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SCOPUS: ar.j, info:eu-repo/semantics/published

L’objectif de notre travail est de contribuer à l’amélioration de la sécurité transfusionnelle. Pour ce faire, nous sommes partis de notre expérience personnelle en banque de sang hospitalière. Le risque infectieux lié aux transfusions, inscrit dans l’esprit de chacun depuis l’affaire du « scandale du SIDA » en France, est aujourd’hui un des risques les mieux maîtrisés. Actuellement, les risques transfusionnels les plus importants sont essentiellement de type immunologique ou liés à des erreurs humaines. Nous avons donc mis en évidence trois axes de travail correspondant chacun à un type de réaction transfusionnelle spécifique choisis parmi ces deux derniers risques. Les données d’hémovigilance internationales publiées nous ont confortés dans l’idée que ces trois sujets représentent une part importante des réactions transfusionnelles notifiées ces dix dernières années. Nous avons choisi de travailler sur la prévention des réactions transfusionnelles hémolytiques de type ABO, des réactions transfusionnelles hémolytiques chez les patients atteints d’anémie hémolytique auto-immune et des réactions d’hyperkaliémie post-transfusionnelle.Notre premier travail a consisté en la démonstration de la faisabilité d’une automatisation complète du contrôle ultime au lit du malade par vérification de la compatibilité entre le groupe ABO du patient et celui de la poche de sang à transfuser. Cet appareil utilise une nouvelle technique de détection d’hémagglutination entièrement conçue et validée au sein de notre laboratoire de recherche et brevetée par l’ULB.La seconde partie du travail consiste en l’évaluation d’un nouvel algorithme de prise en charge transfusionnelle des patients atteints d’anémie hémolytique autoimmune en incluant la réalisation d’un génotypage érythrocytaire permettant ainsi, d’une part, d’éviter les réactions hémolytiques transfusionnelles et, d’autre part, d’éviter de nouvelles alloimmunisations chez ces patients.Dans la dernière partie du travail, no, Doctorat en Sciences biomédicales et pharmaceutiques, info:eu-repo/semantics/nonPublished

The following recommendations, which aim at improving the clinical diagnosis ofTRALI and the laboratory investigations that can support it, were drawn up by a working group of the Superior Health Council. TRALI is a complication of blood transfusion that is both serious and underreported. Systematic reporting may help to develop preventive actions. Therefore, the Superior Health Council recommends that there should be a more stringent surveillance of patients who receive a blood component transfusion. The clinician should pay very close attention to any change in the patient's respiratory status (cf. dyspnoea and arterial desaturation), which should be notified systematically to the haemovigilance contact person in the hospital.

Journal Article, FLWIN, info:eu-repo/semantics/published

The following recommendations, which aim at improving the clinical diagnosis ofTRALI and the laboratory investigations that can support it, were drawn up by a working group of the Superior Health Council. TRALI is a complication of blood transfusion that is both serious and underreported. Systematic reporting may help to develop preventive actions. Therefore, the Superior Health Council recommends that there should be a more stringent surveillance of patients who receive a blood component transfusion. The clinician should pay very close attention to any change in the patient's respiratory status (cf. dyspnoea and arterial desaturation), which should be notified systematically to the haemovigilance contact person in the hospital., Journal Article, Practice Guideline, SCOPUS: ar.j, info:eu-repo/semantics/published

Improvement of transfusion security in sub-Saharan countries requires the determination of priorities taking into account the specific context., Journal Article, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published

