Martha Q Lacy

..3%), all CR. The median survival and progression-free survival were 42.8 and 11.4 months. Unacceptable grade 3 or 4 non-hematologic toxicity (31% with IL-12 subcutaneously and 63% with IL-12 intravenously) was observed...

..These guidelines were developed in the Interest of patient safety and will be reexamined as new data emerge regarding risks and benefits...

..Pomalidomide overcomes resistance in myeloma refractory to both lenalidomide and bortezomib. This trial is registered at http://ClinicalTrials.gov, number NCT00558896...

..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...

..Herein we describe a novel therapeutic approach. Because autologous hematopoietic stem cell transplantation is effective in other plasma cell proliferative disorders, it may be effective in this setting...

..Pomalidomide is currently not FDA-approved. Herein, we summarize what is currently known about the biologic and therapeutic effects of pomalidomide...

..This approach warrants further investigation to confirm this and define the role of vaccine therapy in myeloma...

..We report, to our knowledge, the first phase II trial of pomalidomide administered in combination with low-dose dexamethasone for the treatment of relapsed or refractory multiple myeloma...

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

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

..It also reviews our experience with pomalidomide, a new IMid with remarkable activity in relapsed, refractory MM...

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..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...

..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...

..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...

..CRd is an effective and well-tolerated regimen for upfront therapy of MM with high response rates and excellent 2-year OS, and is suitable for long-term therapy...

..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...

..01). In multivariate analysis of baseline factors, only reduced-dose melphalan predicted shorter OS. HDM is feasible in patients with cardiac amyloidosis, and achievement of HR and organ response is associated with improved survival...

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

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

..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...

..Achievement of renal response was associated with improved survival. These results suggest that early intervention with aggressive therapy is not only justified but recommended to achieve optimal response...

..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...

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

..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...

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

..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...

..5 vs 30.4 months) and a shorter progression-free survival (22.1 vs 13.1 months; P < .001). Absence of a response to induction therapy with thalidomide or lenalidomide predicts a poorer outcome after high-dose therapy...

..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...

..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...

..The toxicity of transplant as well as the outcome appears comparable to younger patients. Patients with MM should not be excluded from HDT solely on the basis of their chronological age...

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

..Additional studies are needed to further define the role of bevacizumab in the management of this group of patients...

..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...

..001). The only predictor of survival was cardiac stage (p  < 0.001). The hematologic response rate is predictive for organ response rates. Both hematologic and organ responses are associated with improved survival...

..Patients with pre-existing MGUS prior to myeloma diagnosis have a better outcome following HDT, reflecting more indolent disease and a favourable biology than those presenting with de novo myeloma...

..The overall 100-day survival rate was 98.9%. Our experience shows that outpatient transplant is feasible for all patients with multiple myeloma and results in shorter hospital stays and low treatment-related mortality rates...

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..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...

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..The trial was registered at www.clinicaltrials.gov (NCT00564889)...

..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)...

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

..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...

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..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...

..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...

..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...

..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...

..However, long-term outcome is dependent on the underlying plasma cell clone, and incorporation of clonal characteristics may allow for better risk stratification...

..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...

..Rev/Dex is a highly active regimen with manageable side effects in the treatment of newly diagnosed myeloma...

..All surviving patients displayed excellent performance status without ongoing chronic graft versus host disease. We conclude that ASCT is an effective salvage therapy for fludarabine-refractory CLL but late relapses can occur...

..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...

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

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

..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...

..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...

..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...

..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...

..The significant expansion of myeloma cells after HDT-ASCT is clearly evident. Clinical trials must be designed that take into account these kinetic aspects of the disease...

..It is not clear whether this paradigm holds true in the context of new therapies, such as immunomodulatory drugs (IMiDs)...

..5 years. This must be remembered when making treatment decisions for these patients and must be factored in when assessing the efficacy of new therapies...

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..Response rates with lenalidomide retreatment were higher than with repeat administration of thalidomide...

..0001). Multivariate analysis demonstrated K-ALC recovery post-ASCT to be an independent prognostic indicator for OS and PFS. These data support our hypothesis that the K-ALC post-ASCT is associated with clinical outcome in NHL...

