References of "Beguin, Yves"
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See detailLow T-cell chimerism is not followed by graft rejection after nonmyeloablative stem cell transplantation (NMSCT) with CD34-selected PBSC.
Baron, Frédéric ULg; Baudoux, Etienne ULg; Frere, Pascale ULg et al

in Bone Marrow Transplantation (2003), 32(8), 829-34

We investigate the feasibility of CD34-selected peripheral blood stem cell (PBSC) transplantation followed by pre-emptive CD8-depleted donor lymphocyte infusions (DLI) after a minimal conditioning regimen ... [more ▼]

We investigate the feasibility of CD34-selected peripheral blood stem cell (PBSC) transplantation followed by pre-emptive CD8-depleted donor lymphocyte infusions (DLI) after a minimal conditioning regimen. Six patients with advanced hematological malignancies ineligible for a conventional myeloablative transplant (n=5) or metastatic renal cell carcinoma (n=1), and with an HLA-identical (n=4) or alternative (n=2) donor were included. The nonmyeloablative conditioning regimen consisted in 2 Gy TBI alone (n=4), 2 Gy TBI and fludarabine (RCC patient, n=1) or cyclophosphamide and fludarabine (patient who had previously received 12 Gy TBI, n=1). Post transplant immunosuppression was carried out with cyclosporin (CyA) and mycophenolate mofetil (MMF). Initial engraftment was achieved in all patients. One out of six patients (17%) experienced grade > or =2 acute GVHD only after abrupt cyclosporin discontinuation and alpha interferon therapy for life-threatening tumor progression. T-cell chimerism was 23% (19-30) on day 28, 32% (10-35) on day 100, 78% (49-95) on day 180 and 99.5% (99-100) on day 365. Three out of four patients who had measurable disease before the transplant experienced a complete response. We conclude that CD34-selected NMSCT followed by CD8-depleted DLI is feasible and preserves engraftment and apparently also the graft-versus-leukemia (GVL) effect. Further studies are needed to confirm this encouraging preliminary report. [less ▲]

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See detailT-cell reconstitution after unmanipulated, CD8-depleted or CD34-selected nonmyeloablative peripheral blood stem-cell transplantation.
Baron, Frédéric ULg; Schaaf-Lafontaine, Nicole ULg; Humblet-Baron, Stéphanie ULg et al

in Transplantation (2003), 76(12), 1705-13

BACKGROUND: We have previously shown that CD8 depletion or CD34 selection of peripheral blood stem cells (PBSC) reduced the incidence of acute graft-versus-host disease (GvHD) after nonmyeloablative stem ... [more ▼]

BACKGROUND: We have previously shown that CD8 depletion or CD34 selection of peripheral blood stem cells (PBSC) reduced the incidence of acute graft-versus-host disease (GvHD) after nonmyeloablative stem-cell transplantation (NMSCT). In this study, we analyze the effect of CD8 depletion or CD34 selection of the graft on early T-cell reconstitution. METHODS: Nonmyeloablative conditioning regimen consisted in 2 Gy total-body irradiation (TBI) alone, 2 Gy TBI and fludarabine, or cyclophosphamide and fludarabine. Patients 1 to 18 received unmanipulated PBSC, patients 19 to 29 CD8-depleted PBSC, and patients 30 to 35 CD34-selected PBSC. RESULTS: T-cell counts, and particularly CD4+ and CD4CD45RA+ counts, remained low the first 6 months after nonmyeloablative stem-cell transplantation (NMSCT) in all patients. CD34 selection (P<0.0001) but not CD8 depletion of PBSC significantly decreased T-cell chimerism. Donor T-cell count was similar in unmanipulated compared with CD8-depleted PBSC recipients but was significantly lower in CD34-selected PBSC recipients (P=0.0012). T cells of recipient origin remained stable over time in unmanipulated and CD8-depleted PBSC patients but expanded in some CD34-selected PBSC recipients between day 28 and 100 after transplant. Moreover, whereas CD8 depletion only decreased CD8+ counts (P<0.047), CD34 selection reduced CD3+(P<0.001), CD8+(P<0.016), CD4+ (P<0.001), and CD4+CD45RA+ (P<0.001) cell counts. T-cell repertoire was restricted in all patients on day 100 after hematopoietic stem-cell transplantation but was even more limited after CD34 selection (P=0.002). CONCLUSIONS: Despite of the persistence of a significant number of T cells of recipient origin, T-cell counts were low the first 6 months after NMSCT. Moreover, contrary with CD8 depletion of the graft that only affects CD8+ lymphocyte counts, CD34 selection dramatically decreased both CD8 and CD4 counts. [less ▲]

