No consensus yet exists on how to handle incidental fnd‐ings (IFs) in human subjects research. Yet empirical studies document IFs in a wide range of research studies, where IFs are fndings beyond the aims of the study that are of potential health or reproductive importance to the individual research participant. This paper reports recommendations of a two‐year project group funded by NIH to study how to manage IFs in genetic and genomic research, as well as imaging research. We conclude that researchers have an obligation to address the possibility of discovering IFs in their protocol and communications with the IRB, and in their consent forms and communications with research participants. Researchers should establish a pathway for handling IFs and communicate that to the IRB and research participants. We recommend a pathway and categorize IFs into those that must be disclosed to research participants, those that may be disclosed, and those that should not be disclosed.

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The monoclonal gammopathies are a group of disorders associated with monoclonal proliferation of plasma cells. The characterization of specific entities is an area of difficulty in clinical practice. The International Myeloma Working Group has reviewed the criteria for diagnosis and classification with the aim of producing simple, easily used definitions based on routinely available investigations. In monoclonal gammopathy of undetermined significance (MGUS) or monoclonal gammopathy, unattributed/unassociated (MG[u]), the monoclonal protein is < 30 g/l and the bone marrow clonal cells < 10% with no evidence of multiple myeloma, other B-cell proliferative disorders or amyloidosis. In asymptomatic (smouldering) myeloma the M-protein is >/= 30 g/l and/or bone marrow clonal cells >/= 10% but no related organ or tissue impairment (ROTI)(end-organ damage), which is typically manifested by increased calcium, renal insufficiency, anaemia, or bone lesions (CRAB) attributed to the plasma cell proliferative process. Symptomatic myeloma requires evidence of ROTI. Non-secretory myeloma is characterized by the absence of an M-protein in the serum and urine, bone marrow plasmacytosis and ROTI. Solitary plasmacytoma of bone, extramedullary plasmacytoma and multiple solitary plasmacytomas (+/- recurrent) are also defined as distinct entities. The use of these criteria will facilitate comparison of therapeutic trial data. Evaluation of currently available prognostic factors may allow better definition of prognosis in multiple myeloma.

Biobanks and archived datasets collecting samples and data have become crucial engines of genetic and genomic research. Unresolved, however, is what responsibilities biobanks should shoulder to manage incidental findings (IFs) and individual research results (IRRs) of potential health, reproductive, or personal importance to individual contributors (using “biobank” here to refer to both collections of samples and collections of data). This paper reports recommendations from a 2-year, NIH-funded project. The authors analyze responsibilities to manage return of IFs and IRRs in a biobank research system (primary research or collection sites, the biobank itself, and secondary research sites). They suggest that biobanks shoulder significant responsibility for seeing that the biobank research system addresses the return question explicitly. When re-identification of individual contributors is possible, the biobank should work to enable the biobank research system to discharge four core responsibilities: to (1) clarify the criteria for evaluating findings and roster of returnable findings, (2) analyze a particular finding in relation to this, (3) re-identify the individual contributor, and (4) recontact the contributor to offer the finding. The authors suggest that findings that are analytically valid, reveal an established and substantial risk of a serious health condition, and that are clinically actionable should generally be offered to consenting contributors. The paper specifies 10 concrete recommendations, addressing new biobanks and biobanks already in existence.

The t(11;14)(q13;q32) results in up-regulation of cyclin D1 and is the most common translocation detected in multiple myeloma, where it is also associated with a lymphoplasmacytic morphology. We performed an interphase fluorescent in situ hybridization (FISH) study to determine the clinical and biologic significance of the abnormality when testing a large cohort of myeloma patients. Bone marrow slides from multiple myeloma patients entered into the Eastern Cooperative Oncology Group phase III clinical trial E9486 and associated laboratory correlative study E9487 were analyzed using interphase FISH combined with immune-fluorescent (cytoplasmic immunoglobulin-FISH) detection of clonal plasma cells. We used FISH probes that hybridize to the 14q32 and 11q13 chromosomal loci. The t(11;14)(q13;q32) was correlated with known biologic and prognostic factors. Of 336 evaluable patients, 53 (16%) had abnormal FISH patterns compatible with the t(11;14)(q13;q32). These patients appeared to be more likely to have a serum monoclonal protein of less than 10 g/L (1 g/dL) (28% vs 15%, P ‫؍‬ .029) and a lower plasma cell labeling index (P ‫؍‬ .09). More strikingly, patients were less likely to be hyperdiploid by DNA content analysis (n ‫؍‬ 251, 14% vs 62%, P < .001). Patients with the t (11;14)(q13;q32)

These consensus guidelines have been compiled with input from the Scientific Advisors of the International Myeloma Foundation. Their production involved several steps including: A 3-day Scientific Advisors meeting, during which each specific area was presented and discussed (May 2002). Review of key literature, especially randomized study results, but also Medline, Internet, Cochrane database searches, and prior guidelines (Br J Haematol 115: 522-540, 2001). Feedback from patients participating in the International Myeloma Foundation, patient programs. These guidelines encompass both the published literature and expert opinions. Recommendations based upon expert opinions are identified as such. The intent is for the guidelines to be international in scope, plus provide recommendations for both clinical practice and research approaches. 'Consensus' reflects general, although not necessarily unanimous, agreement. Details are discussed as appropriate. For convenience, the recommendations are divided into: 1. Diagnostic criteria. 2. Staging and prognostic factors. 3. Frontline therapy. 4. High-dose therapy and transplant. 5. Maintenance therapy. 6. Supportive care and management of specific complications. 7. Novel therapies and new technologies.

Ectopic expression of mutated K-ras or N-ras in the interleukin 6 (IL-6)-dependent ANBL6 multiple myeloma cell line induces cytokine-independent growth. To investigate the signaling pathways activated by oncogenic ras that may stimulate IL-6-independent growth, we compared ANBL6 cells stably transfected with

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