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Biomedical subjects

Bertrand Coiffier

Publications and source records attributed to Bertrand Coiffier.

At least 55 records · Page 3Linked to original sources
PubMed2004

Second treatment with rituximab in B-cell non-Hodgkin's lymphoma: efficacy and toxicity on 41 patients treated at CHU-Lyon Sud.

The purpose of this study was to evaluate retrospectively the effect of a second treatment with rituximab for patients who progressed after a response to a first treatment. We analysed the charts of 41 patients treated at CHU Lyon-Sud between 1997 and May 2003. Patients were treated with rituximab alone or with a combination of rituximab and chemotherapy. The overall response rate (complete and partial response) was 73% for the second treatment. The median time to progression was longer but not significant for the second treatment in comparison with the first one (15.2 versus 11.3 months, P = 0.09). The second treatment was well tolerated. Thus, a second treatment with rituximab should be considered, alone or in combination with chemotherapy, for patients who progress after a first response to rituximab.

Adult↗
PubMed2004

Maintenance therapy with a monthly injection of alemtuzumab prolongs response duration in patients with refractory B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CLL/SLL).

Alemtuzumab, the monoclonal anti-CD52 antibody, has clinical activity in B-cell and T-cell malignancies at the dose of 30 mg three times weekly for 9-12 weeks. This standard regimen induced responses usually shorter than 6 months. To prolong time to progression, we initialized a phase II study with an identical initial scheme until partial response, followed by a maintenance therapy lasting at least 4 months. Eleven heavily pretreated patients (8 with B-chronic lymhocytic leukemia (B-CLL) and 3 with small lymphoctyic lymphoma (SLL)) have been treated with this maintenance regimen (MR patients) and were retrospectively compared to 5 patients (3 B-CLL and 2 SLL) treated with the standard regimen (SR patients). Patients characteristics before treatment were identical in both groups. Objective response was reached by 9 (82%) MR patients and 3 (60%) SR patients (p NS). After the treatment, 8 (73%) MR patients and all SR patients progressed with a median time at 12.2 months and 3 months respectively. Survival time from alemtuzumab was significatively different (P < 0.005). None of the patients died in the MR group with a median follow-up at 16 months. In the SR group, the median survival from alemtuzumab was 5.9 months. We did not observe any differences in terms of hematological toxicites and infections between the two groups. In conclusion, maintenance alemtuzumab therapy seems to increase the time to progression and the survival, without adding hematological toxicities and infectious complications. More patients are needed to confirm this observation.

Aged↗
PubMed2004

Hepatitis C virus infection and B-cell non-Hodgkin's lymphoma: a cross-sectional study in Lyon, France.

OBJECTIVES: The role of hepatitis C virus (HCV) infection in the pathogenesis of non-Hodgkin's lymphoma (NHL) is controversial. A high prevalence of HCV infection in patients with NHL has been reported in Italy and Japan. By contrast, several studies in Northern Europe and Canada have not found any increased prevalence of HCV in B-cell NHL, suggesting a possible geographic variation. We sought to determine whether such an association could be found in patients treated in the Rhone-Alpes region in south-east France. Our main interest was to identify histological subtypes preferentially linked to HCV. METHODS: We determined the prevalence of anti-HCV antibodies in 212 consecutive patients with B-cell NHL diagnosed in our institution between January 1997 and December 1998. The comparison group comprised 974 patients tested for HCV before transfusion at the same hospital during the same period. RESULTS: Anti-HCV antibodies were found in six (2.8%) NHL patients. The distribution by histopathological category was as follows: three gastric mucosa-associated lymphoid tissue (MALT) lymphomas, one marginal lymphoma and two diffuse large-cell lymphomas. Anti-HCV antibodies were found in 20 (2%) of 974 comparison patients. Overall, there was a positive but non-significant trend towards an association between NHL and HCV infection (odds ratio 1.31; 95% confidence interval 0.51-3.36). However, the prevalence of HCV antibodies was significantly higher in MALT lymphoma patients than in the comparison group (odds ratio 9.87; 95% confidence interval 2.59-37.69). CONCLUSIONS: To our knowledge, this is the first French study to show an association between HCV and MALT lymphoma. These results, although derived from a small number of patients, suggest a possible role of HCV in gastric MALT lymphomagenesis.

Adolescent↗
PubMed2004

Effective immunochemotherapy for aggressive non-Hodgkin's lymphoma.

