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Biomedical subjects

C Payen

Publications and source records attributed to C Payen.

At least 19 recordsLinked to original sources
PubMed2000

Randomized study of recombinant interleukin-2 after autologous bone marrow transplantation for acute leukemia in first complete remission.

Immunological control of acute leukemia may be achieved after allogeneic transplant. Despite promising preliminary results, the impact of immunotherapy with interleukin-2 (r-IL-2) on patients with acute leukemia (AL), in first complete remission (CR1) remains unclear. We conducted a prospective multicenter randomized trial to compare outcome in patients with AL in CR1, treated with autologous bone marrow transplantation (BMT) with or without postgraft r-IL-2. One hundred and thirty patients with AL in CR1 (myeloblastic (AML): N = 78; lymphoblastic (ALL): N = 52) were randomized at time of BMT to receive (N = 65) or not (N = 65) r-IL-2. r-IL-2 (RU 49637 from Roussel Uclaf) was started after hematological recovery, as a five cycle regimen (12 M IU/m2/day continuous infusion on day 1-5, 15-17, 29-31,43-45 and 57-59). The two groups were balanced for patient and transplant characteristics. Analysis was based on an intent to treat. Thirty-eight (59%) of the 65 patients randomized into the study group started r-IL-2 at a median of sixty-eight days (23-140) after transplant and received 77% (16-100) of the scheduled dosage. They received a median of 120 x 10(6) IU/m2 (25-156) over 10 (3-13) days during a total median period of 56 (3-78) days. With a median follow-up of 7 years (5.4-8.1 years), 79 patients relapsed (study group: 43 (66%); control group: 36 (55%): p = NS). Survival and leukemia-free survival estimates were 33% (23-45) versus 43% (22-52) and 29% (19-41) versus 36% (24-51) respectively for study and control groups (all p = NS). These results show that leukemic control after autologous BMT is not increased by r-IL-2 therapy. Further studies should investigate more appropriate r-IL-2 schedules and the possibilities offered by better antigen recognition and activated effector cells.

Adult↗
PubMed1999

Familial multiple myeloma: report of fifteen families.

To further define the frequency, clinical and biological features of familial multiple myeloma we performed a retrospective study of related patients who presented with multiple myeloma. Most cases of familial multiple myeloma were observed in siblings (10/15), in whom the mean age at diagnosis was similar to unrelated multiple myeloma. In successive generations the mean age at diagnosis was lower. Monoclonal component was identical (IgG kappa) in seven families. Familial history of monoclonal gammopathy of undetermined significance was observed in three families. Five other prospective studies of 1263 patients identified four affected families (3.2 per 1000 cases of multiple myeloma), and raise the question of a genetic background in multiple myeloma.

Adult↗
PubMed1998

[Hereditary xanthinuria, rare cause of hypo-uric acidemia. 2 cases].

BACKGROUND: Hypouricemia can be observed in uncommon situations as in our two patients with hereditary xanthinuria. CASE REPORTS: In the first case, hereditary xanthinuria was discovered in a 36-year-old man when routine tests revealed hypouricemia. In the second case, a 76-year-old woman, hypouricemia was also a fortuitous discovery. She had major xanthinuria and a radiotranslucid lithiasis in the right kidney. DISCUSSION: Hereditary xanthinuria is characterized by hypouricemia, low urinary urate excretion and increased concentration of xanthine and to a lesser extent hypoxanthine. The disease results from a defect in xanthine oxidase and is considered to be transmitted by autosomal recessive heredity. This rare metabolic disorder is more often asymptomatic and detected by routine chemistry. Development of xanthine lithiasis is directly related to the low solubility of xanthine and is the main complication of the disease, occurring in 30-40% of patients. There is no effective treatment and the only useful measure is to prevent xanthine urolithiasis by maintaining urinary output above 2 l/day.

Adult↗
PubMed1996

A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myélome.

