PubMed Health⌕ Search

Biomedical subjects

Bertrand Coiffier

Publications and source records attributed to Bertrand Coiffier.

At least 73 records · Page 4Linked to original sources

Prevalence and pattern of antinuclear autoantibodies in 347 patients with non-Hodgkin's lymphoma.

The presence of antinuclear autoantibodies (ANA) was investigated in a large cohort of patients with non-Hodgkin's lymphoma (NHL) in order to assess their frequency, specificity and prognostic relevance. ANA were analysed in 347 patients with different histological subgroups of NHL and in 213 controls using an indirect immunofluorescence technique on HEp2 cells. As the appearance of autoantibodies may be found after treatment of NHL, samples were collected at the time of diagnosis of NHL before any therapy. Sixty-six (19%) NHL patients and 12 (5.6%) patients from the control group displayed ANA. The prevalence between the two groups was found to be significantly higher in NHL patients (P < 0.0001) with a marked increased prevalence in follicular and mantle cell lymphoma subgroups. Autoantibodies directed against mitotic proteins or mitotic-associated proteins were found in 6.9% of NHL patients versus 0.5% in the control group (P < 0.001), with a significantly increased incidence in follicular and mantle cell lymphoma subgroups (P < 0.0001). Some 28% of the patients with positive ANA displayed clinical symptoms that could correspond to classical autoimmune manifestations, this frequency appearing to be higher in the marginal zone/mucosa-associated lymphoid tissue lymphoma subgroup. These data demonstrate a significant incidence of ANA before any treatment in NHL occurrence, which seems to be higher in some histological subgroups with particular ANA, such as ANA directed against mitotic proteins or mitotic-associated proteins.

Adolescent↗

Immunochemotherapy: the new standard in aggressive non-Hodgkin's lymphoma in the elderly.

Rituximab is an anti-CD20 chimeric monoclonal antibody that has shown substantial activity in indolent non-Hodgkin's lymphoma (NHL). Recent data indicate that the clinical benefits achieved in the treatment of indolent NHL are mirrored in aggressive NHL. Diffuse large B-cell lymphoma is the most common form of aggressive NHL and accounts for approximately 40% of all NHL cases. Although rapidly fatal if left untreated, diffuse large B-cell lymphoma is responsive to chemotherapy. CHOP has been the gold standard of care in aggressive NHL for over 20 years and, until recently, efforts to improve efficacy have not resulted in substantial increases in clinical benefit. However, long-term survival is seen in less than 50% of patients, highlighting the need for novel therapeutic strategies. The activity of single-agent rituximab in pilot trials in the aggressive setting and its potential to sensitize tumor cells to the effects of chemotherapy, together with its non-overlapping safety profile, have encouraged investigators to combine rituximab with CHOP. The addition of rituximab to CHOP chemotherapy has achieved impressive survival benefits in elderly patients with untreated diffuse large B-cell lymphoma compared with CHOP alone. Importantly, improved response and survival were achieved with minimal additional toxicity, suggesting that immunochemotherapy provides a new standard of care in aggressive NHL. This article reviews the activity of rituximab in aggressive lymphoma and highlights its potential in both previously untreated and relapsed disease.

Aged↗

Outcome in relation to treatment modalities in 48 patients with localized gastric MALT lymphoma: a retrospective study of patients treated during 1976-2001.

The aim of this study was to retrospectively analyze survival and tumor response data in patients with localized gastric MALT lymphoma treated by different treatment modalities other than anti-Helicobacter pylori treatment (diagnosis made before 1993, or after failure of antibiotics + anti-acid), including surgery, chemotherapy or combined treatment. Here we studied a series of 48 patients with stage IE or IIE disease treated during the past 11 years. These patients received different treatments: chemotherapy was proposed to 19 (40%) patients; gastric surgery to 21 (43%) patients, consisting of partial gastrectomy of 7 patients and total gastrectomy in 14 patients; combined treatment to 8 (17%) patients, consisting of surgery + chemotherapy in 7 patients and surgery + chemotherapy + radiotherapy in 1 patient. At diagnosis, 85% of the patients had good PS and no B symptoms. Complete response after treatment was reached in 45 (94%) patients (chemotherapy: 84% of the patients; surgery alone: 95%; combined treatment: 100%). Progression was observed in 16 (33%) patients. No statistical difference in the survival was found among the different therapeutic modalities: 5-year overall survival year FFP survival was 81% for chemotherapy, 86% for surgery alone and 95% for combined treatment. Prognostic factors for survival were age, performance status and hemoglobin level at diagnosis. Considering the natural bias of a retrospective analysis, surgery or chemotherapy was associated with a similar outcome in patients with MALT lymphoma after antibiotics failure.

