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Biomedical subjects

B Coiffier

Publications and source records attributed to B Coiffier.

At least 73 records · Page 4Linked to original sources
PubMed1999

Fludarabine alone compared to CHVP plus interferon in elderly patients with follicular lymphoma and adverse prognostic parameters: a GELA study. Groupe d'Etudes des Lymphomes de l'Adulte.

BACKGROUND: Fludarabine was associated with a good response and was well tolerated in patients with follicular lymphoma in phase II trials and this treatment may be associated with less adverse events than treatment with CHVP plus interferon in elderly patients. PATIENTS AND METHODS: One hundred thirty-one patients older than 59 years with a follicular lymphoma and poor prognosis were randomized between the association of CHVP (12 cycles in 18 months) plus interferon (5 MU TIW for 18 months) or fludarabine alone (25 mg/m2/d x 5 days for 6 cycles, then 20 mg/m2/day for 6 further cycles for 18 months). Poor prognosis was defined by the presence of a large tumor mass, poor performance status, the presence of B symptoms, above normal LDH level, or > or = 3 mg/l beta-microglobulin level. RESULTS: Patients treated with CHVP plus interferon had a higher response to treatment, a longer time to progression and a longer survival than those treated with fludarabine alone (P < 0.05 for all analyses). With a median follow-up of 29 months, the 2-year failure-free survival was 63% for the CHVP-plus-interferon arm compared to 49% for the fludarabine arm and the two-year survival was 77% and 62%, respectively. This benefit was confirmed in a multivariate analysis including initial prognostic parameters. Fludarabine alone was associated with less neutropenia than CHVP plus interferon. Interferon was decreased or stopped in 39% of the patients because of severe fatigue. CONCLUSIONS: CHVP plus interferon over 18 months was associated with a better outcome, even though the combination of interferon plus chemotherapy was less well tolerated than fludarabine.

Aged↗
PubMed1999

Aggressive primary mediastinal non-Hodgkin's lymphomas: a study of 29 cases.

Aggressive primary mediastinal non-Hodgkin's lymphomas (NHL) represent a particular entity among intrathoracic neoplasms. Twenty-nine patients with primary mediastinal aggressive NHL diagnosed and treated in the author's institution were studied. According to the Revised European-American Lymphoma (REAL) classification, there were 15 diffuse large B-cell, eight T-lymphoblastic, four anaplastic, one large T-cell and one Burkitt's lymphomas. The study group consisted of 14 females and 15 males, with a mean age of 38 yrs. Symptoms arose from an aggressive anterior mediastinal mass, with a high prevalence of superior vena caval syndrome, pleural, and pericardial effusions. At the time of diagnosis, disease was confined to supradiaphragmatic areas in 24 patients, while subdiaphragmatic nodal or extranodal involvement was also present in five. All patients received a combination of aggressive chemotherapy regimens, mainly according to the French protocols for the treatment of NHL. A chest radiograph response of <50% after the first course of chemotherapy and failure to achieve a complete remission after the first line of chemotherapy were significantly associated with unfavourable prognosis. Overall 5-yr and 9-yr survival rates were 55 and 48%, respectively. Patients properly diagnosed and treated with a combined modality of chemotherapy can experience prolonged survival.

Adult↗
PubMed1999

Toxicities after peripheral blood progenitor cell transplantation for lymphoid malignancies: analysis of 300 cases in a single institution.

