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P Travade

Publications and source records attributed to P Travade.

At least 19 recordsLinked to original sources
PubMed1995

Timed sequential chemotherapy for previously treated patients with acute myeloid leukemia: long-term follow-up of the etoposide, mitoxantrone, and cytarabine-86 trial.

PURPOSE: To confirm and extend encouraging preliminary results of timed sequential chemotherapy (TSC) in patients with previously treated acute myelogenous leukemia (AML). PATIENTS AND METHODS: We report the results of the regimen of mitoxantrone on days 1 to 3, etoposide on days 8 to 10, and cytarabine on days 1 to 3 and 8 to 10 (EMA) in 133 patients, with a median follow-up of 40 months. RESULTS: Sixty percent of patients, with a 95% confidence interval (CI) ranging from 51% to 68%, achieved complete remission (CR), including 44% (CI, 32% to 57%) of refractory patients and 76% (CI, 64% to 86%) of late first-relapse patients (P = .0002). Twenty-nine percent of patients did not respond to therapy, and 11% died from toxicity. Median duration of neutropenia and thrombocytopenia was 31 days and 29 days, respectively. Severe nonhematologic toxicity included sepsis in 54% of patients and mucositis in 23%. Postinduction therapy included a second course of EMA in 27 patients, maintenance in 10, autologous bone marrow transplantation (BMT) in 12, and allogeneic BMT in 13. Median survival of patients who did not have transplantation performed is 7 months, with 11% (CI, 4% to 18%) survival at 5 years. Median disease-free survival (DFS) is 8 months with 20% (CI, 8% to 32%) DFS at 5 years. Twenty-eight percent (CI, 15% to 44%) of nontransplanted patients who achieved CR had an inversion of CR duration. Previous refractoriness was the main factor associated with poor prognosis for CR achievement, DFS, and survival. CONCLUSION: These results confirm initial reports on TSC and show that approximately 20% of patients with first relapse after therapy can enjoy prolonged DFS using chemotherapy only.

Acute Disease↗
PubMed1994

Membrane fluidity and adherence to extracellular matrix components are related to blast cell count in acute myeloid leukemia.

The level of blast cells in peripheral blood in acute myeloid leukemia (AML) varies in individual patients. The bone marrow egress of hematopoietic cells is an unclear phenomenon in which cell deformability and cytoadhesion to the extracellular matrix are involved. One component of deformability is the membrane fluidity. Using fluorescence polarization, we have studied the fluidity of blast cell membranes from 22 AML patients. This membrane was found to be highly fluid and a statistically significant correlation was found between the increase in membrane fluidity and the number of blast cells in the blood. Studying interaction between blast cells and several components of bone marrow stroma, we found adhesion to fibronectin and fibroblastic extracellular matrix. Adhesion to the extracellular matrix was inversally correlated to the level of blast cells in the blood. The observed increase in membrane fluidity and reduction of adhesion to bone marrow stroma may result in an increase of blast cells egress in AML.

Acute Disease↗
PubMed1994

The hematopoietic stem cell transplantation in Hodgkin's disease: questions and controversies.

Most patients with Hodgkin's disease (HD) are cured with chemotherapy and/or radiotherapy. However, half of those with advanced stage disease (IIIB, IV) do not respond adequately to treatment or relapse. Salvage therapy used in such cases gives from 10% to 50% complete remission but only 10% long term survival. The results of bone marrow transplantation reported in acute leukemia and non-Hodgkin's lymphoma encouraged some authors to develop this new therapeutic strategy in Hodgkin's disease. In the early 1980's promising results were achieved when refractory and relapsed patients were selected to receive myeloablative therapy followed by bone marrow transplantation. Today, high dose chemotherapy with hematopoietic stem cell transplantation (HSCT) is used more and more often in poor prognosis Hodgkin's disease. After a review of the literature concerning the results of transplantation in Hodgkin's disease, we develop the numerous problems associated with this procedure which remain to be solved such as: the optimal indication, the timing of HSCT, the type of graft, the conditioning regimen, the place of radiotherapy and the optimal use of hematopoietic growth factors. We conclude with future prospects.

Age Factors↗
PubMed1994

[Prognostic value of beta-2-microglobulin in Hodgkin disease in young adults].

