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C Nouvel

Publications and source records attributed to C Nouvel.

12 recordsLinked to original sources

Benefit of autologous bone marrow transplantation over sequential chemotherapy in poor-risk aggressive non-Hodgkin's lymphoma: updated results of the prospective study LNH87-2. Groupe d'Etude des Lymphomes de l'Adulte.

PURPOSE: To update the randomized study that compared consolidative sequential treatment (ifosfamide, etoposide, asporaginase, and cytarabine) versus the high-dose regimen of cyclophosphamide, carmustine, and etoposide (CBV) followed by autotransplantation in patients with aggressive non-Hodgkin's lymphoma in first complete remission and to focus on high-intermediate and high-risk patients identified by the international prognostic index. PATIENTS AND METHODS: Nine hundred sixteen patients received induction treatment on the LNH84 protocol with open randomization for the anthracycline. In a subsequent randomization, 541 patients in complete remission were assigned to receive consolidation by either sequential chemotherapy (n = 273) or autotransplant (n = 268). Among the higher risk population (two or three risk factors), 236 patients in complete remission were assessable for the consolidation phase, with 111 in the sequential chemotherapy arm and 125 in the autotransplant arm. RESULTS: Among 541 randomized patients, disease-free survival and survival did not differ significantly between the two consolidative treatment arms. In the higher risk population, CBV was superior to sequential chemotherapy, with 5-year disease-free survival rates of 59% (95% confidence interval, 49% to 69%) and 39% (95% confidence interval, 28% to 50%), respectively (P = .01, relative risk = 1.19). The 5-year survival rate was superior in the CBV group at 65% (95% confidence interval, 56% to 74%) compared with 52% in the sequential chemotherapy group (95% confidence interval, 42% to 62%) (P = .06, relative risk = 1.49). CONCLUSION: This study shows a superior disease-free survival for higher risk patients in complete remission. Dose-intensive consolidation therapy should be considered for patients at higher risk who achieve complete remission after induction treatment.

Adolescent

Aggressive lymphomas with renal involvement: a study of 48 patients treated with the LNH-84 and LNH-87 regimens. Groupe d'Etude des Lymphomes de l'Adulte.

In order to describe renal involvement in aggressive non-Hodgkin's lymphomas (NHLs) and its prognostic significance, we reviewed the outcome of 48 patients with renal involvement treated with the LNH-84 or LNH-87 regimen. Histology was diffuse large cell in 29 (60%) patients; immunoblastic, diffuse mixed cell and lymphoblastic in four each; follicular large cell, diffuse small cleaved cell and diffuse small non-cleaved cell in one each; and unclassified in four. Ann Arbor stage was IV in 44 patients, and IE or IIE in four. Tumour mass > or = 10 cm, performance status (ECOG scale) > 2 and increased LDH level were present in 69%, 20% and 76% of patients respectively. Fifteen patients (31%) had multiple intraparenchymal nodules, 14 (29%) had direct spread into the kidney from a perirenal mass, ten (21%) had a single intraparenchymal nodule and nine (19%) had diffuse infiltration. Twenty-one patients (43%) presented with bilateral lesions. Three patients (6%) presented with acute renal failure. Ten other patients (21%) had serum creatinine > 120 mumol l-1. In 12 of these 13 patients renal function was restored with chemotherapy. Twenty-eight patients (57%) achieved complete remission. Estimated 4 year disease-free survival was 39%. Disease-free survival and actuarial survival at 4 years were estimated to be 58% respectively. Two renal parameters had adverse prognostic significance for survival: renal hilum involvement (P = 0.02) and diffuse renal infiltration (P = 0.01). A Cox model identified only two independent prognostic factors for survival, namely performance status > or = 2 and tumour size > or = 10 cm. We conclude that alteration in renal function occurs in 27% of patients with renal involvement. Systemic chemotherapy improves renal function rapidly. Long-term outcome is similar to that expected in NHL patients presenting with the same prognostic factors.

