Search PubMed⌕ Search

Biomedical subjects

T Philip

Publications and source records attributed to T Philip.

At least 217 records · Page 12Linked to original sources
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

[Role of massive chemotherapy and bone marrow graft in the treatment of non-Hodgkin's lymphoma].

Intensive chemotherapy and high dose chemotherapy with bone marrow transplantation are 2 complementary therapeutic procedures for non Hodgkin's lymphomas. In children, indications for BMT in NHL are limited to patients who fail to achieve complete remission and for patients in sensitive relapse. In adults, the role of BMT is also recognized for patients who fail to achieve remission with initial therapy. The advantage of either conventional regimens or massive therapy with BMT for patients with poor prognostic criteria is still under evaluation (LNH 87 protocol). The PARMA protocol tests, in a multicenter randomized study, the value of BMT for patients in sensitive relapse. Results of BMT for patients with refractory NHL and resistant relapse, remain poor. The role of BMT in low grade lymphomas is debatable. The trials for evaluation of massive chemotherapy and BMT in NHL will contribute to defining the potential role of this therapy in France: a potential 1,000 cases per year may be treated by this method.

Adult↗
PubMed1990

Lymphokine-activated killer cell expansion for clinical trials of adoptive immunotherapy with interleukin-2: optimization of the culture technique.

On leukopheresis products obtained from patients included in a protocol interleukin-2/lymphokine-activated killer (IL-2/LAK) cell therapy, we analyzed, in parallel with the standard culture and on large volumes of these products, different parameters which could either improve LAK cell enhancement or simplify the procedure. We demonstrated first that purification of the mononuclear cells from the leukopheresis product before its culture is not required. An excess of red blood cells and granulocytes (up to 50%) in nonpurified samples improved both the mononuclear cell recovery in short-term culture (4 days) and the activation of LAK cells when the total nuclear cell concentration did not exceed 3 X 10(6)/ml. Different factors can contribute to this enhancing effect: the presence of red blood cells, the liberation of cytokines by granulocytes, or the loss of a population of activated lymphocytes, with liberation of cytokines by granulocytes, or the loss of a population of activated lymphocytes, with larger size and density than resting lymphocytes, during the separation. Supplementation of the medium with 2% heat-inactivated autologous plasma obtained before any treatment rather than with 2% pooled human AB serum does not modify the mononuclear cell recovery in 4-day culture, but it does enhance LAK activity. The inhibitory effect of heat-inactivated autologous plasma on proliferation and activation of LAK cells was never observed, suggesting the absence of suppressive factors in the plasma of the 23 analyzed patients. Similarly, autologous plasma did not modify natural killer and LAK cell functions when added during the cytotoxic assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

[Evaluation of a modified immunomagnetic procedure for the purging of neuroblastoma cells from bone marrow].

The immunomagnetic depletion method for removing tumor cells from bone marrow, previously refined using a Burkitt lymphoma model, was tested with neuroblastoma cells. The efficiency of depletion was quantified by immunofluorescence with a detection limit of 3.3 log of cell depletion corresponding to the elimination of 99.84% of an initial tumor cell content of 10%. A panel of five monoclonal antibodies (UJ13A; UJ127.11; UJ181.4; alpha-Thy1; H11) purged 2.8 log of SKNBE and LAN-1 cells, while two of these antibodies as single agents allowed only for a 1.7 log (UJ13A) and a 1.7 to 2.0 log (alpha-Thy1) depletion. This underlines the advantage of an antibody panel for neuroblastoma purging. The new antibody S-L 11.14, an IgG2a against small cell lung cancer which recognizes 90% of neuroblastoma cells purged 2.8 log.

Antibodies, Monoclonal↗
PubMed1990

High-dose etoposide and cisplatin in refractory or recurrent non-Hodgkin's lymphomas (NHL).

Thirty-one patients, 13 adults and 18 children, were included in a phase II study of combined treatment with CDDP 40 mg/m2 and VP16 100 or 200 mg/m2 for 5 days. Fourteen patients were primary refractory to front-line treatment and 17 were treated at relapse (9 on therapy, 8 off therapy). Four were low-grade follicular lymphomas, 7 intermediate grade lymphomas, and 20 high grade lymphomas. One of the 14 primary refractory cases responded (CR) whereas 3 PR and 10 CR were observed among the 17 relapses. Toxicity was acceptable. 9 patients are still alive after bone marrow transplantation (median survival, 16 months). This combination is an effective salvage regime before autologous bone marrow transplantation for relapsed NHL, but cannot be recommended for progression on front-line therapy.

Adolescent↗
PubMed1990

[Adoptive immunotherapy with interleukin 2 in oncology].