From 1977 to 1989, we measured serum beta-2-microglobulin (beta 2-MG) levels from 64 unselected and untreated patients, between 18 to 50-year-old, affected by Hodgkin's disease. Serum beta 2-MG level was measured by radioimmunoassay (Phadebas beta 2 microtest). Then, all patients received a chemotherapy such as MOPP or alternating MOPP/ABVD followed or not by radiotherapy. Elevated serum beta 2-MG level (> 2.4 mg/l) is associated with advanced stage disease (stage III-IV), presence of systemic symptoms and bulky tumor. Nevertheless, a multivariate analysis shows that the serum beta 2-MG level is the most significant prognostic indicator for disease free survival. The prognostic value of serum beta 2-MG is demonstrated for myeloma and non Hodgkin's lymphoma. A few authors have evaluated the prognostic impact of serum beta 2-MG in Hodgkin's disease. This study requires confirmation by multicentric and prospective trial.

Adolescent↗
PubMed1993

Lineage promiscuity in leukemia studies of T-cell receptor and immunoglobulin genes.

Using appropriate DNA probes, the configurations of the T-cell receptor beta-chain genes and immunoglobulin heavy-chain genes were studied in patients diagnosed as having the following malignancies: 7 chronic myeloid leukemia, 13 acute myeloblastic leukemia, 9 acute lymphocytic leukemia and 20 chronic lymphocytic leukemia. Rearrangements not corresponding to the immunotype were unexpectedly found in lineage neoplasias.

Burkitt Lymphoma↗
PubMed1993

Evaluation of erythropoietic/hematopoietic reconstitution after BMT by highly fluorescent reticulocyte counts compares favorably with traditional peripheral blood cell counting.

Highly fluorescent reticulocyte (HFR) counts and reticulocyte counts were analyzed daily using a Sysmex R-1000 automated reticulocyte counter after 42 BMT in children (median age 7 years, range 10 month-18.5 years). White blood cell levels were also analyzed daily using either traditional counting methods or, when levels were very low, cytocentrifuge preparations. Twenty-eight patients received autologous and 14 allogeneic BMT. After myeloablative therapy, HFR counts fell to zero and rose to 2% of the reticulocyte total after a median time of 10 days (range 6-23 days) post-autoBMT and 14 days (range 9-29 days) post-alloBMT. The appearance of HFR (at least 2% in two successive counts) preceded the attainment of 20 x 10(9)/l reticulocytes in 23 of 26 autoBMT by a median time of 3 days, and in 13 of 13 alloBMT with a median time of 4 days (p < 0.001). Two per cent HFR preceded the attainment of 0.5 x 10(9)/l neutrophils in the majority of BMT by a median time > 6 days (p < 0.001). The attainment of 0.05 x 10(9)/l monocytes was preceded by a rise in HFR in 12 of 26 autoBMT and in 7 of 13 alloBMT. Median times between 2% HFR and monocyte levels of 0.05 x 10(9)/l were respectively 2 (range 0- > 24) and 3 (range: 0- > 19) days after auto and alloBMT. These results show that the evaluation of erythropoiesis following BMT by means of HFR counting provides an early measure of hematopoietic reconstitution which is as precise and considerably more practical than monitoring the monocyte level.

Adolescent↗
PubMed1993

Granulocyte-macrophage colony-stimulating factor in association to timed-sequential chemotherapy with mitoxantrone, etoposide, and cytarabine for refractory acute myelogenous leukemia.

Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF), given intravenously 5 micrograms/kg per day, was administered on days 4-8 of timed-sequential chemotherapy (TSC) with mitoxantrone, 12 mg/m2 per day on days 1-3, etoposide, 200 mg/m2 per day on days 8-10 and cytarabine, 500 mg/m2 per day on days 1-3 and 8-10, in 22 patients aged < 60 years with refractory acute myelogenous leukemia in an attempt to increase recruitment of leukemic cells in S phase before the second sequence of TSC. Thirty-eight patients treated with TSC without GM-CSF in a previous trial served as historical controls. In GM-CSF-treated patients, median duration of neutropenia < 0.5 x 10(9)/1 was 33 days and of platelet transfusion requirement 30 days, without any increase by comparison with controls. WHO grade 3 or more extra-hematologic toxicity included sepsis in 60% of patients, vomiting in 30%, diarrhea in 15%, hyper-bilirubinemia in 15%, and mucositis in 10%, without any difference with controls. Among 20 evaluable patients six individuals (30%), with a 95% confidence interval (CI) ranging from 12-54% achieved complete remission, 11 (55%, CI 31-77%) did not respond to therapy and three (15%, CI 3-38%) died from infection. There was no demonstrable in vivo proliferation of leukemic cells during the 5 days of administration of GM-CSF. The average percentage of bone marrow cells in S phase in five patients was 4.0 +/- 2.8 on day 4 and 7.0 +/- 7.2 on day 8 (p = NS). In this cohort of patients refractory to cytarabine, addition of GM-CSF did not increase efficacy of TSC by comparison with historical controls.

