Dispenzieri, Angela

Abstract Monoclonal gammopathy is a common condition, particularly in the elderly. It can indicate symptomatic multiple myeloma or another overt malignant lymphoid disorder requiring immediate chemotherapy. More frequently, it results from a small and/or quiescent secreting B-cell clone, is completely asymptomatic, and requires regular monitoring only, defining a monoclonal gammopathy of unknown significance (MGUS). Sometimes, although quiescent and not requiring any treatment per se, the clone is associated with potentially severe organ damage due to the toxicity of the monoclonal immunoglobulin or to other mechanisms. The latter situation is increasingly observed but still poorly recognized and frequently undertreated, although it often requires rapid specific intervention to preserve involved organ function. To improve early recognition and management of these small B-cell clone–related disorders, we propose to introduce the concept of monoclonal gammopathy of clinical significance (MGCS). This report identifies the spectrum of MGCSs that are classified according to mechanisms of tissue injury. It highlights the diversity of these disorders for which diagnosis and treatment are often challenging in clinical practice and require a multidisciplinary approach. Principles of management, including main diagnostic and therapeutic procedures, are also described. Importantly, efficient control of the underlying B-cell clone usually results in organ improvement. Currently, it relies mainly on chemotherapy and other anti–B-cell/plasma cell agents, which should aim at rapidly producing the best hematological response.

Key Points Organ progression at second-line therapy predicated inferior survival. Patients relapsing from >VGPR had a longer time to develop organ progression.

PurposeTo evaluate if cardiac magnetic resonance elastography (MRE) can measure increased stiffness in patients with cardiac amyloidosis. Myocardial tissue stiffness plays an important role in cardiac function. A noninvasive quantitative imaging technique capable of measuring myocardial stiffness could aid in disease diagnosis, therapy monitoring, and disease prognostic strategies. We recently developed a high‐frequency cardiac MRE technique capable of making noninvasive stiffness measurements.Materials and MethodsIn all, 16 volunteers and 22 patients with cardiac amyloidosis were enrolled in this study after Institutional Review Board approval and obtaining formal written consent. All subjects were imaged head‐first in the supine position in a 1.5T closed‐bore MR imager. 3D MRE was performed using 5 mm isotropic resolution oblique short‐axis slices and a vibration frequency of 140 Hz to obtain global quantitativein vivoleft ventricular stiffness measurements. The median stiffness was compared between the two cohorts. An octahedral shear strain signal‐to‐noise ratio (OSS‐SNR) threshold of 1.17 was used to exclude exams with insufficient motion amplitude.ResultsFive volunteers and six patients had to be excluded from the study because they fell below the 1.17 OSS‐SNR threshold. The myocardial stiffness of cardiac amyloid patients (median: 11.4 kPa, min: 9.2, max: 15.7) was significantly higher (P = 0.0008) than normal controls (median: 8.2 kPa, min: 7.2, max: 11.8).ConclusionThis study demonstrates the feasibility of 3D high‐frequency cardiac MRE as a contrast‐agent‐free diagnostic imaging technique for cardiac amyloidosis.Level of Evidence:2Technical Efficacy:Stage 2J. Magn. Reson. Imaging 2017;46:1361–1367.

A preclinical study demonstrated anti‐proliferative and apoptotic effect of propranolol on multiple myeloma (MM) cell. Clinical studies suggested that beta‐blocker (BB) might impact the prognosis of breast, prostate, colorectal, ovarian, lung, and skin cancer. This retrospective study evaluated the effect of BB in MM disease‐specific survival (DSS) and overall survival (OS). Among 1,971 newly diagnosed MM patients seen at Mayo Clinic between 1995 and 2010, usage of BB and other cardiac (or antihypertensive) medications were abstracted. Cumulative incidence function and Kaplan–Meier method were used to estimate 5‐year cumulative incidence rate (CIR) of MM death and OS rate, respectively. Nine hundred and thirty (47.2%) patients had no intake of cardiac medications; 260 (13.2%) used BB alone; 343 (17.4%) used both BB/non‐BB cardiac medications; and 438 (22.2%) had non‐BB cardiac drugs. Superior MM DSS was observed in BB only users, compared to patients without any cardiac drugs ( , 0.53, 95% confidence interval [CI], 0.42–0.67, Padj.<0.0001) and non‐BB cardiac drugs users ( , 0.49, 95% CI, 0.38–0.63, Padj.<0.0001). Patients on both BB and other cardiac drugs showed superior DSS than non‐cardiac drugs users ( , 0.54, 95% CI, 0.44–0.67, Padj.<0.0001) and non‐BB cardiac drug users. ( , 0.50, 95% CI, 0.40–0.62, Padj.<0.0001). MM DSS did not differ between BB users with and without other cardiac drugs (Padj.=0.90). Multivariable analysis showed the same pattern for OS. In patients with MM, BB intake is associated with a reduced risk of disease‐specific death and overall mortality in comparison to non‐BB or no use of cardiac drugs. Am. J. Hematol. 92:50–55, 2017. © 2016 Wiley Periodicals, Inc.