Two hundred and seventy-seven consecutive patients with non-Hodgkin's lymphoma (n = 207), Hodgkin's disease (n = 27) and multiple myeloma (n = 43) were intensified from October 1989 until April 1997 and received unmanipulated PBPC transplants. Twenty-three patients received a double intensification, out of a total of 300 PBPC transplantations analyzed. Conditioning regimens consisted of total body irradiation (TBI)-containing regimens (n = 141), BEAM (n = 104), high-dose melphalan (n = 26), ICE (n = 23) or other regimens (n = 6). Eighty-four percent of the patients (119/142) evaluable for long-term hematological reconstitution beyond 180 days achieved normal trilineage blood counts. Abnormal hematological parameters were associated with low numbers of CD34+ cells re-infused and with prior exposure to fludarabine. The 100-day and long-term treatment-related mortality rates were 4% and 4%, respectively. Late complications and treatment-related toxicities were influenced by disease history, use of TBI and exposure to fludarabine. Patients older than 60 years did not have greater toxicities or more frequent treatment-related deaths. This analysis suggests that while leading to a limited morbidity and a low mortality rate, intensive chemotherapy with PBPC transplantation still remains a procedure leading to significant short- and long-term toxicities. Better recognition of the risk factors associated with these complications might allow a further decrease in their incidence.

Adolescent↗
PubMed1999

Translocations involving the short arm of chromosome 17 in chronic B-lymphoid disorders: frequent occurrence of dicentric rearrangements and possible association with adverse outcome.

Unbalanced translocations involving chromosome arm 17p, where the TP53 tumor suppressor gene localizes, are rarely described in chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL), but recent use of molecular cytogenetic techniques have indicated a significant incidence of TP53 deletions, suggesting the involvement of chromosome 17p in these disorders. By conventional karyotype, we have identified unbalanced translocations involving 17p in 14 out of 123 (11%) CLL/SLL patients with clonal abnormalities. Cases were characterized by resistance to chemotherapy and a poor clinical outcome. The karyotypes presented a high incidence of complex rearrangements and 17p translocations were characterized by various partners. In 10 cases a centric fusion was assessed by fluorescent in situ hybridization (FISH) experiments using specific centromeric probes. The incidence of dicentric translocations in these series is therefore significantly higher than usually described, arising in up to 71% (10 out of 14 cases). In all cases, translocations led to a monosomy 17p and to a TP53 monoallelic deletion. The adverse clinical outcome confirms that structural abnormalities involving chromosome 17p are associated with disease progression in patients with chronic lymphoproliferative disorders.

Antineoplastic Agents↗
PubMed1999

Profiles and prognostic values of LDH isoenzymes in patients with non-Hodgkin's lymphoma.

Serum lactic dehydrogenase (LDH) is an important prognostic factor in patients with non-Hodgkin's lymphoma (NHL). We have examined the LDH isoenzyme content in serum and CSF of patients with NHL, at diagnosis and at relapse. In patients with increased serum LDH at diagnosis, the percentage of isoenzyme 2 was increased in 52% of patients and the absolute value of isoenzyme 3 was increased in 64% of patients. In relapsing patients these values were respectively 69% and 65%. Conversely in patients with increased serum LDH due to myeloid regeneration after chemotherapy, isoenzymes 4 and 5, but not isoenzymes 2 or 3, were increased. High absolute values of isoenzyme 3 were correlated with an altered performance status, advanced tumor stage, and aggressive histology whereas high isoenzyme 2 percentages were correlated with altered performance status only. Among patients with high total serum LDH, a high content of isoenzyme 2 and a high absolute value of isoenzyme 3 were correlated with high serum levels of TNFalpha and TNF receptor p75. Analysis of total LDH and LDH isoenzyme profiles in CSF did not reveal any correlation with meningeal involvement by lymphoma. High isoenzyme 2 percentages and high absolute values of isoenzyme 3 in serum were both significantly associated with a shorter freedom-from-progression and overall survival. Isoenzyme 3 remained a prognostic factor for survival even when considering only patients with high total serum LDH at diagnosis. We conclude that there are some characteristic serum LDH isoenzyme profiles in patients with NHL and that some of these specific alterations may help refine the prognostic value of total serum LDH.

Adolescent↗
PubMed1999

Transient acute myopia induced by antilymphocyte globulins.

Acute onset of transient myopia may be induced by several drugs, different mechanisms having been described. We report the occurrence of such an event after intravenous administration of equine antilymphocyte globulins in a patient treated for aplastic anemia. Clinical ocular examination revealed no other abnormality, and ultrasonography disclosed no swelling of the ciliary body. The drug-induced myopia resolved completely after instillation of topical cyclopentolate, suggesting that its mechanism was the occurrence of a ciliary spasm. Acute myopia is a rare event and, to the authors' knowledge, this represents the first case described as being induced by antilymphocyte globulins.

