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Biomedical subjects

T Philip

Publications and source records attributed to T Philip.

At least 253 records · Page 14Linked to original sources

S-L 11.14: a monoclonal antibody recognizing neuroectodermal tumors with possible value for bone marrow purging before autograft.

A new monoclonal antibody (S-L 11.14) raised against small cell lung cancer reacted with all but one neuroblastoma tumor cell sample tested and was relatively specific for such cells within the bone marrow. The ability of S-L 11.14 to eliminate neuroblastoma cells from the bone marrow with an immunomagnetic purging method was evaluated in an experimental model using the LAN.1 and SKNBE neuroblastoma cell lines as targets. Residual malignant cells after the purging procedure were quantified by the Hoechst staining method. The use of S-L 11.14 as a single reagent resulted in a 3-log elimination of malignant cells, a depletion equal to that obtained with a cocktail of five monoclonal antibodies currently used in clinical trials. The addition of the S-L 11.14 antibody to this cocktail did not enhance depletion.

Antibodies, Monoclonal↗

[Current results of intensive chemotherapy as salvage with bone marrow graft in highly malignant T lymphomas. Apropos of 10 cases].

Eleven autologous bone marrow transplantations (ABMT) were performed in 10 patients with T lymphoblastic lymphoma. All patients were grafted because of a very bad prognosis: 2 cases of progressive disease (1 primary failure, 1 resistant relapse): 0/2 alive, 2 late complete remissions: 1/2 alive, 7 sensitive relapses (2/7 alive). Finally, 3 out of 10 patients are survived. This salvage therapy for a failure of a front line strategy with 78% disease-free survival without ABMT seems of interest. ABMT is still indicated as salvage therapy for 20% of these patients.

Adolescent↗

[Metastatic neuroblastoma with secondary hypersecretion of vasoactive intestinal peptide].

A 18-month-old boy with stage 4 neuroblastoma needed intensive care because of prerenal acute renal failure related to an intractable watery diarrhoea syndrome occurring 10 months after the diagnosis of the primary tumor. This diarrhoea was in relation with a late hyperproduction of vasoactive intestinal peptide by the relapsing neuroblastoma itself and stopped with intravenous somatostatin administration.

Diarrhea, Infantile↗

[Evaluation of the transfer of Algerian children with cancer to the Léon-Bérard center (1984-1987)].

From 1984 to 1987, 80 pediatric oncology patients were transferred from Algeria to the centre Léon-Bérard (Lyon, France). Diagnoses were mainly lymphomas neuroblastomas and bone tumours (75% of the total number of cases). Survival (39% at 46 months), number of hospitalization days (12,655) and cost (29,324,254 FF) were calculated. These costs were compared with the mean annual public health allocation per capita in Algeria and with the French limitations on accepting transfer of spending money for children from abroad. New directions are suggested to improve the efficiency of these transfers to optimize the use of limited resources in both countries and to increase survival of individual patients.

Algeria↗

[Treatment of extensive B-cell lymphoma in children: studies of the French Pediatric Oncology Society].

Since 1981 in the French Pediatric Oncology Society, a multidrug intensive-pulsed chemotherapy was proposed for bad prognosis B-cell lymphomas (stage II ORL, III and IV) and for B acute lymphocytic leukemias (B-ALL). Between 1981 and 1984, the nine-drug regimen was based on high-dose cyclophosphamide, high-dose methotrexate and cytosine arabinoside in continuous infusion (regimen LMB-81). No irradiation was performed. CNS prophylaxis was made by high-dose methotrexate and by intrathecal injections. No debulking surgery was recommended. Since 1984, considering the high rate of continuous remission, some modifications were made for reducing the duration and toxicity of the treatment of most B-cell lymphomas without CNS involvement (regimen LMB-84). For B-cell lymphomas with CNS involvement and B-ALL, an intensive high-dose multidrug combination was proposed (regimen LMB-86). Between 1981 and 1984, 153 children (stage II ORL: 6%, III: 63%, IV: 31%) were treated with the LMB-81 regimen. The overall disease-free survival rate is 69%. No relapse occurred after 12 months. Only two CNS relapses were observed. Among stage IV, a worse prognosis was associated with initial CNS involvement (disease free survival: 19%). On the contrary, bone marrow involvement was not an adverse prognostic factor. With the LMB-84, the overall disease free survival rate is 74%. A noteworthy reduction of toxicity is observed.

Actuarial Analysis↗

Pitfalls and solutions in neuroblastoma diagnosis using radioiodine MIBG: our experience about 50 cases.

