Autologous bone marrow transplantation for very bad prognosis neuroblastoma.
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Biomedical subjects
Publications and source records attributed to T Philip.
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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)
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%).
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A single acute IV injection (1 microgram/kg) of the synthetic replicate of Somatocrinin (GRF) in 40 children with growth hormone (GH) deficiency induces a marked plasma GH increase, although heterogeneous. Clinical tolerance is excellent. Compared to Propranolol + Glucagon (P + G), GRF induces a better GH response. It also discriminates better idiopathic GH deficiency (n = 13), where mean GH peak = 6.5 ng/ml (3.3 after P + G) from GH deficiency secondary to a brain tumor (n = 24) where mean GH peak = 15.5 ng/ml (5.0 after P + G) GRF induces a slight Prolactin (Prl) increase, more obvious when basal Prl is elevated. However there is no correlation between GH and Prl responses to GRF even with basal hyperprolactinemia. GH response to GRF seems to slowly decrease after radiation therapy. GRF is a new potent, well tolerated secretagogue of GH and improves the diagnostic quality of the etiology of GH deficiency.
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Monoclonal antibodies bound to polystyrene microspheres containing magnetite have been used to remove tumour cells from bone marrow destined for autologous transplantation. The small magnetic beads can be targeted to the surface of tumour cells to render these magnetic. A flow system using permanent samarium cobalt magnets effects the rapid and efficient removal of "magnetic" tumour cells from bone marrow. The system is designed to be used with any type of tumour cell, so that by changing panels of monoclonal antibody it can be used for "cleaning" the bone marrow in many different malignancies.
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.
In a previous retrospective analysis from the principal paediatric centres of Algeria, Burkitt-type lymphomas (BL) were shown to account for around 46.5% of the total childhood non-Hodgkin's malignant lymphomas in that country. In the present study, a series of 49 abdominal BL from the Paediatric Clinic of Surgery, Mustapha Hospital, Algiers, has been studied. The age distribution shows a peak between 4 and 5 years of age, and the sex ratio is (M:F) 2.26:1. The disease is characterized by a rapid evolution in the absence of therapy. The major problem is an explosive form of the disease, which at present seems difficult to control in this country. Fifteen of the 49 patients (30.6%) died before completion of the first course of chemotherapy; however, complete remission (CR) was obtained for 30 patients (61%). Overall survival was 42.85% (21/49), whereas survival of patients who reached CR is 70% (21/30). When CR was obtained, deaths were related to cerebrospinal fluid involvement, local recurrence, secondary bone marrow involvement or therapeutic accidents. All patients alive with no evidence of disease (NED) 8-months after CR can be considered definitively cured. Epstein-Barr virus (EBV) serology performed on 31 BL patients and on a control group of 25 children with other malignant tumours showed that most Algerian BL have elevated EBV titres. A search for viral markers within malignant cells in 17 patients indicated that 88% (15/17) of the BL cases were EBV-associated. Analysis of the immunological and cytogenetic data showed that, as in the rest of the world, these BL cases involve proliferation of B-cell-type lymphocytes, with characteristic cytogenetic translocations involving chromosome 8. This report represents the most detailed description so far of BL from an area in non-equatorial Africa and the first report of a large series from North Africa.
A total of 233 bone marrow aspirates were obtained from 43 patients with Burkitt's lymphoma (BL). Lymphoma cells were absent and lymphoblastoid cell lines could not be established from 197 samples, which were characterized by limited initial cell proliferation and development of an adherent population, followed by cell death after 2-4 weeks. In 14 aspirates, after a similar pattern of growth, cell proliferation began again after about 6 weeks, with a rapid appearance and growth of cell clumps from the feeder layer--a type of growth typical of spontaneous lymphoblastoid cell lines. In 22 aspirates, growth of malignant cells was observed in culture and cytocentrifuged, stained smears, including marrow samples from 9 patients in whom the presence of BL cells had not been ascertained or even suspected by cytology. Karyotypic anomalies characteristic of BL were found in these cells: t(8;14) in the majority, two t(8;22), two t(2;8), and one t(2;8;9).
Authors summarized the chromosomal anomalies known in Leukemias Lymphomas and solid tumors. Break points are not random but corresponded to oncogenes localizations. A fondamental role in cancerogenesis is played by oncogenes.
Authors report the case of a 19 year old metastatic Ewing's sarcoma, prophylactically treated for suspected tuberculosis by Rifampicin and INH. Hepatic failure was induced by accidental overdose of INH. A high dose containing VCR protocol associated, lead to a coma with convulsions and severe motor peripheral neuropathy partially regressive. Neurological incidents of VCR, INH and their association are reviewed.
Twenty-eight Burkitt's lymphoma(s) (BL) cell lines were analyzed with anti-human immunoglobulins and monoclonal antibodies: Y29/55, B1, and BA1 are slightly different pan-B-reagents; TU1 and BL13 are two discriminating markers of the follicle; RFT1 is a pan-T-reagent expressed on the follicle mantle; AL2 reacts with the common acute lymphoblastic leukemia antigen gp100; and 38:13 recognizes a BL-associated antigen. Those lines were classified into 3 groups according to their membrane phenotype. In the first 2 groups, cell lines were derived from BL of germinal center origin, whereas in the last group they were established from BL cells originating in the bone marrow. All cell lines in the last group were from Caucasian BL, whereas lines from African BL of a high-incidence area were in group 1. North African cases were in group 2. Those distinct subgroups were not related specifically to the reactivity with Epstein-Barr virus nuclear antigen, the type of chromosomal translocation, or the clinical features. The variations induced by growth culture as well as the clinical implications were discussed.