BACKGROUND: The median survival of patients with myeloma after conventional chemotherapy is three years or less. Promising results have been reported with high-dose therapy supported by autologous bone marrow transplantation. We conducted a randomized study comparing conventional chemotherapy and high-dose therapy. METHODS: Two hundred previously untreated patients under the age of 65 years who had myeloma were randomly assigned at the time of diagnosis to receive either conventional chemotherapy or high-dose therapy and autologous bone marrow transplantation. RESULTS: The response rate among the patients who received high-dose therapy was 81 percent (including complete responses in 22 percent and very good partial responses in 16 percent), whereas it was 57 percent (complete responses in 5 percent and very good partial responses in 9 percent) in the group treated with conventional chemotherapy (P < 0.001). The probability of event-free survival for five years was 28 percent in the high-dose group and 10 percent in the conventional-dose group (P = 0.01); the overall estimated rate of survival for five years was 52 percent in the high-dose group and 12 percent in the conventional-dose group (P = 0.03). Treatment-related mortality was similar in the two groups. CONCLUSIONS: High-dose therapy combined with transplantation improves the response rate, eventfree survival, and overall survival in patients with myeloma.

Adult↗
PubMed1996

Vincristine degradation by serum from leukemic patients: role of myeloperoxidase.

Myeloperoxidase (MPO) has been shown to catalyze the in vitro degradation of vincristine (VCR). Given that MPO is a lysosomal enzyme that can be released into the circulation by both normal activated and leukemic myeloid cells, we investigated the possibility that sera from patients with acute myeloblastic leukemia (AML) might exhibit an increased capacity to degrade VCR. 31 serum samples (23 from patients with acute myeloblastic leukemia and 8 from patients with other conditions) were analyzed after incubation with ((3)H)VCR by using HPLC. Sera from patients with AML demonstrated an increased ability to breakdown VCR when compared to either normal sera or to sera from patients with lymphoid leukemias. VCR degradation was significantly increased by adding hydrogen peroxide, an electron donor for MPO, to the sera and was almost completely inhibited by adding 1 mM acetaminophen, an inhibitor of MPO. VCR peroxidation in the presence of hydrogen peroxide correlated both with the number of leukemic blasts in the circulation at the time the sera were obtained and with serum MPO concentrations determined by an immunoassay. These data suggest that the inactivity of VCR in AML may be due in part to its rapid peroxidation to inactive species by the MPO of leukemic myeloblasts.

Acetaminophen↗
PubMed1996

[Experimental prevention of deep venous thrombosis with low-molecular-weight heparin using implantable infusion devices].

We studied the effect of a fractionated heparin, Dalteparine Sodium, on the prevention of thrombosis of veins of the superior vena cava system catheterized by implantable infusion devices. Forty-six patients with solid or lympho-proliferative tumors, whose clinical condition required installation of a such device, were successively included into the study in 1991. The anticoagulant was administered for one month following implantation at the dosage of 2,500 anti-Xa units per day. The development of deep vein thrombosis was investigated by systematic Doppler ultrasound before the first and third months and at 1 year. Three early (D9, D12 and D16) and asymptomatic thrombosis were diagnosed (6.5%). This rate, although clearly more favourable, was not significantly different (p = 0.254) from the rate of 15.2% previously reported in a group of 72 comparable patients, but who did not receive preventive treatment. These results demonstrate the necessity and feasibility of a randomized study on a larger number of patients testing several protocols, before concluding on the efficacy of this type of preventive treatment.

Adolescent↗
PubMed1995

Consolidation treatment of adult acute lymphoblastic leukemia: a prospective, randomized trial comparing allogeneic versus autologous bone marrow transplantation and testing the impact of recombinant interleukin-2 after autologous bone marrow transplantation. BGMT Group.