Journal Article, FLWIN, info:eu-repo/semantics/published

Transcoronary transplantation of progenitor cells has been proposed as a novel therapy for ischemic heart failure. The primary aims were to assess the feasibility of obtaining CD34+ cells from blood without mobilization in chronic conditions and to compare homing with results reported in acute conditions. We also evaluated the effect of CD34+ on endothelial function. In 7 patients with a history of an anterior myocardial infarction (20 +/- 2 months), a large amount of CD34 (18.2 +/- 3.0 x 10(6)) were obtained and an intracoronary infusion into the left anterior descending artery via an over-the-wire balloon catheter was performed. Myocardial homing involved 3.2% +/- 0.6% of injected cells. Endothelial function studied with increasing doses of bradykinin was not significantly modified after 3 months. In the treated group, compared with 5 nonrandomized control patients with a similar clinical history, the only echocardiographic significant change (2-way analysis of variance) was a decrease in end-systolic volume (P < 0.03). In conclusion, large amounts of CD34+ cells can be obtained from blood, without mobilization, in the chronic phase of myocardial infarction. As reported in the acute situation 1 hour after treatment, intracoronary infusion of CD34+ cells results in myocardial homing of a few percents of the cells. In this small group of patients, no effect of this therapy is detected on the endothelial function and only marginal changes are observed on echocardiographic parameters., Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

Recommendations, which aim at standardising and rationalising clinical indications for the transfusion of fresh frozen plasma (FFP) in Belgium, were drawn up by a working group of the Superior Health Council. For this purpose the Superior Health Council organised an expert meeting devoted to "Transfusion Guidelines: Pathogen reduction, products and indications for the transfusion of plasma" in collaboration with the Belgian Haematological Society. The experts discussed the indications for the transfusion of FFP, pathogen reduction for FFP and the practical issues of administering FFP and plasma-derived concentrates. The recommendations formulated by the experts were validated by the working group with the purpose of harmonising FFP transfusion in Belgian hospitals., SCOPUS: re.j, info:eu-repo/semantics/published

Background: An active haemovigilance programme was implemented to survey adverse events (AE) associated with transfusion of platelets photochemically treated with amotosalen and ultraviolet A (PCT-PLT). The results of 5106 transfusions have already been reported. Here we report the results of an additional 7437 PCT-PLT transfusions. Methods: The focus of this ongoing haemovigilance programme is to document all AEs associated with PCT-PLT transfusion. Data collected for AEs include: time of event after starting transfusion, clinical descriptions, vital signs, results from radiographs and bacterial cultures, event severity (Grade 0-4) and causal relationship to PCT-PLT transfusion. Results: One thousand four hundred patients (mean 60 years, range 1-96) received PCT-PLT transfusions. The majority of the patients (53.4%) had haematology-oncology diseases and required conventional chemotherapy (44.8%) or stem cell transplantation (8.6%). Sixty-eight PCT-PLT transfusions were associated with AE. Acute transfusion reactions (ATR), classified as an AE possibly related, probably related, or related to PCT-PLT transfusions were infrequent (n = 55, 55/7437 = 0.7%) and most were of Grade 1 severity. Thirty-nine patients (39/1400 = 2.8%) experienced one or more ATRs. The most frequently reported signs/symptoms were chills, fever, urticaria, dyspnoea, nausea and vomiting. Five AEs were considered severe (≥ Grade 2); however, no causal relationship to PCT-PLT transfusion was found. Repeated exposure to PCT-PLT did not increase the likelihood of an ATR. No cases of transfusion-related acute lung injury and no deaths due to PCT-PLT transfusions were reported. Conclusions: Routine transfusion of PCT-PLT is well-tolerated in a wide range of patients. ATRs related to PCT-PLT transfusion were infrequent and most were of mild severity. © 2008 The Author(s)., SCOPUS: ar.j, FLWIN, info:eu-repo/semantics/published

The following recommendations, which aim at standardising and rationalising clinical indications for the transfusion of red cells in Belgium, were drawn up by a working group of the Superior Health Council. To this end, the Superior Health Council organised an expert meeting devoted to "Guidelines for the transfusion of red cells" in collaboration with the Belgian Hematological Society. The experts discussed the indications for red cell transfusions, the ideal red cell concentrate, the practical issues of administering red cells, and red cell transfusions in patients in a critical condition. The recommendations formulated by the experts were validated by the working group with the purpose of harmonising red cell transfusion in Belgian hospitals., SCOPUS: re.j, info:eu-repo/semantics/published

