Broad genotyping can be efficiently incorporated into an NSCLC clinic and has great utility in influencing treatment decisions and directing patients toward relevant clinical trials. As more targeted therapies are developed, such multiplexed molecular testing will become a standard part of practice.

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Objective: To compare test characteristics of the Farr radioimmunoassay and an automated fluorescence immunoassay (ELIA dsDNA test) for the diagnosis of systemic lupus erythematosus (SLE). Methods: A cross sectional study comprising 440 samples from 440 patients, sent to the laboratory over a three month period for anti-dsDNA testing. Chart review was performed, blinded for test results, to count for each patient the number of American College of Rheumatology criteria for the classification of SLE that were fulfilled. At least four criteria were met by 248 (56%) patients (SLE), one to three criteria by 77 (18%) (lupus-like disease, LLD), and no criterion by 115 (26%) (non-SLE/non-LLD). Results from serum samples from the non-SLE/non-LLD and SLE groups were used to calculate receiver operating characteristic curves. Results: For the Farr assay, specificities of 95% and 99% corresponded to sensitivities of 72% and 56% respectively. For the ELIA dsDNA test these levels of specificity corresponded to sensitivities of 44% and 17% respectively. Conclusions: The Farr radioimmunoassay is superior to the ELIA dsDNA test for identifying patients with SLE.

Thirty-four patients with refractory multiple myeloma were treated with 4-d continuous infusions of vincristine and adriamycin in combination with 4-d pulsed high-dose dexamethasone (VAD). Of 31 evaluable patients, 16 entered a complete remission (50%) and three a partial remission (10%). No difference in response rate was observed between primary refractory and relapsed patients. The median response duration was 9 months and the median survival of the responding patients was 12 months versus 4 months for the non-responders. Ten patients have currently survived longer than 360 d, of which six are stable in complete remission without therapy. All responding patients showed a remarkable improvement of their performance status and 70% of these patients became pain-free. Bacterial infection was the major complication and was probably due to the intensive corticosteroid programme. Severe myelosuppression was rarely observed. Irrespective of the response to VAD, a high beta 2-microglobulin of 4 micrograms/ml or more was a bad prognostic parameter. As early relapses were seen especially in this group of patients, in the patients with a plasma-cell LI% of 3 or more, and in patients with previous anthracyclin treatment, early consolidation, with, for instance, high dose melphalan, might improve the prognosis for these patients.

Immunotherapy based on the delivery of toxic agents to the tumor site using monoclonal antibodies (mAb) may be a promising modality in the treatment of hematological malignancies. In the selection of mAb, both for ex vivo but even more for in vivo therapy, not only their reactivity to the neoplastic cells should be considered, but also reactivity to other body constituents. Here we describe the screening of two human plasma-cell-reactive mAb B-B2 and B-B4, which may be used for immunotherapy of multiple myeloma. Cross-reactivity of B-B2 and B-B4 was determined by immunohistochemistry on a series of tissues. This revealed for both B-B2 and B-B4 a strong staining of epithelial cells in various organs, e.g. lung, liver, skin, kidney and gut, while only a weak and diffuse staining was seen with endothelial cells. In bone marrow reactivity was only found with plasma cells and not with hemopoietic precursors (CD34+ cells). Immunotoxins from B-B2 and B-B4 were constructed by coupling them to the plant-derived ribosome-inactivating protein saporin. Both B-B2 and B-B4 immunotoxins appeared to be efficient in specific inhibition of protein synthesis in plasma cell lines (IC50 respectively 1 nM and 0.1 nm). The immunotoxins were also tested on epithelial cell line A431, on liver cell line HepG2 and on human umbilical vein endothelial cells. The epithelial cell line A431 was reactive with both B-B2 and B-B4, but was only inhibited by B-B4 immunotoxin. Cell line HepG2 was reactive with both mAb, but was not inhibited by either immunotoxin. The endothelial cells showed no reactivity with B-B2 and B-B4 and were not inhibited by either immunotoxin. Bone marrow treated with B-B2 and B-B4 immunotoxin did not show a decrease in colonies of hemopoietic precursor cells. Incubation of multiple-myeloma-derived bone marrow with these immunotoxin resulted in a clear decrease of the number of plasma cells. From these data we conclude that B-B2 and B-B4 immunotoxin can be used for ex vivo bone marrow purging. Discrepancies were found between immunohistochemistry, binding assays and cytotoxicity assays with the mAb and the immunotoxin, which underlines the necessity for these various assays as a preclinical screening.