A prospective, randomized trial was initiated in adult acute lymphoblastic leukemia (ALL) to compare (1) disease-free survival (DFS) after allogeneic or autologous bone marrow transplantation (BMT) and (2) the relapse rate of patients treated with or without interleukin-2 (IL-2) after autologous BMT. A total of 135 previously untreated patients, aged under 55 years, received the Berlin-Frankfurt-Muster (BFM) induction regimen: 126 patients (93%), of which 120 were HLA-typed, achieved complete remission (CR). According to this genetic randomization, patients with (n = 43) or without an HLA-identical sibling (n = 77) were to receive allogeneic or autologous BMT, respectively. The 3-year post-CR probability of DFS was significantly higher in the HLA-identical sibling group than in the non-HLA-identical sibling group (68% v 26%; P < .001). Eligible patients were randomized to receive (n = 30) or not to receive (n = 30) IL-2 after autologous BMT: the 3-year post-BMT probability of continuous CR was similar in both groups (29% v 27%, respectively). We conclude that, in ALL, early allogeneic BMT after the BFM induction regimen is an effective consolidation treatment and that IL-2 does not decrease the high relapse rate observed after autologous BMT.

Adult↗
PubMed1995

Bone marrow involvement in anaplastic large cell lymphoma. Immunohistochemical detection of minimal disease and its prognostic significance.

Bone marrow involvement by anaplastic large cell anaplastic large cell (ALC) lymphoma can be difficult to detect on routine morphologic examination alone. In a series of 42 patients with ALC lymphoma, the authors analyzed: (1) the usefulness of a limited panel of monoclonal antibodies directed against CD30 (Ber-H2, HRS4) and epithelial marrow involvement on routinely processed biopsy specimens; and (2) the prognostic significance of bone marrow involvement as detected on both morphologic and immunohistochemical grounds. On conventional examination, 17% of the patients were found to have bone marrow involvement at diagnosis. However, after immunohistochemical analysis, occult malignant cells were detected in 23% of the patients with negative bone marrow biopsy on routine histology. The low percentage of positive cases on routine morphologic examination compared to immunohistochemical examination was related to: (1) the scarcity of neoplastic cells which were scattered among hematopoietic cells; (2) the difficulty of distinguishing malignant cells from immature hematopoietic elements; and (3) the absence of alteration of the reticulin network. The authors observed a significant association between marrow infiltration and the presence of hematologic abnormalities (mostly anemia or cytopenias) at diagnosis, both in children and adult patients. More importantly, a significant lower survival was seen in patients with bone marrow involvement compared to those without bone marrow involvement. Immunohistochemistry with anti-CD30 and anti-EMA antibodies should be performed systematically in bone marrow biopsies from patients with ALC lymphoma to reliably identify the presence of bone marrow involvement that appears to carry a poor prognosis.

Adolescent↗
PubMed1995

Prognostic significance of karyotype in de novo adult acute myeloid leukemia. The BGMT group.

A group of 201 adult patients, 127 younger and 74 older than 55 years, with de novo acute myeloid leukemia were investigated to determine the prognostic significance of karyotype on early death (toxic or aplastic death occurring before hematopoietic recovery), drug resistance, continuous complete remission (CCR) and survival probabilities at 5 years. A good prognostic impact was found for t(8;21), t(15;17) and inv(16). The best factor proved to be t(8;21) (5-year survival probability: 50%), followed by t(15;17) (5-year survival probability: 39%) and by inv(16) (5-year survival probability: 43%). An intermediate outcome was found in patients with trisomy 8 (27% alive at 5 years) and in patients with numerical abnormalities other than -7 and +8 (33% in CCR and 62% alive at 5 years). Normal karyotypes had a different prognostic impact according to age: intermediate in young and good in older patients. A poor outcome was observed among patients with del(5q)/-5 (median survival: 1 month), with 11q23 rearrangements (median survival: 1.5 months) and with del(7q)/-7 (median survival: 10 months). The 'other structural change' group was also found to be a poor risk population (5-year survival probability: 5%) whereas complex karyotypes were predictive of short survivals only in older patients. Conversely, del(7q)/-7 and +8 as secondary changes, had no prognostic impact.

Acute Disease↗
PubMed1994

Epstein-Barr virus (EBV) replicative gene expression in tumour cells of AIDS-related non-Hodgkin's lymphoma in relation to CD4 cell number and antibody titres to EBV.

