Citations

Despite successful treatment of the clonal plasma cell implicated in its pathogenesis, patients with AL amyloidosis (AL) experience significant morbidity related to underlying amyloid mediated organ dysfunction. While normalization of the serum free light chain measurements [normal ratio of involved and uninvolved free light chains (nFLCr)] is the goal of therapy and centerpiece of hematologic response criteria, achieving (or not achieving) meaningful organ response (OR) is clinically significant for its implications on long‐term symptomatology as well as overall survival (OS), and remains the ultimate goal of treatment. Expectations for organ recovery following successful therapy leading to nFLCr in AL remain poorly described. We evaluated the timeframe and predictive factors for OR, and long‐term outcome, in 313 AL patients who achieved nFLCr following therapy initiation. OR was seen in 80% of surviving AL patients within 1‐year of nFLCr. Patients achieving early OR within 1 year of nFLCr had superior OS compared with those who despite obtaining nFLCr did not achieve early OR. We further evaluated factors predicting OR and OS among patients achieving nFLCr. Higher values of dFLC (involved–uninvolved) at diagnosis predict OR, and early OR predicts improved OS following successful hematologic therapy in AL. Am. J. Hematol. 90:181–186, 2015. © 2014 Wiley Periodicals, Inc.

Cationic quantum dots effectively penetrate biofilms, providing insight for targeting and imaging applications.

Abstract Objective To determine the prognosis of patients with non‐secretory myeloma. Methods We studied 124 patients diagnosed with multiple myeloma who had no monoclonal protein detected on serum and urine immunofixation at diagnosis and on all subsequent follow‐up testing (non‐secretory myeloma). The overall survival ( OS ) of patients with non‐secretory myeloma was compared with 6953 patients with typical myeloma seen during the same time period in whom a monoclonal protein was detected at the time of diagnosis. Results One hundred and twenty‐four patients met criteria for non‐secretory multiple myeloma. The median follow‐up was 102 months (range, 1–204 months). The median progression‐free survival with initial therapy was 28.6 months, and the median OS was 49.3 months. There was a significant improvement in OS since 2001; median survival 43.8 months (prior to 2001) vs. 99.2 months (2001–2012), P < 0.001. OS was superior in patients with a normal baseline FLC ratio ( n = 10) compared to patients with an abnormal ratio ( n = 19), medians not reached in both groups. Prior to 2001, OS was similar in non‐secretory myeloma ( n = 86) and secretory myeloma ( n = 4011), median 3.6 vs. 3.5 yr, respectively, P = 0.63. However, among patients diagnosed between 2001 and 2012, OS was superior in non‐secretory myeloma ( n = 36) compared to secretory myeloma ( n = 2942), median 8.3 vs. 5.4 yr, respectively, P = 0.03. Conclusions Non‐secretory myeloma is an uncommon subtype of multiple myeloma. In the last decade, there has been an improvement in the survival of non‐secretory myeloma and appears superior to secretory myeloma.

Background and Purpose— NINDS (National Institute of Neurological Disorders and Stroke)-SiGN (Stroke Genetics Network) is an international consortium of ischemic stroke studies that aims to generate high-quality phenotype data to identify the genetic basis of pathogenic stroke subtypes. This analysis characterizes the etiopathogenetic basis of ischemic stroke and reliability of stroke classification in the consortium. Methods— Fifty-two trained and certified adjudicators determined both phenotypic (abnormal test findings categorized in major pathogenic groups without weighting toward the most likely cause) and causative ischemic stroke subtypes in 16 954 subjects with imaging-confirmed ischemic stroke from 12 US studies and 11 studies from 8 European countries using the web-based Causative Classification of Stroke System. Classification reliability was assessed with blinded readjudication of 1509 randomly selected cases. Results— The distribution of pathogenic categories varied by study, age, sex, and race ( P <0.001 for each). Overall, only 40% to 54% of cases with a given major ischemic stroke pathogenesis (phenotypic subtype) were classified into the same final causative category with high confidence. There was good agreement for both causative (κ 0.72; 95% confidence interval, 0.69–0.75) and phenotypic classifications (κ 0.73; 95% confidence interval, 0.70–0.75). Conclusions— This study demonstrates that pathogenic subtypes can be determined with good reliability in studies that include investigators with different expertise and background, institutions with different stroke evaluation protocols and geographic location, and patient populations with different epidemiological characteristics. The discordance between phenotypic and causative stroke subtypes highlights the fact that the presence of an abnormality in a patient with stroke does not necessarily mean that it is the cause of stroke.

AbstractBackgroundData regarding multiple myeloma (MM) that develops after kidney transplantation (KTx) are scarce. The outcomes of these patients were evaluated in a retrospective study.MethodsPatients with newly diagnosed MM after KTx were selected. Patients with a diagnosis of MM or those who received treatment for monoclonal gammopathy of renal significance (MGRS) prior to KTx were excluded.ResultsBetween 2001 and 2012, seven patients developed MM after KTx. Reasons for ESRD included ADPKD (1), C1q nephropathy (1), MPGN (2), hypertensive nephrosclerosis (2), and chronic interstitial nephritis (1). Before KTx, only four patients had monoclonal protein studies, four had monoclonal gammopathy of undermined significance (MGUS), and two of them had clonal plasma cells in bone marrow. Median follow‐up after MM was 70 months (range 19–100). Median survival was 80 months. Median time from KTx to MM was 72 months (range 3–204 months). The Kidney allograft failed in four patients due to monoclonal protein‐related renal disease. Five patients received chemotherapy: bortezomib (n = 3), lenalidomide (n = 2), melphalan (n = 1), thalidomide (n = 1), pomalidomide (n = 1), and high‐dose dexamethasone (n = 1). Three patients received ASCT.ConclusionMultiple myeloma after KTx is rare. Most patients who develop MM had MGUS prior to KTx. There is significant renal involvement in these patients. Survival is not worse when compared to MM without KTx. Further work is needed to identify the best treatment options for these patients.

