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Bertrand Coiffier

Publications and source records attributed to Bertrand Coiffier.

At least 37 records · Page 2Linked to original sources

ACVBP versus CHOP plus radiotherapy for localized aggressive lymphoma.

BACKGROUND: Chemoradiotherapy is standard treatment for localized aggressive lymphoma. To determine the optimal therapy for nonelderly persons with low-risk localized lymphoma, we conducted a randomized trial comparing chemoradiotherapy with chemotherapy alone. METHODS: Previously untreated patients less than 61 years old with localized stage I or II aggressive lymphoma and no adverse prognostic factors according to the International Prognostic Index were randomly assigned to three cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus involved-field radiotherapy (329 patients) or chemotherapy alone with dose-intensified doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) plus sequential consolidation (318 patients). RESULTS: With a median follow-up of 7.7 years, event-free and overall survival rates were significantly higher in the group given chemotherapy alone than in the group given CHOP plus radiotherapy (P<0.001 and P=0.001, respectively). The five-year estimates of event-free survival were 82 percent (95 percent confidence interval, 78 to 87 percent) for patients receiving chemotherapy alone and 74 percent (95 percent confidence interval, 69 to 78 percent) for those receiving chemoradiotherapy. The respective five-year estimates of overall survival were 90 percent (95 percent confidence interval, 87 to 93 percent) and 81 percent (95 percent confidence interval, 77 to 86 percent). In a multivariate analysis, event-free and overall survival rates were affected by treatment group, independently of tumor stage and the presence or absence of bulky disease. CONCLUSIONS: In patients under 61 years of age, chemotherapy with three cycles of ACVBP followed by sequential consolidation is superior to three cycles of CHOP plus radiotherapy for the treatment of low-risk localized lymphoma.

Adolescent↗

Monoclonal antibodies in the treatment of indolent lymphomas.

Humanised 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 a lymphoma patient will certainly receive at least one of them once or several times during the evolution of his/her disease. This review covers 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 radiolabelled monoclonal antibodies are catching up quickly. If there are randomised 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. Many questions need to be answered before the best setting for these drugs will be known.

Antibodies, Monoclonal↗

Radio-immunotherapy in low-grade non-Hodgkin's lymphoma.

Radiolabelled monoclonal antibodies (MAbs) differ from naked MAbs because they usually use murine antibodies, however, the next generation will use humanised MAb. Currently two compounds have been widely tested and both have been registered in the USA (yttrium-90 ibritumomab tiuxetan (Zevalin; Idec Pharmaceuticals) and iodine-131 tositumomab formerly known as (131)I-anti-B1 (Bexxar; Corixa Corp.)). The first one has recently been registered in Europe. Both MAbs have activity for the treatment of follicular lymphoma (FL) but few studies have been done outside this indication. In FL, they are associated with a higher response rate than rituximab. Their best indication is currently for patients who are refractory to rituximab but studies are running to define other indications.

Antibodies, Monoclonal↗

[Pathological and clinical correlations in primary cutaneous B-cell lymphomas: a series of 44 cases].

AIMS: histological and clinical relationship study of 44 cases of primary cutaneous B cell lymphoma, classified according to WHO classification. MATERIALS AND METHODS: histological, immunological and molecular analysis was correlated with clinical data. RESULTS: 33 cases (75%) were marginal zone B-cell lymphomas (MZL), with head and trunk predominance (median age = 54 years). Relapses in other mucosa-related sites occurred in 3 patients. Histological transformation implied a more aggressive treatment in 3 cases. A favorable outcome was observed in most cases. 9 (20%) diffuse large B-cell lymphomas (DLBCL) appeared as a unique nodule, with female predominance (median age = 74 years) and 4 lymphoma-related deaths which seemed age-related (> 70 years) with only one lower limb localization. Histological aggressive features were present in 3 patients with a fatal outcome. 2 (5%) WHO grade 3 follicular lymphomas (FL) had an heterogeneous phenotype, with head localization, cutaneous relapses and good outcome. CONCLUSIONS: MZL, the predominant type, has a good prognosis, although transformation can occur, needing a more aggressive treatment. DLBCL, observed in older patients, has clinical and histological prognostic factors identical to extra-cutaneous lymphomas. FL appears rare and has an heterogeneous phenotype. Relationships with its nodal counterpart remains unclear.

