Time filter

Source Type

PubMed | Service dHematologie Clinique et de Therapie Cellulaire, University of Paris Pantheon Sorbonne, Paris Center Necker Cochin, Saint Louis Hospital and 2 more.
Type: | Journal: Leukemia | Year: 2016

Clinically useful pre-transplant predictive factors of acute graft-versus-host-disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-SCT) are lacking. We prospectively analyzed HSC graft content in CD34


D'Aveni M.,University of Paris Descartes | D'Aveni M.,University Paris - Sud | D'Aveni M.,Paris-Sorbonne University | Rossignol J.,University of Paris Descartes | And 31 more authors.
Science Translational Medicine | Year: 2015

Granulocyte colony-stimulating factor (G-CSF) is routinely used to collect peripheral blood stem cells (PBSCs) from healthy donors for allogeneic hematopoietic stem cell transplantation (allo-HSCT). We show that, in both humans and mice, G-CSF mobilizes a subset of CD34+ cells with mature monocyte features. These cells, which are phenotypically and functionally conserved in mice and humans, are transcriptionally distinct from myeloid and monocytic precursors but similar to mature monocytes and endowed with immunosuppressive properties. In response to interferon-γ released by activated T cells, these cells produce nitric oxide, which induces allogeneic T cell death both in vitro and in vivo. These apoptotic T cells are engulfed by macrophages that release transforming growth factor-β and promote regulatory T cell expansion. Indeed, the fraction of CD34+ monocytes in peripheral blood CD34+ cells inversely correlates with the incidence of acute graft-versus-host disease (GVHD) in humans. Therefore, G-CSF-mobilized cells are an attractive candidate population to be expanded ex vivo for cellular therapy against GVHD. Copyright 2015 by the American Association for the Advancement of Science; all rights reserved.


Deschamps R.,Rothschild | Gueguen A.,Rothschild | Parquet N.,Unite d'hemapherese therapeutique | Saheb S.,Service d'hematologie clinique et de Therapie Cellulaire | And 6 more authors.
Journal of Neurology | Year: 2016

Optic neuritis could lead to severe visual impairment despite corticosteroids. Our aim was to evaluate the rate of visual improvement in patients treated with plasma exchange (PLEX) for severe steroid unresponsive optic neuritis and to identify predictive factors of outcome. Thirty-four patients (41 optic nerves damaged) with remaining visual acuity of 0.1 or less despite steroid pulse therapy were treated with PLEX from September 2010 to May 2015. Demographic and clinical neuro-ophthalmic findings, and spectral domain-optical coherence tomography data before PLEX treatment were analyzed. The mean symptom duration before PLEX was 34.6 days (median 28 days; range 6–92 days). After PLEX, the median final visual acuity was 0.8 and in 56 % of cases, final acuity was 0.5 or better. Past history of ipsilateral optic neuritis was associated significantly with poor outcome defined as final acuity less than 0.5. No significant difference in the visual outcome after PLEX was found between multiple sclerosis and neuromyelitis optica. In conclusion, this observational study showed that PLEX as second-line therapy led to a functionally important visual recovery in more than half patients with severe optic neuritis. © 2016, Springer-Verlag Berlin Heidelberg.


PubMed | Service dHemato Oncologie Pediatrique, Service dhematologie clinique et de therapie cellulaire, Service de Reanimation Pediatrique, Assistance Publique Hopitaux de Paris and Service de Reanimation Medicale
Type: | Journal: Hematological oncology | Year: 2016

Trichosporon has recently emerged as a life-threatening opportunistic fungal pathogen, notably in patients with hematological malignancy. Fungemia, sometimes associated with cutaneous lesions and/or pneumonitis, is the major clinical form. Here, we report two cases of patients suffering from acute leukaemia who developed hepatic and/or splenic lesions apart from Trichosporon positive blood cultures. The appearance of hepatic and splenic lesions following the recovery from neutropenia is highly suggestive of a chronic disseminated infection, now considered as an immune reconstitution inflammatory syndrome. Treatment with corticosteroid therapy led to clinical improvement in both cases. Copyright 2016 John Wiley & Sons, Ltd.


