Citations

AbstractImmunoglobulin light chain (AL) Amyloidosis is a condition whereby misfolded proteins generated by plasma cells deposit in tissues causing organ dysfunction. Chemotherapy and autologous stem cell transplant when eligible are standard treatment options. Several studies report long‐term outcomes of patients post‐transplant. However, there is a paucity of literature describing outcomes of relapsed patients post‐transplant. We performed a retrospective study to assess outcomes and therapies employed upon relapse after transplant. Between 1996 and 2009, 410 patients received transplant at the Mayo Clinic as first‐line therapy. Of those patients, 42 (10%) died within 3 months of transplant, 64 (16%) died without documented relapse, 158 (38%) were alive without documented progression, and 146 (36%) had documented progression. Those 146 patients are the subject of our study, and their median time to hematologic relapse/progression was 23.6 months (95%CI 18.3, 26.3 months). Their median overall survival and 5‐yrs overall survival from post‐transplant relapse/progression was 51.7 months (95%CI 34.1–62.3) and 39%, respectively. The most common first regimen for treatment after relapse was lenalidomide or thalidomide. In conclusion, our study indicates that patients with AL amyloidosis fare well post‐transplant relapse/progression. Additionally, it provides a yardstick to design clinical trials to determine best treatment options.

Purpose To provide an update on recent advances in the management of patients with multiple myeloma who are not eligible for autologous stem-cell transplantation. Methods A comprehensive review of the literature on diagnostic criteria is provided, and treatment options and management of adverse events are summarized. Results Patients with symptomatic disease and organ damage (ie, hypercalcemia, renal failure, anemia, or bone lesions) require immediate treatment. The International Staging System and chromosomal abnormalities identify high- and standard-risk patients. Proteasome inhibitors, immunomodulatory drugs, corticosteroids, and alkylating agents are the most active agents. The presence of concomitant diseases, frailty, or disability should be assessed and, if present, treated with reduced-dose approaches. Bone disease, renal damage, hematologic toxicities, infections, thromboembolism, and peripheral neuropathy are the most frequent disabling events requiring prompt and active supportive care. Conclusion These recommendations will help clinicians ensure the most appropriate care for patients with myeloma in everyday clinical practice.

Objectives To define whether the high sensitivity cardiac troponin T (hs-cTnT) assay in patients with immunoglobulin light chain amyloidosis (AL) improves risk prediction. Background Cardiac involvement is the major cause of death in patients with AL amyloidosis. Risk stratification is facilitated by cardiac biomarkers such as cardiac troponin T (cTnT) and N-terminal pro B-type natriuretic peptide (NT-proBNP). Methods Stored serum from patients with newly diagnosed AL was used to measure hs-cTnT, cTnT, and NT-proBNP. Survival modelling was performed. Results The direct numeric result from hs-cTnT measurement cannot merely be substituted for a cTnT measurement in the Mayo AL staging system. The performance of the receiver operator curve derived an hs-cTnT cut-point of 54 ng/L which improves on the value of 35 ng/L validated with the prior iteration of the assay. An alternate staging option using hs-cTnT alone—using the two thresholds 14 ng/L and 54 ng/L—performs as well as either the original Mayo AL staging system or other systems incorporating hs-cTnT. On multivariate analysis, an hs-cTnT alone staging system was independent of period of diagnosis, type of therapy, and NT-proBNP value, the last of which dropped out of the model. Alternate models were explored, but none performed better than the original system or the new hs-cTnT system. Thus, hs-cTnT can be used alone for the staging of disease prognosis. Conclusions A survival model based on hs-cTnT improves the prognostic staging of patients with AL amyloidosis, relegating NT-proBNP to a measure of cardiac response.

Objective Multiple-valve (MUV) procedures currently exhibit higher operative mortality than do single-valve procedures, but a paucity of scientific information exists to explain the observation. This topic was examined using The Society of Thoracic Surgeons Database. Methods All patients in the The Society of Thoracic Surgeons data set undergoing valve surgery (except pulmonary valve and aortic root operations) from 1993 through 2007 were identified (N = 623,039). Baseline characteristics and postoperative outcomes were contrasted between all seven combinations of single-valve and MUV procedures involving aortic, mitral, and tricuspid valves. Seven independent logistic regression analyses were performed, based on the seven procedures, and multivariable risk factors for mortality were compared, with emphasis on single-valve versus MUV procedures. Results Baseline characteristics for MUV procedures (n = 67,926) shared many similarities to those for single-valve procedures (n = 555,113), including age, ejection fraction, and comorbidities. Preoperative renal failure, New York Heart Association class III to IV, nonelective presentation, and reoperation were slightly more common in MUV subsets, and coronary bypass was less frequent. Operative mortality was almost double for MUV as compared with single-valve procedures (10.7% vs 5.7%, P = 0.0001). Categorical predictors with the largest odds ratios for mortality were emergency status, renal failure, and second reoperation. However, predictors for mortality were generally consistent in order and magnitude between the single-valve and MUV subgroups. Conclusions Despite similarities in preoperative profiles of the patients undergoing single-valve and MUV procedures, mortality for MUV surgery remains considerably higher. Determinants of operative mortality and morbidity differ little across the procedural groups, and these findings serve as a benchmark for future studies, as well as suggest a continued search for explanations of poorer MUV outcomes.

