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Biomedical subjects

M Favrot

Publications and source records attributed to M Favrot.

At least 73 records · Page 4Linked to original sources

[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↗

[Cell cultures in Burkitt's lymphoma. Detection of residual disease and application to autologous graft purging].

We describe a new liquid cell culture system for propagating Burkitt lymphoma (BL) cells contaminating the bone marrow (BM). The percentage of BL cells at day 10 of culture is correlated with the number of BL cells in the initial sample, which permits the detection of as few as one BL cell in 10(6) normal cells. We currently use such an assay to detect minimal BM involvement in our patient's follow up. This has allowed to define in which clinical situations the BM collected for autologous transplantation (though cytologically normal) had to be "purged". With the help of this modified liquid system it was possible to quantify the efficacy of various purging procedures on different models; an experimental model of allogenic irradiated BM contaminated with BL cell lines was used. Pre-clinical assays were also conducted on our patients' BM contaminated with their own tumour cells, or on invaded BM collected for autologous transplantation and for which the system had evidenced the efficacy of the purging procedure.

Bone Marrow Cells↗

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↗

Definition of response and remission in children over one year of age with advanced neuroblastoma: proposition for a scoring system.

A two-step evaluation system is proposed to analyze the results of therapy for stage IV neuroblastoma in children over 1 year of age. Since most protocols consist of first-line chemotherapy followed by surgery and often high-dose chemotherapy with bone marrow rescue, "response" should assess the effect of chemotherapy alone and "remission" indicate the status after an attempt to remove the primary tumor. A scoring system is proposed for both steps. The comparability of different studies depends on the use of such common criteria to define patient groups and treatment results.

Adolescent↗

Experimental evaluation of an immunomagnetic bone marrow purging procedure using the Burkitt lymphoma model.

In order to test the numerous variable biological parameters which may contribute to the efficiency of the immunomagnetic depletion method, experiments have been carried out with different Burkitt lymphoma cell lines. The Hoechst dye method, a sensitive assay able to detect 3 log elimination, and a liquid culture assay suitable for identifying an elimination greater than 4 logs, were used to measure malignant cell elimination. These assays showed that the separation of bone marrow mononuclear cells on Ficoll-hypaque, the use of beads in excess, and a double treatment of the samples are needed to obtain optimal depletion of malignant cells. Under these conditions, the immunomagnetic procedure is capable of depleting 1% tumour cell infiltration at the lower limit of detection of a very sensitive culture assay (i.e. greater than 4 log elimination).

Bone Marrow Cells↗

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↗

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↗

T lymphocyte regeneration after transplantation of T cell depleted allogeneic bone marrow.

The regeneration of T cell subsets was studied with double immunofluorescence marker methods in 37 patients who received HLA matched T lymphocyte depleted bone marrow transplants (BMT) as part of the treatment for their haematological disease. A cocktail of anti-pan-T (CD6: MBG6) and anti-suppressor/cytotoxic-T cell (CD8: RFT8) monoclonal antibodies was used with rabbit serum as a source of cytolytic complement to achieve selective T cell lysis. The T8+ cells reached low normal values around 60 days post-transplant and remained within the normal range throughout the study (greater than 150 days). This observation is in contrast to our previously published results in patients who, after receiving BMT without efficient T cell depletion, had increased numbers of circulation T8+ cells from 60 days post-transplant. In the present study Leu-7+, RFT8- cells reached normal values rapidly but the reconstitution of T4+ lymphocytes was slow: low normal levels were reached only around day 150 following BMT. The degree of graft-versus-host disease (GVHD) seemed to be related to the number of residual T cells infused: two of the three patients who received the highest numbers of T cells developed Grade II III; otherwise GVHD was minimal. Among the clinical parameters studied cytomegalovirus (CMV) immune status moderately influenced reconstitution: at 55-90 days post-transplant T8+ cells were present at the upper normal levels in seven out of 15 patients receiving BMT from CMV seronegative donors, but in none of the 16 individuals receiving BMT from seropositive donors. CMV related complications were relatively uncommon. Thus the most significant factor in preventing 'T8+ cell overshoot' and T cell imbalance during regeneration appears to be the depletion of T (including T8+) lymphocytes from marrow. The differences of T8+ cell reconstitution in this and previous studies may reflect a different regeneration pattern from T cell precursors as opposed to inoculated mature T cells.

Adolescent↗

[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↗

An immunohistological approach to persistent lymphadenopathy and its relevance to AIDS.

Recent evidence has shown that not only AIDS but also the majority of 'unexplained' persistent, generalized lymphadenopathy (PGL) are related to HTLV-III/LAV infections. The early detection how these changes may proceed to AIDS then become a prime interest. Eleven patients with PGL (10 homosexual males and one heterosexual haemophiliac) have been studied by immunohistology using monoclonal antibodies to dendritic reticulum cells of the germinal centre, T and B lymphocyte subsets, plasma cells and factor VIII, as an endothelial marker. In six cases only follicular and paracortical hyperplasia was detected, while in five other cases destruction of the dendritic reticulum cell network was seen with this sensitive method. This early destruction may explain the release of activated B cells into the circulation and prove to be an ominous prognostic sign, as it appears to correlate with 'prodromal' symptoms. In four out of 11 cases the depletion of T4+ cells in the paracortex was not as severe as in the blood, indicating that T4+ cells may preferentially settle in tissues at the time of T4 lymphopenia. In addition, germinal centres contained an additional patchy infiltration of T8+ cells. A patient with Kaposi's sarcoma did not show germinal centre destruction but did reveal extensive plasma cell infiltrates. Immunohistology may contribute to the definition of prognosis and analysis of disease progression in patients with PGL.

Acquired Immunodeficiency Syndrome↗

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↗