Adult↗

Current strategies for the treatment of diffuse large B cell lymphoma.

PURPOSE OF REVIEW: This paper reviews the improvement in the treatment of patients with diffuse large B cell lymphoma. RECENT FINDINGS: The outcome in these patients has become better with longer survival because of two major developments: (1) increasing the dose of active drugs and shortening the time between cycles, resulting in dose-dense or dose-intense regimens, and (2) combining rituximab with chemotherapy. Both strategies have been associated with higher response rates, longer event-free survival, and longer overall survival, particularly in patients without adverse prognostic parameters. A combination of both is currently being tested for these poor-risk patients. SUMMARY: Although improvement has been made in low-risk patients, much work has to be done for patients with high-risk lymphoma. It may come with a better definition of genetic abnormalities specifically associated with refractoriness to chemotherapy.

Antibodies, Monoclonal↗

Prevalence of anticentromere F protein autoantibodies in 347 patients with non-Hodgkin's lymphoma.

An association between autoimmunity and hematological malignancies has been reported including the detection of antinuclear autoantibodies (ANAs) in patients suffering from non-Hodgkin's lymphoma (NHL), with a high prevalence of ANAs directed to components of the mitotic apparatus or the mitosis-associated proteins. Previous studies have demonstrated that one of the targets of such ANAs could be the CENP-F protein, especially in some carcinomas. The prevalence and specificity of anti-CENP-F autoantibodies (aAbs) thus were analyzed in 347 patients with different histological subgroups of NHL before any treatment of NHL, along with 150 controls. The detection of these aAbs was performed using two techniques: a radioimmunological assay (RIA) and an indirect immunofluorescence technique (IIF). Twenty-five (7.2%) NHL patients and 2 (1.3%) control patients displayed anti-CENP-F aAbs using RIA. This difference between the two groups was found to be significant (P < 0.01), with a higher prevalence of aAbs in the follicular (13%) and in the marginal zone B and MALT (10.2%) lymphoma subgroups. By IIF, 10 (2.9%) patients with NHL displayed aAbs with a CENP-F or CENP-F-like pattern, whereas none of the control group did. In conclusion, these data demonstrate that a significant incidence of anti-CENP-F aAbs is observed, before any treatment, in some histological subgroups of NHL patients. In addition to the usefulness of anti-CENP-F aAbs as a marker for some NHL subgroups, prospective studies may be important to evaluate the predictive value of anti-CENP-F aAbs for the development of carcinomas.

Adolescent↗

Treatment of diffuse large B-cell lymphoma.

A review of new or emerging ideas concerning diffuse large B-cell lymphomas (DLBCL) is presented with particular emphasis on histologic classification, genetic prognostic factors, and first-line treatments. This lymphoma rests the most heterogeneous of all lymphomas for its clinical characteristics and outcome. This heterogeneity is probably secondary to the fact that a large proportion seems to occur from a transformation of an unknown indolent lymphoma. Current treatment is based on the combination of chemotherapy including cyclophosphamide, adriamycin, vincristine, prednisone (CHOP) or dose-intense CHOP-like regimen, and rituximab (R-CHOP).

Adult↗

Analysis of VH genes in marginal zone lymphoma reveals marked heterogeneity between splenic and nodal tumors and suggests the existence of clonal selection.

BACKGROUND AND OBJECTIVES: To clarify the relationship between splenic (SMZL) and nodal marginal zone (NMZL) lymphomas, we analyzed immunoglobulin variable heavy chain (VH) gene usage and mutation patterns in these tumors. DESIGN AND METHODS: VH genes were cloned and sequenced from 49 lymphoma samples (35 SMZL and 14 NMZL). RESULTS: A biased usage of VH gene was found with overrepresentation of VH1 in SMZL cases (13/35) and VH4 in NMZL cases (7/14). Evidence for antigen driven mutations was identified in 8 SMZL and 4 NMZL cases. Three cases out of 18 with clones analyzed from spleen and peripheral blood demonstrated intra-clonal diversity, with evidence of clonal selection in one case, indicating the possibility of antigen-driven clonal expansion. Eleven SMZL cases (31%) but only 2 NMZL (14%) cases were unmutated. No differences in clinical outcome and overall survival were found between the unmutated and mutated cases. INTERPRETATION AND CONCLUSIONS: The pattern of somatic mutation and the VH gene segment usage appear to differ between SMZL and NMZL, suggesting that these are distinct pathological entities. Moreover, a biased usage of certain sequences suggests that tumor cells in SMZL may be subjected to antigen selection.