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See detailLes lymphomes
Jerusalem, Guy ULg; Hustinx, Roland ULg; Beguin, Yves ULg et al

in Médecine Nucléaire : Imagerie Fonctionnelle et Métabolique (2003), 27(8), 401-410

Actuellement, on arrive à guérir 70-80% des patients atteints de maladie de Hodgkin et 50% des patients atteints de lymphome non-Hodgkinien de malignité intermédiaire ou élevée. Une approche systématique ... [more ▼]

Actuellement, on arrive à guérir 70-80% des patients atteints de maladie de Hodgkin et 50% des patients atteints de lymphome non-Hodgkinien de malignité intermédiaire ou élevée. Une approche systématique concernant le diagnostic, la classification de la maladie et la détermination des facteurs pronostiques permet de choisir la thérapeutique la plus appropriée. Les auteurs passent en revue les examens à réaliser au diagnostic et discutent de la place de la tomographie à émission de positons (TEP) dans cette indication. Ils évoquent ensuite le problème des masses résiduelles. La TEP est maintenant l'examen de choix pour établir le bilan de fin de traitement. Les auteurs discutent également du rôle potentiel de la TEP pour l'évaluation thérapeutique précoce et le suivi régulier des patients après traitement pour lymphome. Enfin, l'aspect particulier des lymphomes de l'enfant est abordé. [less ▲]

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See detailSoluble transferrin receptor for the evaluation of erythropoiesis and iron status.
Beguin, Yves ULg

in Clinica Chimica Acta (2003), 329(1-2), 9-22

Iron transport in the plasma is carried out by transferrin, which donates iron to cells through its interaction with a specific membrane receptor, the transferrin receptor (TfR). A soluble form of the TfR ... [more ▼]

Iron transport in the plasma is carried out by transferrin, which donates iron to cells through its interaction with a specific membrane receptor, the transferrin receptor (TfR). A soluble form of the TfR (sTfR) has been identified in animal and human serum. Soluble TfR is a truncated monomer of tissue receptor, lacking its first 100 amino acids, which circulates in the form of a complex of transferrin and its receptor. The erythroblasts rather than reticulocytes are the main source of serum sTfR. Serum sTfR levels average 5.0+/-1.0 mg/l in normal subjects but the various commercial assays give disparate values because of the lack of an international standard. The most important determinant of sTfR levels appears to be marrow erythropoietic activity which can cause variations up to 8 times below and up to 20 times above average normal values. Soluble TfR levels are decreased in situations characterized by diminished erythropoietic activity, and are increased when erythropoiesis is stimulated by hemolysis or ineffective erythropoiesis. Measurements of sTfR are very helpful to investigate the pathophysiology of anemia, quantitatively evaluating the absolute rate of erythropoiesis and the adequacy of marrow proliferative capacity for any given degree of anemia, and to monitor the erythropoietic response to various forms of therapy, in particular allowing to predict response early when changes in hemoglobin are not yet apparent. Iron status also influences sTfR levels, which are considerably elevated in iron deficiency anemia but remain normal in the anemia of inflammation, and thus may be of considerable help in the differential diagnosis of microcytic anemia. This is particularly useful to identify concomitant iron deficiency in a patient with inflammation because ferritin values are then generally normal. Elevated sTfR levels are also the characteristic feature of functional iron deficiency, a situation defined by tissue iron deficiency despite adequate iron stores. The sTfR/ferritin ratio can thus describe iron availability over a wide range of iron stores. With the exception of chronic lymphocytic leukemia (CLL) and high-grade non-Hodgkin's lymphoma and possibly hepatocellular carcinoma, sTfR levels are not increased in patients with malignancies. We conclude that soluble TfR represents a valuable quantitative assay of marrow erythropoietic activity as well as a marker of tissue iron deficiency. [less ▲]

