Summary
Background
Inflammatory bowel diseases (IBD) are chronic relapsing diseases in which pro‐inflammatory immune cells and cytokines induce intestinal tissue damage and disability. Mesenchymal ...stromal cells (MSCs) exert powerful immunomodulatory effects and stimulate tissue repair.
Aim
To review the current data on mesenchymal stromal cell therapy in IBD.
Method
We searched PubMed and ‘ClinicalTrials.gov’ databases using the terms ‘mesenchymal stromal cells’, ‘mesenchymal stem cell transplantation’, ‘inflammatory bowel diseases’, ‘Crohn disease’ and ‘colitis, ulcerative’. Additional publications were identified from individual article reference lists.
Results
MSCs include inhibition of Th1/Th17 lymphocytes and recruitment of regulatory T lymphocytes, induction of antigen‐presenting cells into a regulatory‐like profile, and stimulation of epithelial cell differentiation and proliferation. More than 200 patients with refractory fistulas have been treated with local injections of MSCs, resulting in complete response in more than half, and in overall response in approximately two thirds of patients. In refractory luminal Crohn's disease, 49 cases of systemic MSC infusions have been reported, while trials with autologous MSCs resulted in mitigated responses, studies using allogeneic MSCs were promising, with around 60% of patients experiencing a response and around 40% achieving clinical remission.
Conclusions
Mesenchymal stromal cells might represent a promising therapy for IBD, especially for Crohn's disease. There remain many unsolved questions concerning the optimal origin and source of mesenchymal stromal cells, dosage and modalities of administration. Moreover, mesenchymal stromal cells still need to prove their effectiveness compared with conventional treatments in randomised controlled trials.
Chronic diseases reduce the availability of iron for effective erythropoiesis. This review summarises clinical consequences of iron deficiency (ID) and anaemia in cancer patients, mechanisms how ...impaired iron homeostasis affects diagnosis and treatment of ID, and data from clinical trials evaluating i.v. iron with or without concomitant erythropoiesis-stimulating agents (ESAs).
Clinical trial reports were identified in PubMed and abstracts at relevant major congresses.
Reported prevalence of ID in cancer patients ranges from 32 to 60% and most iron-deficient patients are also anaemic. Randomised clinical trials have shown superior efficacy of i.v. iron over oral or no iron in reducing blood transfusions, increasing haemoglobin, and improving quality of life in ESA-treated anaemic cancer patients. Furthermore, i.v. iron without additional ESA should be evaluated as potential treatment in patients with chemotherapy-induced anaemia. At recommended doses, i.v. iron is well tolerated, particularly compared with oral iron. No serious drug-related adverse effects were seen during long-term use in renal disease and no effect on tumour growth has been observed in trials with anaemic cancer patients.
Reliable diagnosis and treatment of ID are recommended key steps in modern cancer patient management to minimise impact on quality of life and performance status.
Introduction La synthèse de PRL et de GH a été documentée dans le tissu lymphoïde normal. Une hyperprolactinémie paranéoplasique est rapportée chez quelques rares patients avec une leucémie (See et ...al. BMJ Case Rep 2013). Un seul cas d’acromégalie dépendante d’un lymphome non-Hodgkin a été publiée (Beuschlein et al. NEJM 2000) Observation Une femme africaine de 31 ans consulte pour fièvre et malaises, neuf mois post-partum : le bilan biologique et la biopsie de moelle confirment une leucémie myéloblastique aiguë. Malgré l’arrêt de l’allaitement, elle présente une galactorrhée et une aménorrhée persistante. Avant la première cure de chimio, la prolactine est de 6389 mUI/L. Un test au TRH documente ensuite une hyperprolactinémie à 3639 mUI/L (100–500) stimulable à 10 973 mUI/L. L’IGF1 est élevée à 429 μg/L (73–224). Un test HGPO 75 g démontre une GH basale à 0,64 μg/L avec un nadir de 0,11 μg/L. Au cours de 3 mois de séances de chimiothérapie, on observe une normalisation des paramètres hématologiques. Parallèlement, on observe une diminution progressive de la prolactine (3639–3617–396 mUI/L), de la GH (6,4–1,4–0,28) et de l’IGF1 (429–303–286). Une IRM hypohysaire n’objective pas de lésion hypothalamo-hypophysaire. Un scanner thoraco-abdominal et cérébral sont sans particularités. Discussion La normalisation progressive de prolactine et d’IGF1 au cours de la chimiothérapie et l’absence de lésion hypophysaire associée, rendent plausible une sécrétion paranéoplasique. Étant donné que l’échantillon de moelle était insuffisant cette hypothèse n’a pas pu être documentée.