In the past, CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone) was considered the gold standard treatment for aggressive non-Hodgkin's lymphoma (NHL). CHOP is only curative in approximately 40% of patients, and numerous clinical trials have been carried out to find a treatment that can increase the cure rate. For some patients with aggressive NHL, it is possible to improve survival by intensification of chemotherapy compared with standard CHOP. This approach is not appropriate for all patients, and careful patient selection is necessary to achieve benefit. Early high-dose treatment/autologous stem cell transplantation may be beneficial for some patients, but not in patients with low-risk disease or those over 60 years of age who are not eligible for autologous stem cell transplantation. The most striking and consistent improvement over CHOP chemotherapy in the treatment of aggressive NHL is the addition of rituximab. A phase III randomized study Groupe d'Etudes des Lymphomes de l'Adulte (GELA LNH 98.5) compared rituximab plus CHOP with CHOP alone in treatment of 399 patients aged 60 to 80 years of age with aggressive NHL. The addition of rituximab resulted in higher overall and complete response rates, and at a median follow-up of 3 years, event-free and overall survival were significantly higher in patients treated with rituximab plus CHOP compared with CHOP alone. The benefits of adding rituximab to CHOP were not restricted to a subgroup of patients, but were evident in patients with high- and low-risk disease. The addition of rituximab to CHOP also overcame bcl-2-associated resistance to chemotherapy. There is no standard chemotherapy regimen for relapsed patients, but results from several single-arm studies suggest the addition of rituximab will increase the complete response rate to many different salvage regimens. The development of newer treatment strategies incorporating rituximab may improve the cure rate further.

Antibodies, Monoclonal↗
PubMed2003

Interleukin-10 gene promoter polymorphisms influence the clinical outcome of diffuse large B-cell lymphoma.

The aim of the study was to investigate whether interleukin-10 (IL-10) genetic polymorphisms influence this cytokine production as well as the incidence and outcome of diffuse large B-cell lymphoma (DLBCL). The frequency of IL-10(-1082G) allele was found to be higher in 199 patients with DLBCL as compared with 112 control subjects (0.47 versus 0.39, P =.043). Increased serum levels of IL-10 were associated with adverse prognostic factors and poor DLBCL outcome. The frequencies of IL-10(-819T) and IL-10(-592A) alleles were lower in patients with elevated IL-10 serum levels (0.155 versus 0.32, P =.14). As compared with patients carrying the IL-10(-1082AA) genotype, patients with the IL-10(-1082G) allele (IL-10(-1082GG/GA) genotypes) had higher complete remission rate (78% [confidence interval (CI), 71%-85%] versus 65% [CI, 52%-78%], P =.07), 5-year freedom from progression (FFP) (60% [CI, 52%-68%] versus 40% [CI, 27%-53%], P =.013), and overall survival (OS) (63% [CI, 55%-71%] versus 33% [CI, 20%-45%], P =.0009). Among factors of the International Prognostic Index, IL-10(-1082G) allele remained an independent variable, predicting longer freedom from progression (FFP) (RR [relative risk] =.76, P =.00035) and OS (RR =.78, P =.0015). These results indicate that IL-10 production contributes to the clinical course of DLBCL and that this phenomenon involves a substantial genetic component.

Case-Control Studies↗
PubMed2003

Small lymphocytic lymphoma, marginal zone B-cell lymphoma, and mantle cell lymphoma exhibit distinct gene-expression profiles allowing molecular diagnosis.

Non-germinal center small B-cell lymphomas represent a heterogeneous group of non-Hodgkin lymphomas, the most frequent histologic subtypes being small lymphocytic lymphoma (SLL), splenic marginal zone B-cell lymphoma (MZL), and mantle cell lymphoma (MCL). In order to identify genomic signatures specific for each disease, we analyzed 128 primary tumors using high-density microarrays. Several clusters of genes significantly discriminated the 3 histologic subtypes. Genes associated with cell adhesion, angiogenesis, and inhibition of apoptosis were up-regulated in SLL. Genes associated with intracellular signaling via the AKT1 pathway were up-regulated in splenic MZL. Genes associated with cell cycle control and multidrug resistance were up-regulated in MCL. Using 44 genes selected within the gene clusters discriminant for the 3 lymphoma subtypes, we generated a class prediction score that allowed us to classify the 3 entities in 96% of the cases, including borderline cases. Whereas specific transcriptional profiles easily distinguished all MZL samples, SLL samples, and most of the MCL samples into separate groups, few MCL cases exhibited MZL-type transcriptional profiles. This study demonstrates that SLL, splenic MZL, and MCL possess specific transcriptional profiles that may be relevant to the pathogenesis and the diagnosis of these histologic subtypes.

