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Biomedical subjects

P Viens

Publications and source records attributed to P Viens.

At least 127 records · Page 7Linked to original sources
PubMed1991

Cell surface expression of ICAM-1 (CD54) and LFA-3 (CD58), two adhesion molecules, is up-regulated on bone marrow leukemic blasts after in vivo administration of high-dose recombinant interleukin-2.

High-dose recombinant interleukin-2 (rIL-2) therapy can induce long-term remission in patients with melanoma and renal and colon cancer. More recently, in vivo IL-2 therapy was shown to induce complete or partial remission in some cases of relapsed chemotherapy-resistant acute myeloid leukemia. We have investigated the phenotypic modifications of bone marrow cells obtained from five patients with acute myeloid leukemia in relapse receiving high-dose i.v. rIL-2. We found that, in three of five patients, IL-2 could induce, in vivo, an increase in the expression of CD54/ICAM-1 and to a lesser extent of CD58/LFA-3 on bone marrow leukemic blasts. This demonstrates that rIL-2 modifies directly or indirectly the expression of the cell surface molecules of the tumor cells themselves. Upregulation of such adhesion molecules could account for the enhancement of cell interactions between the tumor and effector cells such as T, natural killer, and phagocytic cells as well as being indicators of differentiation signaling.

Antigens, CD↗
PubMed1991

Prevention of acute GVHD by in vivo use of anti-interleukin-2 receptor monoclonal antibody (33B3.1): a feasibility trial in 15 patients.

Results of allogeneic bone marrow transplantation (BMT) are still impaired due mainly to acute graft-versus-host disease (GVHD). Successful T cell depletion may abolish GVHD but causes increased rates of rejection and relapse. In vivo blocking of the CD25 receptor on T cells induces efficient and selective immunosuppression. We present results of a pilot trial studying the use of a CD25 MoAb (33B3.1) to prevent acute GVHD after allogeneic BMT. Fifteen patients were included in the study; 14 had a fully HLA matched sibling donor. In association with short methotrexate and cyclosporin A post-graft immunosuppression, the patients received 10 mg of 33B3.1 monoclonal antibody daily according to three successive schedules to study toxicity on marrow graft. No major adverse clinical experiences occurred. Engraftment was not delayed; after 4 months, full chimerism was documented in 14/15 studied patients. No human anti-rat antibody was detected during treatment period. No GVHD occurred during the period of antibody administration. Two patients relapsed; seven are alive and well with a median follow-up of 650 days. This study justifies a prospective controlled study to determine the real impact of 33B3.1 on GVHD prophylaxis.

Acute Disease↗
PubMed1990

Hematologic and immunologic effects of the systemic administration of recombinant interleukin-2 after autologous bone marrow transplantation.

T cells from allogeneic bone marrow grafts are responsible for a graft versus leukemia effect. Use of recombinant Interleukin-2 (rIL-2) after autologous bone marrow transplantation (BMT) may enhance immune function and hopefully reproduce the allogeneic reaction. We report here the hematologic and immunologic changes observed in the first 10 patients of a phase 1 trial studying the infusion of IL-2 after autologous BMT. All patients had high-risk malignancies and received 6 days of a constant infusion of IL-2 (Eurocetus, Amsterdam, The Netherlands) at dose of 3 x 10(6) Cetus Units/m2/d, 79 +/- 12 days after autologous BMT. Clinical toxicities involving cutaneous, cholestatic, gastrointestinal, and hemodynamic effects occurred during IL-2 treatment but reversed in all cases. Completion of treatment was 91% of the scheduled dose of IL-2. Hematologic toxicity was moderate and transient with no graft failure. Increases in eosinophil and lymphocyte counts were significant (P less than .05). Stimulation of the immune system was intense and prolonged, manifested by increase numbers of CD3+, CD3+DR+, CD3+ CD25+ lymphocytes, and natural killer (NK) cells (all P less than .01), and increase of Lymphokine-activated killers (LAK) and NK activities (P less than .01 and P less than .05). This study establishes the feasibility of a 6-day administration of rIL-2 after autologous BMT leading to a major immune activation 2.5 months after BMT.

Adolescent↗
PubMed1990

Seroepidemiology of Strongyloides infection in the Southeast Asian refugee population in Canada.

