[Acute and chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation]. / Maladie du greffon contre l'hôte aiguë et chronique après allogreffe de cellules souches hématopoïétiques.

Acute and/or chronic graft-versus-host disease (GVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation (alloHSCT). It is a multisystemic inflammatory and/or fibrotic disease that occurs when the immune cells derived from the graft (and therefore originating from the donor) recognize recipient's healthy tissues as foreign and react against them. Acute GVHD is one of the main causes of non-relapse mortality after alloHSCT. Chronic GVHD can be very disabling in its severe form and can also be responsible for late mortality, mainly due to long-term immune deficiency and opportunistic infections. In contrast, GVHD can be associated with certain beneficial effects in patients transplanted for hematological malignancies, through simultaneous «graft versus tumour¼ positive effects. Therefore, one of the challenges of alloHSCT is the prevention and treatment of severe forms of GVHD without losing the beneficial anti-tumour effects of the graft.

: La maladie du greffon contre l'hôte («greffe-versus-hôte¼, GVH) aiguë et/ou chronique est une complication sérieuse de l'allogreffe de cellules souches hématopoïétiques (CSH). Elle correspond à des manifestations inflammatoires et/ou fibrotiques multisystémiques qui se produisent lorsque les cellules immunitaires dérivées de la greffe (et donc originaires du donneur) reconnaissent les tissus sains du receveur comme étrangers et réagissent contre eux. La GVH aiguë est l'une des principales causes de mortalité hors rechute post-greffe. La GVH chronique peut être très invalidante dans sa forme sévère et peut également être responsable d'une mortalité tardive, principalement due à un déficit immunitaire à long terme et à des infections opportunistes. À l'opposé, la GVH est associée à certains effets bénéfiques chez les patients transplantés pour des hémopathies malignes, par les effets simultanés favorables du «greffon contre la tumeur¼. Par conséquent, l'un des défis de l'allogreffe de CSH est la prévention et le traitement des formes sévères de GVH, sans perdre les effets bénéfiques anti-tumoraux du greffon.

[Cellular immunotherapy at the University Hospital of Liege : advances, challenges and prospects]. / Immunothérapie cellulaire au CHU de Liège : avancées, défis et perspectives.

Cellular immunotherapy consists in using the cells of the immune system as a therapeutic weapon. In this constantly evolving field, the therapeutic strategies developed at the University Hospital of Liege are hematopoietic stem cell transplantation, mesenchymal stromal cells and targeted therapy with CAR-T cells (Chimeric Antigen Receptor T cells). The first two modalities represent a form of non-targeted cell therapy that has been developed over the past decades. While hematopoietic stem cell transplantation is established as the reference treatment for many hematological diseases, mesenchymal stromal cells are still under investigation in various pathologies (notably Crohn's disease, organ transplantation, COVID-19 and pulmonary fibrosis). By contrast, CAR-T cells represent a recently developed and extremely promising targeted immunotherapy. This therapeutic approach has already revolutionized the treatment of B-cell lymphopathies, and has the potential to do the same for many other diseases in the near future.

L'immunothérapie cellulaire consiste en l'utilisation de cellules du système immunitaire comme arme thérapeutique. Dans ce domaine en évolution constante, les stratégies thérapeutiques développées au CHU de Liège sont la greffe de cellules souches hématopoïétiques, les cellules stromales mésenchymateuses et la thérapie ciblée par cellules CAR-T («Chimeric Antigen Receptor T cells¼). Les deux premières approches représentent une forme de thérapie cellulaire non ciblée, développées depuis de nombreuses années. Si la greffe de cellules souches hématopoïétiques est établie comme le traitement de référence de nombreuses hémopathies, les cellules stromales mésenchymateuses sont, quant à elles, toujours à l'étude dans diverses pathologies (notamment maladie de Crohn, transplantation d'organes, COVID-19 et fibrose pulmonaire). À l'opposé, les cellules CAR-T représentent une immunothérapie ciblée, développée récemment et extrêmement prometteuse. Cette modalité thérapeutique a déjà révolutionné le traitement des lymphopathies B, et elle possède le potentiel d'en faire de même pour de nombreuses autres pathologies dans un avenir proche.