Biopsy↗
PubMed2003

Efficacy and safety of rasburicase (recombinant urate oxidase) for the prevention and treatment of hyperuricemia during induction chemotherapy of aggressive non-Hodgkin's lymphoma: results of the GRAAL1 (Groupe d'Etude des Lymphomes de l'Adulte Trial on Rasburicase Activity in Adult Lymphoma) study.

PURPOSE: Hyperuricemia and tumor lysis syndrome are well-known complications during induction treatment of aggressive non-Hodgkin's lymphomas (NHLs). Usual prophylaxis and treatment of hyperuricemia consist of hydration, alkalinization, and administration of allopurinol. This study was designed to evaluate the efficacy and the safety of rasburicase (recombinant urate oxidase) in adult patients with aggressive NHL during their first cycle of chemotherapy. PATIENTS AND METHODS: A total of 100 patients from Groupe d'Etude des Lymphomes de l'Adulte centers, with diffuse large B-cell lymphoma (n = 79); anaplastic large-cell lymphoma (n = 6); peripheral T-cell lymphoma (n = 8); transformation of indolent lymphoma (n = 5); Burkitt's lymphoma (n = 1); and lymphoblastic lymphoma (n = 1) were enrolled from May 2001 to June 2002. Before chemotherapy, 66% of patients had elevated lactate dehydrogenase (LDH), including 28% with LDH above 1,000 U/mL. Eleven percent of patients were hyperuricemic (uric acid [UA] > 450 mmol/L or > 7.56 mg/dL). Rasburicase 0.20 mg/kg/d intravenously for 3 to 7 days was started the day before or at day 1 of chemotherapy. UA levels were measured 4 hours after rasburicase injection, then daily during treatment. RESULTS: All patients responded to rasburicase, as defined by normalization of UA levels maintained during chemotherapy. The control of UA was obtained within 4 hours after the first injection of the drug. Creatinine levels and other metabolites were also controlled with the administration of rasburicase. No patient exhibited increased creatinine levels or required dialysis during chemotherapy. CONCLUSION: Rasburicase is the treatment of choice to control UA and prevent tumor lysis syndrome in adult patients with aggressive NHL.

Adult↗
PubMed2003

Second cancers and late toxicities after treatment of aggressive non-Hodgkin lymphoma with the ACVBP regimen: a GELA cohort study on 2837 patients.

The survival of patients with aggressive non-Hodgkin lymphoma (NHL) is increasing, but the incidence of secondary cancer and late toxicity is poorly defined for those treated with cyclophosphamide-hydroxydaunomycin/doxorubicin-Oncovin-prednisone (CHOP)-like chemotherapy. From February 1984 to January 1998, 2837 patients with aggressive NHL received the control-arm chemotherapy adriamycin-cyclophosphamide-vindesine-bleomycin-prednisone (ACVBP) in 3 consecutive Groupe d'Etude des Lymphomes de l'Adulte (GELA) studies. With a median follow-up time of 74 months, the 5-year overall and event-free survival rates were 60% and 52%. Two hundred two occurrences of nonneoplastic late toxicity were reported, resulting in a 5.35% cumulative probability of incidence at 7 years. Eighty-one second tumors developed, for which the 7-year cumulative incidence rate was 2.75%; 64 were solid tumors, and 17 were hematologic malignancies. In multivariate analysis, age was the only risk factor for the second development of cancer. Epidemiologic analysis allowed a comparison of this NHL group with the general population. Considering all tumors, no excess of second cancer was observed. In the male population, however, there was an excess of lung cancer (standardized incidence ratio [SIR], 2.45; P <.001) and myelodysplastic syndrome/acute myelocytic leukemia (MDS/AML) (SIR, 5.65; P =.006), and in the female population there was an excess of MDS/AML (SIR, 19.9; P <.001). With a long follow-up, the ACVBP regimen was highly effective for the treatment of aggressive NHL. Increases occurred in secondary MDS/AML and in lung cancer among men.

Adolescent↗
PubMed2003

Intensive conventional chemotherapy (ACVBP regimen) compared with standard CHOP for poor-prognosis aggressive non-Hodgkin lymphoma.

