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C Chabannon

Publications and source records attributed to C Chabannon.

At least 19 recordsLinked to original sources
PubMed2006

A phase II trial of rituximab as adjuvant to intensive sequential chemotherapy in patients under 60 years with untreated poor-prognosis diffuse large B-cell lymphoma.

The potential benefit of rituximab as adjuvant to high-dose therapy (HDT) has been investigated in patients under 60 years with poor-risk (age-adjusted international prognostic index at 2-3) CD20+ diffuse large B-cell lymphoma (DLBCL). The treatment consisted of four cycles of high-dose CEOP (cyclophosphamide, epirubicin, vincristine, prednisone), plus etoposide and cisplatin during the two last cycles. Peripheral blood stem cells were collected after cycle 1, and reinfused after cycles 3 and 4. Four weekly rituximab infusions were subsequently delivered. Among the 36 patients included, 30 could complete chemotherapy schedule, and 24/36 received rituximab. A complete response occured in 26/36 patients (72%). With a median follow-up of 30 months, the estimated 5-year overall survival (OS) and event-free survival (EFS) rates (mean +/- s.d.) were 65 +/- 16 and 63 +/- 15%, respectively. For the 24 patients who received both chemotherapy and rituximab, the estimated 5-year OS and EFS rates were 86 +/- 14 and 82 +/- 15%. These data suggest that rituximab after HDT is feasible. Both complete remission rate and survival curves compare favorably with the poor outcome usually observed in high-risk DLBCL patients managed with HDT without rituximab.

Adult↗
PubMed2006

Postoperative serum proteomic profiles may predict metastatic relapse in high-risk primary breast cancer patients receiving adjuvant chemotherapy.

A total of 30-50% of early breast cancer (EBC) patients considered as high risk using standard prognostic factors develop metastatic recurrence despite standard adjuvant systemic treatment. A means to better predict clinical outcome is needed to optimize and individualize therapeutic decisions. To identify a protein signature correlating with metastatic relapse, we performed surface-enhanced laser desorption/ionization-time of flight mass spectrometry profiling of early postoperative serum from 81 high-risk EBC patients. Denatured and fractionated serum samples were incubated with IMAC30 and CM10 ProteinChip arrays. Several protein peaks were differentially expressed according to clinical outcome. By combining partial least squares and logistic regression methods, we built a multiprotein model that correctly predicted outcome in 83% of patients. The 5-year metastasis-free survival in 'good prognosis' and 'poor prognosis' patients as defined using the multiprotein index were strikingly different (83 and 22%, respectively; P<0.0001, log-rank test). In a multivariate Cox regression including conventional pathological factors and multiprotein index, the latter retained the strongest independent prognostic significance for metastatic relapse. Major components of the multiprotein index included haptoglobin, C3a complement fraction, transferrin, apolipoprotein C1 and apolipoprotein A1. Therefore, postoperative serum protein pattern may have an important prognostic value in high-risk EBC.

Adult↗
PubMed2005

rhG-CSF does not affect the phenotype of adult donor peripheral blood NK cells.

Considerable evidence in preclinical models as well as in human transplantation now suggests that donor-derived natural killer (NK) cells can contribute to alloimmune recognition of recipient residual tumour cells. This makes the NK cell population an attractive target for in vitro or in vivo manipulations, in order to improve the antitumour effect of allogeneic transplantation. However, conditions in which allogeneic donor cells are collected vary; several reports have emphasised the different phenotypic and functional properties of T cells derived from marrow, cord blood or mobilised peripheral blood grafts; others have demonstrated different clinical outcomes following blood or marrow transplantation after myeloablative conditioning regimens. NK cells have been examined in this setting; the availability of new tools to study the expression of a variety of surface antigens that are involved in the control of NK cell activity offered us an opportunity to extensively characterise the phenotypic properties of NK cells from donors, before and after administration of pharmacological doses of rhG-CSF used for haematopoietic progenitor mobilisation. Our study suggests that rhG-CSF does not reproducibly alter blood NK cell phenotype in normal individuals, and thus that donor-derived cells are fully equipped to exert their potential antitumour effect.

Blood Donors↗
PubMed2005

Early administration of recombinant erythropoietin improves hemoglobin recovery after reduced intensity conditioned allogeneic stem cell transplantation.

