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B Coiffier

Publications and source records attributed to B Coiffier.

At least 199 records · Page 11Linked to original sources

Prognostic factors in Hodgkin's and non-Hodgkin's lymphomas.

A review of prognostic factors described recently in Hodgkin's and non-Hodgkin's lymphomas is presented with some comments on their interest and value for treatment choice and comprehension of the disease. The most important parameters are divided into three categories: 1) age; 2) extent of the tumor, ie, number of nodal or extranodal sites, bulkiness, stage, lactate dehydrogenase level or beta 2-microglobulin level; and 3) host-tumor interaction, ie, performance status, serum albumin level, and erythrocyte sedimentation rate. These initial parameters permit the stratification of lymphoma patients into subgroups with different outcomes in which different therapeutic modalities are tested.

Adult↗

Prognostic factors in aggressive malignant lymphomas: description and validation of a prognostic index that could identify patients requiring a more intensive therapy. The Groupe d'Etudes des Lymphomes Agressifs.

The objectives of this study were to determine prognostic factors for response to treatment, freedom-from-relapse (FFR) survival, and overall survival of 737 aggressive malignant lymphoma patients treated with the doxorubicin, cyclophosphamide, vindesine, bleomycin, methylprednisolone, methotrexate with leucovorin, ifosfamide, etoposide, asparaginase, and cytarabine (LNH-84) regimen; to construct a prognostic index with factors isolated by multivariate analyses; and to validate this prognostic index with another set of patients. Complete response (CR) was reached in 75% of LNH-84 patients, and 30% of them relapsed. With a median follow-up of 36 months, median FFR survival and median overall survival were not reached. Low serum albumin level, high tumoral mass, weight loss, bone marrow involvement, greater than or equal to 2 extranodal sites, and increased lactic dehydrogenase (LDH) level were associated with a low response rate. Advanced stage, increased LDH level, and nonlarge-cell histologic subtypes (diffuse mixed, lymphoblastic, and small non-cleaved) were statistically associated with a high relapse rate and short FFR survival. Increased LDH level, low serum albumin level, tumoral mass larger than 10 cm, greater than or equal to 2 extranodal sites, advanced stage, and age older than 65 years were statistically associated with short overall survival. Four of these parameters, namely, LDH level, stage, number of extranodal sites, and tumoral mass, were put together to construct a prognostic index. This index partitioned LNH-84 patients into three subgroups of good, intermediate, and poor prognosis (P less than .00001): CR rates of 93%, 83%, and 61%; relapse rates of 12%, 25%, and 45%; 3-year FFR survival of 87%, 73%, and 53%, and 3-year survival of 88%, 71%, and 41%, respectively. This prognostic index was applied to a test set of patients: 155 patients treated on protocols of the Nebraska Lymphoma Study Group. Using this index, these patients had 3-year FFR survival of 70%, 40%, and 22% (P = .0002) and 3-year survival of 79%, 52%, and 31% (P = .005). In patients with aggressive lymphomas, this simple prognostic index could distinguish between patients requiring intensive treatment such as autologous bone marrow transplantation in first complete remission and those who could be treated with standard regimens.

Adolescent↗

[Study of vinorelbine (V) combined with hexamethylmelamine (H) (combination V-H) in adenocarcinoma of the ovary: results a phase I-IIA trial, NHO-88, of ARTAC "ovarian" group].

