Le lymphome du manteau

peer reviewedLe lymphome du manteau représente 3 à 10% des lymphomes non hodgkiniens (LNH). Il est caractérisé par la translocation chromosomique t(11;14) (q13;32), qui est responsable d'une surexpression de la cycline D1. Cette dernière participe à l'oncongenèse en favorisant la progression du cycle cellulaire. L'âge médian au moment du diagnostic est compris entre 60 et 70 ans et le pronostic est assez sombre puisque la survie médiane est estimée à 4 ans. Chez la plupart des patients, le diagnostic est posé à un stade avancé de la maladie. Des sites extra-ganglionnaires sont souvent atteints. Le traitement actuel de première ligne est basé sur de la poly-chimiothérapie suivie, chez les patients jeunes, par une autogreffe de cellules souches hématopoïétiques. L'allogreffe de cellules souches hématopoïétiques après un conditionnement non-myéloablateur pourrait jouer un rôle chez les patients en rechute après autogreffe.Mantle cell lymphoma comprises 3 to 10% of non-Hodgkin's lymphomas. Cyclin D1 expression due to t(11;14) (q13;32) is considered as a hallmark of this lymphoma and plays a pivotal role in the pathophysiology of lymphoma transformation. Median age at diagnosis ranges from 60 to 70 years, and diagnosis is often made at an advances stage with widespread lymphadenopathy and extranodular (particularly bone marrow and gastrointestinal) infiltration. First line treatment consists of combination chemotherapy followed with autologous hematopoietic cell transplantation (HCT) in younger patients, while allogeneic HCT following non-myeloablative conditioning might have a role inpatients relapsing after autologous HCT

Erythropoietin therapy after allogeneic hematopoietic cell transplantation : a prospective randomized trial

We conducted a prospective randomized trial to assess hemoglobin (Hb) response to recombinant human erythropoietin (rhEPO) therapy after hematopoietic cell transplantation (HCT). Patients (n=131) were randomized (1:1) between no treatment (control arm) or erythropoietin (Neorecormon®) at 500 U/kg/week (EPO arm). Patients were also stratified in 3 cohorts: patients undergoing myeloablative HCT with rhEPO to start on day 28, patients given nonmyeloablative HCT (NMHCT) with rhEPO to start on day 28, and patients also given NMHCT but with rhEPO to start on day 0. The proportion of complete correctors (i.e. achieving Hb ≥ 13 g/dL) before day 126 post-transplant (primary endpoint) was 8.1% in the control arm (median not reached) and 63.1% in the EPO arm (median time 90 days) (p<0.001). Hb levels were higher and transfusions requirements decreased (p<0.001) in the EPO arm, but not during the first month in the nonmyeloablative cohort starting rhEPO on day 0. There was no difference in rates of thrombo-embolic events or other complications between the 2 arms. This is the first randomized trial to demonstrate that rhEPO therapy hastens erythroid recovery and decreases transfusion requirements when started one month after allogeneic HCT. There was no benefit to start rhEPO earlier after NMHCT

Erythroferrone and hepcidin as mediators between erythropoiesis and iron metabolism during allogeneic hematopoietic stem cell transplant.

Hematopoietic cell transplantation (HCT) brings important alterations in erythropoiesis and iron metabolism. Hepcidin, which regulates iron metabolism, increases in iron overload or inflammation and decreases with iron deficiency or activated erythropoiesis. Erythroferrone (ERFE) is the erythroid regulator of hepcidin. We investigated erythropoiesis and iron metabolism after allogeneic HCT in 70 patients randomized between erythropoietin (EPO) treatment or no EPO, by serially measuring hepcidin, ERFE, CRP (inflammation), soluble transferrin receptor (sTfR, erythropoiesis), serum iron and transferrin saturation (Tsat; iron for erythropoiesis) and ferritin (iron stores). We identified biological and clinical factors associated with serum hepcidin and ERFE levels. Serum ERFE correlated overall with sTfR and reticulocytes and inversely with hepcidin. Erythroferrone paralleled sTfR levels, dropping during conditioning and recovering with engraftment. Inversely, hepcidin peaked after conditioning and decreased during engraftment. Erythroferrone and hepcidin were not significantly different with or without EPO. Multivariate analyses showed that the major determinant of ERFE was erythropoiesis (sTfR, reticulocytes or serum Epo). Pretransplant hepcidin was associated with previous RBC transfusions and ferritin. After transplantation, the major determinants of hepcidin were iron status (ferritin at all time points and Tsat at day 56) and erythropoiesis (sTfR or reticulocytes or ERFE), while the impact of inflammation was less clear and clinical parameters had no detectable influence. Hepcidin remained significantly higher in patients with high compared to low pretransplant ferritin. After allogeneic HCT with or without EPO therapy, significant alterations of hepcidin occur between pretransplant and day 180, in correlation with iron status and inversely with erythroid ERFE