Adolescent↗
PubMed1992

Evaluation of residual disease in B-cell chronic lymphocytic leukemia patients in clinical and bone-marrow remission using CD5-CD19 markers and PCR study of gene rearrangements.

We evaluated minimal residual disease (MRD) in 23 CD5 + B-chronic lymphocytic leukemia (CLL) patients who achieved clinico-hematological remission confirmed by bone-marrow biopsy. MRD was evaluated by dual marker analysis flow-cytometry using CD5 and CD19 markers, and by the study of Ig heavy chain gene rearrangements using the fast polymerase chain reaction (PCR). According to our laboratory conditions patients were considered to be in complete phenotypic remission when total CD19+ cells were < 25% and the ratio of CD5 + CD19 + /CD19 + cells was < 25%. According to these strict criteria only 9 of the 23 patients were in complete phenotypic remission. In order to evaluate the sensitivity of the above method, PCR analysis of the configuration of the Ig heavy chain gene region was performed in 12 of these patients. Five of 7 patients in complete phenotypic remission retained a detectable monoclonal rearrangement of the Ig heavy chain gene. For the remaining 5 patients in partial phenotypic remission, only one failed to show a monoclonal band and this is probably explained by the presence of an unusual gene rearrangement. In conclusion, this study suggests that PCR is more sensitive than dual marker flow-cytometry for evaluation of residual disease and that it is indeed possible to achieve complete remission at the molecular level, in B-CLL. Nevertheless, we suggest a word of caution as this was a retrospective study, and samples were not assessed before treatment. Thus the possibility that apparent molecular remission might correspond to unusual gene rearrangements cannot be completely excluded in these cases.

Adult↗
PubMed1991

Intensive sequential chemotherapy with mitoxantrone and continuous infusion etoposide and cytarabine for previously treated acute myelogenous leukemia.

Intensive sequential chemotherapy with mitoxantrone, 12 mg/m2/d on days 1 through 3, etoposide, 200 mg/m2/d as a continuous infusion on days 8 through 10, and cytarabine, 500 mg/m2/d as a continuous infusion on days 1 through 3 and 8 through 10 was administered to 72 patients aged less than 60 years with previously treated acute myelogenous leukemia (AML). Forty patients had refractory AML (nonresponse to prior therapy, early first relapse, or multiple relapse) and 32 had late first relapse. Sixty-one percent of patients, with a 95% confidence interval (CI) ranging from 49% to 72%, achieved complete remission (CR), including 45% (CI: 30% to 62%) of refractory patients and 81% (CI: 64% to 93%) of late first relapse patients. Twenty-nine percent of patients (CI: 19% to 41%) did not respond to therapy and 10% (CI: 4% to 19%) died from therapy-related toxicity. Median duration of aplasia was 30 days. Nonhematologic WHO grade 3 or more toxicity included sepsis (57% of patients), vomiting (10%), mucositis (35%), diarrhea (7%), skin rash (6%), and hyperbilirubinemia (11%). Postinduction therapy was attempted in 36 of 44 CR patients: 16 of them received a second course of the same regimen, 7 received maintenance chemotherapy, 4 underwent autologous bone marrow transplantation (BMT), and 9 allogeneic BMT. At a median follow-up of 20 months, 23 of the 44 complete remitters have relapsed, 1 to 14 months after achievement of CR, including 19 of 31 patients not undergoing BMT. Median survival is 7 months with 16% (CI: 4% to 28%) projected survival at 47 months. Median disease-free survival is 6 months with 21% (CI: 3% to 39%) of CR patients projected to remain disease-free at 46 months. Twenty-six percent (CI: 13% to 43%) of the evaluable patients who did not receive transplantation had inversion of CR duration. Among patients younger than 50 years, there was no significant difference in disease-free survival between patients receiving postinduction chemotherapy and those receiving BMT. We conclude that this chemotherapy regimen is highly efficient and could be used as first-line therapy in young patients with AML.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

B-ly-7, a monoclonal antibody reactive with hairy cell leukemia, also defines an activation antigen on normal CD8+ T cells.

