Center Hospitalier Schaffner

Lens, France

Center Hospitalier Schaffner

Lens, France

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Gavriatopoulou M.,National and Kapodistrian University of Athens | Garcia-Sanz R.,Hospital Of Universitario Of Salamanca | Kastritis E.,National and Kapodistrian University of Athens | Morel P.,Center Hospitalier Schaffner | And 9 more authors.
Blood | Year: 2017

In this phase 2 multicenter trial, we evaluated the efficacy of the combination of bortezomib, dexamethasone, and rituximab (BDR) in 59 previously untreated symptomatic patients with Waldenström macroglobulinemia (WM), most of which were of advanced age and with adverse prognostic factors. BDR consisted of a single 21-day cycle of bortezomib alone (1.3 mg/m2 IV on days 1, 4, 8, and 11), followed by weekly IV bortezomib (1.6 mg/m2 on days 1, 8, 15, and 22) for 4 additional 35-day cycles, with IV dexamethasone (40 mg) and IV rituximab (375 mg/m2) on cycles 2 and 5, for a total treatment duration of 23 weeks. On intent to treat, 85% responded (3% complete response, 7% very good partial response, 58% partial response). After a minimum follow-up of 6 years, median progression-free survival was 43 months and median duration of response for patients with at least partial response was 64.5 months. Overall survival at 7 years was 66%. No patient had developed secondary myelodysplasia, whereas transformation to high-grade lymphoma occurred in 3 patients who had received chemoimmunotherapy after BDR. Thus, BDR is a very active, fixed-duration, chemotherapy-free regimen, inducing durable responses and with a favorable long-term toxicity profile (www.ClinicalTrials.gov #NCT00981708). © 2017 by The American Society of Hematology.


Dimopoulos M.A.,National and Kapodistrian University of Athens | Kastritis E.,National and Kapodistrian University of Athens | Owen R.G.,St Jamess Institute Of Oncology | Kyle R.A.,Mayo Medical School | And 21 more authors.
Blood | Year: 2014

Waldenström macroglobulinemia (WM) is a distinct B-cell lymphoproliferative disorder for which clearly defined criteria for the diagnosis, initiation of therapy, and treatment strategy have been proposed as part of the consensus panels of International Workshops on WM (IWWM). As part of the IWWM-7 and based on recently published and ongoing clinical trials, the panels updated treatment recommendations. Therapeutic strategy in WM should be based on individual patient and disease characteristics (age, comorbidities, need for rapid disease control, candidacy for autologous transplantation, cytopenias, IgM-related complications, hyperviscosity, and neuropathy). Mature data show that rituximab combinations with cyclophosphamide/ dexamethasone, bendamustine, or bortezomib/dexamethasone provided durable responses and are indicatedformostpatients. Newmonoclonalan-tibodies (ofatumumab), second-generation proteasome inhibitors (carfilzomib), mam-malian target of rapamycin inhibitors, and Bruton's tyrosine kinase inhibitors are promising and may expand future treatment options. A different regimen is typically recommended for relapsed or refractory disease. In selected patients with relapsed disease after long-lasting remission, reuse of a prior effective regimen may be appropriate. Autologous stem cell transplantation may be considered in young patients with chemosensitive disease and in newly diagnosed patients with very-high-risk features. Active enrollment of patients with WM in clinical trials is encouraged.


Daudignon A.,Center Hospitalier | Poulain S.,Center Hospitalier | Morel P.,Center Hospitalier Schaffner | Bouchindhomme B.,Service dAnatomie et de Cytologie Pathologiques | And 2 more authors.
Leukemia Research | Year: 2010

Small lymphocytic lymphoma (SLL) and chronic lymphocytic leukemia (CLL) are considered as similar entity by the WHO classification. We assessed the distribution of the four prognostic cytogenetic markers (deletion 11q23, 13q14, 17p13 and trisomy 12) and VH mutational status in 32 SLL and 119 CLL. Trisomy 12 was most frequent (36% vs 13%, p=0.014) and 13q14 deletion was less frequent (9% vs 44%, p=0.001) in SLL in comparison with CLL. An over representation of VH3-21 gene usage was found in SLL (17% vs 1%, p=0.011). In conclusion, SLL show specific genetic markers that distinguish them from classical CLL. © 2009 Elsevier Ltd.


Hivert B.,Center Hospitalier Schaffner | Caron C.,Lille University Hospital Center | Petit S.,Service dAnatomo Pathologie | Charpy C.,Estaing University Hospital Center | And 10 more authors.
Blood | Year: 2012

Acquired von Willebr and syndrome is described in patients with Waldenström macroglobulinemia (WM). Assessment of ristocetin cofactor activity (VWF:RCo) and von Willebrand factor (VWF) antigen (VWF:Ag) in 72 consecutive patients with WM showed a negative relation between VWF levels < 130 U/dL and both monoclonal immunoglobulin M concentration (mIgMC) and viscosity. Ten patients with VWF:RCo < 50 U/dL (< 40 for patients with blood group O) fulfilled the acquired von Willebrand syndrome criteria. They had higher mIgMC and viscosity. Reduction in mIgMC was associated with increase in VWF levels. The low VWF:RCo VWF:Ag ratio suggested that high viscosity might be associated with increased shear force and cleavage of multimers. Surprisingly, 43 patients (59%) presented with high VWF:Ag (> 110 U dL). They had higher bone marrow microvessel density and vascular endothelial growth factor expression on bone marrow mast cells. Five-year survival rates of patients with VWF:Ag < 110, between 110 and 250, and more than 250 U/dL were 96%, 71%, and 44%, respectively (P <.0001). High VWF:Ag was also a significant adverse prognostic factor for survival after first-line therapy (P <.0001), independently of the international scoring system. These results support systematic assessment of VWF in patients with WM. The adverse prognostic value of high VWF levels raises issues on interactions between lymphoplasmacytic cells, mast cells, and endothelial cells in WM. © 2012 by The American Society of Hematology.