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See detailComment je traite ... la leucemie myeloide chronique (LMC).
Hafraoui, Kaoutar ULg; Humblet-Baron, Stéphanie ULg; Baron, Frédéric ULg et al

in Revue Médicale de Liège (2003), 58(1), 7-12

This review article describes the identification of the tyrosine kinase BCR/ABL as the hallmark of chronic myeloid leukemias (CML) as well as the development of a specific inhibitor of this tyrosine ... [more ▼]

This review article describes the identification of the tyrosine kinase BCR/ABL as the hallmark of chronic myeloid leukemias (CML) as well as the development of a specific inhibitor of this tyrosine kinase, the STI571 (Glivec, imatinib mesylate). The authors discuss the results of a phase I and three phase II trials reporting the efficacy of STI571 as treatment for CML patients and propose two simplified algorithms that may help to guide decision-making for the individual patient. [less ▲]

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See detailOnce-weekly epoetin beta is highly effective in treating anaemic patients with lymphoproliferative malignancy and defective endogenous erythropoietin production.
Cazzola, Mario; Beguin, Yves ULg; Kloczko, Janusz et al

in British Journal of Haematology (2003), 122(3), 386-93

Epoetin beta, three-times weekly (t.i.w.), is effective in reversing anaemia in lymphoproliferative disorders. The current study investigated whether an epoetin beta dose of 30,000 IU given subcutaneously ... [more ▼]

Epoetin beta, three-times weekly (t.i.w.), is effective in reversing anaemia in lymphoproliferative disorders. The current study investigated whether an epoetin beta dose of 30,000 IU given subcutaneously once weekly (q.w.) was at least as effective as 10,000 t.i.w. administration in anaemic patients with lymphoproliferative malignancy and defective endogenous erythropoietin (Epo) production. Overall, 241 anaemic patients with multiple myeloma, low-grade non-Hodgkin's lymphoma or chronic lymphocytic leukaemia, all with serum Epo values </= 100 mU/ml, were randomized to receive the q.w. (n = 119) or t.i.w. (n = 122) regimen for 16 weeks. The primary efficacy criterion, i.e. the time-adjusted area under the haemoglobin-time curve from weeks 5-16, was comparable between the q.w. and t.i.w. groups [difference = - 0.20 g/dl (90% confidence interval - 0.52-0.11)]. Moreover, response rates were high and similar in both arms (72%vs 75%, q.w. and t.i.w. groups respectively). Baseline serum Epo was predictive of response: the lower serum Epo, the higher the likelihood of response (P = 0.002). Thus, epoetin beta administered q.w. is an effective and convenient treatment for anaemia in patients with lymphoproliferative disorders. Tailoring this treatment modality to subjects with defective endogenous Epo production represents a rational use of epoetin from both a medical and a community perspective. [less ▲]

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See detailLong-term disease-free survival in patients with angioimmunoblastic T-cell lymphoma after high-dose chemotherapy and autologous stem cell transplantation.
Schetelig, Johannes; Fetscher, Sebastian; Reichle, Albrecht et al

in Haematologica (2003), 88(11), 1272-8

BACKGROUND AND OBJECTIVES: Patients with angioimmunoblastic T-cell lymphoma (AIL) have a poor prognosis with conventional treatment. DESIGN AND METHODS: We initiated an EBMT-based survey studying the ... [more ▼]