We undertook a study to determine the specificity of the monoclonal antibody, B-ly-7, for hairy cell leukemia (HCL) by examining the expression in 150 samples from B-cell lymphoproliferative diseases as well as screening for reactivity in a number of other hematologic malignancies. Within the B-cell lineage we found that the expression of B-ly-7 was highly specific for HCL and reacted with all 28 cases examined, as well as with 3 of 9 cases of a variant form of HCL. Cells of other closely related B-cell disorders, prolymphocytic leukemia, and splenic lymphoma with villous lymphocytes were negative. Investigation of the peripheral blood and bone marrow of patients with HCL before and after treatment with alpha-interferon or deoxycoformycin suggests that B-ly-7 may be useful in the assessment of minimal disease after therapy. In addition to HCL, we found that B-ly-7 was positive with cells of three mature, CD4+ T-cell malignancies. In view of the reactivity with malignancies of activated B and T cells, we searched for the expression of B-ly-7 on activated, normal B and T cells and found that B-ly-7 reacted specifically with activated normal peripheral blood CD8+ T cells. B-ly-7 has a number of applications, including the precise classification of mature B-cell neoplasia and the diagnosis HCL and its assessment after treatment. In addition, B-ly-7 recognizes a small subset of T-cell disorders. Its expression on these malignancies and on in vitro activated peripheral blood CD8+ T cells suggests that B-ly-7 detects a lymphocyte activation antigen.

Antibodies, Monoclonal↗
PubMed1990

Detection of Epstein-Barr viral genomes in lymph nodes of Hodgkin's disease patients.

Previous studies using Southern blot analysis or in situ hybridization have shown that approximately 20% of patients with Hodgkin's disease have Epstein-Barr virus (EBV) in involved tissues. We used the more sensitive polymerase chain reaction (PCR) technique to determine if a higher percentage of EBV could be detected. Of the 16 Hodgkin's disease patients studied, the PCR technique detected EBV in eight (50%). No prognostic significance was associated with the presence of EBV in the eight EBV-positive patients, and the presence of EBV was not associated with B cell monoclonality.

Adolescent↗
PubMed1990

The experience of the French Cooperative Group in the treatment of CLL.

This paper summarizes results from clinical trials of the French Cooperative Group in chronic lymphocytic leukemia, CLL 80 and CLL 85 protocols. These protocols were based on the (A, B, C) classification. Nine hundred and seventy three patients were randomised in the CLL 80 protocol, 612 in stage A, 289 in stage B and 72 in stage C. Results from the fourth interim analysis were (1) in stage A, overall survival was better in the untreated group as compared to patients treated by daily chlorambucil with an increased incidence of epithelial cancers in the chlorambucil group; (2) in stage B, there was no improvement in overall survival with the COP regimen as compared to daily chlorambucil; (3) in stage C, the effectiveness of the CHOP regimen was confirmed. More than 1,400 patients have been randomised in the CLL 85 protocol but results from the first interim analysis were only available in stage B (194 patients). At the 6-month evaluation 28% reached complete remission in the CHOP group versus 12% in the chlorambucil-prednisone group. More follow-up is needed to assess the benefit from the CHOP regimen in terms of survival in stage B patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

[Treatment of infection in granulopenic patients. Lessons from international studies].

In febrile neutropenic patients the initial antibiotic therapy must be active against several bacteria, notably enterobacteria, Pseudomonas, Staphylococci and Streptococci. Broad-spectrum beta-lactam antibiotics (ceftazidime, ureidopenicillins, ticarcillin-clavulanic acid, imipenem, etc.) have given excellent therapeutic results. Bacteraemias due to Gram-positive cocci are increasing, most of them being related to infection of indwelling intravascular devices. In several studies vancomycin has been systematically prescribed as an empirical treatment of neutropenic patients. New antibiotics, such as fluoroquinolones or teicoplanin have been used in combination with beta-lactams. Non-absorbable antibacterial or antifungal agents, or even diffusible antimicrobial agents, could be used prophylactically in deep induced neutropenia and in the initial phase of bone marrow transplantation. Prospective randomized studies of different regimens are currently in progress to try and determine the best therapeutic and prophylactic measures against infections in neutropenic patients.

Agranulocytosis↗