMPK (Thr172) and its target acetyl CoA carboxylase (Ser79) was elevated in immature erythroblasts (glycophorin Alow), then decreased conjointly with erythroid differentiation. In erythroblasts, knockdown of the α1 catalytic subunit by short hairpin RNA led to a decrease in cell proliferation and alterations in the expression of membrane proteins (band 3 and glycophorin A) associated with an increase in phosphorylation of adducin (Ser726). AMPK activation in mature erythroblasts (glycophorin Ahigh), achieved through the use of direct activators (GSK621 and compound 991), induced cell cycle arrest in the S phase, the induction of autophagy and caspase-dependent apoptosis, whereas no such effects were observed in similarly treated immature erythroblasts. Thus, our work suggests that AMPK activation during the final stages of erythropoiesis is deleterious. As the use of direct AMPK activators is being considered as a treatment in several pathologies (diabetes, acute myeloid leukemia), this observation is pivotal. Our data highlighted the importance of the finely-tuned regulation of AMPK during human erythropoiesis.