The use of recombinant human erythropoietin (rHuEPO) has been controversial after myeloablative allogeneic Stem cell transplantation (allo-SCT). Reduced intensity conditioning regimens (RIC) offer a novel approach that might translate into a different profile of erythropoietic recovery. We treated 20 consecutive patients with rHuEPO early after matched sibling RIC allo-SCT. Conditioning included fludarabine, busulfan and antithymocyte globulin. EPO treatment was analyzed in terms of toxicity, impact on the frequency of Red blood cell transfusions (RBCT) and kinetics of Hemoglobin recovery within the 60 days post-allo-SCT. Results were compared with 27 matched patients who did not receive rHuEPO. In the first 2 months after allo-SCT all patients receiving rHuEPO (100%) achieved an Hb level > 11 g/dl at a median of 30 (15-35) days post-allo-SCT, as compared to only 63% of the patients not receiving rHuEPO (P = 0.007) at a median of 35 (20-55) days (P = 0.03). A total of 70% (95% CI, 50-90) of rHuEPO patients maintained an Hb over 11 g/dl in the second month as compared to only 19% (95% CI, 4-34) in the other group (P = 0.0004). For patients receiving RBCT, the use of rHuEPO was associated with a trend towards reduced RBCT requirements. This pilot study suggests a potential benefit of early administration of rHuEPO after RIC allo-SCT on early erythropoietic recovery.

Adult↗
PubMed2005

Expression and recombination of the EGFP and EYFP genes in lentiviral vectors carrying two heterologous promoters.

BACKGROUND: Expressing two genes in the progeny of stem and progenitor cells that are transduced with a unique viral vector is desirable in certain situations. We tested the ability of two lentiviral vectors to transduce human cells of hematopoietic origin and concomitantly express two reporter genes, either EGFP (enhanced green fluorescent protein) and DsRed2, or EGFP and EYFP (enhanced yellow fluorescent protein), from two internal promoters. METHODS: The vectors were generated from the pTRIP deltaU3 EF1alpha EGFP lentiviral vector. Following transduction of hematopoietic and non-hematopoietic cell lines, we performed FACS, PCR and Southern blot analyzes to quantify transduction, integration efficiencies and size of integrated lentiviral vectors, respectively. RESULTS: The detection of DsRed2 fluorescence appeared unexpectedly low in human cells of hematopoietic origin. Alternatively, a modification in the flow cytometry assay allowed us to distinguish between the two overlapping fluorescence signals emitted by EGFP and EYFP, when transduced cells were excited with a 488-nm laser beam. However, the low frequency of double-positive EGFP+ EYFP+ cells, and the existence of single-positive, mostly EGFP- EYFP+, cells, prompted us to search for recombinations in the vector sequence. Southern blotting of DNA obtained from transduced cells indeed demonstrated that recombination had occurred between the two closely related EGFP and EYFP sequences. DISCUSSION: These observations suggest that recombination occurred within the EGFP and EYFP genes, which differ by only four amino acids. We conclude that the insertion of two highly homologous sequences into a lentiviral backbone can favor recombination.

Cell Line, Tumor↗
PubMed2004

Autologous stem cell transplantation for acute myelogenous leukemia in first complete remission: a 6-year follow-up study of 101 patients from a single institution.

The objective of the study was to assess the long-term outcome and impact of stem cell source in patients with acute myelogenous leukemia (AML) who received ASCT in first complete remission (CR). A total of 101 patients (median age 46 years) were included in the study. Cytogenetic categories distribution was: favorable: 18%, intermediate: 42%, and unfavorable: 7%. More than one induction course was needed for CR in 21% of patients. In all, 78% of patients had received at least one course of high-dose ara-C before autologous stem cell transplantation (ASCT). Bone marrow (n=58) or peripheral blood stem cells (PBSC) (n=43) transplantation was performed at a median of 3.5 months from CR. Hematologic recovery and hospitalization duration were significantly reduced in the PBSC group. No toxic death was recorded in this group. The median follow-up of survivors is 67 months (range: 15-183). The 6-year survival, disease-free survival (DFS), and relapse probabilities are 44%, 38%, and 54%, respectively. The presence of a favorable karyotype and the use of PBSC are independently associated to better survival, and DFS by multivariate analysis. Our results confirm that long-term DFS can be achieved with high-dose chemotherapy and ASCT in patients with AML. They show that use of PBSC is associated to very low mortality rate and acceptable morbidity and contributes to an improvement of autotransplant results.

Adolescent↗
PubMed2004

Decreased RBCTs after reduced intensity conditioning allogeneic stem cell transplantation: predictive value of prior Hb level.