OBJECTIVE: To determine whether activation of Epstein-Barr virus (EBV) replication in tumour cells of AIDS-related non-Hodgkin's lymphoma (ARNHL) is correlated with CD4+ cell counts and influences antibody response to EBV [anti-Z Epstein-Barr replicative activator (ZEBRA), anti-early antigen (EA), anti-viral capsid antigen (VCA)]. DESIGN: Retrospective study based on immunohistochemistry and in situ hybridization to detect EBV replicative gene products in tissue samples from patients affected by ARNHL and correlation with CD4+ cell counts and results of EBV serology (including anti-ZEBRA activity) in sera from the same patients. METHODS: Seventeen out of 22 cases of ARNHL were selected for the presence of EBV [Epstein-Barr early region (EBER) RNA-positive]. Immunohistochemistry was performed with anti-ZEBRA, anti-EA-restricted, anti-VCA antibodies and in situ hybridization with BHLF1/NotI oligoprobes on tumour samples. Results were statistically correlated with those of CD4+ cell counts (17 out of 17) and with anti-EBV antibody titres (13 out of 17) assessed using standard immunofluorescence method and enzyme-linked immunosorbent assay procedure using recombinant ZEBRA protein and synthetic peptides as antigens. RESULTS: BZLF1 (ZEBRA) or early gene products (EA-R and EA-D/BHLF1/NotI) were detected in a small proportion (< 0.01-5%) of tumour cells in eight of these 17 cases by immunohistochemistry and in situ hybridization. Demonstration of replicative gene expression did not correlate with either low CD4+ cell counts (P > 0.05) or anti-EBV antibody titres (P > 0.05). Anti-ZEBRA activity was not significantly increased in patients affected with ARNHL, the cells of which expressed replicative gene products (P > 0.05). CONCLUSION: The degree of immunodeficiency does not clearly enhance replicative gene expression in tumour cells of ARNHL. EBV serology, including anti-ZEBRA activity, is not a reliable tool for predicting the occurrence of such proliferations.

Acquired Immunodeficiency Syndrome↗
PubMed1994

bcl-2 proto-oncogene and Epstein-Barr virus latent membrane protein-1 expression in AIDS-related lymphoma.

The expression of bcl-2 protein and Epstein-Barr virus (EBV) latent membrane protein 1 (LMP-1) was investigated in 18 cases of lymphoma occurring in the acquired immunodeficiency syndrome (AIDS). EBV small RNAs were detectable in tumour cells in all cases by in situ hybridization with EBER oligonucleotides. LMP-1 expression was detected in 61% of the cases, and 55% were positive for bcl-2. Dual expression of LMP-1 and bcl-2 was found in 8/18 (44%) cases, while five cases (28%) expressed either LMP-1 or bcl-2 and five expressed neither. Thus, there was an inconsistent relationship between the presence of EBV and the expression of bcl-2. One LMP-1 negative case was found to express bcl-2 in reactive lymphocytes but not in lymphoma cells. No clinical features were found to correlate statistically with LMP-1 or bcl-2 expression in the tumour cells. However, CD4 counts at diagnosis were significantly lower in bcl-2 positive cases (P < 0.05). The respective roles of EBV LMP-1 and the expression of bcl-2 in lymphogenesis in AIDS patients remains complex and is not yet fully understood.

Adult↗
PubMed1994

Escalating dose of mitoxantrone with high-dose cyclophosphamide, carmustine, and etoposide in patients with refractory lymphoma undergoing autologous bone marrow transplantation.