We have been among the first authors to point out that false negative cases could be observed with 131I-MIBG scintigraphy for neuroblastoma. We have observed until now ten of such false negative cases, 7 with primary tumor and 3 with bone metastases. Fifty 131I-MIBG scans were performed in 35 children with histologically proven neuroblastoma (24 grade IV) and compared to bone scans, CT and NMR images, ultrasound and clinical results. The visualization of the primary tumor shows a higher sensitivity with MIBG (79%) than with bone scans (47%) and a 100% specificity with each method. MIBG and bone scans, for bone metastases, are similar in the sensitivity (87.5%) but MIBG is much more specific (100%) than bone scan (81%). These results clearly confirm the superiority of MIBG scan for detection of primary tumor as well as bone metastases. However, MIBG is not always the most appropriate investigation, as shown by 11 observed pitfalls. Ten false negative cases have been observed and must be considered: in five out of 10 cases, bone scans performed with 99m Tc-HMDP made the diagnosis (3/7 cases of primary tumor and 2/3 cases of bone metastases). Moreover, one case was not usable due to a large digestive uptake. Our aim is to understand the reasons of the false negative by a meticulous analysis of every single case. The optimal procedure for neuroblastoma diagnosis, extent and follow up clearly seems to be the following strategy: MIBG scan must be firstly performed; in case of non-demonstrative scan the bone scan, which is complementary, will greatly contribute to the diagnosis.

3-Iodobenzylguanidine↗

[Intensive chemotherapy and bone marrow grafting during the consolidation phase of stage IV neuroblastoma].

Sixty-five patients more than one year of age at diagnosis with stage IV neuroblastoma were prospectively treated since january 1983. Seventeen per cent were not consolidated with massive therapy and ABMT (progression: 3 cases; died at induction: 4 cases; died at surgery: 1 case; parental refusal: 2 cases) and all died. Among 49 evaluable cases, 31 were grafted in PR and 18 in CR or VGPR. Actuarial progression free survival at 35 months is 33% for the grafted group and 24% for the whole group. These results are better than previous experience of this group (8% at 30 months).

Actuarial Analysis↗

[Value of immunological analysis for the detection of residual neuroblasts in the bone marrow].

Immunological analysis is complementary of morphological analyses in the detection of neuroblastoma BM metastases. It attests the neuroblastic nature of rare pseudolymphocytic isolated cells. The combination of immunocytochemical technique (alkaline phosphate) and double-immunofluorescence technique allows the detection of as few as 10(-5) residual neuroblastoma cells. At the time of bone marrow harvest, it permits a precise evaluation of malignant cells in the graft.

Bone Marrow↗

[Efficacy of the "8 drugs in a day" protocol in brain tumors in children].

In the present study, the "8 drugs in 1 day" regimen was tested in 54 children: 27 relapses (brain and/or spinal and/or meningeal sites), 10 refractory progressive diseases, 13 macroscopic residual tumors after partial excision and/or radiotherapy; in 4 cases, this regimen was prescribed as first line treatment. The response rate (complete and partial remission) was 46%. Results were very encouraging in medalloblastomas with a response rate of 76.5% whereas in brain stem gliomas it was only 23% and 33% in other astrocytomas. Immediate toxicity, mainly hematological, was very moderate. These results justify to propose this regimen as adjuvant chemotherapy, mostly in medulloblastomas and to plan other similar trials, using the most active drugs which seem presently to be alkylating and platinum-derived agents.

Adolescent↗

High-dose therapy and autologous bone marrow transplantation after failure of conventional chemotherapy in adults with intermediate-grade or high-grade non-Hodgkin's lymphoma.

Adult patients with advanced non-Hodgkin's lymphoma in whom conventional chemotherapy has failed are seldom cured thereafter. We studied 100 such patients with intermediate-grade or high-grade non-Hodgkin's lymphoma who were subsequently treated with high-dose chemotherapy (61 patients) or high-dose chemotherapy plus total-body irradiation (39 patients), with bone marrow transplantation used for hematologic support. Thirty-four patients had disease that had been refractory to primary chemotherapy, and 66 patients had had a complete remission with primary chemotherapy but later relapsed. Before autologous bone marrow transplantation and high-dose chemotherapy, the 66 relapsed patients had also received conventional salvage chemotherapy; 22 had had no response or had had disease progression (a response termed "resistant relapse"), and 44 patients had responded partially or completely (a response termed "sensitive relapse"). After high-dose therapy and bone marrow transplantation, the actuarial three-year disease-free survival was zero in the refractory group, 14 percent in the resistant-relapse group, and 36 percent in the sensitive-relapse group. Patients who had had a complete remission in response to initial chemotherapy had a higher disease-free survival rate than those who had not (P less than 0.001), and patients with sensitive relapse had a higher disease-free survival rate than those with resistant relapse (P less than 0.003). These results should be considered in the planning or interpretation of trials of salvage chemotherapy in adults with non-Hodgkin's lymphoma.