Forty-seven patients with renal carcinoma were included in first line or rescue protocols of immunotherapy including IL2 alone or in association with LAK cells, INF alpha or TNF. The toxicity was mild and the mortality was 2% (1 patient). The response rate was 26%. Nineteen children with neuroblastoma received IL2 either alone or in combination with LAK cells. The morbidity and mortality were higher in patients with end stage disease who had previously received high dose and prolonged chemotherapy. In contrast, the toxicity was mild and transient in patients treated in the months following autologous bone marrow transplantation. The only complete response observed was in 1 child treated with IL2, 4 months after high dose chemotherapy and ABMT. Immunological analysis showed that the immunomodulatory effect of IL2 is very different depending on whether IL2 is used alone or in combination with other cytokines; moreover, the biological effect of IL2 is dependent on the immunological status of the patients prior to IL2 therapy.

Adenocarcinoma↗
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↗
PubMed1990

Hormonal and metabolic effects of chronic interleukin-2 infusion in cancer patients.

Interleukin-2 (IL-2) is secreted during the immune response to trauma, sepsis, and transplant rejection. Its role in the development of the metabolic abnormalities observed in these circumstances is not well defined. We studied the clinical, hormonal, and metabolic response to a 5-day IL-2 infusion (3 x 10(6) U/m2/day) of nine patients with metastatic renal carcinoma. IL-2 induced systemic manifestations after a latent period of 4 h (fever, tachycardia) or 8 h (hypotension). These manifestations persisted until the end of the infusion. Insulin levels were not modified. Among the stress hormones, cortisol increased at the onset of fever and tachycardia, whereas the rise in catecholamines occurred later (24 h) and appeared more as a response to the development of hypotension. The only metabolic effects observed were a late (third day) rise of lactate and a late and transient (third to fourth day) decrease of glycerol and nonesterified fatty acids. These metabolic modifications were temporally related to the development of hypotension and result more likely from low tissue perfusion rather than from a direct or hormone-mediated effect of IL-2.

Adult↗
PubMed1989

High-dose melphalan dosage adjustment: possibility of using a test-dose.

Previous pharmacokinetic studies of i.v. high-dose melphalan (HDM) have demonstrated large interindividual variations in the pharmacokinetic parameters. We therefore studied the possibility of using a test dose of the drug to determine the level of a subsequent therapeutic dose. This study was undertaken to establish whether the pharmacokinetics of melphalan were linear and reproducible within the same patient and determine whether a linear extrapolation could be carried out from the test dose. The first eight patients were studied on two occasions separated by 2 hours (repeatability stage). Although reasonable evidence for linear pharmacokinetics was obtained from these patients, the data suggested a number of factors that might have introduced errors. Therefore, the second group of ten patients were treated on a slightly different protocol on two occasions 24 h apart (linearity stage). The ratios of the two doses ranged from 1 to 8 (repeatability stage) and from 2.6 to 10 (linearity stage). During both stages there was a good correlation between the AUC measured for the second infusion and that predicted from the first (r = 0.929 and r = 0.943, respectively). We conclude that a test dose can be used to determine the subsequent dose of melphalan necessary to produce a desired AUC.

Adolescent↗
PubMed1989

Interleukin-2 with and without LAK cells in metastatic renal cell carcinoma: the Lyon first-year experience in 20 patients.

Thirty-one patients with metastatic renal cell carcinoma were seen at the Centre Léon Bérard from October 1987 to October 1988. According to our protocol, 11 were excluded leaving 20 in the study. The median age was 55 years (range 36 to 79 years). The median number of metastases was 9 (range 2 to 29) and the median number of metastatic sites was 3 (range 1 to 4). Seventeen patients received a continuous infusion of recombinant interleukin-2 (rIL-2) of 3 x 10(6) U/m2/day, on days 1 to 5, with lymphapheresis on days 7 to 10 and IL-2 + LAK on days 11 to 15. Three patients received IL-2 alone. The clinical toxicity of IL-2 was as expected (100% fever, 88% erythema, 88% vomiting, 87% weight gain, 76% oliguria, 76% diarrhoea, 70% pruritus, 70% weakness, 41% severe hypotension, 41% acute renal failure, 33% disorientation, 23% respiratory distress, 12% ventilation and 5% coma) with no toxic deaths. Other toxicity was mild (median platelet nadir was 93,000 and median nadir of Hb 8.1 g/dl) except for the creatinine level which was found to be between 200 and 400 mumol/l in 45% of the courses and over 400 mumol/l in 24% of the courses. Eight capillary leak syndromes were observed. Among the three patients receiving IL-2 alone, one PD, one SD and one early toxicity were recorded. Among 15 evaluable patients receiving IL-2 + LAK, three had PR (20%) and two mixed response (PR and progression before 2 months); two had stable disease and eight had progression. No clinical or biological factor was able to predict response. However, the five objective responses were observed among the eight patients with a capillary leak syndrome. Lymphocyte peaks or platelet nadir were not related to response in this group of patients. The median number of harvested mononuclear cells was 9.8 x 10(10) and the median number of mononucleated cells reinjected was 5.9 x 10(10).

