Showing papers by "Nicolas Mounier published in 2010"
TL;DR: It is found that patients with early relapses after rituximab-containing first-line therapy have a poor prognosis, with no difference between the effects of R-ICE and R-DHAP.
Abstract: Purpose Salvage chemotherapy followed by high-dose therapy and autologous stem-cell transplantation (ASCT) is the standard treatment for relapsed diffuse large B-cell lymphoma (DLBCL). Salvage regimens have never been compared; their efficacy in the rituximab era is unknown. Patients and Methods Patients with CD20+ DLBCL in first relapse or who were refractory after first-line therapy were randomly assigned to either rituximab, ifosfamide, etoposide, and carboplatin (R-ICE) or rituximab, dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP). Responding patients received high-dose chemotherapy and ASCT. Results The median age of the 396 patients enrolled (R-ICE, n = 202; R-DHAP, n = 194) was 55 years. Similar response rates were observed after three cycles of R-ICE (63.5%; 95% CI, 56% to 70%) and R-DHAP (62.8%; 95 CI, 55% to 69%). Factors affecting response rates (P < .001) were refractory disease/relapse less than versus more than 12 months after diagnosis (46% v 88%, respectively), International Pr...
1,256 citations
TL;DR: The results suggest that reduced-intensity allergenic transplantation is an attractive therapeutic option for patients with high-risk DLBCL.
82 citations
TL;DR: R-DHAX is an efficient regimen in patients with relapsed/refractory B-cell NHL even in elderly patients if hematologic toxicities are closely managed.
Abstract: Background Salvage therapy for patients with refractory/relapsed B-cell non-Hodgkin lymphoma (NHL) is based on polychemotherapy, followed by high-dose therapy and autologous stem cell transplantation in eligible patients (HDT/ASCT). R-DHAP combines rituximab with cisplatin, cytarabine, and dexamethasone. Patients and Methods We substituted cisplatin with oxaliplatin to avoid nephrotoxicity and retrospectively analyzed a large series of 91 patients with refractory/relapsed B-cell NHL to evaluate toxicities, response rates (RRs), and survival. Median age at R-DHAX (rituximab/dexamethasone/cytarabine/oxaliplatin) treatment was 60 years (range, 28-82 years). Renal insufficiency was present in 18 patients. The most frequent histologic subtypes were diffuse large B-cell lymphoma (n = 42) and follicular lymphoma (n = 30). Seventeen patients (19%) were naive to rituximab at time of R-DHAX. Results Grade III/IV toxicities were mainly hematologic, including anemia (n = 9), neutropenia (n = 44), and thrombocytopenia (n = 47). Grade I/II neurologic toxicities, sensitive or motor, were observed, and these were mainly transient except for 3 cases of motor neuropathy associated with previous exposure to vincristine. Neither renal toxicities nor degradation of previous renal insufficiency were observed. The overall RR was 75%, with a complete RR of 57%, with no statistical difference between patients previously treated with rituximab versus without rituximab. At a median follow-up of 23 months, 2-year probability rates of overall survival and progression-free survival were 75% and 43%, respectively, with a significant difference between patients treated with HDT/ASCT and patients not eligible for HDT/ASCT. Conclusion R-DHAX is an efficient regimen in patients with relapsed/refractory B-cell NHL even in elderly patients if hematologic toxicities are closely managed.
52 citations
TL;DR: Peripherally inserted central catheters (PICC) represent a simple and effective alternative to intra-venous central devices in onco-hematology, however, physicians have to focus on short-course treatment.
Abstract: Peripherally inserted central catheters (PICC) have the advantage of limiting the risk of accidents during installation and are easy to remove. Its use in oncology remains debated because of possible infectious complications. We analyzed 52 PICC in patients with hematological tumor from Nice Hospital. An installation failure was noted in 5.8% of cases. After a follow-up of 15 months, the complication rate was 26.9%, mainly mechanical complications: obstruction (13.5%) or accidental removal (9.6%). The organic complications such as infection or thrombophlebitis represented 3.8%. The median duration was 26 days [2-291]. The longest duration was associated with PICC for chemotherapy (median: 58 days). Frequent blood samples (above: 2 week) were associated with lower duration (median: 23 days). In conclusion, PICC represent a simple and effective alternative to intra-venous central devices in onco-hematology. However, physicians have to focus on short-course treatment.
20 citations
TL;DR: The inclusion of hematopoietic growth factors in the treatment of patients with HIV-HL may allow for the administration of higher dose-intensity chemotherapy and the prolonged use of antiretroviral drugs, with the aim of improving the survival.
