Service dHematologie Adultes

Paris, France

Service dHematologie Adultes

Paris, France
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Delarue R.,Service dHematologie Adultes | Tilly H.,University of Rouen | Mounier N.,Nice University Hospital Center | Petrella T.,CHU de Dijon | And 20 more authors.
The Lancet Oncology | Year: 2013

Background: Immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has become the standard of care for elderly patients with diffuse large B-cell lymphoma. We aimed to ascertain if a dose-dense R-CHOP regimen administered every 2 weeks (R-CHOP14) was superior to the standard 3-week schedule (R-CHOP21). Methods: We did a randomised phase 3 trial at 83 centres in four countries. 602 patients aged 60-80 years with untreated diffuse large B-cell lymphoma and at least one adverse prognostic factor (age-adjusted international prognostic index ≥1) were eligible for the study. We randomly allocated individuals to R-CHOP-ie, rituximab (375 mg/m2), cyclophosphamide (750 mg/m2), doxorubicin (50 mg/m2), vincristine (1·4 mg/m2, up to 2 mg) all on day 1, and prednisone 40 mg/m2 daily for 5 days-administered every 14 days (n=304) or every 21 days (n=298) for eight cycles. We did permuted-block randomisation (block size four, allocation ratio 1:1) stratified by centre and number of adverse prognostic factors. The primary endpoint was event-free survival. Our analysis was of the intention-to-treat population, and we present the final analysis. This study is registered with ClinicalTrials.gov, number NCT00144755. Findings: Two patients allocated R-CHOP21 were ineligible for the study and were excluded from analyses. After median follow-up of 56 months (IQR 27-60), 3-year event-free survival was 56% (95% CI 50-62) in the R-CHOP14 group and 60% (55-66) in the R-CHOP21 group (hazard ratio 1·04, 95% CI 0·82-1·31; p=0·7614). Grade 3-4 neutropenia occurred in 224 (74%) of 304 patients allocated R-CHOP14 and 189 (64%) of 296 assigned R-CHOP21, despite increased use of granulocyte colony-stimulating factor in the R-CHOP14 group compared with the R-CHOP21 group. 143 (47%) patients in the R-CHOP14 group received at least one red-blood-cell transfusion versus 93 (31%) in the R-CHOP21 group (p=0·0001). 35 (12%) patients allocated R-CHOP14 received at least one platelet transfusion versus 25 (8%) assigned R-CHOP21 (p=0·2156). 155 (51%) patients who were assigned R-CHOP14 had at least one serious adverse event compared with 140 (47%) who were allocated R-CHOP21. Interpretation: In elderly patients with untreated diffuse large B-cell lymphoma and at least one adverse prognostic factor, a 2-week dose-dense R-CHOP regimen did not improve efficacy compared with the 3-week standard schedule. The frequency of toxic side-effects was similar between regimens, but R-CHOP14 was associated with increased need for red-blood-cell transfusion. Funding: Groupe d'Etude des Lymphomes de l'Adulte (GELA), Amgen. © 2013 Elsevier Ltd.


Fitoussi O.,Service dOnco Hematologie | Haioun C.,Unite Hemopathies Lymphoides | Haioun C.,University Paris Est Creteil | Thieblemont C.,Hospital Saint Louis | And 8 more authors.
European Journal of Cancer | Year: 2013

This multicentre, single-arm, open-label phase 2 trial investigated the efficacy and safety of lenalidomide monotherapy in patients with relapsed/refractory peripheral T-cell lymphoma (PTCL). Methods Patients received oral lenalidomide 25 mg once daily on days 1-21 of each 28-day cycle for a maximum of 24 months, until disease progression or development of unacceptable adverse events (AEs). The primary end-point was efficacy; safety was evaluated as a secondary end-point. This study was registered with ClinicalTrials.gov, number NCT00655668. Findings A total of 54 patients with PTCL were treated. The overall response rate was 22% (12 of 54), including complete response (CR) or unconfirmed CR (CRu) in 11% of patients; 31% of patients with angioimmunoblastic T-cell lymphoma (AITL) responded (CR/CRu in 15% of patients). The median progression-free survival and median response duration were 2.5 and 3.6 months, respectively, in the intent-to-treat population, and 4.6 and 3.5 months, respectively, in patients with AITL. Thrombocytopenia and neutropenia were the most common grade 3 or 4 haematological AEs, in 11 (20%) and 8 (15%) patients, respectively. Overall, 19 patients (35%) experienced at least 1 AE leading to study dose interruption or reduction (commonly neutropenia or thrombocytopenia). Serious AEs were observed in 54% of patients and 12 patients died during the study; lymphoma progression (n = 6); and acute respiratory distress syndrome, dyspnea, lung infiltration, neutropenic sepsis, pneumonia and cerebral ischaemia (n = 1 each). Interpretation Lenalidomide exhibited single-agent activity in heavily pretreated patients with PTCL, particularly in patients with AITL. Future development is warranted in specific histologies, such as AITL, and in combination with chemotherapy or other agents considered active in PTCL. Funding Celgene Corporation. © 2013 Elsevier Ltd. All rights reserved.