Acute Disease↗
PubMed1999

Comparison of high-dose therapy and autologous stem-cell transplantation with conventional therapy for Hodgkin's disease induction failure: a case-control study. Société Francaise de Greffe de Moelle.

PURPOSE: To determine the prognostic factors and outcome of first-line induction failure Hodgkin's disease patients who were treated with a salvage regimen of high-dose chemotherapy and autologous stem-cell transplantation, and to compare them with matched, conventionally treated patients. PATIENTS AND METHODS: We retrospectively analyzed data relating to 86 Hodgkin's disease patients who underwent autologous stem-cell transplantation after failure of the first chemotherapy regimen, either because they did not enter a complete remission and experienced progression of disease less than 3 months after the end of their first-line treatment or because they showed evidence of disease progression during first-line therapy. Graft patients were matched with 258 conventionally treated patients (three controls per case) for age, sex, clinical stage, B symptoms, and time at risk; patient data were obtained from international databases. RESULTS: Among the 86 graft patients, the median age at diagnosis was 29 years (range, 14 to 57 years). Thirty-nine percent of patients had stage II disease, 23% had stage III disease, and 38% had stage IV disease. Seventy percent of the patients received chemotherapy and 30% received combined modality therapy; 60% of the patients received a seven- or eight-drug regimen. After this first-line treatment, 91% had disease progression and 9% had a brief partial response. Eighty patients received a second-line treatment; pretransplantation status was as follows: 24% of patients had a complete remission, 38% had a partial remission (PR), 14% had stable disease, and disease progression occurred in 24%. With a median follow-up of 22 months (range, 4 to 105 months) from diagnosis, the 5-year event-free survival and overall survival rates from transplantation were 25% and 35% (95% confidence intervals, 15 to 36 and 23 to 49), respectively. In multivariate analysis, the pretransplantation disease status after salvage therapy was the only significant prognostic factor for survival (PR: relative risk = 2.8, P = .017; progressive disease: relative risk (RR) = 5.26, P < .001). From diagnosis, the 6-year overall survival rates of the graft patients and 258 matched conventionally treated patients were 38% and 29%, respectively (P = .058). CONCLUSION: Autologous stem-cell transplantation represents the best therapeutic option currently available for patients with primary induction failure and is associated with acceptable toxicity. Response to second-line treatment before high-dose chemotherapy is the only prognostic factor that can be correlated with survival.

Adolescent↗
PubMed1999

Multicenter phase II study of fludarabine phosphate for patients with newly diagnosed lymphoplasmacytoid lymphoma, Waldenström's macroglobulinemia, and mantle-cell lymphoma.

PURPOSE: Fludarabine phosphate (F-AMP) has significant activity in follicular lymphoma and in B-cell chronic lymphatic leukemia, where it has demonstrated high complete response (CR) rates. Lymphoplasmacytoid (LPC) lymphoma, Waldenstrom's macroglobulinemia (WM), and mantle-cell lymphoma (MCL) also present with advanced-stage disease and are incurable with standard alkylator-based chemotherapy. A phase II trial was undertaken to determine the activity of F-AMP in patients newly diagnosed with these diseases. PATIENTS AND METHODS: Between 1992 and 1996, 78 patients (aged 18 to 75 years) received intravenous F-AMP (25 mg/m2/d for 5 days, every 4 weeks) until maximum response, plus two further cycles as consolidation. The primary end point was response rate; secondary end points included time to progression (TTP), duration of response, and overall survival (OS). RESULTS: Forty-four (62%) of 71 assessable patients had a response to F-AMP (LPC lymphoma, 63%; WM, 79%; MCL, 41%); the CR rate was 15%. At a median follow-up of 1.5 years, 19 of 44 responding patients have had progression of lymphoma; the median duration of response was 2.5 years. The median survival has not yet been reached. There was no significant difference in the duration of response or OS between patients with different histologies; TTP was shorter in patients with MCL (P = .015). Myelosuppression was relatively common, and the treatment-related mortality (TRM) was 5%, mostly associated with pancytopenia and infection. CONCLUSION: Single-agent fludarabine phosphate is active in previously untreated LPC lymphoma and WM, with only moderate activity in MCL. However, the CR rate is low, and the TRM is relatively high. Its role in combination chemotherapy remains to be demonstrated.