BACKGROUND AND OBJECTIVES: Patients with angioimmunoblastic T-cell lymphoma (AIL) have a poor prognosis with conventional treatment. DESIGN AND METHODS: We initiated an EBMT-based survey studying the impact of high-dose chemotherapy (HDCT) and autologous hematopoietic stem cell transplantation in patients with AIL. Data on 29 patients, who were transplanted between 1992 and 1998 in 16 transplant centers, were collected on standardized documentation forms. RESULTS: The median age at transplantation was 53 years. HDCT was given as part of 1st-line therapy (N=14; 48%) or 2nd/3rd-line therapy (N=15; 52%). Regimens for the mobilization of peripheral blood stem cells (PBSC) included VIPE (N=7; 26%), DexaBEAM (N=6; 22%), CHOP-like regimens (N=6; 22%), other regimens (N=5; 19%) or alternatively growth factor alone (N=3; 11%). The median yield of PBSC was 3.8x106 CD34+cells/kg. Two patients received autologous bone marrow. The HDCT consisted of BEAM-type regimens in 16 patients, ICE-type regimens in 7, and other regimens in 6 patients. There was one treatment-related death. The rate of complete remissions increased from 45% before HDCT to 76% after HDCT. As of January 2003, after a median observation time of living patients of 5 years (range 2.5 to 10 years), 14 patients have died (13 from progressive disease), and 15 patients are alive. The probability of 5-year overall and event-free survival was 44% (95% CI, 22% to 66%) and 37% (95% CI, 17% to 57%), respectively. Long-term disease-free survival was observed in patients transplanted during 1st-line treatment as well as in the context of 2nd/3rd-line therapy. INTERPRETATION AND CONCLUSIONS: There is evidence that AIL is susceptible to high-dose chemotherapy. HDCT and autologous stem cell transplantation should be considered in selected patients with AIL. [less ▲]

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See detailBarotrauma-induced tension pneumoperitoneum.
Canivet, Jean-Luc ULg; Yans, Th; Piret, Sonia ULg et al

in Acta Anaesthesiologica Belgica (2003), 54(3), 233-6

We report the case of a massive tension-pneumoperitoneum developing immediately after starting mechanical ventilation (barotrauma). Careful analysis of CT-data provided meaningful informations in ... [more ▼]

We report the case of a massive tension-pneumoperitoneum developing immediately after starting mechanical ventilation (barotrauma). Careful analysis of CT-data provided meaningful informations in assessing the non surgical pulmonary source of pneumo peritoneum. [less ▲]

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See detailHypochromic mature erythrocytes: a specific marker of iron deficiency
Bovy, Christophe ULg; Beguin, Yves ULg; Gothot, André ULg et al

in Acta Clinica Belgica (2003), 58-3(4), 325

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See detailFollow-up of iron microalbuminuria in hypertensive patients: a belgian promise survey
Bovy, Christophe ULg; Beguin, Yves ULg; Gothot, André ULg et al

in Acta Clinica Belgica (2003), 58-3(4), 328

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See detailBinding and migration across fibronectin and VCAM-1 of cycling hematopoietic progenitor cells.
Gothot, André ULg; Giet, Olivier ULg; Huygen, Sandra et al

in Leukemia & Lymphoma (2003), 44(8), 1379-83

Using different experimental approaches, it has been established that transplantability of hematopoietic/stem progenitor cells is ineffective during transit through the cell cycle. Although primitive stem ... [more ▼]

