Robert A Kyle

..Historically, patients with AL amyloidosis and overt congestive heart failure have had an ominous prognosis with median survival of approximately 6 months...

..This paper provides the current criteria for diagnosis, staging, risk stratification and response assessment of MM...

..The percentage of lymphoplasmacytic cells in the bone marrow, size of the serum monoclonal (M) spike, and hemoglobin value were significant independent risk factors for progression...

..Patients with SWM should be followed and not treated until symptomatic WM develops. Treatment on a clinical trial for those at greatest risk of progression should be considered...

..More than 100 agents are in phase I, II or III clinical trials. The most promising are carfilzomib and pomalidomide...

..Thalidomide produces objective response in approximately 30% of refractory patients. The use of intravenous bisphosphonates is recommended for patients with skeletal lesions. Hypercalcemia and renal failure must be treated promptly...

..To determine the long-term outcome of patients with monoclonal gammopathy of undetermined significance (MGUS)...

..The authors reported on the incidence of multiple myeloma in Olmsted County, Minnesota, between 1991 and 2001 and on trends in multiple myeloma incidence over the last 56 years...

..A monoclonal gammopathy of undetermined significance (MGUS) occurs in up to 2 percent of persons 50 years of age or older. Reliable predictors of progression have not been identified, and information on prognosis is limited...

..We also provide an update on current concepts of diagnosis and therapy, with an emphasis on how treatments have emerged from a historical perspective after certain important discoveries and the results of experimental studies...

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..Testing should be done 2-3 months after the initial recognition of SMM. If the results are stable, the patient should be followed every 4-6 months for 1 year and, if stable, every 6-12 months...

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..To determine the clinical and laboratory features of newly diagnosed multiple myeloma...

..MGUS may be associated with many different disorders, including lymphoproliferative diseases, leukemia, connective tissue disorders, dermatologic diseases, and neurologic disorders...

..During follow-up, 33 of the 48 patients progressed to symptomatic WM. The median time to progression was 4.6 years. The risk of progression to WM was 6% at 1 year, 39% at 3 years, and 55% at 5 years...

..5 g/dL or less, 26% with 1.5 g/dL, 34% for 2.0 g/dL, and 41% for more than 2.5 g/dL...

..Monoclonal gammopathy of undetermined significance may be associated with various disorders, including lymphoproliferative diseases, leukemia, von Willebrand disease, connective tissue diseases and neurologic disorders...

..The M-protein might lead to renal failure, hyperviscosity syndrome, or through the suppression of uninvolved immunoglobulins, recurrent infections. Anemia and hypercalcemia are common complications...

..It was concluded that the patients with IgM MGUS should be followed indefinitely...

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..We used sensitive laboratory techniques to ascertain the prevalence of MGUS in a large population in a well-defined geographic area...

..Prognostic factors for the progression and outcome of this disease are unclear...

..Patients with both MGUS and SMM must be followed up for their lifetime...

..Patients must be treated for at least 6 months before therapy is abandoned because response is slow. Chlorambucil is an effective agent and should be compared with purine analogues or rituxan (Rituximab) in a prospective study...

..The authors have reviewed the treatment of multiple myeloma including the novel agents, thalidomide, bortezomib and lenalidomide...

..Epidemiologic and statistical methods must be used to evaluate these associations...

..Thalidomide produces an objective response in about one third of patients with refractory disease. It currently is being studied in conjunction with dexamethasone for conventional initial therapy...

..This article discusses the recognition, prevalence, natural history, and progression of MGUS. Management of the disease is discussed along with its association with other disorders. Information on smoldering multiple myeloma is included...

..To confirm the findings, we conducted a population-based study on MGUS in the 11 counties of southeastern Minnesota from 1960 to 1994. The risk of progression to a malignant plasma-cell disorder was 1% per year...

..Tobacco use, obesity, diet, and alcohol ingestion are all possible causes of MM. Clusters of MM have been noted. Multiple cases of MM have been found in first-degree relatives...

..The cumulative probability of progression to active MM or amyloidosis was 51% at 5 years, 66% at 10 years and 73% at 15 years; the median time to progression was 4.8 years...

..Moreover, FSGS may respond favorably after the underlying plasma cell disorder is controlled...

..INTERPRETATION AND CONCLUSIONS: The median time to disease progression in patients with multiple myeloma who receive initial therapy with Thal/Dex and who do not undergo ASCT is 18 months...

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..To systematically study the association of monoclonal gammopathy of undetermined significance (MGUS) with all diseases in a population-based cohort of 17,398 patients, all of whom were uniformly tested for the presence or absence of MGUS...

