Place du pegfilgrastim en post autogreffe dans les hémopathies malignes avec étude des facteurs influençant la survie globale et la survie sans progression (étude rétrospective d'une cohorte de 733 autogreffes au CHU de Montpellier)

L'autogreffe occupe une place importante en consolidation des réponses lors des Iymphopathies chroniques. Sa généralisation a été possible grâce aux greffons de cellules souches périphériques et aux facteurs de croissance granulocytaire (G-CSF) qui réduisent la durée d'aplasie et ainsi le risque infectieux. Le pegflgrastim est un G-CSF dont la pharmacocinétique permet une injection unique contre environ une dizaine d'injections pour les G-CSF standards. Afin de comparer l'efficacité du pegfilgrastim (utilisé depuis 2005) par rapport aux G-CSF standards, nous avons analysé une série rétrospective de 733 autogreffes réalisées chez 604 patients entre 2000 et 2009, au CHU de Montpellier, pour des Iymphopathies chroniques. Puis, nous avons analysé l'impact sur la survie globale et la survie sans progression des facteurs présents à l'autogreffe. Comparé aux C-CSF standards, le pegfilgrastim réduit le taux de neutropénies fébriles (p=O,04), le taux de mucites sévères (p<O,01), leur durée (p<O,01), et la durée d'hospitalisation (p<0,01) mais n'améliore pas la durée de l'aplasie. Nous retrouvons les facteurs pronostiques classiques des pathologies concernées. De plus, le pegfilgrastim dans le groupe des myélomes semblerait améliorer la survie globale. Le bortezomib n'étant pas retrouvé comme facteur confondant, une hypothèse explicative serait la réduction, par le pegfilgrastim, des neutropénie fébriles et des mucites sévères (diminution de l'interleukine 6). C'est la plus grande série reflétant l'utilisation des G-CSF en post autogreffe. Malgré les limites d'une série rétrospective nos résultats sont comparables à la littérature. Nos résultats soulèvent plusieurs hypothèses à analyser dans un essai prospectif qui devra mesurer l'impact pharmaco-économique du pegfilgrastim.MONTPELLIER-BU Médecine UPM (341722108) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

PET Adapted Salvage Therapy for Advanced Hodgkin Lymphomas: Towards the Suppression of Positive Interim PET Unfavorable Prognosis? a Report of the Goelams Multicentric Phase 2 Trial LH2007

WOS:000368021800189International audience55th Annual Meeting and Exposition of the American-Society-of-Hematology - New Orleans, LA 201

PET Adapted Salvage Therapy for Advanced Hodgkin Lymphomas: Towards the Suppression of Positive Interim PET Unfavorable Prognosis? a Report of the Goelams Multicentric Phase 2 Trial LH2007

WOS:000368021800189International audience55th Annual Meeting and Exposition of the American-Society-of-Hematology - New Orleans, LA 201

BAFF and APRIL protect myeloma cells from apoptosis induced by interleukin 6 deprivation and dexamethasone.

International audienceIdentification of growth factors in neoplasias may be a target for future therapies by blocking either growth factor receptor interaction or the induced pathway. Using gene expression profiling, we identified overexpression of 2 receptors for a proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF) in malignant plasma cells compared with normal plasma cells. APRIL and BAFF are involved in a variety of tumor and autoimmune diseases, including B-cell malignancies. We confirmed the expression of BAFF and APRIL receptors (B-cell maturation antigen [BCMA], transmembrane activator and calcium modulator and cyclophilin ligand interactor [TACI], and BAFF-R) in a majority of 13 myeloma cell lines and in the purified primary myeloma cells of 11 patients. APRIL and BAFF were potent survival factors for exogenous cytokine-dependent myeloma cell lines and were autocrine growth factors for the RPMI8226 and L363 autonomously growing cell lines. These factors activated nuclear factor (NF)-kappaB, phosphatidylinositol-3 (PI-3) kinase/AKT, and mitogen-activated protein kinase (MAPK) kinase pathways and induced a strong up-regulation of the Mcl-1 and Bcl-2 antiapoptotic proteins in myeloma cells. BAFF or APRIL was also involved in the survival of primary myeloma cells cultured with their bone-marrow environment, and protected them from dexamethasone (DEX)-induced apoptosis. Finally, the serum levels of BAFF and APRIL were increased about 5-fold in patients with multiple myeloma (MM) as compared with healthy donors. Altogether, these data suggest that APRIL/BAFF inhibitors may be of clinical value in MM