0, SCOPUS: re.j, FLWIN, info:eu-repo/semantics/published

Extracorporeal photochemotherapy is an immunomodulatory treatment wich is carried out in three steps: first leukapheresis, then ex vivo PUVA treatment and finally autologous transfusion. Its current "evidence-based" indications are erythrodermic cutaneous lymphoma, graft versus host disease and cardiac graft rejection. However this treatment has already been used with success in many other diseases such as systemic sclerosis, multiple sclerosis, type 1 diabetes and various autoimmune dermatologic diseases. Randomised controlled studies are needed to confirm the efficacy of photopheresis in these diseases. We also review the different hypotheses explaining the mechanism of action of photopheresis., English Abstract, Journal Article, SCOPUS: re.j, info:eu-repo/semantics/published

SCOPUS: ar.j, info:eu-repo/semantics/published

Dendritic cells derived from monocytes cultured in the presence of type I interferon were found to induce efficient T cell responses against tumor antigens in vitro. We vaccinated eight stage III or IV melanoma patients with dendritic cells generated with interferon-beta and interleukin-3, activated by poly I: C, and pulsed with the tumor-specific antigen NA17.A2. This dendritic cell vaccine was well-tolerated with only minor and transient flu-like symptoms and inflammatory reactions at the injection sites. In most patients, isotopic imaging documented dendritic cells (DC) migration from the intradermal injection site to the draining lymph nodes. Finally, mixed lymphocyte-peptide culture under limiting dilution conditions followed by tetramer labeling indicated that three out of eight patients mounted a CD8 T cell response against the NA17.A2 antigenic peptide. We conclude that DC generated in type I-IFN represent an interesting alternative to DC generated in IL-4 and GM-CSF for cancer immunotherapy.

Dendritic cells derived from monocytes cultured in the presence of type I interferon were found to induce efficient T cell responses against tumor antigens in vitro. We vaccinated eight stage III or IV melanoma patients with dendritic cells generated with interferon-beta and interleukin-3, activated by poly I: C, and pulsed with the tumor-specific antigen NA17.A2. This dendritic cell vaccine was well-tolerated with only minor and transient flu-like symptoms and inflammatory reactions at the injection sites. In most patients, isotopic imaging documented dendritic cells (DC) migration from the intradermal injection site to the draining lymph nodes. Finally, mixed lymphocyte-peptide culture under limiting dilution conditions followed by tetramer labeling indicated that three out of eight patients mounted a CD8 T cell response against the NA17.A2 antigenic peptide. We conclude that DC generated in type I-IFN represent an interesting alternative to DC generated in IL-4 and GM-CSF for cancer immunotherapy., Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published

Long-term results of organ transplantation are still limited by serious side effects of immunosuppressive drugs. A major issue, therefore, is to elaborate novel therapeutic protocols allowing withdrawal or minimization of immunosuppressive therapy after transplantation. We report on 3 patients prospectively enrolled in an original protocol designed to promote graft acceptance in living donor liver transplantation, using posttransplant conditioning with high doses of antithymocyte globulin followed by injection of donor-derived stem cells. In 2 patients, early immunosuppression withdrawal was possible, without subsequent graft deterioration. In these 2 cases, in vitro studies showed indices of immunological tolerance as assessed by specific hyporesponsiveness to donor alloantigens in mixed lymphocytes culture. In the third patient, acute rejection rapidly occurred after discontinuation of immunosuppression, and minimal immunosuppression has to be maintained during long-term follow-up. In this case, a clearly distinct immunoreactive profile was observed as compared to tolerant patients, as no specific modulation of the antidonor response was observed in vitro. Of note, no macrochimerism could be detected in any of the 3 patients during the follow-up. In conclusion, these clinical observations demonstrated that, despite the absence of macrochimerism, donor stem cells infusion combined with recipient conditioning may allow early immunosuppression withdrawal or minimization after liver transplantation., Case Reports, Journal Article, Research Support, Non-U.S. Gov't, FLWIN, info:eu-repo/semantics/published

