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Biomedical subjects

I Philip

Publications and source records attributed to I Philip.

At least 109 records · Page 6Linked to original sources
PubMed1986

Metastatic interstitial pneumonitis after autologous bone marrow transplantation. A consequence of reinjection of malignant cells?

Two cases of fatal interstitial pneumonitis developing after an autologous bone marrow transplantation are described. In both cases the autopsy revealed diffuse malignant pulmonary involvement. The first case involved a 4-year-old boy who had a Burkitt's lymphoma; the second case involved a 4-year-old girl with a neuroblastoma. The authors postulate that in these cases, the clinical picture may have been related to reinfusion of malignant cells.

Abdominal Neoplasms↗
PubMed1986

Phenotypic characterization of Ewing sarcoma cell lines with monoclonal antibodies.

The histogenesis of Ewing sarcoma, the second most frequent bone tumor in humans, remains controversial. Four Ewing cell lines were analyzed by immunological methods. A panel of antibodies directed to T, B, and myelomonocytic markers gave negative results. Surface antigens recognized on Ewing cells were found to be related to the neuroectoderm lineage. Ganglioside GD2, a marker of neuroectodermal tissues and tumors, was present on all lines. These were also stained by the mouse monoclonal antibody HNK-1, which detects a carbohydrate epitope present on several glycoconjugates of the nervous system, including two glycoproteins, the myelin-associated glycoprotein and the neural cell-adhesion molecule (N-CAM), and an acidic glycolipid of the peripheral nervous system. The P61 monoclonal antibody, which reacts with a peptide moiety of N-CAM, and a rabbit antiserum, raised to purified mouse N-CAM and not recognizing the HNK-1-defined epitope, were also reactive. By contrast, all antibodies specific for hematopoietic cell surface antigens were totally negative. Besides these antigenic features, Ewing sarcoma cells are characterized by a specific t(11;22)(q24;q12) translocation also observed in neuroepithelioma, a neuroectodermal tumor, suggesting a possible evolutionary related origin. The recent finding that the human N-CAM gene is located at the vicinity of the breakpoint on chromosome 11 indicates that it might be involved in genetic rearrangements occurring in this region.

Antibodies, Monoclonal↗
PubMed1986

Massive therapy and autologous bone marrow transplantation in pediatric and young adults Burkitt's lymphoma (30 courses on 28 patients: a 5-year experience).

A 5-yr experience of massive therapy and autologous bone marrow transplantation (ABMT) for Burkitt's lymphoma is reviewed. Thirty courses were given to 28 patients. Three patients were in resistant relapse and all three died before day 54 post ABMT. Thirteen patients were in non-resistant relapse and seven are alive with non-evidence of disease (NED). All three patients grafted in partial remission (PR) are alive NED including two with initial central nervous system (CNS) disease. Nine patients were grafted in 1st complete remission (CR) either because of long delay to achieve CR or as consolidation in those with initial CNS involvement or leukaemia. Three of these nine are alive including 2/3 with a long delay to CR and 1/5 initial CNS. The overall survival NED for the 28 patients is 46%. The median observation time post ABMT, 22 months. Clear indications for ABMT in BL are in our opinion restricted to about 20% of the patients: non-resistant relapses and PR after initial induction therapy. Massive therapy as consolidation of 1st CR after initial CNS involvement and in resistant relapses should still be considered as experimental. In 14 patients whose marrow was purged there is laboratory evidence suggesting that the purging procedures used in this study may have been incomplete. Purging techniques still require perfection at a laboratory level and their rationale should not be judged on the basis of incomplete procedures.

Adolescent↗
PubMed1986

The role of massive therapy with autologous bone marrow transplantation in Burkitt's lymphoma.

Burkitt's lymphoma has proved to be a very useful model for the evaluation of both massive therapy regimens and purging techniques. Results from several centres now confirm a number of general principles in relation to the use of ABMT procedures in this tumour. Patients in whom conventional chemotherapy has failed can be cured by massive therapy but this should be limited to those who have responded to salvage regimens or have only achieved first PR. Chemoresistant relapse is unlikely to be cured and the high probability of a transient response does not justify the procedure in such cases. Important ongoing clinical studies include the use of ABMT in first CR for CNS disease or B-cell ALL. Results in allogeneic grafts suggest that current massive therapy regimens are curative in only 20-50% of patients (Appelbaum and Thomas, 1983) and new combinations are, therefore, still required. Phase I and II studies in patients with 'resistant relapse' are investigating the use of sequential high-dose alkylating agents and role of TBI. It is of particular importance to develop effective conventional 'salvage' regimens. Recent experience indicates that the combination of high-dose cisplatin and VP 16 is useful; other possibilities include high-dose interferon and high-dose cytarabine. Purging techniques in BL are now at an advanced stage and the combination of immunological and chemical treatments, once of proven efficacy in individual patients at a laboratory level, should be the subject of randomized studies.