Adult↗

Nongastric mucosa-associated lymphoid tissue lymphomas.

Nongastric mucosa-associated lymphoid tissue (MALT)-derived lymphomas arise from various extranodal locations and are usually related to a particular pathogenesis with a possible external (environmental or autoimmune) event inducing the disease. We reviewed 165 patients with nongastric MALT lymphoma among the 243 patients with MALT lymphoma in our database and reviewed reports in the literature to analyze the clinical features of nongastric MALT lymphomas. The site of clinical presentation was related to the lymphoma location and was usually indolent. Dissemination of the disease at diagnosis was noticed in 48% of cases because of the involvement of multiple mucosal sites (48%) or because of a nonmucosal site involvement such as bone marrow, spleen, or liver (52%). With a median follow-up of 4 years, the estimated 5-year overall survival and 5-year freedom-from-progression rates were 89% and 50%, respectively, without any difference between patients with localized or disseminated disease or among different locations. Treatment recommendations for localized disease are based on surgery, local therapy, or chlorambucil. For disseminated disease, treatment recommendations include chemotherapy with fludarabine or chlorambucil or chemotherapy with CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) in cases of large tumor mass

Antineoplastic Agents↗

Cytogenetic and molecular delineation of a region of chromosome 3q commonly gained in marginal zone B-cell lymphoma.

BACKGROUND AND OBJECTIVES: Whole or partial trisomy 3 represents the most recurrent chromosomal abnormality occurring in marginal zone B-cell lymphoma (MZBCL), a distinct subtype of B-cell non-Hodgkin's lymphoma (NHL). By conventional cytogenetic analysis, unbalanced translocations involving chromosome 3 and leading to a partial trisomy 3q were identified in a series of 14 MZBCL patients. Fluorescent in situ hybridization (FISH) experiments were then performed to characterize the breakpoints further and to delineate the extent of the 3q gained region more accurately. DESIGN AND METHODS: We studied 14 cases of MZBCL combining cytogenetics and FISH techniques using specific probes for the long arm of chromosome 3, including the chromosome 3 a satellite probe, a representative panel of yeast artificial chromosome (YAC) clones mapping the chromosomal 3q region (3q11.2 to 3q23) and the chromosome 3 subtelomeric (3q29) probe. RESULTS: In the 14 cases, additional chromosome 3q material was found to be involved in different unbalanced translocations with chromosomes 1, 6, 7, 8, 11, 13, 14, 15, 17, 19 and 21, leading to a derivative chromosome. None of the chromosomal abnormality juxtaposed the 3q regions with the heavy and/or light k and l immunoglobulin gene loci. Eight different breakpoints distributed between the 3q11.2 and the 3q13.32 regions were identified and a common 3q13.32 3q29 overrepresented region was delineated. INTERPRETATION AND CONCLUSIONS: These results suggest that this critical region may be of importance in the pathogenesis of MZBCL and support the hypothesis that a gene dosage effect rather than a specific gene disruption may be involved in the development of this disease.

Chromosome Breakage↗

Monoclonal antibodies in the management of newly diagnosed, aggressive B-cell lymphoma.

Monoclonal antibodies have been used as a therapeutic option for patients with lymphoma for less than 5 years, but they have already changed our perception of how to treat these patients. In this review, the use of different types of monoclonal antibodies in the treatment of patients with diffuse large B-cell lymphoma is analyzed, particularly the combination of rituximab with chemotherapy as a first-line therapeutic option. The putative role of other monoclonal antibodies is discussed.

Antibodies, Monoclonal↗

Human leukocyte antigens class II and tumor necrosis factor genetic polymorphisms are independent predictors of non-Hodgkin lymphoma outcome.