PubMed | University of Arkansas for Medical Sciences, Fred Hutchinson Cancer Research Center, National Cancer Institute, Niguarda Ca Granda Hospital and 15 more.
Type: Journal Article | Journal: Blood | Year: 2014

Waldenstrm macroglobulinemia (WM) is a distinct B-cell lymphoproliferative disorder for which clearly defined criteria for the diagnosis, initiation of therapy, and treatment strategy have been proposed as part of the consensus panels of International Workshops on WM (IWWM). As part of the IWWM-7 and based on recently published and ongoing clinical trials, the panels updated treatment recommendations. Therapeutic strategy in WM should be based on individual patient and disease characteristics (age, comorbidities, need for rapid disease control, candidacy for autologous transplantation, cytopenias, IgM-related complications, hyperviscosity, and neuropathy). Mature data show that rituximab combinations with cyclophosphamide/dexamethasone, bendamustine, or bortezomib/dexamethasone provided durable responses and are indicated for most patients. New monoclonal antibodies (ofatumumab), second-generation proteasome inhibitors (carfilzomib), mammalian target of rapamycin inhibitors, and Brutons tyrosine kinase inhibitors are promising and may expand future treatment options. A different regimen is typically recommended for relapsed or refractory disease. In selected patients with relapsed disease after long-lasting remission, reuse of a prior effective regimen may be appropriate. Autologous stem cell transplantation may be considered in young patients with chemosensitive disease and in newly diagnosed patients with very-high-risk features. Active enrollment of patients with WM in clinical trials is encouraged.


PubMed | Hospital Of Universitario Of Salamanca, General Hospital of Chalkida, Netherlands Cancer Institute, University of Pavia and 4 more.
Type: Journal Article | Journal: Blood | Year: 2016

In this phase 2 multicenter trial, we evaluated the efficacy of the combination of bortezomib, dexamethasone, and rituximab (BDR) in 59 previously untreated symptomatic patients with Waldenstrm macroglobulinemia (WM), most of which were of advanced age and with adverse prognostic factors. BDR consisted of a single 21-day cycle of bortezomib alone (1.3 mg/m


Rose C.,Lille Catholic University | Brechignac S.,University of Paris 13 | Vassilief D.,Service dHematologie | Pascal L.,Lille Catholic University | And 10 more authors.
Leukemia Research | Year: 2010

Background: Iron chelation therapy (CT) improves survival in thalassemia major but its beneficial effects on survival in MDS patients remain uncertain. Methods: We analyzed, by multivariate analysis, survival and causes of deaths in 97 low or intermediate 1 IPSS patients regularly transfused as outpatients, chelated or not, who were included during a month period and followed for 2.5 years. Results: 44 (45%) of patients were not chelated and 53 (55%) received CT, mainly with deferoxamine, for at least 6 months (median duration of chelation 36 months, range 6-131+). During the follow-up period, 66 of the 97 patients died, including 51% and 73% of chelated and non-chelated patients, respectively. Median overall survival was 53 months and 124 months in non-chelated and in chelated patients (p<0.0003). Causes of death did not significantly differ between the two groups (p=0.51). In multivariate Cox analysis, adequate chelation was the strongest independent factor associated with better OS. Conclusion: Iron chelation therapy appears to improve survival in heavily transfused lower risk MDS, but prospective randomized studies are required to confirm our findings, and to determine more precisely the mechanisms of this potential survival benefit. © 2010 Elsevier Ltd.


Morel P.,Center Hospitalier Schaffner | Morel P.,University of Lille Nord de France | Merlini G.,University of Pavia
Clinical Lymphoma, Myeloma and Leukemia | Year: 2011

Using age, hemoglobin level, platelet count, serum β2-microglobulin and monoclonal protein concentrations, the International Scoring System for WM (ISSWM) has been specifically designed for predicting survival after the initiation of first-line therapy. Five-year survival rates of low-, intermediate-, and high-risk patients were 87%, 68%, and 36%, respectively. The aim of the present review was to assess the applicability of this statistical model for making treatment decision in clinical practice, despite the difficulties posed by the characteristics of this rare disease. Finally, we propose that the distribution of ISSWM subgroups should be reported in any treatment reports. © 2011 Elsevier Inc. All rights reserved.


Morel P.,Center Hospitalier Schaffner | Morel P.,University of Lille Nord de France | Merlini G.,University of Pavia
Expert Review of Hematology | Year: 2012

Waldenström macroglobulinemia is characterized by the production of serum monoclonal IgM and lymphoplasmacytic bone marrow infiltration. At least 25% of patients are asymptomatic at diagnosis and treatment is only mandatory in cases of symptomatic disease. Beside reports on treatment results, reviewing risk assessment is another way to describe the clinical course of the disease. This information may be particularly useful when numerous treatment options are available. While the introduction of new treatment approaches reinforces the need for careful risk assessment, the identification of useful prognostic information requires prolonged follow-up in patients who have not been treated with current therapeutic options. This limitation should be taken into account when using and interpreting available prognostic information, especially survival estimates. © 2012 Expert Reviews Ltd.

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