Antibodies, Monoclonal↗
PubMed1986

Histological, cytological and immunological analyses are complementary for the detection of neuroblastoma cells in bone marrow.

On 80 occasions 4 iliac biopsy trephines and 4 iliac aspirations were performed in 37 children with neuroblastoma at various stages of the disease. In 38 of these procedures, tumour cells were detected. In 24% of cases, both trephines and aspirates were positive, whereas in 63% neuroblastoma cells were detected only on the trephines and in 13% only on the aspirates. In addition, in 37% of the stagings, only one out of the 8 investigations was abnormal. Only in one of 33 pathological cases, was BM involvement diagnosed on trephine imprint. No involvement was ever observed on tibial and sternal aspirates without iliac involvement. Immunological studies with two monoclonal antibodies HSAN 1-2 and UJ13A were performed on 56 occasions. Cytohistological and immunological studies were concordant in 39. In 3 studies, the antigens recognized by the two monoclonal antibodies were not expressed by the initial tumour and in 3 additional studies immunological results were falsely negative; but in 11 cases monoclonal antibodies identified residual malignancy despite normal cytohistology. From this study, biopsies appear more helpful to detect malignant cells than aspirates. Immunological staining clearly leads to a better definition of tumour cells in aspirates.

Biopsy↗
PubMed1986

Bone marrow purging procedure in Burkitt lymphoma with monoclonal antibodies and complement: quantification by a liquid cell culture monitoring system.

Using B1, Y29/55 and AL2 monoclonal antibodies (MoAbs) to target Burkitt lymphoma (BL) cell lines, we defined optimal conditions to lyse, in the presence of baby rabbit complement, BL cells in excess bone marrow (BM). After the purging procedure, down to one residual BL cell in 10(6) normal ones was detectable with a liquid cell culture assay. Using a cocktail of three MoAbs, on five different cell lines were observed more than 4 log BL cell depletion in samples contaminated with 1% BL cells and only one failure of the procedure on 17 experiments. However, a sixth line was constantly resistant to the procedure.

Animals↗
PubMed1985

Massive chemotherapy with autologous bone marrow transplantation in 50 cases of bad prognosis non-Hodgkin's lymphoma.

50 cases of advanced, intermediate (18) and high grade (32) non-Hodgkin's lymphoma (NHL) including 16 with Burkitt lymphoma have been treated with very high dose chemotherapy and autologous bone marrow transplantation (ABMT). These cases represent a retrospective analysis of the combined experience of a recently established collaborative group. 31 patients were treated with a protocol used in Lyon, 12 with that used in Marseille and seven with that used in London. Although the details of drug administration differed, each protocol was based on high dose alkylating agent (cyclophosphamide or melphalan), BCNU and cytosine arabinoside. 16 patients had drug resistant progressive NHL. Of these 11 responded to high dose treatment (nine CR, two PR). The duration of CR in this group was short (median 104d) and only one patient was in CR at 1 year. 19 patients had relapsed on previous therapy but were still responding to conventional rescue therapy. Following high dose therapy 47% of these patients are in continuous CR with a median time of observation of 300 d (73-962 d). Seven patients were partial responders to conventional induction therapy. Of these, six had a CR with high dose treatment and are still in CR (range 39-1230 d, median 200 d). Eight patients received high dose therapy as intensification after a long delay to CR with conventional treatment. Of these, four are alive and in remission 124-763 d after treatment. The high dose protocols produced significant morbidity with 25 patients (50%) having major or minor treatment-related complications, and there were seven treatment related deaths (14%). However, these results indicate that durable responses can be obtained with high dose chemotherapy in patients who have been heavily treated and indicate a role for this type of treatment at an earlier stage in advanced non-Hodgkin's lymphoma.

Adolescent↗
PubMed1985

[Burkitt's lymphoma in 1985].

Burkitt Lymphoma is a model for either clinical research and fundamental research. Initially described in Africa, it is the most frequent of all childhood Lymphoma. Burkitt Lymphoma allowed in the laboratory to study the virus cancer relationship, the chromosome cancer relationship, the gene and cancer relationship and the oncogene and cancer relationship. This study is made considerably more easy because of the numerous cell lines which were established from malignant cells at different stages of the disease. Patients who have a complete remission of more than 8 months could be considered as cure of the disease. Then, B.L. is also a model for clinical study because we can conclude rapidly the efficacy or not of a new protocol. Since 1980, overall survival in France has moved from 40 to 80%. Chemotherapy alone is responsible for these results either by conventional protocol or in a small % cases by massive therapy followed by autologous bone marrow transplantation.