Multiple myeloma is the second most common hematologic malignancy and occurs most commonly in elderly patients. Almost all multiple myeloma patients develop bone lesions in the course of their ...disease or have evidence of bone loss at initial diagnosis. Whole-body conventional radiography remains the gold standard in the diagnostic evaluation, but computed tomography, magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography are increasingly used as complementary techniques in the detection of bone lesions. Moreover, the number of lesions detected and the presence of extramedullary disease give strong prognostic information. These new techniques may help to assess treatment response in solitary plasmacytoma or in multiple myeloma. In this article, we review recent data on the different imaging techniques used at diagnosis and in the assessment of treatment response, and discuss some current issues.
Donor killer cell immunoglobulin-like receptor (KIR)-ligand incompatibility is associated with decreased relapse incidence (RI) and improved leukemia-free survival (LFS) after haploidentical and ...HLA-mismatched unrelated hematopoietic stem cell transplantation. We assessed outcomes of 218 patients with acute myeloid leukemia (AML n=94) or acute lymphoblastic leukemia (n=124) in complete remission (CR) who had received a single-unit unrelated cord blood transplant (UCBT) from a KIR-ligand-compatible or -incompatible donor. Grafts were HLA-A, -B or -DRB1 matched (n=21) or mismatched (n=197). Patients and donors were categorized according to their degree of KIR-ligand compatibility in the graft-versus-host direction by determining whether or not they expressed HLA-C group 1 or 2, HLA-Bw4 or HLA-A3/-A11. Both HLA-C/-B KIR-ligand- and HLA-A-A3/-A11 KIR-ligand-incompatible UCBT showed a trend to improved LFS (P=0.09 and P=0.13, respectively). Sixty-nine donor-patient pairs were HLA-A, -B or -C KIR-ligand incompatible and 149 compatible. KIR-ligand-incompatible UCBT showed improved LFS (hazards ratio=2.05, P=0.0016) and overall survival (OS) (hazards ratio=2.0, P=0.004) and decreased RI (hazards ratio=0.53, P=0.05). These results were more evident for AML transplant recipients (2-year LFS and RI with or without KIR-ligand incompatibility 73 versus 38% (P=0.012), and 5 versus 36% (P=0.005), respectively). UCBT for acute leukemia in CR from KIR-ligand-incompatible donors is associated with decreased RI and improved LFS and OS.
The Belgian Hematology Society (BHS) updated the 2013 guidelines for diagnosis and treatment of primary immune thrombocytopenia (ITP) 1. As knowledge about ITP pathophysiology is increasing, the mode ...of action of old therapies is better understood and novel drugs are introduced to target more specific pathways.
Corticosteroids with or without intravenous immunoglobulins (IgIV) remain the first-line treatment. According to the updated international guidelines a short course of corticosteroids rather than a prolonged treatment has to be recommended. The same guidelines stress that consequent therapies as thrombopoietic agents (TPO-RAs) and rituximab should be available independent of duration of ITP.
Although the majority of recommendations is based on very low-quality evidence, it is strongly advised to individualize the ITP management taking patient values. and preferences in account. The main treatment goal in all ITP patients must be to maintain a safe platelet count to prevent or stop bleeding with a minimum of toxicity and not to normalize the platelet count.
Acute kidney injury (AKI) represents a worldwide public health issue of increasing incidence, with a significant morbi-mortality. AKI treatment mostly relies on supportive manoeuvres in the absence ...of specific target-oriented therapy. The pathophysiology of AKI commonly involves ischaemia/reperfusion (I/R) events, which cause both immune and metabolic consequences in renal tissue. Similarly, at the time of kidney transplantation (KT), I/R is an unavoidable event which contributes to early graft dysfunction and enhanced graft immunogenicity. Mesenchymal stromal cells (MSCs) represent a heterogeneous population of adult, fibroblast-like multi-potent cells characterized by their ability to differentiate into tissues of mesodermal lineages. Because MSC have demonstrated immunomodulatory, anti-inflammatory and tissue repair properties, MSC administration at the time of I/R and/or at later times has been hypothesized to attenuate AKI severity and to accelerate the regeneration process. Furthermore, MSC in KT could help prevent both I/R injury and acute rejection, thereby increasing graft function and survival. In this review, summarizing the encouraging observations in animal models and in pilot clinical trials, we outline the benefit of MSC therapy in AKI and KT, and envisage their putative role in renal ischaemic conditioning.
Dans une démarche qui vise à uniformiser les procédures d’allogreffe de cellules souches hématopoïétiques (CSH), la Société française de greffe de moelle et de thérapie cellulaire (SFGM-TC), a ...organisé les quatrièmes ateliers d’harmonisation des pratiques en septembre 2013 à Lille. Dans cet atelier nous abordons les immunosuppresseurs utilisés 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.
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