Lefrere F.,Groupe Hospitalier Necker Enfants Malades | Brignier A.-C.,Service de Biotherapie | Elie C.,University of Paris Descartes | Ribeil J.-A.,Service de Biotherapie | And 6 more authors.
Advances in Therapy | Year: 2011

Introduction: Mobilization techniques for autologous peripheral blood stem cell (PBSC) collection include chemotherapy followed by hematopoietic growth factors, such as granulocyte colony-stimulating factor (G-CSF). Biosimilar versions of G-CSF are now available in Europe. Methods: In this study, 40 patients with a hematological malignancy scheduled to receive biosimilar G-CSF (Zarzio®, Sandoz Biopharmaceuticals, Paris, France) following first-cycle chemotherapy for treatment and autologous PBSC mobilization were prospectively included at a single center. These patients were compared with a historical control group who had been treated with G-CSF (Neupogen®, Amgen, Paris, France) at the same center according to the same clinical protocol. PBSC harvesting was considered successful if at least 3×10 6 CD34+ cells/kg were collected. If three consecutive CD34+ tests were below 10/μL then PBSC harvesting was not performed. Results: Patient characteristics were similar in both groups with no significant differences in age, diagnosis, previous chemotherapy, or chemotherapy mobilization regimen. No significant differences were observed between groups in median CD34+ cells mobilized and collected, or the number of G-CSF injections and leukaphereses required to obtain the minimal CD34+ cell count. Proportion of failures was also similar in both groups. Conclusion: Zarzio® is comparable to Neupogen® for PBSC mobilization and collection after chemotherapy and so may provide a more cost-effective strategy. © Springer Healthcare 2011.


PubMed | University of Paris Pantheon Sorbonne, University Paris - Sud, Laboratoire Of Virologie, Hopital Gustave Roussy and 4 more.
Type: Journal Article | Journal: PloS one | Year: 2014

Over 95% of the adult population worldwide is infected with Epstein-Barr virus (EBV). EBV infection is associated with the development of several cancers, including Hodgkin lymphoma (HL). Elevated levels of anti-EBV antibodies have been associated with increased risk of HL. There is growing evidence that genetic factors control the levels of antibodies against EBV antigens. Here, we conducted linkage and association studies to search for genetic factors influencing either anti-viral capsid antigen (VCA) or anti-Epstein Barr nuclear antigen-1 (EBNA-1) IgG levels in a unique cohort of 424 individuals of European origin from 119 French families recruited through a Hodgkin lymphoma (HL) patient. No major locus controlling anti-VCA antibody levels was identified. However, we found that the HLA region influenced anti-EBNA-1 IgG titers. Refined association studies in this region identified a cluster of HLA class II variants associated with anti-EBNA-1 IgG titers (e.g. p=510(-5) for rs9268403). The major allele of rs9268403 conferring a predisposition to high anti-EBNA-1 antibody levels was also associated with an increased risk of HL (p=0.02). In summary, this study shows that HLA class II variants influenced anti-EBNA-1 IgG titers in a European population. It further shows the role of the same variants in the risk of HL.


Delarue R.,Service dHematologie adultes
Oncologie | Year: 2011

Rituximab is associated with late-onset neutropenia, which occurs after the end of therapy. This side effect was initially considered a rare phenomenon, but recent studies have suggested an incidence rate between 5 and 30%. Although its physiopathology is poorly understood, recent advances have suggested that production of large granular lymphocytes and/or disruption of B-cell homeostasis during B-cell recovery after rituximab therapy could explain the occurrence of neutropenia. This complication is not usually associated with life-threatening complications, and treatment is based on antibiotics and G-CSF, if indicated. Retreatment after the first episode of neutropenia is probably associated with an increased risk of relapse. Besides this complication, the use of rituximab alone or with chemotherapy is associated with an increased risk of neutropenia and infection during treatment. These infectious complications are usually benign, mostly within the ORL and bronchus tract. © 2011 Springer Verlag France.