The lack of decisive progress in ovarian cancer chemotherapy in recent years led the ARTAC "Ovary" group to initiate a study based on the hypothesis of collateral sensitivities. In this phase I-II trial, NHO-88, the V-H combination (associating vinorelbine (VNB) and hexamethylmelamine (HMM) was studied in patients with advanced ovarian adenocarcinomas, most of which had become resistant to previous chemotherapy. The aim of the study was to find an active combination without complete cross resistance with first-line platinum salt based combinations, such as CAP, FAP or CACb-300. A pilot feasibility study was first carried out to determine the maximum tolerated weekly dose (MTWD) of VNB (20 mg/m2/week), HMM being administered per os on days 1-14 of every 28-day cycle at a standard dose of 250 mg/m2/day. An open phase II-A study was further carried out according to a 2-step sequential analysis method for phase II clinical trials. We observed: 1), a good tolerance of the V-H combination apart from frequent neutropenia; 2), a response rate of 35% (95% confidence interval: 23-47%); 3), a median response duration of 4 months (range: 1-7 months); 4), in some cases, the absence of a complete cross-resistance between the V-H regimen and the previously administered platinum-based combinations. These results, which are currently being validated (phase II-B ongoing), constitute the first step in the search for active systems of sequential or alternate chemotherapeutic regimens for the treatment of advanced carcinomas.

Adenocarcinoma↗

High risk myelodysplastic syndrome coexistent with chronic lymphocytic leukemia for more than 9 years: inhibition of the myeloid clone by the lymphoid clone?

We describe a patient in whom the concomitant diagnosis of refractory anemia with excess of blasts (16% on initial marrow examination) and chronic lymphocytic leukemia was made more than 9 years ago. The myeloid clone showed a complex karyotypic abnormality. Evolution has so far been remarkably stable, without transformation into acute leukemia. Clonogenic assays showed that patient's serum inhibited the patient's own granulocyte-macrophage colony-forming units (CFU-GM). This inhibition was also present for a control subject's CFU-GM and acute myeloid leukemia clonogenic cells. This raises the problem of a down-regulation of the myeloid clone by the malignant lymphoid clone in this patient, and the possible mechanisms for this are discussed.

Bone Marrow↗

Pentostatin in refractory chronic lymphocytic leukemia: a phase II trial of the European Organization for Research and Treatment of Cancer.

Pentostatin was used to treat 26 patients with advanced B-cell chronic lymphocytic leukemia resistant to conventional treatment. Twenty patients had progressive disease on previous regimens and six had had partial remission and then relapsed 3-34 months after previous chemotherapy. Eleven patients had previously been treated with three different regimens. 10 had been treated with two regimens, and five had been treated with one regimen. Pentostatin was administered at a dosage of 4 mg/m2 weekly for 3 weeks, then 4 mg/m2 every other week for 6 weeks and once a month for 6 months. Seven of 26 assessable patients (27%) achieved partial remission and five (19%) achieved clinical improvement. The median duration of partial remission until relapse or death was 210 days. Myelosuppression was minor and transient in responsive patients, indicating some degree of selective effect on lymphocytes. Except for one patient who died of cerebral hemorrhage during the first 6 weeks of treatment, no drug-related deaths were registered. Major toxic effects included nausea in 17 patients (mainly grade 1), infections in 15, and liver enzyme elevations in five. Thus, pentostatin is active, even in patients with advanced B-cell chronic lymphocytic leukemia that is refractory to multiple chemotherapy regimens. Response can be achieved with mild myelosuppression.

Adult↗

Massive mediastinal extramedullary hematopoiesis in hereditary spherocytosis: a case report.

A case of extramedullary hematopoiesis (EMH) with a massive mediastinal mass in a 72-year-old woman with hereditary spherocytosis is reported. Several cases of EMH have been described in nonsplenectomized adults with hereditary spherocytosis, and it is thought to be a consequence of long-term stimulation of erythropoiesis. The exact mechanism remains controversial. EMH should be considered in the differential diagnosis of an asymptomatic paravertebral mass.

Aged↗

Peripheral T-cell lymphomas have a worse prognosis than B-cell lymphomas: a prospective study of 361 immunophenotyped patients treated with the LNH-84 regimen. The GELA (Groupe d'Etude des Lymphomes Agressives).