Actuarial Analysis

Comparison of autologous bone marrow transplantation with sequential chemotherapy for intermediate-grade and high-grade non-Hodgkin's lymphoma in first complete remission: a study of 464 patients. Groupe d'Etude des Lymphomes de l'Adulte.

PURPOSE: Intensive chemotherapy followed by autotransplantation has given promising results in partially responding or sensitive relapsed patients with aggressive non-Hodgkin's lymphoma. In 1987, we designed a randomized study to evaluate the potential benefit of a high-dose regimen containing cyclophosphamide, carmustine, and etoposide (CBV) followed by autotransplantation over a consolidative sequential chemotherapy (ifosfamide, etoposide, asparaginase, and cytarabine) in patients in first complete remission with intermediate- and high-grade non-Hodgkin's lymphoma. PATIENTS AND METHODS: Patients were younger than 55 years and had at least one adverse prognostic factor. Induction treatment was that of the LNH84 protocol with an open randomization on the anthracycline. Patients in complete remission were further randomly assigned to receive either consolidation procedure. RESULTS: After induction treatment, 464 patients were assessable for the consolidation phase. With a median follow-up duration of 28 months, the 3-year disease-free survival rate was 52% (95% confidence interval, 45% to 59%) in the sequential chemotherapy arm and 59% (95% confidence interval, 52% to 66%) in the autologous transplant arm (P = .46, relative risk = 0.90). The 3-year survival rate did not differ between sequential chemotherapy and autotransplantation, at 71% (95% confidence interval, 64% to 78%) and 69% (95% confidence interval, 62% to 76%), respectively (P = .60, relative risk = 1.11). CONCLUSION: For such a subset of patients, consolidation with the CBV regimen followed by autologous bone marrow transplantation is not superior to sequential chemotherapy.

Adolescent

Platelet density analysis: a tool for the detection of acquired storage pool disease in man.

This study was designed to evaluate the usefulness of platelet density analysis in the detection of acquired storage pool defects in human patients. Two groups of patients were investigated: 19 subjects affected with a myeloproliferative disorder (group I) where abnormal platelets are released from the megakaryocytes and 11 patients hospitalized in an intensive care unit (Group II) where normal platelets are injured in the circulation. Platelet density distribution after isopycnic centrifugation on a discontinuous stractan density gradient, dense granule markers (serotonin, ATP and ADP) and alpha granule markers (intraplatelet beta-thromboglobulin and platelet factor 4) were simultaneously determined. An increased proportion of the percentage of light platelets was observed in 16 patients of group I and nine of group II; an increased ATP/ADP ratio was observed in 12 patients of group I and 10 of group II. Both the tests were abnormal in 11 patients of group I and nine of group II. In group I, the level of serotonin was low and was related to the percentage of light platelets. The alpha granule specific proteins were normal in the two groups. These results indicate that platelet density analysis may serve as a screening test to detect exhausted platelets in human diseases.

Adenosine Diphosphate

Coulter Counter studies of hypotonic-induced macrothrombocytosis in normal subjects and in idiopathic thrombocytopenic purpura patients.

The addition of distilled water to platelet rich plasma converts the platelets into large spherocytes without lysis. This phenomenon implies an evagination of the platelet membrane which participates in the surface connecting system. An adaptation of the direct microscopic method (Milton & Frojmovic, 1979) to the Coulter Counter is reported. The maximum increase in platelet volume without platelet lysis was obtained for 120 mOsm. These volume changes are a consequence of a shift in the platelet volume distribution curve towards higher values without loss of log normality, while the volume dispersion is only slightly modified. This suggests that the amount of evaginable platelet membrane is correlated to the size of the platelet. The size parameters (volume, surface, diameter) of hypotonic-induced spherocytes closely agree with those reported in the original microscopic method. Application of this technique to ITP-platelets suggests a reduced evaginable platelet membrane; this fact probably reflects the abnormal demarcation of platelet territories at the megakaryocytic level.

