Search

Despite modern antimicrobial treatments, bacterial and fungal infections remain major complications in neutropenic patients. Granulocyte transfusions appeared in the 1950s-60s but first clinical trials were limited by the difficulty of transfusing enough viable granulocytes. The refinement of apheresis techniques as well as donor pretreatment with corticosteroids and/or granulocyte colony-stimulating growth factor (G-CSF) have led to improved collection yield. Despite this, uncertainties remain regarding the real clinical usefulness of granulocyte transfusions. Few studies have been carried out since the G-CSF era and the quality of scientific evidence remains low, mainly because of small case series. The largest prospective randomized controlled study published so far failed to demonstrate any benefit of therapeutic granulocyte transfusions on mortality or infection control. However, the quality of this trial is limited due to its low statistical power (insufficient patient recruitment). Moreover, granulocyte transfusions are complex procedures, burdensome for the donor, expensive and associated with a significant risk of adverse effects. Therefore, the current place of granulocyte transfusion in clinical practice is guided by the experience of each center. With the increasing emergence of multi-resistant germs, it is likely that granulocyte transfusion will become interesting in the coming years. Standardization of collection and administration procedures and the final proof of their (in)effectiveness will remain the challenges for the future.

Chimeric antigen receptor T cells (also known as CAR-T cells) have already made their way into the therapeutic arsenal of specific hematological cancers, significantly improving the prognosis of patients. The prospect of such an innovative and effective treatment in solid tumors is very attractive. For this reason, several clinical studies have been initiated. Unfortunately, the antigenic heterogeneity and microenvironmental hostility of these solid tumors currently limit the effectiveness of CAR-T cells. New strategies are being sought to counteract these therapeutic obstacles.

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 tumour» 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.

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.

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.

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.

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.

Fever of unknown origin (FUO), with more than 200 potential causes, can represent a real diagnostic challenge. For the work-up of FUO, the first step is to pay attention to each element revealed by a detailed history, a complete physical examination and by some basic diagnostic tests. These elements may constitute some clues that can guide the physician for the prescription of further appropriate diagnostic examinations and procedures. If there is no real specific clues,a pet-scan seems to be useful for the work-up of FUO.

Chronic Graft-Versus-Host Disease (GVHD) is a frequent complication of allogeneic hematopoietic cell transplantation. This review article describes recent advances in the classification and treatment of chronic GVHD.

Cerebral venous thrombosis is a rare cause of stroke. Clinical presentation is not very specific and can be very variable. Imaging establishes the diagnosis in the majority of cases. Specially, magnetic resonance venography has high sensitivity and is presently the gold standard. Long term prognosis of cerebral venous thrombosis is generally good and few patients remain handicapped in the long term. Evolution is however unpredictable. Treatment strategies follow three axes: anti-thrombotic treatment, symptomatic measures and treatment of the cause if one is found.

Electroconvulsive therapy (formerly called sismotherapy, electronarcosis or shock therapy) is a therapeutic tool used in several psychiatric illnesses. It consists in the induction of a generalized convulsive seizure by a transcranial electric stimulation. If it is true that this tool continues to stigmatise the collective imagination in giving rise to dread and suspicion (considered by some people as a barbarian or obsolete therapy), it is however an effective (sometimes irreplaceable) and well tolerated treatment. Over the last decades, ECT has generated renewed interest in psychiatric therapy. It constitutes today the oldest biological therapeutic tool still in use in psychiatry.