The prognostic significance of phenotype in malignant lymphomas (ML) is a matter of controversy. Here we analyze the clinical presentation, response to treatment, and survival of the 361 phenotyped patients with ML who were treated by the LNH-84 regimen. Histologic subtypes were diffuse-small cell in 10 patients, diffuse mixed in 69, diffuse large-cell in 177, immunoblastic in 94, and anaplastic large-cell in 11. One hundred and eight patients (30%) had a peripheral T-cell ML and 253 (70%) a B-cell ML. Most of B-cell MLs were of diffuse large-cell type, and the T-cell MLs were distributed among diffuse mixed and immunoblastic subtypes. T-cell MLs had an aggressive presentation with more patients having advanced stage (21% versus 41% stage II, 53% versus 45% stage IV, p = .0002), and B symptoms (58% versus 42%, p less than .01). The only significant difference in clinical manifestations were the higher frequency of gastrointestinal involvement in B-cell MLs (20% versus 2%, p less than .0001) and the more frequent spleen (39% versus 21%, p = .0005) and skin (19% versus 3%, p less than .0001) involvement in T-cell MLs. There was no difference in response to the LNH-84 regiment between the two subgroups, but T-cell ML patients relapsed at a higher rate (43% versus 29%, p less than .001). T-cell ML patients have a significantly shorter freedom-from-relapse (FFR) survival (median: 34 months versus not reached, logrank test: p = .002) and a non-significant shorter overall survival (median: 42 versus 50 months).(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗

Prognosis of aggressive lymphomas: a study of five prognostic models with patients included in the LNH-84 regimen.

Four prognostic models described for aggressive malignant lymphomas and the classical Ann Arbor staging system were used to compare the survival of 737 patients treated with the LNH-84 regimen. The aim of the study was to determine the optimal prognostic system at the time of diagnosis. Three institutions have described these models after multivariate analyses: the Dana Farber Cancer Institute (DFCI1 and DFCI2), the MD Anderson Hospital (MDAH), and the Memorial Sloan-Kettering Cancer Center (MSKCC). The models were constructed with the following variables: performance status, LDH level, and tumor extension. The latter is the most difficult to assess: it was considered as the number of extranodal sites and the diameter of the largest mass in DFCI1, stage and the diameter of the largest mass in DFCI2, the number of extranodal and extensive nodal sites in MDAH, and the number of nodal sites and their localization in MSKCC. Univariate studies with LNH-84 regimen patients showed all these variables to have major prognostic significance (logrank tests: P less than 10(-4)). All five prognostic systems divided patients into three subgroups: good, intermediate, and poor prognosis. Logrank analyses of survival showed highly significant differences (X2 greater than 90 and P less than 10(-6)) between the subgroups. No gross difference was found between the models, and none was better than the others. A new, internationally accepted prognostic system for the expression and comparison of treatment results in aggressive malignant lymphomas should include major univariate prognostic parameters and must be reliable and easy to use in clinical practice. Until such time, stage or LDH level are the best alternatives.

Antineoplastic Combined Chemotherapy Protocols↗

The dendritic reticulum cell pattern in B cell lymphomas of the small cleaved, mixed, and large cell types: an immunohistochemical study of 48 cases.

An immunohistochemical study was designed to study the dendritic reticulum cell (DRC) patterns in 48 cases of B cell non-Hodgkin's lymphomas of the small cleaved, mixed, and large cell types, both follicular (20 cases) and diffuse (28 cases), in order to evaluate the possible influence of DRCs on homing and the differentiation of neoplastic B cells. Three DRC patterns were observed. In the follicular lymphomas, DRCs constituted nodular networks of variable density. In the diffuse lymphomas, DRCs were present either as isolated and scattered cells (17 cases) or constituted irregular meshworks of variable sizes (11 cases). These DRC patterns correlate with B cell immunophenotypes. Like follicular lymphomas, and unlike diffuse lymphomas without DRC networks, diffuse lymphomas with DRC networks constantly expressed the pan B antigens and one marker characteristic of normal germinal center cells, CD21 antigen, the C3d receptor. The finding of organized DRC networks in a significant number of diffuse lymphomas does not substantiate the hypothesis that DRCs may play a role in the homing of neoplastic B cells. The correlations observed between DRC patterns and B cell immunophenotypes suggest that the persistence and/or the development of DRC networks within follicular center cell-type lymphomas are related to the degree of functional differentiation of neoplastic B cells.