PubMed | Service dhematologie clinique et de Therapie Cellulaire, Hopital University Bicetre, Rothschild and Unite dhemapherese therapeutique
Type: Journal Article | Journal: Journal of neurology | Year: 2016

Optic neuritis could lead to severe visual impairment despite corticosteroids. Our aim was to evaluate the rate of visual improvement in patients treated with plasma exchange (PLEX) for severe steroid unresponsive optic neuritis and to identify predictive factors of outcome. Thirty-four patients (41 optic nerves damaged) with remaining visual acuity of 0.1 or less despite steroid pulse therapy were treated with PLEX from September 2010 to May 2015. Demographic and clinical neuro-ophthalmic findings, and spectral domain-optical coherence tomography data before PLEX treatment were analyzed. The mean symptom duration before PLEX was 34.6 days (median 28days; range 6-92 days). After PLEX, the median final visual acuity was 0.8 and in 56% of cases, final acuity was 0.5 or better. Past history of ipsilateral optic neuritis was associated significantly with poor outcome defined as final acuity less than 0.5. No significant difference in the visual outcome after PLEX was found between multiple sclerosis and neuromyelitis optica. In conclusion, this observational study showed that PLEX as second-line therapy led to a functionally important visual recovery in more than half patients with severe optic neuritis.


Hirsch P.,Service dHematologie Clinique et de Therapie Cellulaire | Hirsch P.,University Pierre and Marie Curie | Qassa G.,Service dHematologie Clinique et de Therapie Cellulaire | Marzac C.,University Pierre and Marie Curie | And 12 more authors.
Leukemia and Lymphoma | Year: 2015

The benefit associated with chemotherapy in older patients with acute myeloid leukemia (AML) is debated. The prognostic impact of molecular mutations in these patients is unknown. We identified 79 patients with AML aged 75 years or over. Forty-two received chemotherapy and 37 supportive care only. In intensively treated patients, overall survival was longer (p < 0.001). Achieving complete remission was associated with longer survival (p < 0.001). NPM1 mutations tended to be associated with a higher complete remission rate (p = 0.12). In multivariate analysis, FLT3-ITD was associated with poorer survival (p = 0.049). Patients harboring FLT3-ITD and no NPM1 mutation had a poorer prognosis than others (p = 0.02). Intensive treatments can benefit a portion of elderly patients. FLT3-ITD and NPM1 mutational status might be useful for prognosis stratification. © 2014 Informa UK, Ltd.


Mohty M.,Service dHematologie Clinique et de Therapie Cellulaire | Mohty M.,French Institute of Health and Medical Research | Mohty M.,University Pierre and Marie Curie | Brissot E.,University Pierre and Marie Curie | And 3 more authors.
Biology of Blood and Marrow Transplantation | Year: 2013

Bortezomib, the first-in-class proteasome inhibitor, has become one of the standard treatments in multiple myeloma. The agent is thought to exert its antimyeloma effects through the inhibition of NF-κB. However, evidence suggests that bortezomib also affects additional cell survival pathways, such as the p44/42 mitogen-activated protein kinase pathway, and inhibitory effects on IL-6, TNF-α, and vascular endothelial growth factor have also been demonstrated. These diverse effects have prompted the investigation of bortezomib's activity in various immune and inflammatory processes. This review summarizes the data reported with bortezomib in the prevention of graft-versus-host disease, antibody-mediated graft rejection, and anti-angiogenesis and in the treatment of rheumatoid arthritis, multiple sclerosis, and other inflammatory diseases. The positive results obtained suggest a role for bortezomib in these different indications, and therefore further investigations are warranted. © 2013 American Society for Blood and Marrow Transplantation.