PURPOSE: We conducted a dose-finding study of mitoxantrone (MITO) in combination with high-dose cyclophosphamide, carmustine (BCNU), and etoposide (CBV) in refractory lymphoma undergoing autologous bone marrow transplantation (ABMT). The objective were to determine the following: (1) the maximum-tolerated dose of MITO, (2) the extramedullary toxicity of this regimen, (3) its antitumor activity, and (4) the pharmacokinetic characteristics of MITO at each dose level. PATIENTS AND METHODS: Escalating doses of MITO (15 to 90 mg/m2, single bolus infusion on day -8) followed by CBV were administered to 20 patients (mean age, 38.5 years) with refractory lymphoma. MITO concentrations were determined by high-performance liquid chromatography (HPLC). RESULTS: No toxic death occurred. The maximum-tolerated dose appears to be 75 mg/m2. Two of five patients treated with 90 mg/m2 developed severe organ toxicity, versus zero of 15 treated with doses up to 75 mg/m2. Duration of neutropenia was longer for patients treated with 90 mg/m2 (31.7 days) than for patients treated with doses up to 75 mg/m2 (22.1 days) (P < .05). A linear relationship was observed between administered dose of MITO and (1) plasma peak value, (2) area under the curve (AUC), and (3) plasma concentration on the day of marrow infusion (day 0). Hematologic toxicity was related to the terminal half-life (T1/2) of MITO, and day-0 plasma concentration. A high complete response (CR) rate was observed (60%), and eight of 11 (73%) patients treated with MITO > or = 60 mg/m2 achieved a CR. CONCLUSION: MITO (up to 75 mg/m2) and CBV can be administered with acceptable toxicity and a promising CR rate in this poor-risk population, justifying further phase II studies.

Adult↗
PubMed1993

[Deep venous thrombosis on implantable infusion devices. A prospective study of 72 patients with Doppler ultrasonography of veins of the neck (jugular, subclavian and brachiocephalic trunk)].

Seventy-two consecutive patients with totally implanted catheters for administration of chemotherapy for solid tumours or lymphomas were studied prospectively to assess the prevalence of venous thrombosis. During the follow-up period of 343 (6-1,177) days, 11 cases of venous thrombosis (15.2%), of which 45% were partial and only 36% symptomatic were observed. Venous thrombosis was an early complication, 6/11 cases being observed within 1 month of implantation. No clinical or biological predisposing factor, apart from the presence of malignant disease, could be identified. Doppler ultrasonography is a good method of following-up these patients. This method should become an essential diagnostic tool in this field.

Adult↗
PubMed1993

Risk factors for cytomegalovirus infection in BMT recipients transfused exclusively with seronegative blood products.

Risk factors for developing cytomegalovirus (CMV) infection and pneumonitis were analysed in 100 unselected consecutive patients undergoing allogenic BMT. This series is homogeneous because of the same diagnostic procedures, BMT technique and supportive care (exclusive seronegative blood products, no CMV immunoglobulin, no prophylactic antiviral). The incidence of CMV infection and CMV interstitial pneumonitis (CMV-IP) were 44% and 13% respectively, of whom five patients died. Variables such as age, sex, underlying disease, conditioning regimen and occurrence of GVHD were not found as significant risk factors. We confirm that the only major factor was recipient's serology as CMV infection and IP occurred in 4% and 0% respectively among negative recipients (R-) compared with 79% and 25% among positive R. In contrast to some studies among R+, neither donor's immunity nor recipient's CMV humoral response improved the clinical outcome. This study validates the good predictive value of viremia and urinary virus excretion for the occurrence of CMV-IP (respectively positive in 11 and 13 patients out of 13 with IP), always preceding IP by a median of 37 and 27 days. The highest risk patients for lethal CMV-IP were older recipients (> 30 years). Thus, prospective prophylactic trials with antiviral agents are suggested in such viremic or viruric patients. Furthermore, the use of seronegative blood products is highly effective and sufficient to prevent CMV infection in R-patients.

Adolescent↗
PubMed1992

Intensive combined therapy for previously untreated aggressive myeloma.