Evaluation et prise en charge de la surcharge en fer post-greffe recommandations de la SFGM-TC

peer reviewedAssessment and management of post-transplant iron overload: Guidelines of the Francophone Society of Marrow Transplantation and Cellular Therapy (SFGM-TC) To harmonize clinical practice in hematopoietic stem cell transplantation, the Francophone Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the sixth annual series of workshops which brought together practitioners from all member centers and took place in September 2015 in Lille. The main aim of this session was to describe the impact, evaluation and treatment of post-transplant iron overload

Real-World Insights on the Management of Immune-Mediated Thrombotic Thrombocytopenic Purpura (iTTP) With Caplacizumab

peer reviewe

Iron sucrose - characteristics, efficacy and regulatory aspects of an established treatment of iron deficiency and iron-deficiency anemia in a broad range of therapeutic areas

Introduction: Iron is a key element in the transport and utilization of oxygen and a variety of metabolic pathways. Iron deficiency is a major cause of anemia and can be associated with fatigue, impaired physical function and reduced quality of life. Administration of oral or intravenous (i.v.) iron is the recommended treatment for iron-deficiency anemia (IDA) in different therapeutic areas. Areas covered: This article provides an overview of studies that evaluated i.v. iron sucrose for anemia and iron status management, either alone or in combination with erythropoiesis-stimulating agents, across various diseases and conditions. Expert opinion: Iron sucrose is an established, effective and well-tolerated treatment of IDA in patients with acute or chronic conditions such as chronic kidney disease, inflammatory bowel disease, pregnancy (second and third trimester), postpartum period, heavy menstrual bleeding and cancer who need rapid iron supply and in whom oral iron preparations are ineffective or not tolerated. Available data on patient blood management warrant further studies on preoperative iron treatment. First experience with iron sucrose follow-on products raises questions about their therapeutic equivalence without comparative clinical data in newly diagnosed patients or patients on existing chronic treatment

Erythropoiesis and iron metabolism after hematopoietic stem cell transplantation

After hematopoietic stem cell transplantation (HCT), many patients present anemia, which can persist for months due to an inadequate Epo production for the degree of the anemia. In this thesis, we performed two randomized studies with erythropoiesis-stimulating agents (ESA) therapy after allogeneic (including myeloablative and non-myeloablative conditioning) and autologous transplantation. We showed a great efficacy of this growth factor to ensure full erythroid reconstitution when initiated soon after engraftment, and not immediately after the transplant. Furthermore, as iron parameters are quite disturbed following HCT, we sought to study iron metabolism after HCT (which has not been much investigated), integrating the role of hepcidin, the key regulator in iron metabolism. Hence, we demonstrated that hepcidin levels prior to and following autologous HCT were influenced by iron stores and changes in erythropoietic activit

Erythropoietin therapy after allogeneic hematopoietic cell transplantation : a prospective randomised trial.

Based on the impairment of erythropoietin production after allogeneic hematopoietic cell transplantation (HCT), we previously reported in a phase-2 trial that recombinant human erythropoietin (rhEPO) therapy was very efficient when started one month after transplantation. We also demonstrated that anemia after nonmyeloabalative (NM) HCT was less sensitive to rhEPO therapy than after conventional allogeneic HCT. This prompted us to confirm these findings in a prospective randomised trial. One hundred and thirty-one patients were randomised (1:1) between no treatment (arm 1) or erythropoietin (Neorecormon) at the dose of 500 U/kg/week (arm 2). Once the target Hb (13g/dL) has been attained, the dose of rhEPO was reduced by half, while it was withheld when Hb was = 14g/dL. Cohort A included 42 patients on day 28 after myeloablative HCT, cohort B 39 patients on day 28 after NMHCT, and cohort C 50 patients on day 0 of NMHCT. Primary endpoints included proportion of complete correctors (i.e. patients reaching Hb = 13g/dL) and median time to achieve Hb correction in each arm. The proportion of complete correctors before day 126 posttransplant was 0% in group 1A vs 52.4% in group 2A, 0% in group 1B vs 69.5% in group 2B and 19.1% in group 1C vs 70.2% in group 2C. Median time to achieve Hb = 13g/dL was not reached in group 1B vs 49 days in group 2B; 363 and 59 days in groups 1A and 1B respectively and 363 and 87 days in groups 3A and 3B respectively (figure 1). Hb evolution in each group is shown in figure 2. Seventyone patients (47/62 in control groups and 24/57 in treated groups, p=0.0003) required red blood cell transfusions. The difference was most pronounced in cohort B. There was no difference in rates of thrombo-embolic events or other complications between the two arms. In conclusion, this is the first trial to demonstrate that EPO therapy hastens erythroid recovery and decreases transfusion requirements when started one month after allogeneic HCT

Hemophagocytic lymphohistiocytosis on Epstein-Barr Virus reactivation

peer reviewedNous présentons le cas d’une patiente âgée de 43 ans se présentant aux urgences pour altération de l’état général et pour dyspnée. Cette patiente est sous immunosuppresseurs dans le cadre d’une maladie de Behçet et va développer un lymphome ainsi qu’une lymphohistiocytose hémophagocytaire suite à une réactivation de l’Epstein- Barr Virus (EBV). Ce cas clinique permet de présenter une brève revue de littérature sur la lymphohistiocytose hémophagocytaire (LHH)