Pascal L.,Lille Catholic University | Pascal L.,Laboratoire dImmunologie HLA | Mohty M.,Service dHematologie Clinique et de Therapie Cellulaire | Mohty M.,University Pierre and Marie Curie | And 13 more authors.
Bone Marrow Transplantation | Year: 2015

This study aimed to assess the impact of antithymocyte globulin (ATG) on patient outcome in a retrospective series of 91 patients (median age: 12 years) who underwent unrelated single-unit cord blood transplantation (allo-CBT) following a myeloablative conditioning regimen. Cord blood units were HLA-matched (6/6, n=18; 21%), one-Ag mismatched (n=30, 35%) or two-Ag mismatched (n=38; 44%). In this series, the OS, nonrelapse mortality (NRM) and cumulative incidence of relapse were 47±6%, 23±4% and 48±5%, respectively. Among 46 patients who received ATG as part of the conditioning regimen, the incidence of acute and chronic GVHD was lower than that in the group of 45 patients who did not receive ATG (20% vs 43%; P=0.03). However, multivariate statistical analysis revealed that the ATG use was associated with decreased OS and EFS rates and a high incidence of NRM (hazard ratio (HR)=1.99, 95% confidence interval (CI): 1.11-3.59, P=0.02), (HR=1.83, 95% CI: 1.08-3.10, P=0.02) and (HR=2.54, 95% CI: 1.03-6.26, P=0.04), respectively. Therefore, our results do not support the use of ATG as part of a myeloablative-conditioning regimen before single-unit allo-CBT in younger patients with hematological malignancies. © 2015 Macmillan Publishers Limited.


Arbez J.,French Institute of Health and Medical Research | Arbez J.,University of Franche Comte | Saas P.,French Institute of Health and Medical Research | Saas P.,University of Franche Comte | And 10 more authors.
Cytotherapy | Year: 2015

Background aims: This study aimed to characterize the immune effectors contained in the grafts from donor mice mobilized by granulocyte colony-stimulating factor (G-CSF) and plerixafor and to evaluate their impact on the development of acute graft-versus-host-disease (aGVHD). Methods: Mobilization was done with G-CSF alone or G-CSF plus plerixafor (G+P). Results: In grafts collected after G+P mobilization, we observed a significantly higher proportion of c-kit+Sca-1+ hematopoietic stem cells compared with G-CSF. A significant increase in the percentage of plasmacytoid dendritic cells was detected in the G+P graft compared with G-CSF graft. We also studied the ability of stem cell grafts mobilized with G+P to induce GVHD in a mouse model. We observed higher mortality (P < 0.001) associated with increased aGVHD clinical score (P < 0.0001) as well as higher pathology score in the intestine of mice receiving G+P as compared with G-CSF grafts (P < 0.001). Moreover, the exacerbated aGVHD severity was associated with upregulation of CCR6 expression on both CD4+ and CD8+ T cells from the G+P grafts, as well as on T cells from mice transplanted with G+P grafts. Conclusions: In conclusion, we showed that grafts mobilized with G+P exhibited functional features different from those mobilized with G-CSF alone, which increase the severity of aGVHD in the recipients. © 2015 International Society for Cellular Therapy.


Forcade E.,Service dHematologie clinique et de Therapie cellulaire | Leguay T.,Service dHematologie clinique et de Therapie cellulaire | Vey N.,Institute Paoli Calmettes | Baruchel A.,Service dImmuno Hematologie | And 6 more authors.
Biology of Blood and Marrow Transplantation | Year: 2013

T-ALL relapsing after allogeneic stem cell transplantation is unusual but classically associated with poor outcome. Recently, encouraging results have been reported with Nelarabine in relapse or refractory cases. On behalf of the Group of Research in Adult ALL (GRAALL), we conducted a retrospective analysis of patients receiving Nelarabine following relapse after transplantation. Eleven patients received Nelarabine as salvage therapy in this situation. Most of them were transplanted in first Complete Remission (CR), and received a myeloablative conditioning regimen in 7 cases. Relapse occurred with a median time of 199 days. Nelarabine was given at 1.5g/m2/day (Day 1, D3, D5) alone (N = 5) or in association (N = 6). The overall hematological response rate was 81%. Neurologic toxicity represents the main adverse event (N = 4), mainly gradeI-II. Event free survival and overall survival at 1 year were 70 and 90% respectively. Nelarabine is a valuable option for salvage therapy in T-cell acute lymphoblastic leukemia relapsing after transplantation. © 2013 American Society for Blood and Marrow Transplantation.

Loading Service dHematologie Clinique et de Therapie Cellulaire collaborators
Loading Service dHematologie Clinique et de Therapie Cellulaire collaborators