..To determine the long-term effects of a combined regimen of lenalidomide and dexamethasone (Rev-Dex) on time to progression, progression-free survival, and overall survival (OS) in patients with multiple myeloma...

..3% vs 9.2%, P = .058) and peripheral neuropathy (10.4% vs 0.9%, P < .001). Len/dex appears well-tolerated and more effective than thal/dex. Randomized trials are needed to confirm these results...

..To conduct in vitro studies as well as a phase 2 clinical trial in patients with smoldering or indolent multiple myeloma to determine if interleukin 1 (IL-1) inhibitors can delay or prevent active myeloma...

..Grade 3-4 nonhematologic adverse events were noted in 55% of patients. Randomized trials are needed to determine the role of early therapy in SMM...

..02). Angiogenesis is increased in solitary plasmacytoma and is a significant predictor of progression to myeloma and provides further evidence of its importance in the pathogenesis of myeloma...

..CONCLUSIONS: Thalidomide is useful in the treatment of patients with relapsed multiple myeloma and produced durable response in approximately one third of patients, with median response duration of nearly 1 year...

..These results need confirmation in larger, prospectively designed studies...

..To examine whether the outcome of patients with primary systemic amyloidosis (AL) has improved over time and to identify predictors of early mortality in patients with AL...

..To determine the incidence of monoclonal gammopathy of undetermined significance (MGUS) in the general population and to estimate the duration of occult MGUS before first diagnosis...

..The use of modern testing is imperative to characterize a patient's risk for progression. PET/CT plays an important role in the diagnostic work-up...

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..Outcomes of undiagnosed celiac disease (CD) are unclear. We evaluated the morbidity and mortality of undiagnosed CD in a population-based sample of individuals 50 years of age and older...

..To determine the prognostic value of serum uric acid (UA) in patients with primary systemic (light chain) amyloidosis (AL)...

..Outside a randomized clinical trial, these results present the strongest data supporting the role of PBSCT in selected patients with AL...

..It also highlights the importance of achieving at least a 90% reduction in the FLC-diff to improve the outcome of patients with light-chain AL...

..Renal involvement is common in multiple myeloma. In this study, we examined kidney biopsy findings in patients with multiple myeloma and correlated them with their clinical renal and hematologic characteristics...

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..We conclude that the number of circulating PCs measured by flow cytometry in patients with newly diagnosed MM is an independent predictor of survival...

..Others have reported that N-terminal pro-brain natriuretic peptide (NT-proBNP) is a valuable prognostic marker. We sought to develop a staging system for patients with AL...

..5 g/dL) or higher (high risk, n = 18). The corresponding progression rates at 5 years were significantly different in the low, intermediate, and high groups: 13%, 26%, and 62%, respectively (P < .001)...

..This set of recommendations represents such an effort-the development of a set of consensus guidelines by a group of experts to manage patients with newly diagnosed disease based on an interpretation of the best available evidence...

..Among this cohort of patients with myeloma, failure to respond to single agent steroid did not have an adverse impact on eventual outcome...

..The serum immunoglobulin FLC ratio is an important additional determinant of clinical outcome in patients with SMM...

..9 vs 37.1 months; P < .001. In multivariate analysis, dFLC was independent of other prognostic factors. The type of light chain impacts the spectrum of organ involvement and the FLC burden correlates with survival in AL...

..Autologous stem cell transplant should be considered in all eligible patients with relapsed disease...

..We conclude that the degree of bone marrow angiogenesis is a prognostic marker in patients with multiple myeloma and does not decrease significantly after therapy...

..In summary, serum immunoglobulin profiles are unique in POEMS syndrome as compared with other plasma cell disorders...

..The remaining 20% are characterised by absence of IgH expression; we aimed to assess prevalence of a corresponding precursor entity, light-chain MGUS...

..Patients with relapsed or refractory disease may be treated with dexamethasone, thalidomide and dexamethasone, bortezomib (Velcade, PS-341), or lenalidomide (Revlimid, not yet approved by the Food and Drug Administration)...

..2 years vs 2.3 years, respectively; P = .01)...

..This study validates the high-risk features defined by FISH and CG in the Mayo risk-stratification model for patients with MM predominantly treated with novel therapies based on immunomodulatory agents...

..Similar translocations are found in both MGUS and MM, including t(4;14)(p16.3;q32) and t(14;16)(q32;q23). Moreover, Delta 13 is common in MGUS and unlikely to play a predominant role in the evolution of MGUS to MM...