BACKGROUND: RBCT (RBCT) requirements of stem cell transplant (SCT) recipients are often substantial and may be related to transplant type. STUDY DESIGN AND METHODS: An analysis was done of RBCT requirements and Hb recovery kinetic in the first 60 days after HLA-identical sibling allogeneic SCT in a series of 110 consecutive patients treated for various malignant diagnoses. Patients were prepared with either an antithymocyte globulin (ATG) and reduced intensity chemotherapy-based conditioning (RIC) (n=64) or a myeloablative conditioning regimens (MAC; n=46). Patients received marrow (n=64) or PBPCs (n=46). RESULTS: Overall, intensity of conditioning regimen (RIC vs. MAC; p=0.0005) and graft source (PBPC vs. marrow; p<0.0001) independently predicted RBCT requirements. Hb recovery was accelerated after RIC when compared to MAC allo-SCT (p=0.02). In RIC patients, RBCTs were inversely correlated to Hb level before conditioning (p<0.0001) and the dose of ATG (p=0.009). Moreover, Hb level before allo-SCT significantly influenced Hb recovery kinetic after RIC but had no impact on RBCT requirements and Hb recovery after MAC. CONCLUSION: Thus, RIC conditioning creates a different pattern of erythropoiesis recovery as compared to a MAC regimen and suggest a need for studies aimed at further reducing RBCT and accelerating Hb recovery.

Adolescent↗
PubMed2003

Preclinical evaluation of an automated closed fluid management device: Cytomate, for washing out DMSO from hematopoietic stem cell grafts after thawing.

Infusion of dimethylsulfoxide (DMSO) contained in cryopreserved and thawed hematopoietic stem cell (HSC) grafts is frequently associated with mild or moderate adverse reactions, and occasionally with more severe events including neurological symptoms. The severity of these complications is related to the amount of residual DMSO. We evaluated a recently available, closed, automated and 'cgmp (current good manufacturing practice) compliant' device (CytoMate) for its ability to wash out DMSO at the expense of a limited loss of viable CD34(+) cells. A total of 16 procedures were carried out with 39 blood HSC bags intended for destruction. Mean amounts of DMSO for each cellular product (one, two or three bags) were between 12.2 and 39.6 g before thawing; after the washing procedure, residual DMSO quantities were between 0.1 and 3.7 g. When set up to reproducibly allow for a more than 96% elimination of DMSO, processing of thawed cells with the CytoMate cell processor resulted in a mean recovery of viable total cells, CD34(+) cells and lymphocyte subsets above 60%. We conclude that this simple and efficient washing technique is suitable for routine processing of HSC grafts. Clinical studies will demonstrate whether a reduction in the incidence of adverse effects associated with DMSO infusion is observed.

Automation↗
PubMed2003

Occult tumor cell contamination in patients with stage II/III breast cancer receiving sequential high-dose chemotherapy.

The purpose of this study was to evaluate the presence of micrometastatic cells in the apheresis products from patients with breast cancer, and also to determine if repeated infusion of contaminated products had any clinical impact. A total of 94 patients with high-risk breast cancer were enrolled in a prospective single center study to evaluate the use of dose-intensified chemotherapy (doxorubicine 75 mg/m(2) and cyclophosphamide 3000 or 6000 mg/m(2) for four cycles) with repeated (x 2) stem cell reinfusion. All women were monitored for the presence of metastatic cells in aphereses, collected after first course of intensive chemotherapy, and following additional mobilization with rhG-CSF. Epithelial cells were screened with monoclonal antibodies directed to cytokeratin. Eight of the 94 patients had detectable tumor cells in one or several aphereses collected after intensive chemotherapy; this was unrelated to other tumor characteristics, including size, histology, Scarff Bloom and Richardson (SBR) grading (presence or absence of hormone receptors). Hemato-poietic reconstitution was similar in the cells from these eight patients, and in the total patient population. Three of these eight patients relapsed. This study has confirmed that contamination of apheresis products remains a rare event, which does not seem to affect clinical evolution, even when reinfused into the patient.

Adult↗
PubMed2003

Functional characterization of human CD34+ cells that express low or high levels of the membrane antigen CD111 (nectin 1).