AbstractResearch demonstrates that patients with fibromyalgia who have higher positive and lower negative affect have lower symptom burden. Affect has been shown to be associated with resilience. This study examined the relationship between affect, resilience and fibromyalgia symptom burden in a clinical sample of patients with fibromyalgia. We hypothesized that (a) positive and negative affect would be associated with fibromyalgia symptom burden; (b) resilience would be associated with positive and negative affect; (c) resilience would be associated with fibromyalgia symptom burden; and (d) the connection between resilience and fibromyalgia symptom burden would be mediated by both positive and negative affect. A sample of 858 patients with fibromyalgia completed questionnaires. Mediation modelling revealed statistically significant direct effects of resilience on fibromyalgia symptom burden (β = −0.10, P < 0.001) and statistically significant indirect effects of resilience on fibromyalgia symptom burden through affect (β = −0.36, P < 0.001), suggesting that both resilience and affect influence fibromyalgia symptom burden. Our results suggest that improving affect through resiliency training could be studied as a modality for improving fibromyalgia symptom burden. Copyright © 2013 John Wiley & Sons, Ltd.

There are no systematic data regarding nonmaintained induction for those patients with multiple myeloma (MM) who do not receive consolidative autologous stem cell transplantation. Of 173 patients with newly diagnosed MM treated with lenalidomide and dexamethasone (LenDex) as primary therapy, 31 patients had their lenalidomide discontinued for reasons other than progression or alternate therapy. Median progression free survival (PFS) from the time of discontinuing lenalidomide was longer in patients who received lenalidomide ≥1 year (39 vs. 13 months, P < 0.05); there was no difference in PFS for those treated for 1–2 years as compared to ≥2 years. Among those taking lenalidomide for ≥1 year PFS was superior in patients who were in very good partial response (VGPR) or better as compared to those with partial response (48.4 versus 14.8 months, P < 0.05). All patients who progressed and were rechallenged with LenDex responded. These analyses illustrate that discontinuation of lenalidomide after 1 year among those patients achieving a ≥VGPR can result in long‐term disease control. Am. J. Hematol. 89:302–305, 2014. © 2013 Wiley Periodicals, Inc.

Purpose To study the impact of achieving stringent complete response (sCR), an increasingly attainable goal, after autologous stem-cell transplantation (ASCT) in patients with multiple myeloma (MM). Patients and Methods Maximal response rates were determined in 445 consecutive patients who underwent ASCT within 12 months of diagnosis of MM. The patients achieving varying degrees of complete response (CR) are the focus of our study. Results One hundred and nine patients (25%) achieved sCR after ASCT. The median overall survival (OS) rate from the time of transplantation for patients attaining sCR was not reached (NR), in contrast to those patients achieving conventional complete response (CR; n = 37; OS, 81 months) or near CR (nCR; n = 91; OS, 60 months; P < .001). Five-year OS rates were 80%, 53%, and 47% for sCR, CR, and nCR, respectively. The median time to progression (TTP) from ASCT of patients achieving sCR was significantly longer (50 months) than TTP of patients achieving CR or nCR (20 months and 19 months, respectively). On multivariable analysis, post-ASCT response of sCR was an independent prognostic factor for survival (hazard ratio, 0.44; 95% CI, 0.25 to 0.80; versus CR; P = .008), in addition to proliferation rate, pre-ASCT cytogenetics, and performance status. OS rates of patients attaining sCR continued to remain superior at 2-year landmark (median, NR v 70 months for conventional CR group; P = .007). Conclusion Improved long-term outcome is seen after ASCT with achievement of sCR when compared with lesser degrees of responses. Myeloma trials reporting the response rates should identify patients achieving sCR and CR separately, owing to markedly disparate outcomes of the two categories.

Key PointsMGUS patients have significantly increased cortical bone porosity and reduced bone strength relative to matched controls.