We conducted a randomized trial to compare the intensive conventional chemotherapy regimen ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone) with standard CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) in previously untreated patients with poor-risk aggressive lymphoma. Patients aged 61 to 69 years who had aggressive non-Hodgkin lymphoma with at least one prognostic factor of the age-adjusted international prognostic index (IPI) were included. ACVBP consisted of an induction phase of intensified chemotherapy and central nervous system (CNS) prophylaxis followed by a sequential consolidation phase. Of the 708 patients registered for the study, 635 were eligible. The rate of complete response was 58% in the ACVBP group and 56% in the CHOP group (P =.5). Treatment-related death occurred in 13% of the ACVBP group and 7% of the CHOP group (P =.014). At 5 years, the event-free survival was 39% in the ACVBP group and 29% in the CHOP group (P =.005). The overall survival was significantly longer for patients treated with ACVBP, at 5 years it was 46% compared with 38% for patients treated with CHOP (P =.036). CNS progressions or relapses were more frequent in the CHOP group (P =.004). Despite higher toxicity, the ACVBP regimen, used as first-line treatment for patients with poor-risk aggressive lymphoma, is superior to standard CHOP with regard to both event-free survival and overall survival.

Aged↗
PubMed2003

Clinical activity of rituximab in extranodal marginal zone B-cell lymphoma of MALT type.

The clinical activity of rituximab has been evaluated in a phase 2 study in both untreated and relapsed mucosa-associated lymphoid tissue (MALT) lymphomas. Treatment consisted of 4 standard (375 mg/m2) weekly doses. Thirty-five patients were enrolled, and 34 completed the treatment program. The primary lymphoma location was stomach in 15 patients, and extragastric in 20. Eleven patients had previously been treated with chemotherapy. At study entry 12 patients had Ann Arbor stage IE, 3 had stage IIE, and 20 had stage IV disease. The overall response rate was 73% (95% confidence interval, 56%-87%), with 15 complete responses and 10 partial responses, and the response rate was significantly higher in the chemotherapy-naive patients, who had an 87% response rate compared with 45% of the previously treated patients (P =.03). The median response duration was 10.5 months. At a median follow-up of 15 months, 9 patients (26%) relapsed. The median time to treatment failure was 14.2 months in the whole series, but it was significantly longer (22 versus 12 months) in the chemotherapy-naive patients compared with those who had prior chemotherapy (P =.001). Most adverse events were of mild to moderate severity with no grade 4 toxicity. This study indicates that rituximab is safe with significant activity in MALT lymphomas.

Adult↗
PubMed2003

Rituximab plus CHOP (R-CHOP) overcomes bcl-2--associated resistance to chemotherapy in elderly patients with diffuse large B-cell lymphoma (DLBCL).

In diffuse large B-cell lymphoma (DLBCL), the combination of rituximab and CHOP (cyclophosphamide, doxorubicine, vincristine, prednisone; R-CHOP) has been shown to be more effective than CHOP for the treatment of elderly patients. Bcl-2 protein expression has been associated with poor prognosis in patients with DLBCL. To establish whether or not rituximab reduces bcl-2-associated treatment failure, we studied bcl-2 protein expression and clinical outcome in patients included in the Groupe d'Etude des Lymphomes de l'Adulte LNH-98-5 trial. Patients between 60 and 80 years of age were randomized to receive 8 cycles of either CHOP or R-CHOP every 3 weeks. Of the 399 patients included, 292 with histologically proven DLBCL had material available for bcl-2 study. Tumors were considered positive when at least 50% of tumor cells expressed bcl-2 protein. There were 193 (66%) bcl-2+ patients and 99 (34%) bcl-2- patients. The response rates for R-CHOP and CHOP were, respectively, 78% and 60% (P =.01) in bcl-2+ patients and 76% and 73% (P =.7) in bcl-2- patients. At a median of 2 years of follow-up, R-CHOP was significantly associated with a better overall survival than CHOP in bcl-2+ patients (67% +/- 9% versus 48% +/- 11%, P =.004). In bcl-2- patients there was no statistically significant difference (72% +/- 12% versus 67% +/- 14%, P =.6). In addition, R-CHOP was associated with significantly better event-free survival than CHOP in bcl-2+ patients (58% +/- 10% versus 32% +/- 10%, P <.001) but not in bcl-2- patients (60% +/- 13% versus 40% +/- 15%, P =.13). Multivariate analysis confirmed the significant benefit for survival and event-free survival of R-CHOP in bcl-2+ patients. These results suggest that rituximab is able to prevent chemotherapy failure in patients with bcl-2 protein overexpression.

Aged↗
PubMed2003

Monoclonal antibodies combined to chemotherapy for the treatment of patients with lymphoma.