A trial was initiated to determine the feasibility and efficacy of a three-phase treatment including: (1) induction chemotherapy (IC); (2) high-dose melphalan with total body irradiation supported by unpurged autologous bone marrow transplantation (ABMT); and (3) interferon (IFN) alpha maintenance treatment, in previously untreated aggressive myeloma. Thirty-five consecutive patients, ages under 65 years, were enrolled. Initial induction therapy was randomized between the VAD regimen (vincristine, doxorubicin, dexamethasone) or the VMCP regimen (vincristine, melphalan, cyclophosphamide, prednisone) that were found to give similar results as IC. Thirty-one of 35 (89%) patients, with good performance status and normal renal function after IC, received ABMT. IFN alpha was started soon after ABMT and was well tolerated. Fifteen of 35 (43%) patients achieved complete response (CR) and 14 of 35 (40%) achieved partial response (PR). Low pretreatment beta 2 microglobulin was the only predictive factor for accomplishing CR. The duration of response was significantly affected by the magnitude of response. The 33-month, post-ABMT probability of progression-free survival was 85% for patients in CR versus 24% for patients in PR. The 42-month, post-diagnosis probability of survival was 81%. This overall strategy may represent an advance in the management of multiple myeloma. Furthermore, the high rate and long duration of CR that we observed in patients with low beta 2 microglobulin suggest that such patients may preferentially benefit from this strategy.

Aged↗
PubMed1992

Prognostic significance of karyotype in a twelve-year follow-up in childhood acute lymphoblastic leukemia.

We report a follow-up of 49 children with acute lymphoblastic leukemia (ALL) diagnosed between 1972 and 1978 (follow-up 12-18 years). This series allowed us to analyze the predictive value of karyotype in a long-term follow-up. Karyotypes were abnormal in 33 cases (67.3%): pseudodiploidy in 11 (22.4%), hyperdiploidy > 50 chromosomes in 8 (16.3%), hyperdiploidy 47-50 chromosomes in 11 (22.4%), and hypodiploidy in 3 cases (6.1%). Event-free survival (EFS) and survival studies showed that the outcome of patients was determined only by treatment and karyotype. Eleven patients have survived, nine in first remission (6 years 5 months to 15 years 2 months), and two are in second remission (3 years 8 months and 8 years 2 months). All ploidy groups are represented in these patients. Late relapses can occur in the hyperdiploid > 50 group, thus accounting for shorter EFS than expected, but because of the unusually long second remission of one patient, the rate of surviving patients was higher for this ploidy group than for all other ploidy groups together. Conversely, patients with only numerical abnormalities (no matter which ploidy group they belonged to), had a better outcome than did patients with structural changes or normal karyotypes and no discrepancy between EFS and survival curves was observed in this chromosomal group. Thus, our results suggest that numerical changes only should be considered an indicator of low risk factor, but our results, based on partially banded karyotypes, need to be verified by a current method and therapy.

Adolescent↗
PubMed1992

[Incidence, treatment and prognosis of cancer of the pancreas in Haute-Garonne (1982-1986)].

The characteristics of incident cases of pancreatic carcinoma found in the area of Haute-Garonne (France), as determined by the Digestive Cancer Registry, are reported. Two hundred and forty-six new cases were collected during a 5 year period in a population of 820,000 inhabitants. The annual standardized incidence rate per 100,000 inhabitants was 4.7 for men and 2.6 for women, respectively. This represents a low risk and corresponds to 7 percent of all intestinal tract tumors. The tumors were shown histologically to be adenocarcinoma in 85 percent of cases. The tumor was localized in the head of the gland in 64 percent of cases, while metastases were present at the time of diagnosis in 43 percent of cases. Ultrasonography was the initial investigation (44 percent of cases) and was performed well before endoscopic retrograde wirsungography (12.8 percent) and computed tomography (18 percent). Eighty-six percent of the patients were operated on. Curative surgery, however, was possible in only 12.5 percent of patients. The incidence of carcinoma remained stable during the observation period and no change was noticed with regard to housing conditions. During follow-up, 50 of 215 patients died within one month following the diagnosis (23 percent). Actuarial survival was 36 percent at 6 months, 17.4 percent at one year, and 3.6 percent at 3 years. These data were comparable to those observed in the Côte-d'Or and Calvados areas. These findings suggest that the French Digestive Tumor Registries should develop co-operative studies particularly in the analytic epidemiological fields.

Actuarial Analysis↗