Michel Symann

Immunodetection of small cell lung cancer metastases in bone marrow using three monoclonal antibodies

Detection of bone marrow metastases by indirect immunofluorescence methods was investigated using three monoclonal antibodies (MoAbs) raised against small cell lung cancer (SCLC). These antibodies, designated anti-LCA1, -LCA2 and -LCA3, recognize three different antigens on the surface of SCLC cells. Eighty-four bone marrow samples from 74 different patients were studied. Whereas tumor cells were found in 32 (38%) by MoAb staining, only 10 (12%) were positively identified using conventional morphological methods. Nine out of the morphologically positive specimens showed reactivity with at least two monoclonal antibodies. Among the 32 samples proven positive by immunofluorescence, an important antigenic variability was noted. Anti-LCA1 recognized tumor cells in 62%, anti-LCA2 and anti-LCA3 in 53%. Due to the recognition of bone marrow involvement by fluorescence methods in 26% of the 34 patients classified as limited disease, a new subgroup of limited disease patients was defined whose prognosis remains undetermined. Our results confirm the utility of immunodetection in the diagnosis of SCLC bone marrow metastases and emphasize the advantage of using a panel of MoAbs with different antigenic specificities. Further study is needed to determine the prognostic significance of bone marrow involvement established by immunodetection.

In vivo stimulation and inhibition of granulopoiesis: the effect of an inflammatory reaction on murine diffusion chamber granulopoiesis.

Humoral factors influencing granulopoiesis have been evaluated using diffusion chambers (DC) implanted in the peritoneal cavity of mice challenged by an aseptic abcess produced by the subcutaneous implantation of copper rods. This resulted in an increase in peripheral blood neutrophils and an increase in tibial granulocytic elements. When DC loaded with bone‐marrow cells were implanted into mice stimulated the day before by an aseptic abcess significantly more CFU‐s, CFU‐c, proliferative and non‐proliferative granulocytes were produced, as compared to DC implanted into control hosts. When DC were implanted 4‐6 d after the induction of inflammation in mice a significant depression of DC granulopoiesis was observed. Levels of serum and DC fluid CSF and serum inhibitors of in vitro colony growth showed no correlation with DC myelopoiesis. The data show that mice undergoing an inflammatory reaction elaborate first humoral substance(s) enhancing CFU‐s and granulocytic growth in DC and next inhibitory factor(s) of DC granulopoiesis.

Monoclonal antibodies for the in vitro detection of small cell lung cancer metastases in human bone marrow

Three rat monoclonal antibodies were selected for the immunodetection of small cell lung cancer metastases in bone marrow and other hematologic samples. By membrane immunofluorescence, they define three distinct surface antigens here termed lung cancer-associated antigens or LCAs. The latter are widely expressed on small cell lung cancer and non-small cell lung cancer cells/cell lines, but not detectable on a variety of normal and transformed bone marrow, blood and lymphoid cells. Anti-LCA1 (IgM) is similar to the many anti-lacto-N-fucopentaose III IgM antibodies rasied against human tumors. In contrast, anti-LCA2 (IgG2b) and anti-LCA3 (IgG2a) define surface proteins of 29, 32, 41 and 98 kilodaltons, respectively, that have not been reported earlier. These three reagents have immunodiagnostic potential, since in combination they label all 49 lung cancer cell lines tested. Their ability to detect lung cancer metastases in patients bone marrow samples is documented in an accompanying paper.

Carboplatin in association with etoposide and either adriamycin or epirubicin for untreated small cell lung cancer: A dose escalation study of carboplatin

A multi-center, open trial was conducted to determine the maximal tolerable dose of carboplatin in combination with conventional doses of both etoposide and an anthracycline for the treatment of previously untreated small cell lung cancer (SCLC) patients. Ninety-five patients [48 with limited disease (LD) and 47 with extensive disease (ED)¦ received a total of 376 courses of treatment. Carboplatin was given on day 1 at a dose of 250 mg m−2 in 60 courses, 300 mg m−2 in 69, 330 mg m−2 in 236 and 350 mg m-2 in 11, with 120 mg m−2 etoposide on days 1, 3 and 5 and either 40 mg m-2 adriamycin or 60 mg m−2 epirubicin on day 1. Epirubicin was not administered before carboplatin reached the dose of 330 mg m−2. Courses were repeated every 3 weeks. The main toxicity was hematological. The first course of therapy induced a dose-dependent decrease of leucocyte, neutrophil and platelet counts: all patients, except one, who received 350 mg m−2 carboplatin had a neutropenia below 200 μ−1 and a thrombopenia below 100,000 μl−1. Three patients died of septicemia. Other toxicities were well tolerated. After three courses, patients were re-staged by performing a mandatory fiberoptic bronchoscopy and a thoracic computed axial tomography (CAT). The overall objective response rate for 86 evaluable patients was 91% (98% for LD) with 21% complete remissions (30% for LD). All 23 hepatic and six brain sites, evaluable after chemotherapy alone, responded. This new combination, in which the recommended dose of carboplatin is 330 mg m−2, should be evaluated in a prospective study for SCLC.

Management of Non-Hodgkin’s Lymphomas: Conclusions of the First Intercity Meeting, 1986

On 15 December 1986 in Strasbourg (France) the first Intercity Meeting of the European School of Oncology was held with a survey of the current status of non-Hodgkin’s lymphoma (NHL) management. The conclusions of this meeting are presented here. The Working Formulation for clinical use [1] (Table 1) is used throughout this paper.