[The Arsène Burny Cancer Institute (ICAB) and its new building for the Integrated Oncology Center (CIO) at the CHU de Liège]. / L'Institut de Cancérologie Arsène Burny (ICAB) et son nouveau bâtiment du Centre Intégré d'Oncologie (CIO) au CHU de Liège.

The Arsène Burny Cancer Institute (ICAB) of the CHU de Liège is the reference university medical center, open to its environment, dedicated to cancer care. Transversality, academic expertise, quality of care and direct links with research are at the heart of this ambitious achievement, which is much more than a building. The Integrated Center of Oncology (CIO) is the new ICAB building, dedicated to outpatient cancer care and high performance technical platforms such as radiotherapy with its Cyberknife, oncology imaging with its radiopharmacy, the Laboratory of Cell and Gene Therapy, the Liège University Hospital Biobank, or the laboratories grouped together within Unilab, while hospitalizations remain in the existing towers of the CHU.

L'Institut de Cancérologie Arsène Burny (ICAB) du CHU de Liège est le centre médical universitaire de référence, ouvert sur son environnement, consacré à la prise en charge du cancer. Transversalité, expertise universitaire, qualité des soins et liens directs avec la recherche sont au coeur de cette réalisation ambitieuse qui est bien plus qu'un bâtiment. Le Centre Intégré d'Oncologie (CIO) est le nouveau bâtiment de l'ICAB, dédié à la prise en charge ambulatoire du cancer et à des plateaux techniques de haute performance comme la radiothérapie avec son Cyberknife, l'imagerie oncologique avec sa radiopharmacie, le Laboratoire de Thérapie Cellulaire et Génique, la Biothèque Hospitalo-Universitaire de Liège, ou encore les laboratoires réunis au sein de l'Unilab. L'hospitalisation, quant à elle, reste dans les tours existantes du CHU.

[Editorial. Oncology, at a turning point in its history]. / Éditorial. L'oncologie, à un tournant de son histoire.

No abstract available.

[Allogeneic hematopoietic stem cell transplantation : general principles and recent progress]. / Allogreffes de cellules souches hématopoïétiques Principes généraux et progrès récents.

Hematopoietic stem cell transplantation is a potentially curative therapeutic option for many oncologic and non-oncologic hematological diseases. There is a constant evolution regarding donor choice, conditioning regimen intensity and immunosuppressive treatments, which leads to a reduction in morbidity and mortality during and after transplantation. In this article, we describe the general principles of hematopoietic stem cell transplantation and discuss the progress of global patient management after transplantation.

L'allogreffe de cellules souches hématopoïétiques constitue un traitement potentiellement curatif pour de nombreuses pathologies hématologiques cancéreuses ou non cancéreuses. Une évolution constante dans le choix du donneur, de l'intensité du conditionnement et des stratégies de traitements immunosuppresseurs, permet une réduction de la morbidité et de la mortalité durant et après la greffe. Cet article a pour but de réexpliquer les principes généraux d'une allogreffe et de discuter des nouvelles avancées et adaptations dans la prise en charge globale des patients greffés.

[Overview of the general management of acute leukemia for adults]. / Principes généraux de la prise en charge des leucémies aiguës de l'adulte.

Acute leukemias are a heterogeneous group of malignant hemopathies which are subdivided according to the cytological orientation of the pathological blast cell into lymphoblastic (ALL) and myeloblastic (AML) acute leukemias. Recent advances in the biological and genetic understanding of these diseases have led to improved treatments. Specific chemotherapy treatment or so-called «targeted¼ treatments, advances in bone marrow transplantation and better supportive care have gradually improved the prognosis. This review, focused on the adult patient, aims to describe recent progress in terms of diagnosis, prognostic markers and therapy.

