A Dispenzieri

..We have demonstrated that CD represents a spectrum of disease that can be differentiated by simple prognostic factors that provide a framework for further study. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc...

..More universal recognition of and more scientific inquiry into the underpinnings of the disease will provide direction toward the best treatment strategies in the future...

..To determine whether the free light chain (FLC) assay provides prognostic information relevant to the general population...

..We conclude that pomalidomide appears to be a valuable drug covering an unmet clinical need in patients with previously treated AL. The trial is registered at www.clinicaltrials.gov as NCT00558896...

..Prompt recognition and institution of both supportive care measures and therapy directed against the plasma cell result in the best outcomes...

..In this review, the authors review the pathogenesis, diagnosis and differential diagnosis of AL amyloidosis along with the prognosis and state-of-the-art management for patients with this affliction...

..The author provides perspective about the risks for the most active and commonly used single-agent and combination myeloma therapies...

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..The role of anti-VEGF therapies, immune modulatory drugs, and proteasome inhibitors has not yet been defined, but drugs with known high rates of treatment related neuropathy should not be considered as first line therapy...

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

..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...

..Until the pathogenesis is fully understood, these are the mainstays of treatment for patients with POEMS syndrome...

..Of the 14 evaluable patients, all have had neurologic improvement or stabilization. Other features have improved substantially. PBSCT for POEMS syndrome is effective therapy but may also be associated with significant morbidity...

..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...

..In AL patients, we saw limited activity of single-agent lenalidomide, but significant activity of the combination with dexamethasone, which warrants further investigation...

..Achievement of FLC response was a better predictor of survival than achievement of complete hematologic response or normalization of the FLC ratio. FLC measurements both before and after PBSCT are important predictors of patient outcome...

..Unraveling the mechanisms of the syndrome both in the context of ASCT and in general are challenges for the future...

..Patients ended treatment due to progressive disease (18 patients), death (3) and other (2). The data suggest that imatinib is not an active agent in patients with relapsed or refractory multiple myeloma...

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

..Until the pathogenesis is fully understood, these are the mainstays of treatment for patients with POEMS syndrome...

..These distinctions affect important management decisions. Other related disorders include primary systemic amyloidosis, POEMS syndrome, and acquired Fanconi syndrome...

..Whenever possible, patients should be treated on clinical trials...

..Overall response rate was 94% including seven very good partial responses and five complete responses. Addition of 153Sm EDTMP to melphalan conditioning appears to be safe, well-tolerated and worthy of further study...

..Although baseline values of FLC are prognostic in newly diagnosed myeloma patients, serial measurements do not appear to have added value in patients who have M-proteins measurable by electrophoresis...

..Patients with CD are at increased risk for developing frank malignant lymphoma...

..Prompt recognition and institution of both supportive care measures and therapy directed against the plasma cell result in the best outcomes...

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..Additional features of the syndrome often develop, but the complications of classic multiple myeloma rarely develop...

..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...

..Addition of high-dose (153)Sm-EDTMP to melphalan conditioning appears to be safe, well tolerated, and worthy of further study in the context of novel agents and in the Phase III setting...

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

..Median time on the study was 72 days, range was 25 to 333 days. All 12 have withdrawn from the study (side-effects, 6; progression, 4; and death, 2 patients). AL patients do not tolerate high dose thalidomide...

..024 microg/L, less than 0.01 microg/L, and 0.084 microg/L, and for cTnI were 0.1 microg/L, 0.05 microg/L, and 0.24 microg/L, respectively. After multivariate analysis, cTnT proved a better predictor of survival than cTnI...

..This paper provides consensus guidelines for the use of this important assay, in the diagnosis and management of clonal PCD...

..In high-risk patients, upfront bortezomib results in response rates that are comparable to those reported for unselected cohorts, but single agent bortezomib is not sufficient as primary therapy...

..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...

..The combination of pomalidomide and dexamethasone (Pom/dex) is highly active and well tolerated in patients with lenalidomide-refractory myeloma...

..Amyloidosis may present with autonomic neuropathy (AN) that renders peritransplant care problematic. The purpose of this study was to determine the outcome of patients with AN during and after ASCT...

..6 months for Dex and were not reached for Thal-Dex and Len-Dex groups, P=0.2. For patients undergoing early ASCT for myeloma, the nature of initial treatment utilized has no long-term impact on the outcome of ASCT...

..We recommend collection of PBSC within 6 months of initiation of therapy with lenalidomide containing regimens to minimize the risk of mobilization failures...

..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...

..In conclusion, ALC is correlated with clinical outcome and requires further study. (Blood. 2001;98:579-585)..

..The median hospital stay was 3.5 days shorter in the group not receiving growth factor. It is feasible and reasonable to perform autologous SCT for multiple myeloma without administering growth factors...

..The addition of Thal to standard ZLD produces anti-tumor responses whereas ZLD alone does not. Thal/ZLD also prolongs TTP from AMM to MM. This study provides the rationale for further studies in patients with AMM to delay chemotherapy...

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

..The patient progressed from being wheelchair-bound to independent ambulation. An aggressive approach should be considered in patients with POEMS syndrome in whom standard therapeutic measures fail...