Abstract: Hodgkin Lymphoma (HL) represents one of the most common types of a non-AIDS-defining tumour that occurs in the HIV population, and its incidence is increasing in the post Highly Active Anti-retroviral Therapy (HAART) era. Despite the aggressiveness of that disease, the outcome of patients with HIV-HL has improved with better, combined antineoplastic and antiretroviral approaches. New and effective antiretroviral drugs, in conjunction with nucleoside analogs, improve the control of the underlying HIV infection when used during treatment of HL with chemotherapy. The inclusion of hematopoietic growth factors in the treatment of patients with HIV-HL may allow for the administration of higher dose-intensity chemotherapy and the prolonged use of antiretroviral drugs, with the aim of improving the survival. In addition, new functional imaging tools, like the Positron Emission Tomography (PET), may help to guide treatment and minimize long term toxicity.
17 citations
Journal Article•
TL;DR: A rare case of HHV-8–positive PEL in an elderly, HIV-negative woman who presented with pleural effusion and was in clinical remission after intracavitary cidofovir is reported.
Abstract: Primary effusion lymphoma (PEL) is a rare type of non-Hodgkin lymphoma that mainly occurs in immunodeficient patients and is associated with infection by human herpes virus-8 (HHV-8). It develops in serous cavities, causing lymphomatous effusions in the absence of lymphadenopathy or organomegaly.1,2 Previous studies suggested that PEL occurs almost exclusively in HIVinfected patients. It was first described in association with Kaposi sarcoma.1,2 Subsequently, the authors of several studies demonstrated that PEL develops in non-AIDS patients with HHV-8 infection, suggesting that HHV-8 infection plays a key role in PEL.3 We report a rare case of HHV-8–positive PEL in an elderly, HIV-negative woman who presented with pleural effusion and was in clinical remission after intracavitary cidofovir. We also review the few recent reports of nonAIDS–related HHV-8–positive PEL.
17 citations
TL;DR: This phase 2 trial was undertaken to evaluate the efficacy and safety of rituximab combined with intravenous fludarabine and mitoxantrone for patients with recurrent/refractory follicular lymphoma who had high tumor burden according to GELF criteria.
Abstract: BACKGROUND: This phase 2 trial was undertaken to evaluate the efficacy and safety of rituximab combined with intravenous fludarabine and mitoxantrone (R-FM) for patients with recurrent/refractory follicular lymphoma who had high tumor burden according to Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria. METHODS: Fifty patients were enrolled who had received a maximum of 2 previous regimens, including 1 cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)/CHOP-like regimen but no previous exposure to rituximab, fludarabine, or mitoxantrone. At baseline, 58% of patients had bulky disease (lesion > 7 cm), 56% had high-risk Follicular Lymphoma International Prognostic Index (FLIPI) scores (range, 3-5), and 22% were refractory. Treatment consisted of 4 courses of R-FM (rituximab 375 mg/m(2) intravenously on Day 1, fludarabine 25 mg/m(2) intravenously on Days 2 through 4, and mitoxantrone 10 mg/m(2) intravenously on Day 2, recycling at Day 28) and consolidation with 2 courses of fludarabine and mitoxantrone (the same regimen without rituximab). RESULTS: The best response (84% overall response rate including 68% complete response/complete response unconfirmed) was achieved after 4 courses of R-FM. Response rates were high regardless of age, refractoriness to last previous therapy, and FLIPI score. After a median follow-up of 4 years, the 3-year progression-free survival rate was 47%, the event-free survival rate was 41%, and the 3-year overall survival rate was 66%. Grade ≥ 3 neutropenia and infections were the most common toxicities and occurred in 72% and 14% of patients, respectively. CONCLUSIONS: Cytoreduction with 4 courses of R-FM was safe and highly efficient in patients with recurrent/refractory follicular lymphoma who had high tumor burden; however, better consolidation than FM is needed to further improve outcome.
15 citations
TL;DR: Cette revue propose de presenter les donnees fondamentales sur le role des HDAC and of detailler the resultats actualises des differents agents en cours de developpement.
Abstract: HDAC, by modifiing relations between DNA and histones, are major proteins of the epigenetic regulation. They play part in the signal transduction and in many cellular processes: cell cycle control, apoptosis, protein degradation, angiogenesis, invasion and cell motility. In several models of cancer HDAC inhibitors (HDACIs) are able to up regulate tumor suppressing gene (p53, p21, pRB...) and to down regulate oncogenes (SRC, HIF-Ialpha,HER2...). Many inhibitors are currently in clinical development and promising results have been reported in cutaneous T cell lymphoma, Hodgkin's disease and non-hodgkin lymphoma. Combination with chemotherapy and molecular targeted agents seem to be effective in myeloma, lung cancer and myeloid neoplasms. In this review, we focus on recent biologic and clinical data that highlitght the anti-neoplastic role of HDACIs.
11 citations
TL;DR: It is confirmed that early relapse, prior rituximab exposure and secondary aaIPI had adverse prognostic value and COO remains a major factor in relapsed/refractory DLBCL.
7 citations
TL;DR: The anaplastic lymphoma kinase gene (ALK) code for a receptor tyrosine-kinase generates activation of anti apoptotic and survey pathways that makes it a prime target for these 2 subtypes of disease.