Les leucémies aiguës sont un ensemble hétérogène d'hémopathies malignes qui se subdivisent, en fonction de l'orientation cytologique de la cellule blastique pathologique, en formes lymphoblastique (LLA) et myéloblastique (LMA). Les récents progrès dans la compréhension biologique et génétique de ces maladies ont permis d'améliorer les traitements. Le traitement spécifique de chimiothérapie ou traitements dits «ciblés¼, les progrès de la greffe de moelle et de meilleurs soins de support ont permis d'améliorer graduellement le pronostic. Cette revue, centrée sur le patient adulte, a pour objectif de décrire les progrès récents en termes de diagnostic, de marqueurs pronostiques ainsi que thérapeutiques.

[Diffuse large B-cell lymphoma: a revolutionary treatment based on genetically-modified immune cells called CAR T cells]. / Le lymphome diffus à grandes cellules B : nouveau traitement révolutionnaire par des cellules immunitaires génétiquement modifiées appelées «CART cells¼.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Firstline immunochemotherapy cures approximatively 60 % of patients. The prognosis of patients with refractory disease or with relapsed disease within the first two years after the end of treatment is highly unfavourable. Since June 2019, a new third-line treatment with CAR T cells (chimeric antigen receptor T cells) seems to completely modify the prognosis of these patients. A significant proportion of long-lasting complete responses is obtained with this revolutionary treatment. Quick specialized intervention is required for the unique side effects of this therapy.

Le lymphome B diffus à grandes cellules (LBDGC) est le type histologique de lymphome non Hodgkinien le plus fréquent. Le traitement de première ligne par immunochimiothérapie ne permet de guérir qu'environ 60 % des patients. Les patients présentant une maladie réfractaire à une première ligne de traitement ou en rechute dans les deux premières années suivant le traitement présentent un mauvais pronostic. Disponible depuis juin 2019, un nouveau traitement de 3ème ligne sous forme d'immunothérapie par CAR T cells (acronyme anglais de «chimeric antigen receptor T cells¼) semble modifier complètement le pronostic de ces patients, avec l'obtention d'une proportion importante de réponses complètes de longue durée. Les effets indésirables spécifiques liés à ce traitement demandent une prise en charge rapide et spécialisée.

[Multiple myeloma : an overview of advances in biology and treatment]. / Le myélome multiple : un tour d'horizon des nouveautés dans sa biologie et son traitement.

Multiple myeloma is the second most common hematological malignancy, characterized by an uncontrollable proliferation of clonal plasma cells. Although progresses in understanding its pathobiology and its treatment are made every day, it remains incurable. Since myeloma is more and more common, especially in the elderly, we would like to propose an overview of its pathobiology, diagnostic criteria and treatment «guidelines¼.

Deuxième pathologie hématologique la plus fréquente, le myélome multiple est une maladie plasmocytaire qui reste actuellement incurable. Pourtant, tous les jours, des progrès sont effectués au niveau de la compréhension de sa physiopathologie et de l'élaboration de stratégies de traitement. Vu son caractère de plus en plus répandu, surtout chez la personne âgée, nous proposons un tour d'horizon de sa physiopathologie, de ses critères diagnostiques et des grandes lignes de sa prise en charge.

[Anemia in patients with severe chronic obstructive pulmonary disease, a comorbity more common than previously thought]. / L'anémie dans la bronchopneumopathie chronique obstructive sévère : une comorbidité plus fréquente qu'on ne le croit.

Chronic Obstructive Pulmonary Disease (COPD) is traditionally associated with polycythemia which results from chronic hypoxemia. Nevertheless, recent studies have shown that anemia may be more frequent than expected in patients with COPD. In this retrospective study, we investigated the prevalence of hemoglobin disorders in a cohort of 100 patients with stable, moderate to severe COPD (II to IV GOLD classification). We identified 31 % patients with anemia while only 15 % had polycythemia. Anemia was more frequent in male patients. We also demonstrated a negative correlation between hemoglobin and CRP levels (R=-0.56, p inferior to 0.0001). COPD patients with anemia had experienced a higher rate of hospitalizations for exacerbation in the previous year than those with polycythemia (p inferior to 0.05). Anemia is a frequent comorbidity in COPD; it is associated with systemic inflammation and a propensity to hospitalization for exacerbation.

