Although serum beta2 microglobulin (beta2 M) is an easy parameter to measure, and over-expressed in a large number of lymphoproliferative diseases, its prognostic value has been largely ...underestimated. The present study examined the influence of beta2M levels on overall survival (OS) of patients with follicular lymphoma (FL).
The prognostic role of beta2M was evaluated in 236 patients with FL identified from the databases of the Gruppo Italiano per lo Studio dei Linfomi (GISL) and treated with anthracycline-based regimens from 1993 to 2003.
Elevated serum beta2M levels were found in 82 patients (35%). According to multivariate logistic regression analysis, elevated beta2M levels were associated with elevated lactate dehydrogenase (LDH) (p=0.021), age (p=0.029), and number of involved nodal areas (p<0.001). The percentage of elevated beta2M levels increased progressively with increasing FLIPI scores (17%, 38%, and 63% in the low-, intermediate-, and high-risk groups, respectively). Five-year OS was 61% (95% CI, 47-73%) and 89% (95% CI, 82-93%) for patients with elevated vs normal beta2M levels respectively (p<0.001). Cox regression analysis showed that beta2M level had an independent and stable prognostic value (HR=3.0; 95%CI, 1.6-5.7). In a multivariate analysis the impact of beta2M level on survival was independent of FLIPI score, with a HR of 2.94 (95% CI, 1.54-5.62).
Our results demonstrate that in patients treated in the pre-rituximabera, beta2M level was an independent prognostic marker in addition to FLIPI score. We thus suggest that beta2M be routinely assessed and tested in future prognostic studies of FL patients treated with combination chemotherapy and anti-CD20 agents.
Abstract
CD138 (Syndecan1) is highly expressed on multiple myeloma (MM) cells. In this study, we examined the anti-MM effect of murine/human chimeric CD138-specific monoclonal antibody (mAb) nBT062 ...conjugated with highly cytotoxic maytansinoid derivatives
in vitro
and
in vivo
. These agents significantly inhibited growth of CD138-positive MM cell lines and primary tumor cells from MM patients, without cytotoxicity against peripheral blood mononuclear cells from healthy volunteers. In MM cells, they induced G2/M cell cycle arrest followed by apoptosis associated with cleavage of PARP and caspase-3, -8 and -9. Non-conjugated nBT062 completely blocked cytotoxicity induced by nBT062-maytansinoid conjugate, confirming that binding is required for inducing cytotoxicity. Moreover, nBT062-maytansinoid conjugates blocked adhesion of MM cells to bone marrow stromal cells (BMSCs). Co-culture of MM cells with BMSCs, which protects against dexamethasone-induced death, had no impact on the cytotoxicity of the immunoconjugates. Importantly, nBT062-SPDB-DM4 and nBT062-SPP-DM1 significantly inhibited MM tumor growth
in vivo
in both human multiple myeloma xenograft mouse models and in SCID-human bone grafts (SCID-hu mouse model). These studies provide the preclinical framework supporting evaluation of nBT062-maytansinoid derivatives in clinical trials to improve patient outcome in MM.
A case of vertebral artery dissection and consequent basilar artery thrombosis in a 6-year-old patient is reported. The patient was treated with subcutaneous low-molecular-weight heparin at ...therapeutic doses (enoxaparin, 100 IU/kg twice daily) for 3 weeks, then reduced to 2,000 IU/day for 3 more weeks. After this time a magnetic resonance angiogram was obtained that showed complete recanalization of the left basilar artery. Enoxaparin proved to be a safe and useful therapy for thrombosis accompanying vertebral artery dissection.
The collection of the American Museum of Natural History, New York, includes a set of four elaborately painted 19th-century Tsimshian house posts that have been on continuous open display for more ...than a century. Over time, these objects have accumulated surface grime, and several coating layers applied in undocumented past restoration campaigns, some of which have yellowed with age. The combination of heavy soiling and multiple coatings has obscured the underlying polychromy, shifting the colors of the wood and paints, and yielding improper surface appearances. Further, some of the coatings appeared to have sunk into the media-lean paints, complicating removal. Questions regarding the number, types, and timing of coating applications, as well as the nature of some of the paint below, set the stage for an in-depth technical study aiming to inform the conservation treatment of these poles being undertaken in connection with the renovation of the Northwest Coast Hall at the museum. Microscopic examination of numerous cross sections removed from the four house posts under polarized and ultraviolet (UV) illumination shed light on the number of coating layers present in selected areas and their location in relation to the overall stratigraphy. Micro-invasive analysis of samples relied on a combination of spectroscopic and chromatographic techniques, including transmission Fourier-transform infrared (FTIR) spectroscopy, attenuated total reflection (ATR)-FTIR spectroscopy, and pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS), aiming to determine the exact chemical composition of the coatings. Portable X-ray fluorescence (XRF), FTIR, Raman, and scanning electron microscopy with energy-dispersive X-ray spectroscopies (SEM/EDS) provided insight into the color palette used, with a focus on green paints. Investigation of the coatings revealed the application of multiple layers, including cellulose nitrate and localized areas of polyvinyl acetal. Analysis of the paint identified a limited range of inorganic pigments and, additionally, assisted in tackling issues that arose during the cleaning of specific colored areas. Results from this technical study helped address outstanding questions regarding this group of historical Tsimshian house posts, informing the development of a suitable treatment tailored to the safe removal or reduction of surface coatings and grime, ultimately improving the legibility of the design and colors.
A chemotherapeutic protocol using carmustine in combination with vincristine and prednisone was tested in dogs with multicentric malignant lymphosarcoma. Of seven dogs treated, six (85.7%) achieved ...complete remission. A partial response occurred in one dog. Median survival time was 224 days (mean 386 days), and median duration of remission was 183 days (mean 323 days). Marked neutropenia was observed following carmustine administration. There were no significant alterations in platelets and red blood cell counts during treatment, and no abnormalities attributable to the chemotherapy were found in serum biochemical profiles. Results of this study showed that carmustine is an effective alternative option in the treatment of canine lymphosarcoma.
PDF