Adult↗
PubMed1999

Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group.

Standardized guidelines for response assessment are needed to ensure comparability among clinical trials in non-Hodgkin's lymphomas (NHL). To achieve this, two meetings were convened among United States and international lymphoma experts representing medical hematology/oncology, radiology, radiation oncology, and pathology to review currently used response definitions and to develop a uniform set of criteria for assessing response in clinical trials. The criteria that were developed include anatomic definitions of response, with normal lymph node size after treatment of 1.5 cm in the longest transverse diameter by computer-assisted tomography scan. A designation of complete response/unconfirmed was adopted to include patients with a greater than 75% reduction in tumor size after therapy but with a residual mass, to include patients-especially those with large-cell NHL-who may not have residual disease. Single-photon emission computed tomography gallium scans are encouraged as a valuable adjunct to assessment of patients with large-cell NHL, but such scans require appropriate expertise. Flow cytometric, cytogenetic, and molecular studies are not currently included in response definitions. Response rates may be the most important objective in phase II trials where the activity of a new agent is important and may provide support for approval by regulatory agencies. However, the goals of most phase III trials are to identify therapies that will prolong the progression-free survival, if not the overall survival, of the treated patients. We hope that these guidelines will serve to improve communication among investigators and comparability among clinical trials until clinically relevant laboratory and imaging studies are identified and become more widely available.

Clinical Trials as Topic↗
PubMed1999

Low-grade stage III-IV follicular lymphoma: multivariate analysis of prognostic factors in 484 patients--a study of the groupe d'Etude des lymphomes de l'Adulte.

PURPOSE: To identify the prognostic factors that influence overall survival (OS) in patients with stage III-IV follicular lymphomas and evaluate the clinical usefulness and the prognostic value of the International Prognostic Index (IPI). PATIENTS AND METHODS: Four hundred eighty-four patients with Ann Arbor stage III-IV follicular lymphomas treated in two phase III trials from 1986 to 1995 were screened for this study. All histologic slides were reviewed by two hematopathologists. The influence of the initial parameters on survival was defined by univariate (log-rank test) and multivariate (Cox model) analyses. RESULTS: The poor prognostic factors for OS (age > 60 years, "B" symptom(s), > or = two extranodal sites, stage IV disease, tumor bulk > 7 cm, at least three nodal sites > 3 cm, liver involvement, serous effusion-compression or orbital/epidural involvement, and erythrocyte sedimentation rate > 30 mm/h) that were significant in univariate analysis were subjected to multivariate analysis. Three factors remained significant: B symptom(s) (risk ratio = 1.80), age greater than 60 years (risk ratio = 1.60), and at least three nodal sites greater than 3 cm (risk ratio = 1.71). When the IPI was applied to these patients, the score was 1, 2, 3, and 4-5 in 49%, 39%, 11%, and 2%, respectively, and it was significant for progression-free survival (P =.002) and OS (P =.0001). CONCLUSION: Three prognostic factors for poor OS were identified: B symptoms, age greater than 60 years, and at least three nodal sites greater than 3 cm. The IPI was prognostic for OS, but in this population, a very low number of patients belonged to the high-risk groups.

Adult↗
PubMed1999

Granisetron plus or minus alprazolam for emesis prevention in chemotherapy of lymphomas: a randomized multicenter trial. Granisetron Trialists Group.