Tumor necrosis factor (TNF) production and non-Hodgkin lymphoma (NHL) outcome was found to be related to the TNF(-308) polymorphism. To explore whether this could be linked to neighboring polymorphisms, we genotyped the TNF(-376,-308,-238,-163), lymphotoxin alpha (LTalpha)(+252), and HLA DRB1 alleles in 204 patients with NHL and 120 controls. TNF(-308A) was the only allele associated with higher TNF and its p55 and p75 receptors' levels (P =.009, P =.03, and P =.007) and lower complete remission rates (P =.006). Freedom from progression (FFP) and overall survival (OS) were shorter in patients with TNF(-308A) (P =.009 and P =.02), null HLA DRB1*02 allele (P =.007 and P =.14), or both genetic markers (P =.004 and P =.005). Multivariate analysis incorporating International Prognostic Index (IPI) identified TNF(-308A) (P <.0001, relative risk [RR] = 1.63; P <.0001, RR = 1.51) and null HLA DRB1*02 alleles (P =.015, RR = 1.18; P <.0001, RR = 1.25) as independent factors for FFP and OS. These results indicate the existence of at least 2 inherited factors involved in NHL outcome.

Base Sequence↗

Shortened first-line high-dose chemotherapy for patients with poor-prognosis aggressive lymphoma.

PURPOSE: Randomized trial LNH93-3 was conducted on patients who had poor-prognosis aggressive lymphoma and were younger than 60 years with two to three factors of the age-adjusted International Prognostic Index to evaluate the benefit of early high-dose therapy (HDT) with autologous stem-cell transplantation (ASCT). PATIENTS AND METHODS: Patients were randomized between doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) chemotherapy followed by sequential consolidation and an experimental shortened treatment consisting of three cycles with escalated doses of cyclophosphamide, epirubicin, vindesine, bleomycin, and prednisone and collection of peripheral-blood stem cells. On day 60, HDT was administered with 1,3-bis(2-chloroethyl)-1-nitrosourea, etoposide, cytarabine, and melphalan followed by ASCT. RESULTS: Eligible patients (n = 370) with aggressive lymphoma were analyzed. For ACVBP (181 patients) and HDT (189 patients), respective complete remission rates were 64% and 63%. With a median follow-up of 60 months, 5-year overall survival and event-free survival for ACVBP and HDT were 60% +/- 8% and 46% +/- 8% (P =.007) and 52 +/- 8% and 39 +/- 8% (P =.01), respectively. Survival was independently affected by age greater than 40 years (P =.0003), T-cell phenotype (P =.009), bone marrow involvement (P =.003), and HDT treatment group (P =.04). CONCLUSION: Early HDT with ASCT in high-risk patients was inferior to the ACVBP chemotherapy regimen. These results indicate that the received dose-intensity before HDT was too low when compared with ACVBP and HDT and was given too early.

Adolescent↗

CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma.

BACKGROUND: The standard treatment for patients with diffuse large-B-cell lymphoma is cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Rituximab, a chimeric monoclonal antibody against the CD20 B-cell antigen, has therapeutic activity in diffuse large-B-cell lymphoma. We conducted a randomized trial to compare CHOP chemotherapy plus rituximab with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. METHODS: Previously untreated patients with diffuse large-B-cell lymphoma, 60 to 80 years old, were randomly assigned to receive either eight cycles of CHOP every three weeks (197 patients) or eight cycles of CHOP plus rituximab given on day 1 of each cycle (202 patients). RESULTS: The rate of complete response was significantly higher in the group that received CHOP plus rituximab than in the group that received CHOP alone (76 percent vs. 63 percent, P=0.005). With a median follow-up of two years, event-free and overall survival times were significantly higher in the CHOP-plus-rituximab group (P<0.001 and P=0.007, respectively). The addition of rituximab to standard CHOP chemotherapy significantly reduced the risk of treatment failure and death (risk ratios, 0.58 [95 percent confidence interval, 0.44 to 0.77] and 0.64 [0.45 to 0.89], respectively). Clinically relevant toxicity was not significantly greater with CHOP plus rituximab. CONCLUSIONS: The addition of rituximab to the CHOP regimen increases the complete-response rate and prolongs event-free and overall survival in elderly patients with diffuse large-B-cell lymphoma, without a clinically significant increase in toxicity.

Aged↗

Combination of chemotherapy and monoclonal antibodies for the treatment of lymphoma.