..More importantly it provides further compelling evidence that MM is composed of subgroups of patients categorized according to their underlying genomic aberrations...

..CONCLUSION) The new ISS is simple, based on easy to use variables (Sbeta2M and serum albumin), and recommended for early adoption and widespread use...

..The role of supportive care strategies for patients with bone disease, such as the use of bisphosphonates, is also discussed...

..Treatment is generally directed at the underlying condition. Not all patients require treatment, and many can be followed and treated symptomatically...

..5% vs. 4.2%, P = 0.129) were higher with Rd. Results of this case-matched analysis suggest that there is significant additive value when clarithromycin is added to Rd. Randomized phase III trials are needed to confirm these results...

..The pathophysiologic basis for this should be determined because elevated bone turnover, for example, might be treatable...

..We conclude that the presence of amyloid cardiomyopathy and an increased creatinine concentration had the greatest impact on survival...

..However, the panel felt that current data are inadequate to support the use of any prognostic marker to select the timing and type of therapy, and called for studies on the application of prognostic markers in WM...

..The priority area of needed future research is maintenance therapy posttransplantation with nothing versus interferon alpha versus other agents such as corticosteroids or thalidomide or its derivatives...

..In conclusion, FS associated with monoclonal gammopathy does not appear to confer an additional risk of subsequent evolution to MM. ESRD occurs late in the disease process...

..CONCLUSION: There is a dramatic increase in fractures around the time of diagnosis of myeloma, most of which are pathologic fractures. The most important predictor of overall fracture risk is oral corticosteroid use...

..However, neither system was strongly predictive of outcomes, indicating the need for newer schemes incorporating other prognostic markers...

..Future studies are needed to uncover genetic and environmental underpinnings of our finding, and to define the relationship between hypergamma-globulinemia, monoclonal gammopathy of undetermined significance (MGUS), and multiple myeloma...

..The presence of an abnormal kappa/lambda FLC ratio in the serum was associated with a higher risk of MGUS progression (relative risk 2.5; 95% confidence interval: 1.6-4.0; P < 0.001)...

..pylori infection (33%) by serology, breath or stool testing between patients with MGUS and those with negative monoclonal protein studies. There was no evidence of resolution of MGUS with H. pylori therapy...

..The authors will review the neurologic complications of MM, monoclonal gammopathy of undetermined significance (MGUS), Waldenström macroglobulinemia (WM), POEMS syndrome, amyloidosis, and cryoglobulinemia...

..0; 95% CI, 1.4 to 2.8) and MGUS probands (RR, 3.3; 95% CI, 2.1 to 4.8). The increased risk of MGUS in first-degree relatives of MGUS or MM patients implies shared environment and/or genetics...

..Using this system, 49%, 38%, and 13% of patients were in stage I, stage II, and stage III, respectively. Determining levels of circulating biomarkers may be the most powerful tool for staging patients with AL undergoing PBSCT...

..Although not conclusive, this result lends further support to the hypothesis that angiogenesis is a relevant therapeutic target in myeloma...

..It is also prognostic for poor survival and PFS following SCT for myeloma. We recommend that all three methods of estimating BMPC% be routinely performed and that the highest value be used for prognostic purposes...

..We found that the relationship between renal recovery and free light chain reduction was present only in patients with biopsy proven cast nephropathy showing the importance of extracorporeal light chain removal in this disease...

..A system including both these risk factors allows better prediction of outcome...

..007. BM MVD at the time of initial diagnosis is an important prognostic factor for OS and PFS in patients undergoing autologous transplantation as frontline therapy for myeloma...

..65). The lack of response to initial induction therapy does not appear to preclude a good response to SCT. We recommend that patients with primary refractory MM be offered early SCT...

..2%) of those had translocation (11;14)(q13;q32) for an overall prevalence of the abnormality of 55%. IgH translocations are common in AL, especially the t(11;14)(q13;q32)...

..This article addresses the extent to which eligibility to undergo HSCT is a favorable prognostic feature and explores prognostic factors within the subset of eligible patients...

..Therapeutic efforts to maintain an intact immune system may be crucial in maximizing chemotherapeutic and/or immunotherapy efforts in this disease...

..Conversely, the 75% of patients remaining have more favorable outcomes using existing - albeit non-curative - therapeutic options...

..0001). These findings suggest that a high PCLI in patients with apparently stable, plateau phase MM is an adverse parameter that may predict a short time to disease progression and death...

..Angiogenesis is correlated with the plasma cell labeling index but not the bone marrow plasma cell percentage. A simple visual grading of angiogenesis is an efficient alternative to microvessel density estimation...