Adult↗

Best treatment of aggressive non-Hodgkin's lymphoma: a French perspective.

The Groupe d'Etude des Lymphomes de l'Adulte (GELA) has conducted several phase II and III studies in patients with aggressive lymphoma, diffuse large B-cell lymphoma (DLBCL), and T-cell lymphomas during the past 20 years, in France and Belgium. These studies, have demonstrated that the outcome of patients with DLBCL may be improved and that the standard CHOP (cyclophosphamide, doxorubicin HCl, vincristine [Oncovin], prednisone) regimen is not sufficient to cure a large number of patients. The first improvement was the demonstration of superiority of a dose-dense and dose-intense regimen, ACVBP (doxorubicin [Adriamycin], cyclophosphamide, vindesine, bleomycin, prednisone). The second improvement was made in young patients with poor-risk lymphoma by intensifying their treatment with high-dose therapy and autotransplant. The third and most significant improvement was in the results associated with the combination of rituximab (Rituxan) and chemotherapy. Current studies look at decreasing the. number of patients truly refractory to chemotherapy, decreasing relapse rate with rituximab maintenance, and finding an appropriate regimen for patients with T-cell lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗

First-line treatment of follicular lymphoma in the era of monoclonal antibodies.

This review describes the recent evolution in the first-line treatment of patients with follicular lymphoma. In cases without adverse prognostic parameters, delayed treatment still is the best option. The combination of rituximab plus chemotherapy in patients with adverse prognostic parameters is the treatment associated with the highest complete response rates and the longer time to progression compared to chemotherapy or rituximab alone. The best chemotherapy regimen is not yet described. Also yet to be described is the place of radioimmunotherapy versus rituximab plus chemotherapy. High-dose therapies with autologous stem-cell transplant have a place in the treatment of these patients but not in first line.

Antibodies, Monoclonal↗

[The role of HLA DRB1 genetic polymorphisms in non-Hodgkin's lymphomas].

The role of tumor necrosis factor (TNF)-308A polymorphic allele on non-Hodgkin's lymphoma (NHL) outcome was documented in the previous studies, although the role of the neighboring polymorphisms was unknown. The aim of the present study was to asses the frequencies and distributions of the HLA DRB1, TNF-308 and lymphotoxin alpha (LTalpha)+252 allelic polymorphisms in NHL patients and healthy controls and their influence on NHL outcome. The HLA DRB1, TNF-308 and LTalpha +252 allelic frequencies and distributions didn't differ significantly between patients and healthy controls, thus it is unlikely that polymorphisms within the above mentioned sites confer susceptibility for lymphoma occurrence. Among the polymorphic alleles HLA DRB1*03, TNF-308A and LTalpha +252A remaining in linkage disequilibrium, TNF-308A was the only allele associated with higher TNF and its p55 and p75 receptors' plasma levels (p = 0.009, p = 0.03, and p = 0.007), lower complete remission rates (p = .006), shorter freedom from progression (FFP) and overall survival (OS) (p = 0.009 and p = 0.017, respectively). Among the polymorphic HLA DRB1 alleles, null HLA DRB1*02 was the sole allele along with the TNF-308A that remained independent factors for shorter FFP (relative risk [RR] = 1.18, p < 0.02 and RR = 1.63, p < 0.0001, respectively) and OS (RR = 1.25, p < 0.0001 and RR = 1.51, p < 0.0001, respectively). Innate immunity reflected by inherited HLA DRB1 genes repertoire and genetic propensity of the host to regulate TNF production and/or other closely linked genes influences clinical course and outcome of NHL.

Aged↗

Follicular lymphoma international prognostic index.