ObjectiveCD5+ B cells have been conceptualized as a possible surrogate for Breg cells. The aim of the present study was to determine the utility of CD5+ B cells as biomarkers in antineutrophil cytoplasmic antibody–associated vasculitis (AAV).MethodsThe absolute and relative numbers (percentages) of CD5+ B cells (explanatory variables) were measured longitudinally during 18 months in 197 patients randomized to receive either rituximab (RTX) or cyclophosphamide (CYC) followed by azathioprine (AZA) for the treatment of AAV (Rituximab in ANCA‐Associated Vasculitis [RAVE] trial). Outcome variables included disease activity (status of active disease versus complete remission), responsiveness to induction therapy, disease relapse, disease severity, and, in RTX‐treated patients, relapse‐free survival according to the percentage of CD5+ B cells detected upon B cell repopulation.ResultsCD5+ B cell numbers were comparable between the treatment groups at baseline. After an initial decline, absolute CD5+ B cell numbers progressively increased in patients in the RTX treatment arm, but remained low in CYC/AZA‐treated patients. In both groups, the percentage of CD5+ B cells increased during remission induction and slowly declined thereafter. During relapse, the percentage of CD5+ B cells correlated inversely with disease activity in RTX‐treated patients, but not in patients who received CYC/AZA. No significant association was observed between the numbers of CD5+ B cells and induction treatment failure or disease severity. The dynamics of the CD5+ B cell compartment did not anticipate disease relapse. Following B cell repopulation, the percentage of CD5+ B cells was not predictive of time to flare in RTX‐treated patients.ConclusionThe percentage of peripheral CD5+ B cells might reflect disease activity in RTX‐treated patients. However, sole staining for CD5 as a putative surrogate marker for Breg cells did not identify a subpopulation of B cells with clear potential for meaningful clinical use. Adequate phenotyping of Breg cells is required to further explore the value of these cells as biomarkers in AAV.

Disease overview: Multiple myeloma accounts for approximately 10% of hematologic malignancies. Diagnosis: The diagnosis requires 10% or more clonal plasma cells on bone marrow examination or a biopsy proven plasmacytoma plus evidence of associated end‐organ damage. If end‐organ damage is not present, the presence of 60% or more clonal plasma cells in the marrow is also considered as myeloma. Risk stratification: In the absence of concurrent trisomies, patients with 17p deletion, t(14;16), and t(14;20) are considered to have high‐risk myeloma. Patients with t(4;14) translocation are considered intermediate‐risk. All others are considered as standard‐risk. Risk‐adapted intial therapy: Standard‐risk patients can be treated with lenalidomide plus low‐dose dexamethasone (Rd), or a bortezomib‐containing triplet such as bortezomib, cyclophosphamide, dexamethasone (VCD). Intermediate‐risk and high‐risk patients require a bortezomib‐based triplet regimen. In eligible patients, initial therapy is given for approximately 4 months followed by autologous stem cell transplantation (ASCT). Standard risk patients can opt for delayed ASCT if stem cells can be cryopreserved. In patients who are not candidates for transplant, initial therapy is given for approximately 12 to 18 months. Maintenance therapy: After initial therapy, lenalidomide maintenance is considered for standard risk patients who are not in very good partial response or better, while maintenance with a bortezomib‐based regimen should be considered in patients with intermediate or high risk myeloma. Management of refractory disease: Patients with indolent relapse can be treated first with 2‐drug or 3‐drug combinations. Patients with more aggressive relapse often require therapy with a combination of multiple active agents. Am. J. Hematol. 89:998–1009, 2014. © 2014 Wiley Periodicals, Inc.

AbstractBackgroundPlasma amyloid‐β (Aβ) peptide levels have been examined as a low‐cost accessible marker for risk of incident Alzheimer's disease (AD) and dementia, but results have varied between studies. We reassessed these associations in one of the largest, prospective, community‐based studies to date.MethodsA total of 2189 dementia‐free, Framingham Study participants aged >60 years (mean age, 72 ± 8 years; 56% women) had plasma Aβ1‐42 and Aβ1‐40 measured and were followed prospectively (mean, 7.6 ± 3.0 years) for dementia/AD.ResultsIncreased plasma Aβ1‐42 levels were associated with lower risk of dementia (Aβ1‐42: hazard ratio [HR] = 0.80 [0.71‒0.90], P < .001; Aβ1‐42‐to‐Aβ1‐40 ratio: HR = 0.86 [0.76‒0.98], P = .027) and AD (Aβ1‐42: HR = 0.79 [0.69‒0.90], P < .001; Aβ1‐42‐to‐Aβ1‐40 ratio: HR = 0.83 [0.72‒0.96], P = .012).ConclusionOur results suggest that lower plasma Aβ levels are associated with risk of incident AD and dementia. They encourage further evaluation of plasma Aβ levels as a biomarker for risk of developing clinical AD and dementia.