As part of a screening and treatment program for intestinal parasite infections offered to newly arrived Southeast Asian refugees in Canada between July 1982 and February 1983, a total of 232 sera were tested for Strongyloides infection using an enzyme-linked immunosorbent assay (immunoglobulin G). These results were compared with coprologic results and eosinophil counts. The seroprevalence was 76.6% (131 of 171) among Kampucheans, 55.6% (15 of 27) among Laotians, and 11.8% (4 of 34) among Vietnamese. A statistically significant relation (p less than 0.001) was found between Strongyloides serology and Strongyloides infection on stool examination (prevalence, 24.7%) among Kampucheans. Eosinophilia (greater than or equal to 10%) was found to be significantly associated with both infection measures. Using coprologic results as the "gold standard," the properties of the serologic test were estimated to be: sensitivity (95%), specificity (29%), positive predictive value (30%), and negative predictive value (95%). These estimates should be regarded as minimal values, as stool examination for Strongyloides infection can be an unreliable diagnostic reference. Further evaluation of the discrepancies observed between coprologic and serologic testing is required to determine the usefulness of these tests in epidemiologic studies.

Adolescent↗
PubMed1990

[High doses of alkylating agents and bone marrow autograft in ovarian cancer with poor prognosis: a retrospective analysis of 40 patients treated in France].

Reviewed in this study are 40 patients treated by high-doses of alkylating agents followed by autologous marrow rescue for ovarian cancers. All patients received this therapy after extensive surgery and a median of 6 cycles of CDDP containing regimens (CAP or CHAP). All patients, except 4, who showed evidence of progression, had a second surgical exploration before the high dose chemotherapy. Conditioning regimens consisted of: melphalan at a dosage greater than 140 mg/m2 for all patients; in addition, 2 received Endoxan 120 mg/kg and 1 busulfan 16 mg/kg. Autologous marrow rescue was infused 24 h after the conditioning regimen. Severe, but reversible aplasia and mucositis were the most common toxicities. Three patients died from this procedure, 2 from infection and 1 from secondary leukemia. Twelve out of 15 patients evaluated responded (80%) showing evidence of activity in patients who did not respond to first line chemotherapy. Duration of response was short, especially for patients treated for progressive disease rather than in partial or complete response at the time of high doses chemotherapy. With a median follow up of 23 months (range 8.54) 19 patients survived (15 with non-evolutive disease) leading to a projected survival rate of 39% between 27 months and 5 years. These results are encouraging for poor risk patients who failed to respond to initial chemotherapy. For patients who have small or no residual disease after initial therapy, the place of such intensification should be confirmed prospectively in a larger cohort of patients.

Adenocarcinoma, Mucinous↗
PubMed1990

Autologous bone marrow transplantation for B cell malignancies after in vitro purging with floating immunobeads.

We report here 16 autologous bone marrow transplantations (ABMT) for poor prognosis B or pre-B malignancies (16 acute lymphoblastic leukemias (ALL), three Burkitt lymphomas, one multiple myeloma) in 11 adults and five children where in vitro purging was accomplished by means of floating immunobeads. This method was developed to avoid non-specific killing by complement or toxin or batch-to-batch variability and provides a 3 log reduction of tumor in a model of B lymphoid malignancies. Low density bone marrow mononuclear cells were incubated for 30 min at 4 degrees C with anti CD10 (ALB2 Immunotech) and/or anti CD19 (Bg4) monoclonal antibodies (MoAb) and then mixed with low density polypropylene beads precoated with a rat antimouse MoAb. After 1 h at 4 degrees C the beads with target cells were decanted; the depleted marrow was collected through a microfilter and cryoperserved. After immunodepletion the recovery of nucleated cells was 75% with a median of 0.75 x 10(8) cells/kg (range 0.3-3.6) and the recovery of hematopoietic progenitors was 83% with a median of 2.9 x 10(4) CFU-GM/kg. The conditioning regimen consisted of busulfan 16 mg/kg and melphalan 140 mg/m2 for three patients, fractionated total body irradiation (TBI) following melphalan 140 mg/m2 for nine patients, TBI and cyclophosphamide 120 mg/m2 for two patients and TBI associated with melphalan and cyclophosphamide for two patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

High dose melphalan and autologous marrow rescue in advanced epithelial ovarian carcinomas: a retrospective analysis of 35 patients treated in France.

