Morie A Gertz

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..We investigated whether treatment with multiple alkylating agents improved the response rate or survival time, compared with melphalan and prednisone therapy...

..Virtually all patients are candidates for a trial of therapy, and it is possible to find a nontoxic regimen that can be administered to virtually any patient...

..Presented herein are early data on the phase I portion of a phase I/II study of oblimersen in WM to identify the maximum tolerated dose and to evaluate response in patients with symptomatic WM...

..Rituximab therapy has been found to be effective in mixed cryoglobulinemia, with decreases in cryoglobulin values and improvement in complement values...

..We report criteria that centers can now use to define organ involvement and uniform response criteria for reporting outcomes in patients with light-chain AL...

..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...

..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...

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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...

..Therefore, graphical analysis of B cell lineage trees and mathematical quantification of tree properties provide novel insights into the process of B cell clonal evolution in AL...

..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...

..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...

..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...

..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...

..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...

..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...

..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...

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

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

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

..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...

..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...

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

..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...

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

..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...

..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...

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..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...

..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...

..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...

..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...

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..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...

..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...

..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...

..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)...

..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...

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

..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...

..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...

..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...

..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 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...

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

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..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...

..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 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...

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

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

..Three patients had IgH translocation t(11;14)(q13;q32). No abnormalities were seen at 17p13(p53). The monosomy 13 is in line with other plasma cell disorders while the low prevalence of hyperdiploidy and abnormalities at 14q32 is unique...

..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...

..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)...

..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...

..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...

..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...

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

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

..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...

..Factors predicting an initial increase in IgM levels could not be identified...

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

..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...

..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...

..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...

..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...

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

..11) Corticosteroids may be useful in the treatment of symptomatic mixed cryoglobulinemia. (12) Splenectomy is rarely indicated but has been used to manage painful splenomegaly and hypersplenism...

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

..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...

..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...

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

..The goal of this retrospective study was to compare the efficacy and toxicity of lenalidomide-dexamethasone (len/dex) vs. melphalan-prednisone-lenalidomide (MPR) as upfront therapy for newly diagnosed elderly patients with myeloma...

..Liver biopsy was safe. Some patients benefit from systemic chemotherapy...

..Treatment needs to be individualized based on patient age, the clinical manifestations of Waldenström's, and the patient's potential for developing toxic side effects of the selected treatment regimen...

..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...

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

..Additionally, mutational clusterspots were identified at specific positions in the nucleotide and deduced protein sequence that could potentially contribute to destabilizing interactions resulting in a propensity to form amyloid...

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

..It is possible that GCSF may have directly (activating endothelial cells) or indirectly (activation of underlying autoimmune disorder) contributed to TMA in this patient...

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

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

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

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

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

..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...

..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...

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

..This review describes development of the International Staging System and details prognostic factors that may further our understanding of the biology of multiple myeloma...

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

..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...