..The outcome may not be different from that of younger patients in terms of TRM and EFS...

..Patients who relapse within 12 months of an auto-SCT have a poor outcome and should be offered trials evaluating novel treatment approaches...

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..18. No significant differences were observed in the progression-free and overall survival at 1 year post transplant. Single agent dexamethasone appears to be an effective alternative to VAD for induction therapy prior to HDT in myeloma...

..Methods are needed to reduce treatment-related toxicity so that more patients can receive full-dose conditioning chemotherapy...

..Thalidomide has significant activity in early-stage myeloma and has the potential to delay progression to symptomatic disease. This approach must be further tested in randomized trials...

..0012 and P < 0.0001, respectively). CONCLUSION: We conclude that high-dose cyclophosphamide does not increase overall CR rates or improve TTP for patients with myeloma undergoing ASCT...

..Additional randomized trials are needed to determine if thalidomide will delay progression to active multiple myeloma...

..Our data suggested that CY damaged the microenvironment and slowed engraftment. By lengthening the period between the completion of apheresis and stem cell reinfusion, the microenvironment may recover and result in faster engraftment...

..008), but platelet transfusion requirements did not differ (P=0.95). We concluded that thalidomide does not substantially affect peripheral cell mobilization or engraftment...

..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...

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..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)...

..Improved supportive care and refined patient selection have improved the safety margin of patients undergoing auto-SCT; short-term mortality showed a more than 40% decrease after 2005...

..04). Topotecan can safely be dose escalated to 4.5 mg/m(2)/d in combination with CY, carboplatin and AHSCT. This trial is registered at ClinicalTrials.gov as NCT00652691...

..Transplantation should be offered to selected patients over age 65 years or selected patients with creatinine elevation...

..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...

..Nevertheless, consistent with reported experience of others, overall outcomes remain less than optimal and unpredictable...

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..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...

..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...

..Overall survival measured from trial entry was significantly shorter for patients with treatment-emergent EMD compared with those who did not have EMD, (median 16 months versus not reached, P=0.002)...

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

..Non-staphylococcal bacteremia was detected in 16% of patients. The median hospital stay was 9 days. It is feasible and reasonable to withhold growth factor therapy after autologous stem cell transplantation in patients with AL...

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

..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...

..However, the impact of ASCT on renal function is unclear. This study retrospectively reviewed the effect of ASCT on renal function in patients with LCDD...

..The prevalence of skin eruptions was not diminished by the concurrent use of systemic corticosteroids. Most skin eruptions were mild and did not necessitate withdrawal of lenalidomide therapy...

..The mean post-transplant hospital stay for those with GI tract bleeding was 37 days compared with 14.5 days for those who did not have GI tract bleeding (P = 0.0047)...

..Multivariate analysis demonstrated A-ALC as an independent prognostic indicator for OS and TTP. These results indicate that an infused dose of autograft lymphocytes significantly impacts clinical outcome post-APHSCT in MM...

..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...

..PS-341 is a potent, selective in vivo radiosensitizer that may substantially affect the efficacy of skeletal-targeted radiotherapy in multiple 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...

..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...

..4, and 6.5 months, respectively. CMCs at the time of ASCT is an independent prognostic factor and in combination with cytogenetics provides a powerful scoring system that stratifies patients and guides management...

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

..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...

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

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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...

..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...

..CONCLUSION: The remarkably long stabilization of amyloid deposition in this patient may be attributed to early diagnosis, early institution of therapy, and, possibly, favorable genetic factors...

..Our study shows the risk of MPGN recurrence and progression depends on identifiable pretransplant characteristics, has variable clinical impact, and can result in graft failure...

..TTP after tandem transplants (with its higher associated mortality) cannot be superior to TTP achieved with optimally timed serial transplants. Individualized HDT-ASCT for patients with MM is possible and may optimize results...

..Also of importance are prognosis, features that predict outcome, the suitability of transplant candidates, and post-transplantation maintenance therapy...

..To identify and assess the clinical features and treatment response of light chain (AL) amyloidosis diagnosed in patients with previous diagnosis of multiple myeloma (MM)...

..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...

..008). The prognostic value of circulating PBPCs may help select treatment for patients with AL...

..These data provide a robust example of the use of graphical quantification methods in delineating the role of neoplastic precursors in the pathogenesis of hematopoietic malignancies...

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

..Beta2-microglobulin > or =4 mg/l was associated with a threefold increase in the risk of death when added to the prognostic model. We describe a simple prognostic model for overall survival for newly diagnosed patients with WM...

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

..Both 1q21 gain and increase gene expression level were significantly associated with reduced survival. However, neither is an independent prognostic marker in MM on multivariate Cox proportional hazard analysis...

..MV-NIS, given by vein, should kill myeloma cells. Using simple scans, we should be able to track where MV-NIS goes in the body. ..

..The ultimate goal of the proposed studies is to improve the prognosis of patient with this fatal disease. ..

..MV-NIS, given by vein, should kill myeloma cells. Using simple scans, we should be able to track where MV-NIS goes in the body. ..

..MV-NIS, given by vein, should kill myeloma cells. Using simple scans, we should be able to track where MV-NIS goes in the body. ..