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Biomedical subjects

M C Favrot

Publications and source records attributed to M C Favrot.

At least 55 records · Page 3Linked to original sources
PubMed1990

Interleukin 2 immunotherapy in children with neuroblastoma after high-dose chemotherapy and autologous bone marrow transplantation.

Four children with persistent neuroblastoma after marrow ablative chemoradiotherapy and autologous bone marrow transplantation received continuous infusion of recombinant interleukin 2, 75 to 120 days after the graft. Recombinant interleukin 2 therapy did not induce any major or nonreversible toxicity, hematological toxicity in particular. One patient entered complete remission for 9 months and a second patient had a long-lasting normalization of urinary catecholamine metabolites with more than 50% regression of bone marrow metastases (8 months). In three children, recombinant interleukin 2 and a second patient entered complete remission for 9 months therapy was followed by major increase and activation of circulating natural killer cells which amounted to 80% of the circulating mononuclear cells.

Bone Marrow Transplantation↗
PubMed1990

Functional and immunophenotypic modifications induced by interleukin-2 did not predict response to therapy in patients with renal cell carcinoma.

Twenty-five patients with renal cell carcinoma were treated with continuous infusion of IL-2 (3 x 10(6) units/m2/day) with or without lymphokine-activated killer (LAK) cells; 5 responded to therapy. Functional and immunophenotypic modifications of the peripheral blood lymphocytes (PBLs) did not predict response to therapy. Systemic administration of interleukin-2 (IL-2) during 5 days caused a preferential proliferation of natural killer (NK) cells, although CD4+ T cells remained the predominant circulating population, in particular in three of the five responding patients. The IL-2 low-affinity receptor was induced only on CD4+ T cells. B cells did not proliferate and immunoglobulin levels were not modified by IL-2. In the peripheral blood, the NK function increased but the LAK function in vivo remained low. The T-cell proliferative response in mixed lymphocyte cultures (MLCs) decreased after therapy. Four days of ex vivo culture of PBLs with IL-2 did not modify T and NK distributions, but increased the coexpression of CD8 on NK cells and NKH1 density; it decreased the coexpression of CD16 and induced LAK cell function. Three weeks after the end of the first course of therapy and before the second course was started, all immunological parameters returned to baseline levels, except the T-cell proliferative response in MLCs. The second course of IL-2 therapy induced the same modifications as the first one, with the exception of a higher CD4+ T-cell proliferation.

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↗
PubMed1989

Clinical value of N-myc oncogene amplification in 52 patients with neuroblastoma included in recent therapeutic protocols.

Southern blot analysis of neuroblastoma (NB) cell DNA from 52 patients (58 samples) allowed the detection of an N-myc amplification on three of the 13 BM samples and three of 13 tumor samples at diagnosis, on two of 17 tumor samples taken after induction therapy, on three of seven BM samples and two of the five local tumor samples taken after relapse. N-myc was amplified in two of the 15 patients with stage I to III NB and in 10 of the 36 patients with stage IV neuroblastoma over 1 year of age. Conclusions from the analysis are as follows: first tumor samples obtained on previously treated patients are histologically modified and detection of N-myc amplification is not accurate; consequently N-myc amplification must be defined at diagnosis. Surgical biopsies of the primary tumors can, however, be delayed and malignant cells obtained by ultrasound-guided punctures or analyzed on bone marrow samples if they represent more than 50% of the total population. Second, any attempt to define the prognostic value must be performed on a group of patients treated with a new aggressive protocol of chemotherapy; it will require a multiparametric analysis including, in particular, results of an extensive clinical staging at diagnosis and histological criteria.

Child↗
PubMed1989

Immunological detection of neuroblastoma cells in bone marrow harvested for autologous transplantation.

