A panel of members of the 2009 International Myeloma Workshop developed guidelines for risk stratification in multiple myeloma. The purpose of risk stratification is not to decide time of therapy but to prognosticate. There is general consensus that risk stratification is applicable to newly diagnosed patients; however, some genetic abnormalities characteristic of poor outcome at diagnosis may suggest poor outcome if only detected at the time of relapse. Thus, in good-risk patients, it is necessary to evaluate for high-risk features at relapse. Although detection of any cytogenetic abnormality is considered to suggest higher-risk disease, the specific abnormalities considered as poor risk are cytogenetically detected chromosomal 13 or 13q deletion, t(4;14) and del17p, and detection by fluorescence in situ hybridization of t(4;14), t(14;16), and del17p. Detection of 13q deletion by fluorescence in situ hybridization only, in absence of other abnormalities, is not considered a high-risk feature. High serum β(2)-microglobulin level and International Staging System stages II and III, incorporating high β(2)-microglobulin and low albumin, are considered to predict higher risk disease. There was a consensus that the high-risk features will change in the future, with introduction of other new agents or possibly new combinations.

The antibody-mediated delivery of therapeutic agents to sites of angiogenesis is an attractive strategy for anticancer therapy, but is largely unexplored in hematologic malignancies. In the present study, we show that the extra domain B (EDB) of fibronectin, a marker of angiogenesis, is expressed in B-cell non-Hodgkin lymphoma (NHL) and that the human monoclonal anti-EDB antibody L19 can selectively localize to the lymphoma-associated subendothelial extracellular matrix. In vivo, the preferential accumulation of the antibody at the tumor site was confirmed by quantitative biodistribution analyses with radioiodinated antibody preparations. The fusion protein L19-IL2, which mediates the delivery of interleukin-2 (IL-2) to the neovasculature, displayed a superior antilymphoma activity compared with unconjugated IL-2 in localized and systemic xenograft models of NHL. When coadministered with rituximab, L19-IL2 induced complete remissions of estab- IntroductionConventional cytotoxic therapies of cancer often do not discriminate between tumor and normal tissues. To achieve therapeutically relevant concentrations in the tumor mass, large drug doses have to be administered to the patient, leading to a poor therapeutic index and unacceptable toxicities to healthy tissues. The selective delivery of therapeutic agents to the tumor site using antibodies against tumor-associated antigens represents a promising strategy to overcome the disadvantages of conventional cancer therapies. 1-3 Antigens expressed in the tumoral neovasculature are especially attractive targets for antibody-based pharmacodelivery applications due to their inherent accessibility for blood-borne agents. [4][5][6] The efficacy of targeting either tumor endothelial cells or the modified subendothelial extracellular matrix has been demonstrated in a variety of animal models of solid cancers using antibodies functionalized with different effector moieties, 4,[7][8][9][10][11][12][13][14] leading to the clinical development of immunocytokines and radioimmunoconjugates for the therapy of solid tumors. 6,15 Tumortargeting strategies based on the preferential accumulation of biopharmaceuticals around new blood vessels could also be conceivable for the therapy of leukemias and lymphomas, since the dependence of hematologic malignancies on a functional neovasculature has been highlighted already a decade ago. 16,17 Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy, with now more than 60 000 new cases being diagnosed each year in the United States. 18 The approval of rituximab, a chimeric monoclonal immunoglobulin G1 (IgG1) antibody specific to CD20, represented a major step toward a more selective and effective therapy of NHLs of B cell origin. While first shown to be effective in relapsed follicular lymphoma, anti-CD20 immunotherapy is nowadays incorporated in front-line therapy schemes of follicular and diffuse large B-cell lymphoma. 18 However, in spite of the unquestionable clinical effectiveness of rituximab, a high percentage of patients ...

We describe a novel method for producing homogeneous eukaryotic N-glycoproteins. The method involves the engineering and functional transfer of the C. jejuni glycosylation machinery in E. coli to express glycosylated proteins with the key GlcNAc-Asn linkage. The bacterial glycans were then trimmed and remodeled in vitro by enzymatic transglycosylation to fulfill a eukaryotic N-glycosylation. It provides a potentially general platform for producing eukaryotic N-glycoproteins.

CEUS improved liver metastases diagnosis in comparison with baseline US while it revealed similar diagnostic performance and confidence to contrast-enhanced CT in patients considered suitable for US and with proven or suspected liver metastases at baseline US.