..Thalidomide, an agent with antiangiogenic properties, is effective in relapsed myeloma. We report the results of a study combining thalidomide and dexamethasone as initial therapy for myeloma...

..Plasma VEGF is also useful in monitoring disease activity after treatment and correlates with clinical improvements better than hematologic response...

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

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

..We hypothesized that patients with CR before HDT-ASCT (BCR) will have their disease burden reduced further and experience a longer TTP and perhaps OS...

..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...

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

..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...

..The kidney is affected by immunoglobulin light chain amyloidosis (AL) in more than 50% of patients who present with the disease, but long-term predictors for and outcomes after renal replacement therapy are not well described...

..The actuarial risk of myelodysplasia development at ten years was 18%. As the survival of patients with plasma cell disorders improves, myelodysplasia may be a more common cause of morbidity and mortality for this group...

..This study was undertaken to determine the prognostic importance of renal response after high-dose melphalan and stem cell transplantation...

..This paper reviews a diagnostic pathway clinicians can use to diagnose the disorder, assess a patient's prognosis, and logically plan a therapeutic strategy...

..The presence of t(4;14) identifies a subset of patients whose time to progression is only 8.2 months. These patients receive minimal benefit from autologous stem cell transplantation and are candidates for novel therapeutic approaches...

..4'-Iodo-4'-deoxydoxorubicin (IDOX) has been reported to bind to and lead to the catabolism of amyloid deposits. A multicenter study attempted to develop a dosing schedule to confirm those results...

..This experience supports the feasibility of sequential living donor KTx and autologous SCT for carefully selected patients with ESRD due to 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...

..The classification of MM into hyperdiploidy and nonhyperdiploidy is dictated largely by the recurrent (primary) IgH translocations in the latter...

..To review the characteristics and outcomes of amyloidosis patients treated with high-dose chemotherapy and stem cell reconstitution...

..We hypothesize that premature Blimp-1 expression coupled to altered and deficient Pax5 expression causes some proliferating B cells to prematurely differentiate to plasma cells in MM...

..New therapies developed over the past 5 years include high-dose chemotherapy with stem cell reconstitution, combinations of alkylating agents with dexamethasone, and, most recently, thalidomide...

..No anti-myeloma activity was observed in vivo. As administered, flavopiridol has disappointing activity as a single agent in advanced myeloma...

..001), even after eliminating bias from early death. The degree of response was affected by the intensity of chemotherapy conditioning, septal thickness, and cardiac biomarkers. Hematologic response translates to longer survival...

..Systemic chemotherapy would not be expected to have any beneficial effect on other forms of amyloid and carries significant risk...

..We describe nearly 300 patients who had treatment combining high-dose chemotherapy and stem cell transplantation at Mayo Clinic and review the recent literature...

..We describe 2 patients in whom primary surgical salvage was performed successfully for ONJ. Our experience indicates that with appropriate technique, primary surgical treatment may offer benefit to selected patients with ONJ...

..This study showed that, in newly diagnosed MM, ALC is an independent prognostic factor for OS, suggesting a significant role of host immune status in the survival of MM...

..Updated diagnostic criteria for these disorders, risk-stratification models to determine prognosis, and the current management of these two entities are discussed in this review...

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

..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...

..01) and maximum blood urea level (P = 0.03). Ten patients (all with creatinine levels > or = 150 micromol/l) were treated with tissue plasminogen activator; only two had a significant response and only one survived beyond day 120...

..To assess the activity of von Willebrand factor-cleaving protease (vWF-CP) in patients with thrombotic thrombocytopenic purpura (TTP) complicating bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT)...

..8 vs 29.9 months; P < .001). In this study, we demonstrate improved outcome of patients with myeloma in recent years, both in the relapsed setting as well as at diagnosis...

..2-Methoxyestradiol (2ME2) is an endogenous product of estradiol metabolism with antiangiogenic and antineoplastic properties. We report on the first phase II trial of 2ME2 in multiple myeloma...

..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...

..The relationship of ALC-15 with clinical outcomes in primary systemic amyloidosis is unknown...