Carcinoma, Renal Cell↗
PubMed1989

Tumor-specific loss of 11p15.5 alleles in del11p13 Wilms tumor and in familial adrenocortical carcinoma.

We have compared constitutional and tumor genotypes in nine cases of hereditary Wilms tumor (WT) and in three unrelated cases of familial adrenocortical carcinoma (ADCC). Since susceptibility to these tumors can be observed in malformation syndromes associated with a constitutional deletion of band 11p13 (WT) and with a constitutional duplication of band 11p15.5 (WT, ADCC), we investigated these two candidate regions by using 11p polymorphic markers. As expected, somatic chromosomal events, resulting in a loss of heterozygosity limited to region 11p15.5, were observed in the tumor of two familial cases of adrenocortical carcinoma. Surprisingly, however, analysis of the WT of two patients with a constitutional deletion of band 11p13, associated with aniridia, genitourinary abnormalities, and mental retardation (WAGR syndrome), revealed a loss of heterozygosity limited to region 11p15.5. These data therefore suggest that observation of a specific loss of heterozygosity may not necessarily point to the site of the initial germinal mutation. Together with previous similar observations of a loss of heterozygosity limited to 11p15.5 in breast cancer and in rhabdomyosarcoma, our data suggest that region 11p15.5 may carry a non-tissue-specific gene that could be involved in genetic predisposition, in tumor progression, or in both.

Adrenal Cortex Neoplasms↗
PubMed1989

Immunomagnetic depletion of malignant cells from autologous bone marrow graft: from experimental models to clinical trials.

Using experimental modes with normal allogeneic bone marrow (BM) contaminated with Burkitt or neuroblastoma cell lines, and a liquid culture assay, we demonstrated that, when used in optimal conditions, the immunomagnetic depletion technique permitted a reproducible elimination of 3-4 log malignant cells. Results were very similar to those obtained with the complement lysis procedure in Burkitt lymphoma. This immunomagnetic procedure was used in 123 cases of autologous bone marrow transplantation (ABMT) in children with neuroblastoma. The analysis of the cases demonstrated, first, that the procedure induced a significant loss of mononuclear cells but was not toxic for BM precursors. Delays to engraftment observed in a few patients were probably due to the combination of pejorative factors, especially the damage caused to the micro-environment by previous heavy and prolonged chemotherapy or the double ABMT programme. Second, patients presented with profound T-cell defect with undetectable IL2 secretion up to 1 year post-graft but they all had normal NK functions from the first month post-graft, these functions exceeding normal values on the second and third months post-graft. Finally, in 20 cases, dual-immunofluorescence staining permitted the demonstration that the autograft contained malignant cells before purging that were eliminated by the immunomagnetic depletion.

Bone Marrow↗
PubMed1989

[Cytokines and their receptors networks: biology and therapeutic possibilities].

Cytokinins are biological proteins which permit the transmission of signals from one cell to another. These proteins are secreted by groups of specialized cells and are fixed on specific receptors on the surface of responding cells. However, since receptors may be widely distributed, and since the activation of a cell usually permits the release of other cytokinins and a succession of reactions, cytokinins have pleiotropic effects. Cloning of the genes encoding for these cytokinins and their obtention on a large scale by genetic recombination techniques have allowed a better understanding of their biological characteristics and their use in therapy. This cytokinin network is particularly wide in the hematopoietic and in the immune systems. In the present study, we describe the biological properties of the main interleukins and hematopoietic cell growth factors, together with their therapeutic applications, particularly in hemato-oncology.

Biological Factors↗
PubMed1989

[Primary brain tumors in children. I].

The most frequent solid tumors in the pediatric age group are central nervous system tumors. Despite dramatic improvements in neurosurgery, radiotherapy and chemotherapy, the overall prognosis remains poor, and is often associated with late deleterious effects, including neuropsychologic disorders, endocrine deficiencies and physical abnormalities. In part I, we describe the common presenting symptoms and signs in children with brain tumors. We expose the significant advances in histology, immunohistochemistry, cytogenetic, radiology and therapeutic approaches during the past ten years.

Antigens, Neoplasm↗