Monoclonal antibodies (MoAbs) have transformed the treatment of lymphomas. The first reports of studies using MoAbs appeared 8 years ago, and current therapy for lymphoma patients usually includes treatment with MoAbs once or several times during the course of their disease. This review covers the use of MoAbs in combination with chemotherapy for the treatment of patients with lymphoma. Rituximab, an unconjugated anti-CD20 chimeric antibody, is certainly the most widely used MoAb, but the use of other unconjugated or radiolabeled MoAbs is increasing quickly. MoAbs are effective if used alone, but the duration of effectiveness is limited. Therefore, when MoAbs are used in curative treatment, they are combined with chemotherapy. There are randomized studies demonstrating the benefit of adding MoAbs to the treatment regimen of patients with diffuse large B-cell lymphoma, but results of ongoing studies regarding the benefit in other lymphomas have not been reported. Many questions must be answered before the best setting for MoAbs in the treatment of lymphoma patients can be determined.

Antibodies, Monoclonal↗

Factors predictive of early death in patients receiving high-dose CHOP (ACVB regimen) for aggressive non-Hodgkin's lymphoma: a GELA study.

Death during the induction phase of chemotherapy remains a common event in patients with aggressive non-Hodgkin's lymphoma (NHL). In a series of patients with aggressive NHL homogeneously treated with intensive induction chemotherapy [ACVB (doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone) regimen], we determined the clinical and biological parameters that were predictive of early death. Early death was defined as death, for whatever reason, occurring within 100 d of randomization. Predictive factors were identified by logistic regression and an index predictive for individual risk of early death was designed. Among the 2210 patients treated with ACVB, there were 162 (7.3%) early deaths. There was no significant reduction in the rate of early death between 1987 and 1998. In a multivariate analysis, age > 60 years, Eastern Cooperative Oncology Group performance status > 1, serum lactate dehydrogenase > normal, serum albumin < 30 g/l, leucocyte counts > 10 x 10(9)/l and haemoglobin levels < 8.5 g/dl were found to be independent predictive factors for early death. An early death index was designed, enabling the evaluation of the individual risk of early death in young (range 2-31% risk of early death) and elderly patients (range 5-53%). Clinical and biological parameters available at diagnosis can help physicians identify patients with aggressive lymphoma at low or high risk of early death.

Adolescent↗

Rituximab in combination with CHOP improves survival in elderly patients with aggressive non-Hodgkin's lymphoma.

Diffuse large B-cell lymphoma (DLCL) is the most frequently diagnosed subtype of non-Hodgkin's lymphoma (NHL), and more than 50% of cases present in patients over 60 years of age. Although cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) is currently regarded as the gold standard treatment for DLCL, less than half of the elderly patients treated are cured. Therefore, it is essential that new strategies are developed. Rituximab is a chimeric monoclonal antibody that is directed against the B-cell-specific antigen CD20 that is expressed on 80% of NHLs. Pilot trials combining rituximab with CHOP have suggested an efficacy advantage in both indolent and aggressive B-cell NHL, with no significant impact on toxicity. The Groupe d'Etude des Lyphomes de l'Adulte LNH-98.5 trial is the first randomized clinical trial to compare rituximab plus CHOP with CHOP alone in lymphoma patients. The trial compared the two treatment regimens in elderly patients with aggressive DLCL. Interim data (18-month follow-up) from this trial showed that the addition of rituximab to CHOP results in a statistically superior benefit in survival compared with CHOP alone. These groundbreaking data are the first in 20 years to show statistical improvement over CHOP and this suggests that rituximab plus CHOP may become the new gold standard treatment for elderly patients with DLCL.

Aged↗

Aggressive lymphoma: improving treatment outcome with rituximab.

The standard therapy for patients with aggressive lymphoma is cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy, which achieves a complete response in more than 60% of patients but is curative in only about 40-50%. More aggressive and/or dose-intensified chemotherapy regimens have failed to provide significant survival advantages compared with CHOP, and may have higher toxicity. Rituximab, a chimeric monoclonal antibody to the CD20 antigen, is effective as monotherapy in aggressive lymphoma and in combination with chemotherapy has demonstrated high response rates in phase II trials. A scheduled interim analysis of a randomized, prospective trial comparing rituximab plus CHOP with CHOP alone in elderly patients with untreated diffuse large B-cell lymphoma has shown significantly better response rates and survival with rituximab plus CHOP compared with CHOP alone. These results represent the first significant improvement in overall survival over CHOP in aggressive lymphoma for over 20 years. The addition of rituximab was not associated with significant additional toxicity over that seen with CHOP alone. Ongoing studies are underway to establish whether the survival benefit of rituximab plus CHOP is seen in younger patient populations. Rituximab in combination with chemotherapy is also being evaluated as salvage treatment for patients who relapse after initial chemotherapy. In a preliminary analysis of a study in 50 patients with refractory or relapsed aggressive lymphoma, rituximab plus etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (EPOCH) chemotherapy has demonstrated promising results when used as sole salvage therapy and as an induction therapy prior to autologous stem-cell transplantation, again without significant additional toxicity.