Anxiety can increase the risk of chemotherapy related emesis. We have studied the role of a benzodiazepine (alprazolam: A) in addition to granisetron for controlling emesis in patients treated with moderately emetogenic chemotherapy for malignant lymphomas according to an anxiety scale (Covi score). Two hundred twenty-five patients receiving at least 3 cycles of chemotherapy including adriamycin and/or cyclophosphamide and/or epirubicin and/or dacarbazine were randomized. Patients in arm G (n = 111) received 3 mg i.v. granisetron 10 min before chemotherapy at cycles (C) 1, 2 and 3 while in arm G+A (n = 114), alprazolam (A) was added per os 1 mg 1 hour before chemotherapy (H-1) and 0.5 mg at H+6 for C1. At C2 and C3, A was given 0.75 or 1.5 mg at H-48, H-24, H-1 and 0.5 mg at H+6. Patients characteristics were comparable between the 2 arms. Complete response rates (i.e. no emesis or at least slight nausea) were similar in both arms: G: 83, 94 and 93% versus G+A: 89, 93 and 97% in C1, C2 and C3 respectively. Nevertheless, the Covi score of the population was low rendering difficult the study of the factor "anxiety". Somnolence was significantly more frequent in the G+A arm (p < 0.0001).

Adolescent↗
PubMed1999

Modulation of costimulatory molecules on follicular lymphoma cells by TNF and CD40.

TNF has recently been implicated in the formation of germinal center cells in lymphoid organs. Follicular lymphoma (FL) is thought to represent the pathological counterpart of germinal center B-cell. High levels of TNF and its soluble receptors were found in the plasma of FL patients whereas the transcripts of these molecules were previously found to be present in FL patients lymph nodes. We therefore studied here the effects of TNF on the expression of costimulatory molecules implicated in the cytotoxic T cell response on purified FL cells. In contrast to results described with B-type chronic lymphocytic leukemia, also characterized by high levels of circulating TNF, none of the tested samples showed a regulation of CD80, CD86, CD27 and CD70 in response to TNF. To confirm that the lack of regulation of these molecules was not due to the FL cells inability to modulate their expression, we therefore analyzed costimulatory molecules expression after CD40 pathway stimulation. After culture with human CD40L-transfected L-cells, an up-regulation of CD80, CD86 and CD70 expression was observed, while TNF addition in this model did not influence these changes. In this context, the CD27 molecule was down-regulated except in a single case, where its expression was increased. Taken together, this data demonstrates that in vitro expression of costimulatory molecules such as CD80, CD86, CD27 and CD70, which are implicated in the anti-tumoral response, can be regulated by CD40 ligand but not by TNF.

Aged↗
PubMed1999

Indolent nonfollicular lymphomas: characteristics, treatment, and outcome.

Indolent lymphomas are defined by their low aggressiveness at diagnosis compared with large-cell or T-cell lymphomas: small lymph nodes or blood involvement usually existing for months or years, no B symptoms, and good performance status. However, except in mucosa-associated lymphoid tissue (MALT) lymphoma, the disease is usually disseminated and this indolent presentation does not preclude a good outcome. Indolent lymphomas consist of follicular lymphoma, small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL), marginal-zone lymphoma (MZL), and mantle-cell lymphoma (MCL) as defined in the World Health Organization (WHO) classification. A review of morphologic characteristics, clinical presentation, prognostic factors, and outcome is presented here for each of these entities. Despite the absence of good prospective or retrospective studies in the literature, some orientations for the treatment of these patients are given, as well as some ideas for future studies.

Humans↗
PubMed1999

Treatment of aggressive non-Hodgkin's lymphoma.

Clinically aggressive lymphomas are defined by the Revised European-American Classification for lymphoid neoplasms as diffuse large B-cell lymphoma, peripheral T-cell lymphoma, anaplastic large cell lymphoma, and lymphoblastic lymphoma. Mantle cell lymphoma is atypical due to its indolent presentation and refractoriness to treatments. A review of current therapeutic possibilities for these different lymphomas is presented.

Antineoplastic Combined Chemotherapy Protocols↗