We retrospectively evaluated the feasibility and antitumour efficacy of high dose melphalan (HDM) followed by autologous marrow rescue in 35 patients with common epithelial ovarian cancers. All patients initially had advanced disease (FIGO III-IV) and received HDM after extensive surgery and a median of 6 cycles of cis-DDP containing regimens CAP or CHAP. All, except three patients who showed evidence of progression, had a second surgical exploration before high dose chemotherapy. Melphalan was given at a dosage greater than or equal to 140 mg/m2 followed 24 h later by autologous marrow rescue. Severe but reversible aplasia and mucositis were the most common toxicities: three patients died from the procedure, two from infection and one from secondary leukaemia. HDM was effective in 75% of evaluable patients; this was evidence of activity in patients who failed to respond to first line chemotherapy. The duration of response was short, particularly for patients treated with progressive disease at the time of high dose chemotherapy rather than in partial or complete remission. With a median follow-up of 23 months (range 8-54) after high dose chemotherapy, 19 patients are alive (15 with non-progressive disease) with a projected survival of 47% between 2 and 5 years.

Adult↗
PubMed1989

5-FU therapeutic monitoring with dose adjustment leads to an improved therapeutic index in head and neck cancer.

This 4 year study reports on a pharmacokinetic study for the widely used regimen of cis-platin plus continuous 5-day 5-FU as first-line chemotherapy of head and neck cancer, and the benefit of such data for real-time therapy management. Pharmacokinetic analysis of 177 cycles for 77 patients from a group of 89 patients (group 1; 228 cycles) revealed that both the time-concentration product (AUC) for the entire cycle and the half-cycle AUC (AUC0-3 days) were predictive of cycle toxicity. Real-time analysis of individual AUC0-3 days was used to decide whether to reduce the dose during the second half of the cycle for a total of 249 cycles (81 patients; group 2). The dose in the second half of the course was reduced in 40% of the group 2 courses. There was a statistical difference in complete response rates between group 1 (31%) and group 2 (47%), (0.02 less than P less than 0.05) and a statistically significant reduction was observed in the incidence of toxic cycles (greater than grade 2, group 1 = 20% versus group 2 = 12.4%; 0.02 less than P less than 0.05). Pharmacokinetic follow-up of these patients has proved to be an objective means to improve therapeutic index significantly.

Adult↗
PubMed1989

Effect of screening and treatment on imported intestinal parasite infections: results from a randomized, controlled trial.

A randomized, controlled trial was undertaken to evaluate the effects of a screening program for intestinal parasite infection in newly arrived Southeast Asian refugees to Montréal, Québec, Canada, during 1982-1983. Families assigned to the screened groups were examined, infected persons were treated and followed until they were infection-free, and all screened families were reexamined at six months. Families assigned to the control groups were examined at six months only. Statistically significant prevalence differences in unadjusted and adjusted estimates over the six-month study period were found between screened persons and controls for each of three groups of refugees from Kampuchea, Laos, and Vietnam, respectively. In general, the greatest prevalence differences ascribed to the screening program were observed in hookworm and Ascaris lumbricoides infections. Continued high levels of Giardia lamblia and Strongyloides stercoralis infection were observed at six months; this raises concerns over the effective therapeutic management of infected persons, the risk of local transmission, and the relevance of screening for intestinal parasites in new arrivals from endemic areas.

Asia, Southeastern↗
PubMed1988

The effect of cyclosporin A on Trypanosoma musculi infection of mice.

Cyclosporin A treatment of mice infected with Trypanosoma musculi mimicked the effect of T-cell deprivation in increasing the parasitemia and lowering the antibody responses. However, in contrast to T-cell deprivation, cyclosporin A treated mice were still able to clear the parasites from the blood. As expected, T-cell deprived mice were not responsive to cyclosporin A. It is suggested that antibodies against T-independent antigens of the parasite are ineffective in promoting elimination of the trypanosomes. These findings support the importance of T-helper cells in the final elimination of T. musculi from the blood of mice.

Animals↗
PubMed1988

[Randomized trial of empirical antibiotic therapy in febrile episodes after bone marrow transplantation. Comparison of an aminoglycoside-beta lactam (tobramycin-ticarcillin) combination with 2 beta-lactam antibiotics (ticarcillin-latamoxef)].

From February 1986 to July 1987, 87 patients who underwent an autologous or allogeneic bone marrow transplantation were randomized to receive ticarpen tobramycin or ticarpen moxalactam for their first febrile episode. Forty received ticarpen tobramycin and 47 ticarpen moxalactam. The two groups were similar according to age, sex, conditioning regimen, underlaying pathology and duration of granulocytopenia. We observed 58.6% of fever unknown origin and 37% of bacteremia. A similar number of clinical and bacteriological successes occurred in the two groups. Hepatic and renal toxicities were similar in the two groups. Vancomycin was widely used in these patients without particular justification. We conclude that the use of two beta lactam is a possible antibiotherapy in marrow transplantation where renal function should be preserved from additional toxicity.

Adolescent↗