Il est classiquement rapporté qu'une polycythémie survient en réponse à une hypoxémie chez les patients souffrant de BronchoPneumopathie Chronique Obstructive (BPCO) sévère. Néanmoins, certaines données récentes ont souligné la présence d'une anémie dans une proportion non négligeable de cas. Nous avons évalué, dans une étude rétrospective, la prévalence des troubles de l'érythropoïèse au sein d'une cohorte de 100 patients BPCO stables (de stades II à IV selon la classification de GOLD). Une anémie était présente chez 31 % de ces sujets tandis qu'une polycythémie était retrouvée dans 15 % des cas. L'anémie était plus souvent observée dans le sexe masculin. Une corrélation inverse existait entre le taux d'hémoglobine et la CRP (r = - 0,56, p inférieur à 0,0001). Les patients BPCO avec anémie avaient été plus souvent hospitalisés pour exacerbation au cours de l'année précédente (p inférieur à 0,05). L'anémie est plus fréquente que la polycythémie chez le patient BPCO sévère; elle est associée à une inflammation systémique et à une tendance accrue aux hospitalisations pour exacerbation.

Cellular immunotherapy in multiple myeloma: lessons from preclinical models.

The majority of multiple myeloma patients relapse with the current treatment strategies, raising the need for alternative therapeutic approaches. Cellular immunotherapy is a rapidly evolving field and currently being translated into clinical trials with encouraging results in several cancer types, including multiple myeloma. Murine multiple myeloma models are of critical importance for the development and refinement of cellular immunotherapy. In this review, we summarize the immune cell changes that occur in multiple myeloma patients and we discuss the cell-based immunotherapies that have been tested in multiple myeloma, with a focus on murine models.

Allogeneic hematopoietic stem cell transplantation in solid organ transplant recipients: a retrospective, multicenter study of the EBMT.

We conducted a questionnaire survey of the 565 European Society for Blood and Marrow Transplantation centers to analyze the outcome of allogeneic hematopoietic stem cell transplantation (alloSCT) in recipients of solid organ transplantation (SOT). We investigated 28 patients with malignant (N = 22) or nonmalignant diseases (N = 6), who underwent 31 alloSCT procedures: 12 after kidney, 13 after liver and 3 after heart transplantation. The incidence of solid organ graft failure at 60 months after first alloSCT was 33% (95% confidence interval [CI], 16-51%) for all patients, 15% (95% CI, 2-40%) for liver recipients and 50% (95% CI, 19-75%) for kidney recipients (p = 0.06). The relapse rate after alloSCT (22%) was low following transplantation for malignant disorders, despite advanced stages of malignancy. Overall survival at 60 months after first alloSCT was 40% (95% CI, 19-60%) for all patients, 51% (95% CI, 16-86%) for liver recipients and 42% (95% CI, 14-70%) for kidney recipients (p = 0.39). In summary, we show that selected SOT recipients suffering from hematologic disorders may benefit from alloSCT and experience enhanced long-term survival without loss of organ function.

[Current management of marginal zone lymphomas]. / Prise en charge actueLe du lymphome de la zone marginale.

Marginal zone lymphomas (MZL) encompass three sub-types: MALT (Mucosae Associated Lymphoid Tissue) MZL, nodal MZL and splenic MZL. Immunophenotyping is essential for accurate diagnosis. Helicobacter Pylori is frequently associated with gastric localizations and its eradication can be sufficient for cure. Treatment of nodal MZL is similar to that of follicular lymphoma. Eradication of hepatitis C virus, frequently associated with splenic MZL development, can be sufficient. Without HCV infection, splenectomy constitutes first line therapy. As other indolent lymphomas, disseminated MZL are incurable and treatment should be started only in symptomatic patients.

A European patient record study on diagnosis and treatment of chemotherapy-induced anaemia.