Humanized monoclonal antibodies have transformed the treatment of patients with lymphomas. The first application of these new drugs appeared less than 10 years ago but currently one patient will certainly receive them once or several time during the evolution of his disease. This review will cover the use of these monoclonal antibodies alone or in combination with chemotherapy. Rituximab, an unconjugated anti-CD20 chimeric antibody, is certainly the most widely used but other unconjugated or radiolabeled monoclonal antibodies catch up quickly. If there are randomized studies demonstrating the benefit of adding these drugs to the treatment of patients with lymphoma, very few studies have compared the activity of the different monoclonal antibodies. A lot of questions needs to be answered before the best setting of these drugs will be known.

Antibodies, Monoclonal↗
PubMed2003

Splenic marginal-zone lymphoma: a distinct clinical and pathological entity.

In the World Health Organization classification system, splenic marginal-zone lymphoma (splenic MZL) is described as an indolent B-cell lymphoma, which generally presents as splenomegaly with involvement of the bone marrow and peripheral blood. Presence of disease in peripheral lymph nodes and extranodal locations is uncommon. Splenic MZL is characterised by micronodular infiltration of the spleen with marginal-zone differentiation; the immunophenotype is usually IgM+ IgD+/- cytoplasmic-Ig-/+ pan B antigens+ CD5- CD10- CD23- CD43-/+ cyclin D1-; and the most common genetic abnormalities are deletions at 7q22-7q32. Most patients with splenic MZL live for a long time but classic prognostic factors cannot distinguish between patients who are likely to have good and poor outcomes. However, immunological events, such as haemolytic anaemia and immune thrombocytopenia, or the presence of a monoclonal component, are significantly associated with shorter survival. Splenectomy is considered the first-line treatment of choice for splenic MZL; it results in only partial remission, but responses are generally sufficient for correcting cytopenia, improving quality of life, and increasing survival.

Chromosomes, Human, Pair 7↗
PubMed2003

Smoking and non-Hodgkin's lymphoma: a case-control study in the Rhône-Alpes region of France.

OBJECTIVE: To study the relation between smoking and non-Hodgkin's lymphoma (NHL), in the Rhône-Alpes region of France. METHODS: We conducted a hospital-based case-control study that included 180 cases of NHL and 360 age-, gender-matched hospital controls. Matched univariable and multivariable logistic regression models were used for analysis. RESULTS: For the whole study population as well as for men, smoking does not elevate the risk of NHL. However, the risk of NHL is higher for women who currently smoke compared to women who have never smoked (odds ratio [OR] = 2.40, 95% confidence interval [95% CI] = 1.19-4.84). Among ever smokers, the OR of NHL is 5.04 (95% CI = 1.40-18.12) for women who have smoked for more than 30 years compared with those who have never smoked. Similarly, women who started to smoke before the age of 20 years compared with women who have never smoked are at greater risk of developing NHL (OR = 2.40, 95% CI = 0.99-5.85). In the total population (women and men), smoking may be associated with one histologic subtype, follicular NHL with an adjusted OR for the current smokers compared to subjects having never smoked of 3.20, 95% CI = 0.79-12.97. CONCLUSIONS: In spite of the small number of subjects in the subgroups, a relation is observed between smoking and NHL among women, but not men, and in the total population a relation is suggested between smoking and follicular NHL.

Adult↗
PubMed2003

Once-weekly epoetin beta is highly effective in treating anaemic patients with lymphoproliferative malignancy and defective endogenous erythropoietin production.

Epoetin beta, three-times weekly (t.i.w.), is effective in reversing anaemia in lymphoproliferative disorders. The current study investigated whether an epoetin beta dose of 30,000 IU given subcutaneously once weekly (q.w.) was at least as effective as 10,000 t.i.w. administration in anaemic patients with lymphoproliferative malignancy and defective endogenous erythropoietin (Epo) production. Overall, 241 anaemic patients with multiple myeloma, low-grade non-Hodgkin's lymphoma or chronic lymphocytic leukaemia, all with serum Epo values </= 100 mU/ml, were randomized to receive the q.w. (n = 119) or t.i.w. (n = 122) regimen for 16 weeks. The primary efficacy criterion, i.e. the time-adjusted area under the haemoglobin-time curve from weeks 5-16, was comparable between the q.w. and t.i.w. groups [difference = - 0.20 g/dl (90% confidence interval - 0.52-0.11)]. Moreover, response rates were high and similar in both arms (72%vs 75%, q.w. and t.i.w. groups respectively). Baseline serum Epo was predictive of response: the lower serum Epo, the higher the likelihood of response (P = 0.002). Thus, epoetin beta administered q.w. is an effective and convenient treatment for anaemia in patients with lymphoproliferative disorders. Tailoring this treatment modality to subjects with defective endogenous Epo production represents a rational use of epoetin from both a medical and a community perspective.

Adult↗