Nectins are recently described adhesion molecules that are widely expressed on many tissues, including the hematopoietic tissue. Nectin 1 (CD111) is expressed on a higher proportion of mobilized peripheral blood (mPB) than cord blood (CB) CD34+ cells, and of CD34+/CD38+ cells when compared with CD34+/CD38- cells. We studied functional properties of human CB and mPB CD34+ cells that express low or high levels of CD111. CD34+/CD111(dim) cells contain a higher proportion of cells in G0/G1 phase than CD34+/CD111(bright) cells. CD34+/CD111(bright) cells contain more erythroid progenitors: CFU-E, than their counterparts, which on the opposite contain more HPP-CFC. Limiting dilution analyses demonstrate a higher frequency of immature progenitors: cobblestone-area colony-forming cells, CD34+/CD111(dim) than in CD34+/CD111(bright) cells. In vitro differentiation assays demonstrate a higher frequency of B-, T- and dendritic-cell precursors, but less NK-cell precursors in CD34+/CD111(dim) cells. Evaluation of engraftment in NOD-SCID mice shows that SCID repopulating cells are more frequent among mPB CD34+/CD111(dim) cells. Liquid culture of CD34+/CD111(dim) cells with erythropoietin shows that CD111 expression increases simultaneously with CD36, following CD71 and before glycophorin A expression. In conclusion, immature human hematopoietic progenitors express low levels of CD111 on their surface. During erythroid differentiation CD34+ cells acquire higher levels of the CD111 antigen.

Animals↗
PubMed2002

Randomized, controlled, dose-range study of Ro 25-8315 given before and after a high-dose combination chemotherapy regimen in patients with metastatic or recurrent breast cancer patients.

PURPOSE: To evaluate the safety, pharmacokinetics, and efficacy of three different dose levels of pegylated granulocyte colony-stimulating factor (Ro 25-8315) on progenitor cell mobilization and hematologic recovery in cancer patients. PATIENTS AND METHODS: Breast cancer patients (n = 36) were randomly assigned to receive before (part I) and after (part II) chemotherapy either a single-dose injection of Ro 25-8315 (20 microg/kg, n = 9; 60 microg/kg, n = 9; 100 microg/kg, n = 10) or a standard daily dose of filgrastim (part I, 10 microg/kg/d; part II, 5 microg/kg/d) (control group, n = 8). RESULTS: Overall, Ro 25-8315 was well tolerated. In part I, more progenitor cell mobilization was observed with Ro 25-8315 100 microg/kg. The peak of circulating CD34(+) cells was obtained at day +5 in the four groups, and the absolute neutrophil count (ANC) returned to less than 20 x 10(9)/L by day +15. In part II, high levels of circulating CD34(+) cells (> 20 cells/microL) were obtained in all four groups. The chemotherapy-induced neutropenia (< 1 x 10(9)/L) was similar in the four groups. Ro 25-8315 100 microg/kg was more effective than filgrastim in reducing the number of patients with an ANC less than 0.5 x 10(9)/L on day +12 after chemotherapy. CONCLUSION: A single injection of Ro 25-8315 100 microg/kg might be the optimal dose for steady-state peripheral-blood progenitor cell mobilization. A single injection of 20, 60, or 100 microg/kg could be as efficient as daily administration of filgrastim to correct chemotherapy-induced cytopenia. The optimal dose of Ro 25-8315 should be determined according to the planned chemotherapy regimen.

Adult↗
PubMed2002

Aiolos and Ikaros: regulators of lymphocyte development, homeostasis and lymphoproliferation.

Aiolos and Ikaros encode hemopoietic-specific zinc finger transcription factors that are important regulators of lymphocyte differentiation. Aiolos and Ikaros play a critical role in regulating B and T cell development. Gene targeting studies in mice have shown that inactivation of Ikaros family proteins leads to a complete absence of T, B, NK and dendritic cells, whereas a reduction of Ikaros activity induce hyperproliferation and lymphomas. Aiolos knock-out mice have quantitatively normal lymphoid cells but have chronically activated B cells producing autoantibodies and develop lymphomas with increased frequency. These proteins are involved in the control of gene expression and, associated to nuclear complexes, participate in nucleosome remodeling. This protein family governs cell fate decisions and regulates homeostasis through complex isoforms expression and dimerization. Changes in this regulatory network may reflect differentiation and proliferation adjustments made in lymphoid progenitors and precursors. The direct involvement of aberrant Ikaros protein expression in human hematological oncogenesis, although suggested by several studies, remains to be settled at the genomic level. These points will be discussed in the present review.

Amino Acid Sequence↗
PubMed2002

Modulations of dose intensity of doxorubicin and cyclophosphamide in association with G-CSF and peripheral blood stem cells in adjuvant chemotherapy for breast cancer: comparative evaluation of completion and safety of three intensive regimens.