Abstract: The anaplastic lymphoma kinase gene (ALK) code for a receptor tyrosine-kinase. The fusion proteins from the ALK gene have been identified in oncohaematology malignancies including ALK positive anaplastic lymphoma large cell and non small cells lung cancer with EML4-ALK fusion gene. Constitutive activation generated by modification of this protein leads activation of anti apoptotic and survey pathways that makes it a prime target for these 2 subtypes of disease. Strategies and therapeutic molecules targeting the fusion protein are under development and preliminary results are encouraging. Therefore the mapping of the tumors is essential to help provide treatment specific to each entity. The best example is the chronic myeloid leukemia and the discovery of the fusion gene bcr-abl and of imatinib.
5 citations
TL;DR: Findings do not support the use of a chemotherapy regimen more intensive than ACVBP in patients aged ≤60 years with LIR aggressive lymphoma and lead to a randomized comparison of R-ACVBP and R-CHOP in this patient population.
Abstract: One-third of patients aged <= 60 years with aggressive lymphoma are at low-intermediate risk (LIR). Before the rituximab era, we prospectively compared ACVBP with ECVBP, a similar regimen including epirubicin instead of doxorubicin and increased dose intensity of cyclophosphamide, followed by conventional consolidation with an increased amount and dose intensity of cytosine-arabinoside, methotrexate, etoposide, and ifosfamide, in 652 patients with LIR aggressive lymphoma. The overall response rate, 5-year event-free survival (EFS), and survival were estimated to be 86%, 60%, and 74%, respectively, with no differences between the two arms. In patients with diffuse large B-cell lymphoma (DLBCL) who received ACVBP, the 5-year EFS and survival were estimated at 69% and 82%. These findings do not support the use of a chemotherapy regimen more intensive than ACVBP in patients aged <= 60 years with LIR aggressive lymphoma. The results in the control arm, without rituximab, have led to a randomized comparison of R-ACVBP and R-CHOP in this patient population.
TL;DR: Pneumoblastoma: a rare lung tumour occurring as a long-term complication after allogeneic haematopoietic cell transplantation.
Abstract: Pneumoblastoma: a rare lung tumour occurring as a long-term complication after allogeneic haematopoietic cell transplantation
Journal Article•
TL;DR: Clinical trials including PET scans to evaluate early response to chemotherapy, aim to treat early stages with chemotherapy alone and modern radiation techniques are being developed to restrict the target volume to initially involved nodes only.
Abstract: A risk-adapted strategy for adult patients with Hodgkin's lymphoma is based on risk factors at diagnosis. First line chemotherapy with the gold standard ABVD regimen, with 3 or 4 courses for patients without or with risk factors, respectively, followed by radiation therapy targeting the initially affected areas (involved-field RT), at a dose of 30 Gy, is the treatment of choice for all early-stage supradiaphragmatic disease. Treatment for disseminated disease is based on chemotherapy alone. According to prognostic index, 8 cycles of ABVD or more intensive regimen like BEACOP are indicated. At the present time, clinical trials including PET scans to evaluate early response to chemotherapy, aim to treat early stages with chemotherapy alone and modern radiation techniques are being developed to restrict the target volume to initially involved nodes only. For advanced stages, PET scan may help to define optimal treatment and primary failures from first line chemotherapy.
TL;DR: Targeting autophagy appears as an attractive therapeutical strategy to circumvent AZA resistance in both established MDS cell lines and cells from MDS patients.
TL;DR: Genomewide single nucleotide polymorphism (SNP) analysis in MDS and AML patients treated by AZA showed correlations between some CNA/UPD and response to AZA and OS, such as 1/a UPD at 9p21 (6% of patients) associated to a better hematologic improvement (X2, p=0.037).
TL;DR: A multi-center phase II trial using R-GemOx to confirm the efficacy and safety of an outpatient salvage regimen for patients with DLBCL non eligible for HDT, finding an overall response rate of 0.8011.
Abstract: 8011 Background: We conducted a multi-center phase II trial using R-GemOx: R (375mg/m2, d1), Gem (1,000 mg/m2,d2) and Ox (100 mg/m2, d2) to confirm the efficacy and safety of an outpatient salvage regimen for patients (pts) with DLBCL non eligible for HDT(El gnaoui. Ann Oncol 2007). Methods: The primary objective was to determine the overall response rate (ORR) after 4 cycles given every 2 weeks. Patients were planned to receive 8 cycles if at least in PR after 4 cycles. Between August 2003 and January 2009, 49 pts with refractory (n=6)/relapsing (n=43, including early relapse 2 in 34 pts (71%). Median delay between last treatment and R-GemOx was 14 months (m). 36 pts were in first relapse and 7 in second. Results: Sequential analyses were performed every five pts using triangular test. After 4 cycles, responses were: CR/CRu: 21 (44%)...