The prognosis of follicular lymphomas (FL) is heterogeneous and numerous treatments may be proposed. A validated prognostic index (PI) would help in evaluating and choosing these treatments. Characteristics at diagnosis were collected from 4167 patients with FL diagnosed between 1985 and 1992. Univariate and multivariate analyses were used to propose a PI. This index was then tested on 919 patients. Five adverse prognostic factors were selected: age (> 60 years vs < or = 60 years), Ann Arbor stage (III-IV vs I-II), hemoglobin level (< 120 g/L vs > or = 120 g/L), number of nodal areas (> 4 vs < or = 4), and serum LDH level (above normal vs normal or below). Three risk groups were defined: low risk (0-1 adverse factor, 36% of patients), intermediate risk (2 factors, 37% of patients, hazard ratio [HR] of 2.3), and poor risk (> or = 3 adverse factors, 27% of patients, HR = 4.3). This Follicular Lymphoma International Prognostic Index (FLIPI) appeared more discriminant than the International Prognostic Index proposed for aggressive non-Hodgkin lymphomas. Results were very similar in the confirmation group. The FLIPI may be used for improving treatment choices, comparing clinical trials, and designing studies to evaluate new treatments.

Adult↗

Clinical efficacy, tolerability, and safety of SAM486A, a novel polyamine biosynthesis inhibitor, in patients with relapsed or refractory non-Hodgkin's lymphoma: results from a phase II multicenter study.

PURPOSE: SAM486A is a new inhibitor of S-adenosyl-methionine-decarboxylase, a key enzyme for polyamine biosynthesis. It is more potent than the first generation S-adenosyl-methionine-decarboxylase inhibitor methylglyoxal bis-guanylhydrazone. This Phase IIa study reports the findings of SAM486A monotherapy in patients with refractory or relapsed non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Forty-one previously treated patients with either diffuse large cell, follicular, or peripheral T-cell NHL were treated i.v. with 100 mg/m(2) SAM486A as a daily 1-h infusion for 5 days repeated every 3 weeks. Treatment was continued for a total of eight cycles or until disease progression. RESULTS: Two patients, both with large B-cell lymphoma, showed a complete response at cycle 3 that was maintained for >or=13 and >or=28 months. Five patients had a partial response, and 3 had stable disease at last follow-up. The overall response rate (complete response plus partial response) was 18.9% for evaluable patients (7 patients). Anemia was the primary hematological toxicity and observed in 7 (17.1%) patients. Five patients experienced grade 3/4 anemia. Four patients (9.8%) experienced grade 3/4 febrile neutropenia and grade 3/4 thrombocytopenia, respectively. Nonhematological toxicities were mild to moderate in intensity. The most frequent side effects were nausea (39%), vomiting (22%), diarrhea (19.5%), asthenia (17.1%), abdominal pain (14.6%), and flushing (9.8%). CONCLUSION: SAM486A has a promising clinical activity in patients with poor prognosis NHL and manageable safety profile. To further define the role of SAM486A, in the treatment of NHL, additional studies are warranted.

Adenosylmethionine Decarboxylase↗

Second autologous transplantation after failure of a first autologous transplant in 18 patients with non-Hodgkin's lymphoma.

High-dose chemotherapy and autologous marrow or peripheral stem cell support offers the best chance of cure in some subgroups of patients with non-Hodgkin's lymphoma (NHL). Less is known about the role of a second course of myeloablative chemotherapy in patients who relapse after a first autologous transplant. The aim of this retrospective study was to evaluate the disease outcome, morbidity and mortality associated with second autologous transplantation in patients with NHL. Between 1985 and 2001, 225 patients who had received autologous transplantation for NHL in two institutions in Lyon relapsed. Of these 225 patients 18 underwent a second autologous transplantation. The median age at second transplant was 41 years. There were six indolent lymphomas and 12 aggressive lymphomas. The median follow-up from the second transplant was 42 months. The OS rate at 2 and 5 years were 58 and 27%, respectively. The PFS rate at 2 and 5 years was 36%. Five patients are alive without disease 20 to 100 months after the second transplant. Seven patients died of disease recurrence. Four (22%) toxic deaths occurred: one of pulmonary fibrosis, one of fungal infection and cardiac failure and two of acute leukaemia. A minority of patients with NHL recurrence after a first transplant can be cured by a second course of myeloablative chemotherapy at the cost however of high-risk toxic death.

Adult↗