Using different experimental approaches, it has been established that transplantability of hematopoietic/stem progenitor cells is ineffective during transit through the cell cycle. Although primitive stem cells are responsive to mitogenic stimulation in optimized ex vivo conditions, defective engraftment of generated cells may limit their detection in standard transplantation models as well as their use in clinical cell therapy. The activation level of adhesion receptors is modulated by stimulation of cytokine receptors via "inside-out" signaling. This prompted us to study the interactions of progenitor cells with fibronectin (Fn) in different phases of the cell cycle. We first demonstrated that adhesion to Fn was stimulated in S/G2 + M as compared to G0/G1, in ex vivo cultured CD34+ cells, with a predominant usage of very late antigen (VLA)-5 over that of VLA-4. We next determined that maximal Fn binding in active phases of the cell cycle limited cell motility toward stromal cell-conditioned medium. It was also observed that VLA-4 and VLA-5 ability to mediate adhesion or migration varied independently during cell cycle transit. Finally, in synchronized progenitor cells executing a first cell cycle ex vivo, a reversible increase in Fn binding was associated with a reversible decrease in adhesion to vascular cell-adhesion molecule (VCAM)-1. Overall, these observations suggest that defective engraftment of cycling stem/progenitor cells may result, at least in part, from abnormal trafficking related to changes in the activation level of adhesion receptors. [less ▲]

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See detailTraitement moléculaire du cancer: le STI571, un inhibiteur des tyrosines kinases
Humblet-Baron, Stéphanie ULg; Baron, Frédéric ULg; Pirson, Laurence ULg et al

in Revue Médicale Suisse (2002), 60(598), 1504-1508

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See detailModulation par le cycle cellulaire de l'implantation des cellules souches hématopoïétiques
Gothot, André ULg; Giet, Olivier ULg; Huygen, S. et al

in Hématologie (2002), 8

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See detailLe métabolisme du fer
Beguin, Yves ULg

in Hématologie (2002), 8

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See detailChanging pattern of bacterial susceptibility to antibiotics in hematopoietic stem cell transplant recipients.
Frere, Pascale ULg; Hermanne, J.-P.; Debouge, M.-H. et al

in Bone Marrow Transplantation (2002), 29(7), 589-94

Adequate infection prophylaxis and empirical antibiotic therapy are of critical importance after hematopoietic stem cell transplantation (HSCT). We examined the evolution of bacterial susceptibility to ... [more ▼]

Adequate infection prophylaxis and empirical antibiotic therapy are of critical importance after hematopoietic stem cell transplantation (HSCT). We examined the evolution of bacterial susceptibility to antibiotics in 492 patients (198 allografts and 294 autografts) transplanted between 1982 and 1999 and evaluated whether ciprofloxacin prophylaxis and an empirical antibiotic regimen (glycopeptide + third-generation cephalosporin) were still valid. We collected all susceptibility tests performed during the initial hospitalization on blood cultures as well as routine surveillance cultures and analyzed susceptibility to ciprofloxacin and to major antibiotics used in our unit. Gram-positive cocci rapidly became resistant to ciprofloxacin (susceptibility around 70% in 1990 to less than 20% in 1998) but sensitivity to glycopeptides remained unaltered. There was a rapid decline in the number of patients colonized with Gram-negative bacilli in the early years of ciprofloxacin prophylaxis. However, susceptibility to ciprofloxacin fell sharply from around 90% in 1990 to around 30% in 1999. In parallel, susceptibility to ceftazidime also decreased to less than 80% in recent years. Piperacillin (+/- tazobactam) did not show any variation over time and its efficacy remained too low (about 60%). Imipenem as well as recently introduced cefepim and meropenem showed stable and excellent profiles (>90% susceptibility). In conclusion: (1) quinolone prophylaxis has now lost most of its value; (2) the choice of a third-generation cephalosporin for empirical antibiotic therapy may no longer be the best because of the emergence of Gram-negative strains resistant to beta-lactamases, such as Enterobacter sp. More appropriate regimens of empirical antibiotic therapy in HSCT recipients may be based on the use of a carbapenem or fourth-generation cephalosporin. [less ▲]

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