Bay J.-O.,Estaing University Hospital Center | Peffault de Latour R.,Service dhematologie greffe de moelle | Bruno B.,Service dhematologie pediatrique | Coiteux V.,Service des maladies du sang | And 10 more authors.
Pathologie Biologie | Year: 2013

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 third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here the SFGM-TC addressed the issue of post-transplant CMV and EBV reactivation, and EBV-related Lymphoproliferative Disorders. © 2013.


Diagnosis of malignant lymphoma is mainly based on the presence of enlarge lymph nodes and/or spleen, with or without general symptoms. Diagnosis requires a pathological analysis of a lymph node after a surgical or radiological procedure. An extra-nodal involvement could be associated or even be the unique sign of lymphoma. Main localizations are from digestive tract, skin and head and neck area. Complications such as tumour lysis syndrome or compressive syndrome could led to an emergency initial management. In all cases, patients must be treated in an hematological department where treatment will be based on histological sub-type, initial examinations, prognostic score and associated diseases.


PubMed | Service dHematologie Adultes
Type: Journal Article | Journal: Drugs & aging | Year: 2013

Mantle cell lymphoma is a distinct subtype of B-cell non-Hodgkin lymphoma, accounting for 3-10 % of all non-Hodgkin lymphoma cases. The median age at diagnosis is nearly 70 years. The prognosis of patients is based on the Mantle Cell Lymphoma International Prognostic Index, which is calculated on the basis of four independent prognostic factors (age, performance status, serum lactate dehydrogenase and leukocyte count). Treatment of elderly patients with de novo untreated mantle cell lymphoma is based on rituximab combined with chemotherapy. The most commonly used regimen is the classical CHOP21 (cyclophosphamide, doxorubicin, vincristine and prednisone) regimen. Bendamustine is also an option, especially for patients with cardiac comorbidities. In elderly patients who are relatively young and fit, an approach based on treatment usually used for younger patients, with cytarabine-based induction followed by autologous stem cell transplantation, should be discussed. Treatment of relapsing patients is based on the use of newer effective drugs, including bortezomib, lenalidomide and thalidomide, and mammalian target of rapamycin (mTOR) inhibitors, such as temsirolimus. These drugs are often combined with rituximab and can be prescribed in combination with chemotherapy. Promising new drugs are Bruton tyrosine kinase inhibitors and other inhibitors of the phosphoinositide 3-kinase (PI3K)-mTOR-protein kinase B (AKT) pathway. Despite these new advances, mantle cell lymphoma remains an incurable disease, and further basic and clinical research is warranted.


PubMed | Service dhematologie adultes
Type: Journal Article | Journal: La Revue du praticien | Year: 2010

Diagnosis of malignant lymphoma is mainly based on the presence of enlarge lymph nodes and/or spleen, with or without general symptoms. Diagnosis requires a pathological analysis of a lymph node after a surgical or radiological procedure. An extra-nodal involvement could be associated or even be the unique sign of lymphoma. Main localizations are from digestive tract, skin and head and neck area. Complications such as tumour lysis syndrome or compressive syndrome could led to an emergency initial management. In all cases, patients must be treated in an hematological department where treatment will be based on histological sub-type, initial examinations, prognostic score and associated diseases.


PubMed | Service dhematologie adultes
Type: Journal Article | Journal: La Revue de medecine interne | Year: 2013

Thrombocytosis is a common finding when performing a blood count. It is often consecutive to an underlying condition and then does not lead to thrombotic complications. If a reactive thrombocytosis is eliminated, thrombocytosis is primitive, rarely hereditary and most often associated with hematological malignancies. Essential thrombocythemia must be recognized, by eliminating the differential diagnoses that are myelodysplastic syndromes associated with thrombocytosis and other myeloproliferative disorders. The treatment is based on the prevention of thrombotic risk and the possible introduction of a cytoreductive therapy. Life expectancy is close to that of the general population and mainly depends on the occurrence of myelofibrosis or transformation to acute myeloid leukemia.

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