B-Lymphocytes↗

A translocation involving a specific breakpoint (q35) on chromosome 5 is characteristic of anaplastic large cell lymphoma ('Ki-1 lymphoma').

Two cases of non-Hodgkin's lymphoma are reported in which a chromosomal translocation was observed involving the same site (q35) on the long arm of chromosome 5. The other breakpoint involved in the translocation was chromosome 2 (p23) in one case and chromosome 3 (q12) in the other. Both cases were large cell lymphomas expressing CD30 antigen ('Ki-1 lymphoma'). One was clearly of T lymphoid origin, the other probably B cell derived. One other case of a Ki-1 lymphoma with 2;5 translocation (involving the same breakpoint on chromosome 5) has been reported previously, and it is suggested that this cytogenetic abnormality may be specifically associated with Ki-1 lymphoma. The literature contains a further eight cases of lymphoid neoplasms with a translocation involving a breakpoint at q35 on chromosome 5. They have all been described as cases of 'malignant histiocytosis', but the present findings make it likely that these cases were in reality also examples of Ki-1 lymphoma. The breakpoint at the q35 region on chromosome 5 is close to the position of the fms proto-oncogene, suggesting that an abnormality affecting this gene might possibly play a causal role in 'Ki-1 lymphoma'. However, DNA restriction fragment analysis of the present cases showed no evidence that the breakpoint on chromosome 5 involves the fms gene or its immediate vicinity.

Adolescent↗

LNH-84 regimen: a multicenter study of intensive chemotherapy in 737 patients with aggressive malignant lymphoma.

From July 1984 to September 1987, 737 patients with aggressive malignant lymphoma (ML) were treated by an intensive regimen (LNH-84) comprising three or four courses of doxorubicin, 75 mg/m2; cyclophosphamide, 1,200 mg/m2; vindesine, 2 mg/m2 x 2; bleomycin, 10 mg x 2; and prednisolone, 60 mg/m2 x 5 (ACVB), consolidation with high-dose methotrexate, ifosfamide, etoposide, asparaginase, and cytarabine, and a randomized late intensification with two courses of cytarabine, cyclophosphamide, teniposide, bleomycin, and prednisone (AraCVmB). Four hundred forty-two patients had intermediate-grade ML, 221 highgrade ML, and 74 unclassified ML. Most of the patients had advanced disease: stage IIE (23%), III (13%), or IV (47%); 38% disseminated nodes; 38% two or more extranodal sites; and 41% a tumoral mass greater than 10 cm. Five hundred fifty-three patients (75%) went into complete remission (CR), 63 (9%) into partial remission, 62 (8%) failed to respond, and 59 (8%) died during ACVB courses, 17 of them from progression of the disease. With a median follow-up of 23 months, the estimated 2-year overall survival time to failure (TTF), and time to relapse (TTR) survival are 67%, 56%, and 67%, respectively. Patients receiving a late intensification had the same relapse rate as the other patients. A persistent fibronecrotic mass was found in 150 patients (20%) and did not influence the relapse rate. Toxicity was mainly neutropenia and infection during the ACVB courses, with 40 patients (5%) dying from septic complications while responding to treatment. Fifty-three percent of the patients had a neutropenia less than 0.500 x 10(9)/L, 58% fever (6% grade 4), and 49% a documented infection (8% grade 4). These results obtained with the LNH-84 regimen demonstrate that this therapeutic scheme is an effective treatment for aggressive ML.

Adolescent↗