In about 50% of patients with stage IV neuroblastoma, micrometastases are present in the bone marrow when it is harvested for an autograft to follow induction therapy, and the risk of graft contamination by neuroblastoma cells has been the rationale for the use of a purging procedure. However, bone marrow metastases are detected with trephine biopsies which only explore the sites biopsied and do not reflect potential contamination of the pooled marrow harvested for autograft. A two-colour fluorochrome labelling method is described which permits as few as 1 neuroblastoma cell in 100,000 normal bone marrow cells from the autograft to be detected. Three monoclonal antibodies (UJ13A, H11 and 11.14) which react with neuroblastoma cells are used as single reagent in combination with a fourth anti-panleucocyte antibody. This method requires only 2 h for the analysis of three million marrow cells from the autograft, and is more effective than alkaline phosphatase staining with the same monoclonal antibodies. Results were compared with conventional techniques (four biopsies and four aspirates) carried out at the same time in 34 consecutive patients. Of 18 cases with negative aspirates and biopsies, neuroblastoma cells were detected in two autografts by the immunological method. Of 16 cases with positive aspirates and/or biopsies, 10 autografts were positive by the immunological method and six were negative. Thus, marrow micrometastases were detected in 16 of the 34 patients, but the autograft contained malignant cells in only 12 of these patients and the immunological analysis demonstrated that the use of a purging procedure allowed the elimination of neuroblastoma cells from the autograft before its reinjection to the patients.

Antibodies, Monoclonal↗
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

[Immunodeficiency and cancer].

The analysis of cancers associated with immunodeficiencies (either congenital, iatrogenic or acquired) enabled us to define the possible role of these deficiencies in the sequence of events leading to cancer and in particular the emergence of hematopoietic proliferations. Immunodeficiency increases the risk of viral infection, and in severe deficiencies, uncontrolled infections (Epstein-Barr virus) are directly responsible for the appearance of polyclonal proliferations; in moderately severe deficiencies, the hyperstimulation of the immune system by repeated infections increases the number of mutagenic events, but the immortalization of a malignant clone is a late event, which may or may not be linked to a viral infection. On the other hand, some intrinsic congenital or acquired abnormalities of lymphoid cells may be responsible both for immunodeficiency and carcinogenesis (chromosomic fragility). Apart from any immunological reaction, the immune system plays a role in the proliferation and differentiation events in various tissues; and any dysregulation of the latter may indicate the emergence of a cancer.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Systemic interleukin-2 therapy in children with progressive neuroblastoma after high dose chemotherapy and bone marrow transplantation.

Two children with active metastatic neuroblastoma after high dose chemotherapy and bone marrow transplantation (BMT) received a high dose continuous infusion of interleukin-2 (IL2) 120 days after an autologous BMT for patient 1 and 90 days after an allogeneic non T cell-depleted BMT for patient 2. Usual side effects of IL2 therapy were observed without life-threatening complications or any major hematological toxicity. The reactivation of graft-versus-host disease during IL2 infusion in patient 2 was the major BM-related complication but it improved with IL2 interruption and corticosteroids. IL2 induced a complete remission (9+ months) in patient 1 with the disappearance of bone metastases and local tumor but patient 2 progressed after cessation of therapy. Patient 1 presented with a large excess of circulating NK cells in the period after autologous BMT and IL2 induced a preferential outgrowth of this lymphocyte subset.

Adrenal Cortex Hormones↗
PubMed1988

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↗
PubMed1988

[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↗
PubMed1988

[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↗
PubMed1988

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

Immunological analysis is complementary to morphological investigation to detect bone marrow (BM) metastases in neuroblastoma patients. It is essential at time of BM harvest for an autograft, since it is the only examination which allows a precise evaluation of the graft contamination by malignant cells. Simple indirect immunofluorescence staining with anti-neuroblastoma monoclonal antibodies (UJ13A and HSAN 1-2) allows a final detection of about 1% malignant cells in the BM, and 1% when cells are gathered in clumps. The use of an immunocytochemical method (alkaline phosphatase) together with double immunofluorescence staining permits to detect as few as one residual neuroblastoma cell in 10(4) normal ones. These two methods used together have allowed to assess the neuroblastoma nature of rare isolated cells with pseudo-lymphocytic aspect.

Alkaline Phosphatase↗