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

Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF

Tissue-resident macrophages can develop from circulating adult monocytes or from primitive yolk sac-derived macrophages. The precise ontogeny of alveolar macrophages (AMFs) is unknown. By performing BrdU labeling and parabiosis experiments in adult mice, we found that circulating monocytes contributed minimally to the steady-state AMF pool. Mature AMFs were undetectable before birth and only fully colonized the alveolar space by 3 d after birth. Before birth, F4/80(hi)CD11b(lo) primitive macrophages and Ly6C(hi)CD11b(hi) fetal monocytes sequentially colonized the developing lung around E12.5 and E16.5, respectively. The first signs of AMF differentiation appeared around the saccular stage of lung development (E18.5). Adoptive transfer identified fetal monocytes, and not primitive macrophages, as the main precursors of AMFs. Fetal monocytes transferred to the lung of neonatal mice acquired an AMF phenotype via defined developmental stages over the course of one week, and persisted for at least three months. Early AMF commitment from fetal monocytes was absent in GM-CSF-deficient mice, whereas short-term perinatal intrapulmonary GM-CSF therapy rescued AMF development for weeks, although the resulting AMFs displayed an immature phenotype. This demonstrates that tissue-resident macrophages can also develop from fetal monocytes that adopt a stable phenotype shortly after birth in response to instructive cytokines, and then self-maintain throughout life

Low T-cell chimerism is not followed by graft rejection after nonmyeloablative stem cell transplantation (NMSCT) with CD34-selected PBSC.

peer reviewedWe investigate the feasibility of CD34-selected peripheral blood stem cell (PBSC) transplantation followed by pre-emptive CD8-depleted donor lymphocyte infusions (DLI) after a minimal conditioning regimen. Six patients with advanced hematological malignancies ineligible for a conventional myeloablative transplant (n=5) or metastatic renal cell carcinoma (n=1), and with an HLA-identical (n=4) or alternative (n=2) donor were included. The nonmyeloablative conditioning regimen consisted in 2 Gy TBI alone (n=4), 2 Gy TBI and fludarabine (RCC patient, n=1) or cyclophosphamide and fludarabine (patient who had previously received 12 Gy TBI, n=1). Post transplant immunosuppression was carried out with cyclosporin (CyA) and mycophenolate mofetil (MMF). Initial engraftment was achieved in all patients. One out of six patients (17%) experienced grade > or =2 acute GVHD only after abrupt cyclosporin discontinuation and alpha interferon therapy for life-threatening tumor progression. T-cell chimerism was 23% (19-30) on day 28, 32% (10-35) on day 100, 78% (49-95) on day 180 and 99.5% (99-100) on day 365. Three out of four patients who had measurable disease before the transplant experienced a complete response. We conclude that CD34-selected NMSCT followed by CD8-depleted DLI is feasible and preserves engraftment and apparently also the graft-versus-leukemia (GVL) effect. Further studies are needed to confirm this encouraging preliminary report

Cerebral toxoplasmosis following allogeneic hematopoietic peripheral blood stem cell transplantation with non-myeloablative conditioning

peer reviewedWe report the occurrence of a cerebral toxoplasmosis 52 days after a non-myeloablative allogeneic stem cell transplantation as treatment for acute myeloid leukemia.Nous présentons le cas d'un patient ayant hbénéficié d'une mini-allogreffe de cellules souches hématopoïétiques dusang périphérique pour une leucémie myéloïde aiguë qui développa une toxoplasmose cérébrale 52 jours après sa greffe

Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF

Tissue-resident macrophages can develop from circulating adult monocytes or from primitive yolk sac-derived macrophages. The precise ontogeny of alveolar macrophages (AMFs) is unknown. By performing BrdU labeling and parabiosis experiments in adult mice, we found that circulating monocytes contributed minimally to the steady-state AMF pool. Mature AMFs were undetectable before birth and only fully colonized the alveolar space by 3 d after birth. Before birth, F4/80hiCD11blo primitive macrophages and Ly6ChiCD11bhi fetal monocytes sequentially colonized the developing lung around E12.5 and E16.5, respectively. The first signs of AMF differentiation appeared around the saccular stage of lung development (E18.5). Adoptive transfer identified fetal monocytes, and not primitive macrophages, as the main precursors of AMFs. Fetal monocytes transferred to the lung of neonatal mice acquired an AMF phenotype via defined developmental stages over the course of one week, and persisted for at least three months. Early AMF commitment from fetal monocytes was absent in GM-CSF-deficient mice, whereas short-term perinatal intrapulmonary GM-CSF therapy rescued

Unsupervised High-Dimensional Analysis Aligns Dendritic Cells across Tissues and Species.