PURPOSE: Patients with cancer frequently experience chemotherapy-induced anaemia (CIA) and iron deficiency. Erythropoiesis-stimulating agents (ESAs), iron supplementation and blood transfusions are available therapies. This study evaluated routine practice in CIA management. METHODS: Medical oncologists and/or haematologists from nine European countries (n=375) were surveyed on their last five cancer patients treated for CIA (n=1,730). Information was collected on tests performed at diagnosis of anaemia, levels of haemoglobin (Hb), serum ferritin and transferrin saturation (TSAT), as well as applied anaemia therapies. RESULTS: Diagnostic tests and therapies for CIA varied across Europe. Anaemia and iron status were mainly assessed by Hb (94%) and ferritin (48%) measurements. TSAT was only tested in 14%. At anaemia diagnosis, 74% of patients had Hb ≤ 10 g/dL, including 15% with severe anaemia (Hb <8 g/dL). Low-iron levels (ferritin ≤ 100 ng/mL) were detected in 42% of evaluated patients. ESA was used in 63%of patients, blood transfusions in 52 % and iron supplementation in 31% (74% oral, 26% intravenous iron). Only 30% of ESA-treated patients received a combination of ESA and iron supplementation. Blood transfusions formed part of a regular anaemia treatment regimen in 76% of transfused patients. Management practices were similar in 2009 and 2011. CONCLUSION: Management of anaemia and iron status in patients treated for CIA varies substantially across Europe. Iron status is only assessed in half of the patients. In contrast to clinical evidence, iron treatment is under utilised and mainly based on oral iron supplementation. Implementation of guidelines needs to be increased to minimize the use of blood transfusions.

[Utilisation of immunosuppressants in the prevention of a graft versus host reaction: report by the SFGM-TC]. / Immunosuppresseurs dans la prévention de la réaction du greffon contre l'hôte : rapport de la SFGM-TC.

In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the fourth annual series of workshops which brought together practitioners from all member centers and took place in September 2013 in Lille. Here we report our recommendations regarding the use of immunosuppressive treatment in the prevention of graft versus host disease: report by the SFGM-TC.

[Monoclonal gammopathies of undetermined significance - update for referring physicians]. / Gammapathie monoclonale de signification indéterminée : information destinée aux médecins referents.

Monoclonal gammopathies of undetermined significance (MGUS) are frequently diagnosed in the global population. Because of its possible transformation into a hematological malignancy, the identification of a MGUS requires a regular and generally long follow-up. However, this risk of transformation differs between the individuals and different laboratory criteria have been identified as predictive factors for progression and were combined in scoring systems that allow correct classification of individuals. The management of these patients needs to be adapted according to the calculated risk profile.

[Mesenchymal stromal cells and organ transplantation]. / Cellules stromales mésenchymateuses et transplantation d'organes.

Mesenchymal stromal cells (MSC) are multipotent and self-renewing cells. MSC are studied for their in vivo and in vitro immunomodulatory effects, in the prevention or the treatment of isehemic injury, and for their potential properties of tissue or organ reconstruction. Over the last few years, the potential role of MSC in organ transplantation has been studied both in vitro and in vivo, and their properties make them an ideal potential cell therapy after solid organ transplantation. A prospective, controlled, phase 1-2 study has been initiated at the CHU of Liege, Belgium. This study assesses the potential risks and benefits of MSC infusion after liver or kidney transplantation. Even if the preliminary results of this study look promising, solely a prospective, randomized, large scale, phase 3 study will allow the clinical confirmation of the theoretical benefits of MSC in solid organ transplantation.

[Allogeneic hematopoietic stem cell transplantation: what is the upper age limit?]. / Allogreffe de cellules souches hématopoïétiques chez le patient agé: jusqu' a quel age?

In the last decades, the upper age limit for allogeneic hematopoietic cell transplantation has increased from 50-60 years to 70-75 years of age, in part due to the development of allogeneic transplantation following reduced-intensity or truly nonmyeloablative conditioning. This review describes challenges and opportunities of allogeneic hematopoietic cell transplantation in the elderly.

[Clinical case of the month. Chemotherapy, immunodepression and secondary neoplasms: a case report]. / Chimiothérapie, immunodépression et cancers secondaires: rapport d'un cas clinique.

We report the case of a multi-metastatic mucinous adenocarcinoma of the colon discovered pre-mortem in a patient with a history of multiple myeloma. This case gives the opportunity to discuss the prognostic value of histological typing of colorectal cancer and secondary neoplasms to chemotherapy and/or immunodepression.