Adolescent↗

Use of a liquid cell culture assay to quantify the elimination of Burkitt lymphoma cells from the bone marrow.

A new liquid cell culture assay for propagating Burkitt lymphoma (BL) cells in the presence of excess allogeneic irradiated bone marrow (BM) has been standardized. The Burkitt cell lines used in this assay were newly established from the tumours of our patients and were either EBV(+) or EBV(-). The phenotypic characteristics of lines were similar to those of the original malignant tumours. With the help of this liquid assay it was possible to evaluate the efficacy of in vitro procedures designed to completely eliminate malignant cells from harvested BM prior to autologous transplantation (i.e., immunomagnetic depletion or antibody-complement-mediated cytolysis). With six out of the seven cell lines tested, the assay permitted the detection of as few as one BL cell in 4 X 10(6) normal BM cells and the measurement of up to 5 log BL cell elimination from 1% contaminated samples.

Antibodies, Monoclonal↗

Neuroectoderm-associated antigens on Ewing's sarcoma cell lines.

The histogenesis of Ewing's sarcoma, the second most frequent primary bone tumor in humans, remains controversial. Ten Ewing cell lines were analyzed by immunological methods. Surface antigens recognized on Ewing cells were found to be related to the neuroectoderm lineage. They included ganglioside GD2, a marker of neuroectodermal tissues and tumors, and an acidic glycolipid detected by monoclonal antibody HNK-1 in the nervous system. The P61 rat monoclonal antibody that reacts with a peptide moiety of neural cell adhesion molecule (N-CAM) and a rabbit antiserum raised to purified mouse N-CAM also stained Ewing cells. Flow cytometry analysis performed using these reagents allowed the definition of four distinct Ewing phenotypes: all reagents equally stained group 1 lines; group 2 lines were strongly reactive with anti-N-CAM reagents, by contrast with a fainter staining with HNK-1 and anti-GD2 antibodies; all reagents but P61 were strongly reactive with group 3 lines; in group 4, Ewing lines were stained by P61 but only poorly by the anti-N-CAM antiserum. Several antibodies to melanoma and neuroblastoma associated antigens including two monoclonal antibodies to the nerve growth factor receptor were also found to react with Ewing cells. By contrast, all antibodies detecting antigens specifically expressed in hematopoietic cell lineages were totally unreactive. HLA class II antigens were never detected while the level of expression of class I antigens varied to a large extent. Ewing cells are characterized by a specific t(11;22)(q23-24;q12) translocation also observed in neuroepithelioma, a neuroectodermal tumor. Thus, Ewing's sarcoma cells share antigenic and karyotypic features with derivatives of the neuroectoderm possibly indicating a related histogenesis.

Antigens, Neoplasm↗

High-dose melphalan, vincristine, and total-body irradiation with autologous bone marrow transplantation in children with relapsed neuroblastoma: a phase II study.

Seven children with neuroblastoma who had relapsed on or after conventional therapy (3 originally stage IV, 3 stage III, 1 stage II) were entered on a study of "massive therapy" with purged autologous bone marrow rescue. In 5 patients attempts were made to reinduce remission with alternative chemotherapy, and a partial or complete response was achieved in 3. The massive therapy regimen comprised melphalan, vincristine, and total-body irradiation. Of 6 patients with measurable disease, all showed objective response to high-dose therapy (5 partial, 1 complete remission), but the median duration of remission was only 5 months (range 1/2 to 10). One patient remains disease-free at 18 months post graft. This patient was the only one treated in second complete remission. These data confirm the high response rate achieved by high-dose melphalan, total-body irradiation regimens, but it appears unlikely that a single high-dose chemoradiotherapy procedure will cure patients after relapse, particularly if they are unresponsive to conventional salvage regimens. Such protocols may, however, have a role as consolidation in first remission. The use of double-autograft procedures is an alternative that warrants further investigation in patients with relapsed neuroblastoma.

Adolescent↗