Dendritic cells (DCs) are professional antigen-presenting cells that hold great therapeutic potential. Multiple DC subsets have been described, and it remains challenging to align them across tissues and species to analyze their function in the absence of macrophage contamination. Here, we provide and validate a universal toolbox for the automated identification of DCs through unsupervised analysis of conventional flow cytometry and mass cytometry data obtained from multiple mouse, macaque, and human tissues. The use of a minimal set of lineage-imprinted markers was sufficient to subdivide DCs into conventional type 1 (cDC1s), conventional type 2 (cDC2s), and plasmacytoid DCs (pDCs) across tissues and species. This way, a large number of additional markers can still be used to further characterize the heterogeneity of DCs across tissues and during inflammation. This framework represents the way forward to a universal, high-throughput, and standardized analysis of DC populations from mutant mice and human patients

Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF

Tissue-resident macrophages can develop from circulating adult monocytes or from primitive yolk sac–derived macrophages. The precise ontogeny of alveolar macrophages (AMFs) is unknown. By performing BrdU labeling and parabiosis experiments in adult mice, we found that circulating monocytes contributed minimally to the steady-state AMF pool. Mature AMFs were undetectable before birth and only fully colonized the alveolar space by 3 d after birth. Before birth, F4/80(hi)CD11b(lo) primitive macrophages and Ly6C(hi)CD11b(hi) fetal monocytes sequentially colonized the developing lung around E12.5 and E16.5, respectively. The first signs of AMF differentiation appeared around the saccular stage of lung development (E18.5). Adoptive transfer identified fetal monocytes, and not primitive macrophages, as the main precursors of AMFs. Fetal monocytes transferred to the lung of neonatal mice acquired an AMF phenotype via defined developmental stages over the course of one week, and persisted for at least three months. Early AMF commitment from fetal monocytes was absent in GM-CSF–deficient mice, whereas short-term perinatal intrapulmonary GM-CSF therapy rescued AMF development for weeks, although the resulting AMFs displayed an immature phenotype. This demonstrates that tissue-resident macrophages can also develop from fetal monocytes that adopt a stable phenotype shortly after birth in response to instructive cytokines, and then self-maintain throughout life

Traitements actuels du lymphome folliculaire

After diffuse large B-cell lymphoma, follicular lymphoma is the most frequent non-Hodgkin's lymphoma. It remains incurable, except for localized diseases. Advanced disease has to be treated only in the presence of clinical and/or biology aggressiveness. These patients should be treated by rituximab (Mab-Thera) associated to polychemotherapy comprising cyclophosphamide, vincristine and prednisone. After this therapy, the benefit of rituximab in maintenance has to be confirmed. Autologous stem cell transplantation is also an interesting option. The other therapeutic options comprise radio-immunotherapy with 90Y ibritumomab tiuxetan (Zevalin) and bortezomib (Velcade).Lymphome le plus fréquent après le lymphome B diffus à grandes cellules, le lymphome folliculaire de stade avancé reste incurable. Les formes avancées ne doivent être traitées qu'en présence de signes cliniques et/ou biologiques signant l'agressivité de la maladie. Le traitement de première ligne associe le rituximab (MabThera) à la polychimiothérapie à base de cyclophosphamide, vincristine et prednisone. Après ce traitement, le bénéfice du rituximab en maintenance doit être validé. L'autogreffe de moelle est réservée au traitement des rechutes des patients jeunes. L'allogreffe de moelle est une option intéressante pour les patients éligibles. Les autres options thérapeutiques disponibles en cas de rechute comprennent l'immuno-radiothérapie par 90Y-ibritumomab tiuxétan (Zevalin) et, plus récemment, le bortézomib (Velcade)

Lymphome du manteau : prise en charge 2011

Le lymphome du manteau (LM) représente 6% des lymphomes non hodgkiniens (LNH). Le diagnostic repose sur l'immunophénotypage et la démonstration de la présence de la location entre les chromosomes 11 et 14, avec surexpression de la cycline D1. Le traitement de première ligne du sujet jeune associe trois cures de R-CHOP21 alternées avec trois cures de R-DHAP21, suivies d'une autogreffe conditionnée par irradiation corporelle totale, cyclophosphamide et aracytine. Le sujet de plus de 65 ans peut bénéficier de huit cures de R-CHOP21. L'intérêt du traitement de maintenance est en cours d'évaluation. L'allogreffe de cellules souches hématopoïétiques offre une chance de guérison aux patients en rechute en bon état général. Les traitements ciblés permettront une amélioration du pronostic de cette maladie