Granulocyte--colony-stimulating factor administered for autologous hematopoietic stem cell isolation from blood may favor restenosis in patients implanted after acute myocardial infarction (AMI). We therefore tested the isolation of peripheral-blood CD34+ cells without mobilization in six patients with AMI. After large-volume cytapheresis and positive CD34+ cell selection, 3.6 to 27.6 million CD34+ cells were obtained. We performed intra-coronary implantation of these cells and recorded no restenosis or arrhythmia. We used positron emission tomography (PET) to assess myocardial-labeled CD34+ cell homing, which accounted for 5.5% of injected cells 1 hour after implantation. In conclusion, large amounts of CD34+ cells, in the range reported in previous studies, can be obtained from nonmobilized peripheral blood. PET with [18F]-fluorodeoxyglucose cell labeling is an efficient imaging method for homing assessment., Evaluation Studies, Journal Article, Research Support, Non-U.S. Gov't, FLWIN, info:eu-repo/semantics/published

Despite limited clinical efficacy in large trials, dendritic cells (DC)-based immunization has yielded impressive responses in some patients. Key questions remain to be solved in order to optimize this therapeutic vaccine. Among them, the nature of the DC type used and its state of maturation are pivotal. Besides myeloid DC which are mostly used in clinical trials, a new DC type has been recently described resulting from the differentiation of monocytes in the presence of type I IFNs. In the present study, we analyze the features of type I IFNs DC generated in the presence of either IL-3 (IL-3-DC) or GM-CSF (GM-CSF-DC) and compare their capacity to respond to poly(I:C) and to subsequently trigger T-cell activation. The two DC types disclose a similar immunophenotype characterized by high levels of chemokines receptors, co-stimulatory and HLA molecules expression. After poly(I:C) maturation, both DC types display a marked upregulation of CD80, CD83 and CD86 and the same pattern of gene expression. In addition, poly(I:C) stimulated them to secrete IFN-alpha and IL-12p70. Both DC types elicit potent allogeneic reactions. Priming of autologous T cells by IL-3-DC or GM-CSF-DC pulsed with an HLA-A2 restricted melan-A derived peptide, lead to the expansion of peptide specific CTL secreting high amounts of IFN-gamma. We conclude that poly(I:C) matured IL-3-DC and GM-CSF-DC share similar phenotype and functional properties including the capacity to prime tumor-associated antigen specific CTL., Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

Gene delivery into dendritic cells (DC) is most efficiently achieved by viral vectors. Recombinant canarypox viruses (ALVAC) were validated safe and efficient in humans. We aimed firstly to evaluate DC transduction by ALVAC vectors, then to investigate if such infection induced or not the maturation of the DC, and finally to assess the efficiency of ALVAC-MAGE-transduced DC to activate specific CTL clones. Clinical grade DC from melanoma patients were generated from blood monocytes and infected with a recombinant ALVAC virus encoding either a marker gene (EGFP) or the MAGE-1-MAGE-3 minigenes. According to the patient-donor, 22+/-16% of immature DC were successfully transduced. Flow cytometry analysis of surface markers expressed on DC after ALVAC infection did not reveal a mature phenotype. Moreover, ALVAC transduction did not interfere with the capacity of the DC to further mature under poly:IC stimulation. But most importantly, our results demonstrated that DC from HLA-A1 patient-donors infected with the recombinant ALVAC MAGE-1-MAGE-3 minigenes virus were capable of activating a MAGE 3/A1 CTL clone more efficiently than same DC loaded with MAGE 3/A1 peptide, as shown by increased IFN-gamma secretion. These results could be the basis for the development of a new clinical strategy in melanoma patient's immunotherapy., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