Africa↗
PubMed1985

Massive therapy and autologous bone marrow transplantation in very bad prognosis Burkitt's lymphoma.

During 1980-1983, two major advances were made in the treatment of Burkitt's lymphoma (BL): conventional but aggressive chemotherapy raised the overall survival rate from 42% with the SFOP1 protocol, COPAD, to 80% with SFOP protocols LMB 01 and 02; and massive chemotherapy followed by autologous bone-marrow transplantation (ABMT) enabled 40% of relapses to be cured. Ten patients included in the COPAD protocol were treated with massive therapy: seven because of relapse, one because of partial remission after two months' induction therapy and two because of long delay before first complete remission (CR). The therapy used was bischloroethyl nitrosourea, cytosine arabinoside, cyclophosphamide (CPM) and 6-thioguanine (BACT) in nine cases and CPM in one. The response rate was 100%, and disease-free survival was reached in five of ten cases, including four with no evidence of disease for over two years. In nine of ten patients who received ABMT, the bone marrow (BM) was not decontaminated, and BM involvement was found at death prior to day 86 from ABMT in four of five failures. Clinical and cytological analyses led to no firm conclusion about the role, if any, of reinjected BM in this outcome: a liquid-culture monitoring system used in six cases showed BM malignant cells present in the graft in one early relapse and absent in two relapses in which BACT failed; in three long-term survivors, no malignant cell was found in the graft. This first group of ten showed the efficiency of BACT and the necessity of purging BM in at least some cases before ABMT. Of the second group, selected from 43 patients given LMB 01 and 02 protocols, eight were treated by massive therapy and ABMT: one with localized stages I and II disease, four with stage III and three with stage IV. These patients received massive therapy either because of early relapse, progressive disease, partial remission after induction therapy or long delay before CR, or as a consolidation of CR in cases of central nervous system or cerebrospinal fluid involvement. In this group, four of eight are disease-free; three of them had normal BM by in-vitro liquid-culture monitoring; their BM was not decontaminated and they had no BM relapses. In the other five cases, BM was decontaminated by Asta Z in one and by y-29/55 antibody in four.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1985

Indication for bone-marrow harvesting and purging in Burkitt's Lymphoma: a three-year experience.

Between 1980 and 1983, 317 bone-marrow (BM) aspirates from 63 cases of Burkitt's lymphoma (BL) were studied with an in-vitro liquid culture monitoring system. BL cell lines were obtained in culture from 14 of 15 patients with cytologically positive marrow. The in-vitro monitoring system was shown to be useful regardless of Epstein-Barr virus (EBV) status, clinical status of patients and cytogenetic anomalies (8 t(8;14) 2 t(8;22) 2 When BM was cytologically normal or suspect, i.e., less than 5% BL cells, the in-vitro monitoring system was shown to be more sensitive than cytological examination in 25 of 56 cases (44%). The sensitivity of the test is 1/100 000, i.e., 3 logs inferior to the level of detection by cytology. When BM was harvested from all patients in complete remission after two months of chemotherapy, marrow purging proved not to be necessary (38/38 negative cultures); 7/10 of those patients will have been harvested to no purpose (no more than 30% with indication for autologous BM transplantation). When BM was harvested at relapse or in partial remission, the purging procedure was shown to be necessary in 9 of 16 cases (56%).

Bone Marrow↗
PubMed1984

Chromosome study of Ewing's sarcoma (ES) cell lines. Consistency of a reciprocal translocation t(11;22)(q24;q12).

A detailed banded chromosome analysis was performed in five established Ewing's sarcoma (ES) cell lines originating from four unrelated patients in relapse. Of various numerical and structural abnormalities, a reciprocal translocation between chromosomes #11 and #22, t(11;22)(q24;q12), was observed in four of the lines. The t(11;22) was seen in every cell in three lines; in the fourth, it was seen in only 21% of the cells considered stemline, but the der(22) was present in the remaining 79% of cells. These results suggest that t(11;22)(q24;q12) is a chromosomal change specific to ES cells, in which the rearrangement of chromosome #22 could be the consistent karyotypic feature and the crucial step in terms of cell proliferation. Other, nonrandom chromosomal changes were found: monosomies 2p11----2pter, 10q25----10qter, and 17pter----17q11, and partial trisomies 1q21----1q31 and 8q24.1----8q24.2. The role of the therapeutic regimen received by these patients must be evaluated with regard to the formation of a wide variety of homogeneously staining regions, which were observed in every cell line, particularly on the short arm of chromosome #7, which was observed in three of the five cell lines.

Cell Line↗