Antibodies, Monoclonal↗

Treatment of splenic marginal zone B-cell lymphoma: an analysis of 81 patients.

Splenic marginal zone B-cell lymphoma (MZL), with or without villous lymphocytes, is an indolent lymphoma, presenting with massive splenomegaly, generally associated with bone marrow dissemination. In patients requiring therapy, splenectomy has been reported as the treatment of choice. We reviewed the cases of 81 patients with splenic MZL. Patients presented with stage IV disease at diagnosis in 95% of the cases. Autoimmune events (hemolytic anemia, immune thrombocytopenia, acquired coagulation disorders, positive Coomb's test) were observed in 16 patients, and a monoclonal (M) serum component was detected in 46% of the patients. Twenty patients did not receive any initial treatment at diagnosis. Splenectomy was proposed in 79% of the treated patients, with adjuvant chemotherapy in 47% of patients. Median survival was 10.5 years and was significantly shorter in the presence of an M component, an elevated b2-microglobulin level, leukocyte count > 20000/microL, and lymphocytes > 9000/microL. Disease progression was significantly more frequent in patients presenting an immunological event or an M component. Seventy percent of the patients had persistent involvement of bone marrow and/or peripheral blood after splenectomy. Disease progression was significantly more frequent in partial responders than in complete responders (P < 0.005), but overall survival, risk of histologic transformation, and risk of death from lymphoma were not different in the 2 groups. Moreover, patients with cytopenia at diagnosis treated by splenectomy alone rapidly recovered normal hematological parameters. We conclude that splenectomy is an efficient treatment for splenic MZL, but that it may be delayed until the occurrence of symptoms or cytopenia.

Adult↗

Treatment paradigms in aggressive non-Hodgkin's lymphoma in elderly patients.

Half of the patients newly diagnosed with lymphoma are > 60 years of age and can thus be defined as elderly. Older patients treated for lymphoma may not tolerate the high-dose therapies used in younger patients, usually because of the presence of concomitant diseases. Diffuse large B-cell lymphoma represents > 50% of all lymphomas seen in elderly patients. Clinical presentation and prognostic parameters are identical to those described in young patients. However, response rate is usually lower in elderly patients compared to young patients, even if the patients are treated with a CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) regimen. Therefore, event-free and overall survival rates are shorter in the elderly patients, even if disease-free survival is not really shorter than in young patients. Rituximab added to the CHOP regimen has recently been shown to dramatically improve the survival of these older patients without increasing the toxicity of the treatment.

Age Factors↗

Rituximab in the treatment of diffuse large B-cell lymphomas.

A review of the use of rituximab (Rituxan; Genentech, Inc, South San Francisco, CA, and IDEC Pharmaceuticals, San Diego, CA) in diffuse large B-cell lymphomas is presented, focusing on the recent presentation of the combination of CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) plus rituximab in elderly patients. This combination increased the response rates, event-free survival, and overall survival of patients older than 60 years in comparison with CHOP alone. The toxic events observed with the combination were not more numerous or severe than those observed with CHOP alone. Rituximab is a chimeric anti-CD20 antibody that increases the treatment options in patients with B-cell lymphomas.

Antibodies, Monoclonal↗

Hepatitis B virus reactivation in patients receiving chemotherapy for cancer treatment: role of Lamivudine prophylaxis.

Hepatitis B virus (HBV) reactivation is a frequent complication in inactive HBV carriers at time of chemotherapy or following this chemotherapy. This complication appeared during or after chemotherapy and was not increased by the use of rituximab alone or combined with chemotherapy. This is a severe complication most frequently seen in lymphoma patients. Lamivudine have efficacy to treat the patients once the clinical disease is present. However, lamivudine prophylaxis beginning before chemotherapy and until at least 6 months after the end of chemotherapy is recommended for all HBV carriers. Hepatitis C virus is usually not associated with reactivation and prophylaxis should not be used.

Antineoplastic Agents↗