Cost-effectiveness of Pegfilgrastim versus Filgrastim after high-dose chemotherapy and autologous stem cell transplantation in patients with lymphoma and myeloma

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Granulocyte-macrophage colony-stimulating factor potentiates rituximab in patients with relapsed follicular lymphoma: results of a phase II study.

International audiencePURPOSE: We hypothesized that granulocyte-macrophage colony-stimulating factor (GM-CSF) could potentiate the clinical activity of rituximab given its individual and cooperative effects on Fc gamma RIIa- and Fc gamma RIIIa-expressing cells. A phase II clinical study combining GM-CSF and rituximab was initiated in patients with relapsed follicular lymphoma (FL) to determine the clinical and biologic responses, as well as safety of the combination. PATIENTS AND METHODS: Thirty three patients with relapsed FL were treated with GM-CSF 5 microg/kg/d on days 1 to 8 and rituximab 375 mg/m(2) on day 5 of each 21-day cycle for four cycles. Clinical response and tolerability were examined according to international criteria. Biologic monitoring included evaluation of immune cells involved in rituximab activity. RESULTS: Of 33 evaluated patients, a 70% overall response rate (complete response plus complete response unconfirmed, 45%) and a median progression-free survival (PFS) of 16.5 months were achieved. Outcome was influenced by the quality of response and the Follicular Lymphoma International Prognostic Index (FLIPI), where low- and intermediate-risk FLIPI groups were associated with significantly better PFS. After treatment there was a significant increase in granulocyte and monocyte counts. Examination of dendritic cell response showed an overall increase in plasmacytoid dendritic cells, especially in non-complete response patients, after treatment. Addition of GM-CSF did not impair tolerance to rituximab, and adverse events were rare and mild. DISCUSSION: GM-CSF plus rituximab results in high response rates, along with a tolerable safety profile in patients with relapsed or progressive FL. The improved efficacy over rituximab monotherapy may be due to increases seen in monocyte, granulocyte, and dendritic cell populations

Increased plasma-immune cytokines throughout the high-dose melphalan-induced lymphodepletion in patients with multiple myeloma: a window for adoptive immunotherapy.

International audienceHigh-dose melphalan (HDM) followed by autologous stem cell transplantation (ASCT) is a standard treatment for patients with multiple myeloma. However, lymphocyte reconstitution is impaired after HDM. Recent work has suggested that the lymphopenia period occurring after various immunosuppressive or chemotherapy treatments may provide an interesting opportunity for adoptive antitumor immunotherapy. The objective of this study was to determine an immunotherapy window after HDM and ASCT, evaluating T cell lymphopenia, and measuring circulating immune cytokine concentrations in patients with multiple myeloma. The counts of T cell subpopulations reached a nadir at day 8 post-ASCT (day 10 post-HDM) and recovered by day 30. IL-6, IL-7, and IL-15 plasma levels increased on a median day 8 post-ASCT, respectively, 35-fold, 8-fold, and 10-fold compared with pre-HDM levels (p < or = 0.05). The increases in IL-7 and IL-15 levels were inversely correlated to the absolute lymphocyte count, unlike monocyte or myeloid counts. Furthermore, we have shown that CD3 T cells present in the ASC graft are activated, die rapidly when they are cultured without cytokine in vitro, and that addition of IL-7 or IL-15 could induce their survival and proliferation. In conclusion, the early lymphodepletion period, occurring 4-11 d post-HDM and ASCT, is associated with an increase of circulating immune cytokines and could be an optimal window to enhance the survival and proliferation of polyclonal T cells present in the ASC autograft and also of specific antimyeloma T cells previously expanded in vitro