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Biomedical subjects

P Travade

Publications and source records attributed to P Travade.

At least 55 records · Page 3Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

[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↗

New trends in CLL treatment.

We review here results obtained from the various treatment modalities that have been used in CLL patients: chemotherapy; radiotherapy; splenectomy; leukapheresis; monoclonal antibodies and other immunomodulating agents. We conclude that it is still unclear whether patients in stage A (good prognosis) should be treated; intermediate forms of the disease (stage B) should, in most cases, be treated, but a better treatment than chlorambucil has not emerged; results from the Cooperative Group on CLL of Société Française d'Hématologie indicate that significant progress in the therapy of the advanced stage (stage C) has been achieved with the introduction of the CHOP regimen, using low doses of adriamycin; radiotherapy, splenectomy and immunomodulators such as levamizol, interleukins or interferons, and possibly monoclonal antibodies, are now being actively tested; the results are not yet conclusive.

Antibodies, Monoclonal↗

[Severe infections associated with chronic lymphoid leukemia. 159 infectious episodes in 60 patients].

This retrospective hospital study concerns 159 infectious episodes observed in 60 patients with chronic lymphoid leukaemia (CLL) staged A, B or C on first admission. The most frequent site of infection was pulmonary (33%), followed by ENT and stomatological infections (15%), septicaemia (9%), urinary and genital tracts infections (9%), herpes virus infections (9%), skin and soft tissue purulent sepsis (8%), digestive tract (3%) and meningeal (1%) infections and isolated fever (8%). Seventy nine bacteria were isolated, including 35 Gram-positive cocci (Staphylococcus spp. 12, Streptococcus spp. 13, D. pneumoniae 5, Enterococcus spp. 5), 43 Gram-negative bacilli (Enterobacteriaceae 36, Pseudomonas spp. 5, Haemophilus influenzae 2) and 1 M. tuberculosis. The other documented infections were: candidiasis 11, viral infections 19 (including 17 of the herpes group) and 2 parasitoses (1 pneumocystosis, 1 toxoplasmosis). Sixteen patients died of toxic -infectious shock (9 cases, including 1 meningitis) or pneumonia (7 cases, including one chicken-pox). Stage C leukaemia and granulopenia (less than 1 X 10(9) PN/l) were associated with significantly more frequent and severe infections.

Adult↗

Translocation t(3;20) associated with thrombocythemia in Ph-positive CML.

A patient with Philadelphia (Ph) chromosome positive chronic myelocytic leukemia is described who also developed an abnormality of chromosome #3, i.e., t(3;20)(p21;p13), in blast crisis. This abnormality may be connected with the advent thrombocythemia. The disease was a thrombopenia in the initial phase.

Adult↗

[Biological aspects of chronic lymphoid leukemia].

The present study is concerned with clinical prognostic classifications of chronic lymphocytic leukemia derived from numerous statistics and multivariate survival analysis. We analyse the prognostic significance of some biological patterns: bone marrow histological studies, lymph node biopsies, size, structure and doubling time of blood lymphocytes, tumoral markers and karyotype analysis. The problem of the monoclonal clone origin is discussed: differentiation abnormality or proliferation of a physiological clone.

Female↗