BACKGROUND AND AIM OF THE STUDY: The induction of transplantation tolerance, defined as the survival of a functioning allograft in the absence of continuing immunosuppressive therapy, would be a major advance. Clinical and experimental data have shown that transplantation tolerance could be induced by pre-transplant myeloconditioning and infusion of donor hematopoietic cells. We investigated the feasibility and safety of a protocol to induce tolerance to HLA mismatched living-donor liver graft by pre-transplant non-myeloablative conditioning followed by donor stem cells (SC) infusion, in patients with advanced liver cancers. PATIENTS AND METHODS: Two patients with intrahepatic cancers who did not fulfill criteria for cadaver liver transplantation were included in the study. Preparative regimen consisted in cyclophosphamide and anti-thymocyte globulin, followed by infusion of purified donor CD34(+) stem cells. Living-donor liver transplantation (LDLT) using the liver right lobe was performed after hematological reconstitution, respectively 40 and 55 days after donor stem cell infusion. Immunosuppressive therapies were discontinued when liver graft function returned to normal. RESULTS: The procedure could be completed in the two patients. No severe toxicity of the preparative regimen was observed. Neither patient presented graft versus host reaction after donor stem cell infusion. A transient macrochimerism was observed in the first case, while no chimerism could be detected in the second. Immunosuppression was discontinued, respectively 90 and 28 days, after liver transplantation, without subsequent rejection episode. In the two cases, liver function remained normal for the study period. In both patients, the period of immune reconstitution was prolonged, as illustrated by persisting low CD4(+) cell counts. Mixed lymphocyte cultures, performed after immunosuppression withdrawal, demonstrated donor specific hyporesponsiveness in the first case, but in a context of glo, Case Reports, Evaluation Studies, Journal Article, SCOPUS: ar.j, info:eu-repo/semantics/published

SCOPUS: le.j, info:eu-repo/semantics/published

New immunotherapies derived from biotechnology offer fascinating perspectives in different fields of medicine including anti-infectious vaccines, cancer, organ transplantation and autoimmune diseases. In this paper, we illustrate how the Department of Immunology can contribute to the development of these new treatments within a academic hospital such as the Erasme Hospital at the Université Libre de Bruxelles., English Abstract, Journal Article, Review, info:eu-repo/semantics/published

SCOPUS: le.j, info:eu-repo/semantics/published

BACKGROUND: Mechanisms of action of extracorporeal photochemotherapy (ECP) in graft-versus-host disease are incompletely understood. It has been proposed that phagocytosis of apoptotic bodies by monocytes and macrophages induces their activation, a process that increases production of immunosuppressive cytokines. We analyzed apoptosis and cytokine secretion in an autologous coculture system combining peripheral blood lymphocytes (PBL) obtained after ex vivo ECP treatment and nonirradiated peripheral blood mononuclear cells (PBMC). METHODS: We studied 11 leukapheresis products treated by ECP from six patients with resistant limited or extensive chronic graft-versus-host disease. Purified PBL obtained by monocyte depletion of the buffy coat from leukapheresis products were mixed with nonirradiated PBMC. Nonirradiated PBL were used as control. Cytokine production was tested at the mRNA level by real-time reverse transcriptase-polymerase chain reaction for interleukin (IL)-10, IL-1 receptor antagonist (IL-1Ra), IL-1beta, tumor necrosis factor-alpha, and IL-12p40. RESULTS: Morphologic analysis and flow cytometry displayed important lymphocyte apoptotic features culminating at 24 to 48 hr. Coculture of patient's PBMC with ultraviolet-irradiated PBL as compared with nonirradiated PBL resulted in significant increase of IL-10 mRNA (3418+/-1015 versus 10596+/-3402 mRNA copy numbers; P=0.001) and IL-1Ra mRNA (23890+/-6166 versus 41767+/-10181 mRNA copy numbers; P=0.001). Incubation with a neutralizing anti-IL-10 monoclonal antibody resulted in a marked decrease of IL-1Ra mRNA levels. CONCLUSION: Our findings are consistent with the fact that ECP modifies patient's autologous lymphocytes by inducing a process of apoptosis that activates monocytes and macrophages, leading to increased synthesis of IL-10 and IL-1Ra mRNAs. The induction of this latter mediator is dependent on IL-10., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

The epidemiology and clinical outcome of multiple myeloma in human immunodeficiency virus (HIV)-positive patients is poorly documented. There are uncertainties concerning the optimal management of this rare disorder. We report on the use of myeloablative chemotherapy with autologous stem cell transplantation in an HIV-positive patient with multiple myeloma., SCOPUS: ar.j, SCOPUS: ar.j, info:eu-repo/semantics/published