The aim of this study was to evaluate and to compare in terms of toxicity the modulations of dose intensity of cyclophosphamide and doxorubicin in adjuvant chemotherapy for high-risk breast cancer. Four cycles of sequential high-dose chemotherapy with doxorubicin and cyclophosphamide (AC), supported with G-CSF and peripheral blood stem cells (PBSC) were administered to 81 women. Three successive cohorts were studied: doxorubicin (75 mg/m(2)) + cyclophosphamide (3000 mg/m(2)) every 21 days (group 1), doxorubicin (75 mg/m(2)) + cyclophosphamide (3000 mg/m(2)) every 15 days (group 2), and doxorubicin (75 mg/m(2)) + cyclophosphamide (6000 mg/m(2)) every 21 days (group 3). Seventy-five patients received four cycles of treatment with a total of 310 cycles administered. The received dose intensity of doxorubicin was higher in group 2 and that of cyclophosphamide was lower in group 1 than in the other two groups. Hematological and extra-hematological toxicities, as well as the number and duration of hospitalizations for toxicity, were significantly higher in group 3. We conclude that the group 3 regimen is associated with toxicities comparable to autologous transplantation. Increasing dose intensity of doxorubicin and cyclophosphamide is feasible in an outpatient setting and safe in groups 1 and 2 with the support of hematopoietic factor and PBSC.

Adult↗
PubMed2002

Intensive sequential dose dense chemotherapy with stem cell support as first-line treatment in advanced ovarian carcinoma: a phase II study.

From August 1995 to December 1997, 15 patients with stage III-IV ovarian cancer were treated with outpatient intensive chemotherapy with G-CSF and stem cell support. The first cycle consisted of cyclophophamide IV 6 g/m(2); second, third, fourth and fifth paclitaxel 250 mg/m(2) and the sixth and seventh carboplatin AUC 18. CD34(+) cells were collected after the first cycle and reinfused after completion of cycles 6 and 7. Fourteen patients had stage IIIc and one patient had stage IV disease with liver metastases. All patients underwent laparotomy to maximize tumor debulking. This was optimal in eight patients and suboptimal in seven patients. Second-look surgery was performed in 14 patients. All patients had macroscopic complete responses and 10 patients had complete histologic response. Median follow-up was 48 months (range, 20 to 62). Twelve patients had further progression at a median of 27 months (range, 9 to 42) and nine are alive, three without evidence of disease progression. This pilot study shows that dose-dense chemotherapy with paclitaxel and carboplatin is associated with low toxicity and may improve the outcome of patients with poor prognosis ovarian cancer.

Adult↗
PubMed2002

Features of large granular lymphocytes (LGL) expansion following allogeneic stem cell transplantation: a long-term analysis.

Large granular lymphocyte (LGL) proliferation typically follows a chronic course during which major features are cytopenia and immune abnormalities. Elevated numbers of LGL were reported in a few cases following allogeneic stem cell transplantation (allo-SCT). In this report, we present a retrospective analysis of LGL cases that occurred following allo-SCT in a cohort of 201 consecutive patients transplanted over a period of 7 years. Six cases were identified and LGL expansion occurred more frequently following a reduced fludarabine and anti-T lymphocyte globulin-based preparative regimen (4 cases/49), than after a conventional myeloablative regimen (2 cases/152). Expansion of LGL was seen between 3 and 15 months following allo-SCT. Hematopoiesis, with mild to severe cytopenia, was a favored target for LGL. Autoimmune manifestations including polyarthritis and hypergammaglobulinemia were also observed. LGL proliferation was observed in the context of chronic antigenic stimulation associated with recurrent viral infections especially CMV. Moreover, five out of these six high risk patients achieved a long-term complete remission concomitant or following LGL expansion. These data suggest that LGL might be a subset of effector lymphocytes which may participate to the graft-versus-tumor effect.

Adult↗
PubMed2002

Analysis of donor NK and T cells infused in patients undergoing MHC-matched allogeneic hematopoietic transplantation.

We retrospectively analyzed the percentages and absolute numbers of T cells, natural killer (NK) cells and NK cell subsets in cryopreserved samples of either bone marrow or blood non-T cell-depleted allogeneic MHC-matched hematopoietic grafts. Using flow cytometry, we found higher numbers of NK cells in aphereses than in bone marrow collections. We further investigated the distribution of NK cell subsets, defined by the cell surface expression of MHC class I-specific receptors, in these allogeneic grafts. The distribution of NK cell subsets from the two different origins were similar, with the exception of the CD158a/h(+) NK cell subset, whose size appeared to be smaller in bone marrow. The search for relations between the numbers of infused cells and post-transplantation events demonstrated that increasing numbers of infused T cells but not NK cells are related with decreased overall survival. Our study highlights the toxicity of infused T cells but not NK cells in allogeneic MHC-matched hematopoietic grafts. These data pave the way for further trials to investigate the effect of NK cell infusion in MHC-matched allogeneic transplantation, and in particular whether ex vivo NK cell expansion and activation may enhance the anti-tumoral effect of the procedure and decrease its morbidity.

Adolescent↗