Blood Platelets

Platelets in myeloproliferative disorders. III: Glycoprotein profile in relation to platelet function and platelet density.

Membrane glycoproteins (GP) are implicated in platelet functions. In myeloproliferative diseases (MD), some of these functions are known to be perturbed. 16 patients with various MD were investigated for platelet functions (retention to glass beads, epinephrine- and ristocetin-induced aggregation), platelet density distribution and PAS-staining glycoprotein profile on SDS-polyacrylamide-gel-electrophoresis. An abnormal GP pattern (moderate reduction of GP (Ib + Is) and GP IIb with corresponding increase in GP IIIb) was demonstrated but no relation to platelet dysfunction or density distribution was observed. No differences between the various types of MD were noticed although the group of polycythaemia vera was the less perturbed for platelet function, platelet density and also GP profile.

Blood Platelets

Platelets in myeloproliferative disorders. II. Serotonin uptake and storage: correlations with mepacrine labelled dense bodies and with platelet density.

Platelet serotonin (5-HT) uptake and storage in the presence and absence of reserpine were studied simultaneously with platelet volume, density and dense bodies content (mepacrine test) in 33 patients affected with myeloproliferative disorders (MD): 12 chronic myeloid leukaemia (CML), 9 polycythaemia vera (PV), 6 essential thrombocythaemia (ET) and 9 agnogenic myeloid metaplasia (AMM). Observations were (1) a dramatic reduction of the initial velocity (Vi) uptake and of the granular pool of 5-HT; (2) a slight reduction of the number of platelet dense bodies which, in many cases, were less fluorescent than in controls; (3) an increase of the percentage of light platelets while platelet volume was mostly normal; (4) a significant correlation between the number of dense bodies per platelet volume unit and either the percentage of light platelets (r = 0.76) or the size of the granular pool of 5-HT (r = 0.81). These results support evidence of a quantitative and qualitative acquired storage pool syndrome in these patients. In addition, the Vi studies demonstrate that the serotonin uptake across the plasmatic membrane is abnormal.

Blood Platelets

Platelets in myeloproliferative disorders. I. A comparative evaluation with certain platelet function tests.

Certain platelet functions were evaluated in 24 patients with secondary polycythaemia (SP) and in a large number of patients suffering from myeloproliferative disorders (MD'S): 89 patients with chronic myeloid leukaemia (CML) at different stages of development, 58 with polycythaemia vera (PV), 23 with essential thrombocythaemia (ET), and 25 with agnogenic myeloid metaplasia (AMM). Bleeding time, epinephrine-induced platelet aggregation and adhesiveness agreed with those generally reported in the literature; they are independent of thrombocytosis, the haemoglobin level and the leucocyte count. Macrothrombocytosis, evaluated by an electronic method, was only found in CML, mainly during acute blast crisis. An increased percentage of light platelets was a constant feature in all groups except in the SP and in 20% of the PV. The most severe abnormalities were observed in AMM and CML in the acute stage; in the chronic phase of CML there is no correlation between the severity of platelet abnormalities and the survival of the patients.

Blood Platelets

Platelet volume, density and 5 HT organelles (mepacrine test) in acute leukaemia.

Qualitative platelet parameters (volume, 5 hydroxy-tryptamine (5 HT) organelles studied by the mepacrine test, and density) were evaluated in 31 patients with acute leukaemia: 11 myelomonocytic (AML), 8 lymphoblastic (ALL), 12 granulocytic (AGL). Macrothrombocytosis was observed in most of the cases of AML, was rare in AGL and was never found in ALL. The 5 HT organelles/volume ratio was normal in AGL and ALL but was significantly decreased in AML. In contrast, platelet density distribution was always abnormal whatever the platelet volume and 5 HT organelle concentration. Thus, using simple new methods, convenient even in cases of thrombocytopenia, we demonstrate that qualitative platelet abnormalities are a constant feature in acue leukaemia and that they are more severe in AML.

Blood Cell Count