info:eu-repo/semantics/published

Assessment of T-cell activation is pivotal for evaluation of cancer immunotherapy. We initiated a clinical trial in patients with MAGE-A1 and/or -A3 tumors using autologous DC pulsed with MAGE peptides aimed at analyzing T-cell-derived, IFN-gamma secretion by cytokine flow cytometry and ELISPOT. We also tested whether further KLH addition could influence this response favorably. Monocyte-derived DC were generated from leukapheresis products. They were pulsed with the relevant MAGE peptide(s) alone in group A (n=10 pts) and additionally with KLH in group B (n=16 pts). A specific but transient increase in the number of peripheral blood T lymphocytes secreting IFN-gamma in response to the vaccine peptide(s) was observed in 6/8 patients of group A and in 6/16 patients of group B. We conclude that anti-tumor vaccination using DC pulsed with MAGE peptides induces a potent but transient anti-MAGE, IFN-gamma secretion that is not influenced by the additional delivery of a nonspecific, T-cell help., Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

info:eu-repo/semantics/published

Two rapidly evolving areas of cell therapy are the use of stem cells and cancer immunotherapy. The primitive pluripotent hematopoietic stem cells (HSCs), which have the capacity to self-renew and to repopulate the different blood cell lineages, are responsible for the maintenance of the hematopoietic system. Two major sources of stem cells are bone marrow and apheresis products of peripheral blood after mobilization with G-CSF and/or chemotherapy. HSC transplantation allows for the restoration of the hematopoietic and immune systems in cancer therapy. Immunotherapy has been classified as 'active' or 'passive' depending on whether the immunotherapy is designed to activate the patient's immune system to mount an immune response towards his/her own tumor or designed to transfer immune components 'already' directed against the patient's cancer. This latter approach, also termed 'adoptive immunotherapy,' includes the use of lymphokine-activated killer cells and tumor-infiltrating lymphocytes, tumor-specific lymphokine-activated killer cells and autolymphocyte therapy, stem cell transplantation in leukemic relapse, adoptive immunotherapy of Epstein-Barr virus (EBV) lymphoma using EBV-specific cytotoxic T lymphocytes, and activated monocytes- macrophages. Another approach for cancer immunotherapy, termed 'active immunotherapy,' is based on the induction of an antitumor response in the patient by, e.g. the use of manipulated tumor cells or professional antigen- presenting cells loaded with tumor antigens. In addition to its use in cancer treatment, cell therapy is also being explored as a treatment strategy for other disorders of the hematolymphoid system, such as autoimmune diseases (AIDs). It has also been proposed that HSCs may be useful in creating tolerance in patients requiring solid organ transplantation. As cell therapy becomes more common, regulatory decisions must be made concerning whether to give cellular products the status of drugs or biological products., SCOPUS: re.j, info:eu-repo/semantics/published

(Impact factor: 0.5), info:eu-repo/semantics/published

BACKGROUND: Dendritic cell (DC)-based vaccine is a promising approach for cancer therapy. Pioneer trials have been conducted using DC generated in research conditions. There is now a need for generating DC in clinical grade conditions, including the use of closed systems, avoidance of FCS and respect of good manufacturing practices (GMP). METHODS: DC were generated from 84 leukapheresis products of 27 cancer patients enrolled in two Phase I/II trials of vaccination of either MAGE+tumors (n = 24) or prostate cancer (n = 3). Monocytes were seeded in culture bags in a serum-free medium supplemented with IL-4 and GM-CSF. After a 7 day culture, DC were collected and most were pulsed with various MAGE-derived peptides. RESULTS: After a short leukapheresis (mean time: 66 min; mean processed blood: 5 L), a mean of 6 x 10(9) WBC were collected, from which 2.25 x 10(9) were seeded. The culture procedure yielded a large number of DC (mean: 62 x 10(6) DC) harboring the expected phenotype of immature DC (CD1a(+) CD14(-) HLA-DR(+) CD80(+) CD86(+) CD83(-)). This phenotype was not altered by peptide loading. These DC, either fresh or thawed, were functionally effective invitro. Their s.c. and i.v. injections were devoid of any short-term side effect and associated with the induction of immune responses in the patients. DISCUSSION: Large numbers of functional immature clinical grade DC can be generated in a closed system from leukapheresis products in cancer patients. These results provide the basis for large-scale studies of cancer immunotherapy under improved safety conditions., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

info:eu-repo/semantics/nonPublished