Amyloid Light-chain Amyloidosis Research Articles

MR neurography biomarkers to characterize peripheral neuropathy in AL amyloidosis.

To detect, localize, and quantify peripheral nerve lesions in amyloid light chain (AL) amyloidosis by magnetic resonance neurography (MRN) in correlation with clinical and electrophysiologic findings. We prospectively examined 20 patients with AL-polyneuropathy (PNP) and 25 age- and sex-matched healthy volunteers. After detailed neurologic and electrophysiologic testing, the patient group was subdivided into mild and moderate PNP. MRN in a 3.0 tesla scanner with anatomical coverage from the lumbosacral plexus and proximal thigh down to the tibiotalar joint was performed by using T2-weighted and dual-echo 2-dimensional sequences with spectral fat saturation and a 3-dimensional, T2-weighted inversion recovery sequence. Besides evaluation of nerve T2-weighted signal, detailed quantification of nerve injury by morphometric (nerve caliber) and microstructural MRN markers (proton spin density, T2 relaxation time) was conducted. Nerve T2-weighted signal increase correlated with disease severity: moderate (420.2 ± 60.1) vs mild AL-PNP (307.2 ± 17.9; p = 0.0003) vs controls (207.0 ± 6.4; p < 0.0001). Proton spin density was also higher in moderate (tibial: 525.5 ± 53.0; peroneal: 553.6 ± 64.5; sural: 492.0 ± 56.6) and mild AL-PNP (tibial: 431.6 ± 22.0; peroneal: 457.6 ± 21.7; sural: 404.8 ± 25.2) vs controls (tibial: 310.5 ± 14.1; peroneal: 313.6 ± 11.6; sural: 261.7 ± 11.0; p < 0.0001 for all nerves). T2 relaxation time was elevated in moderate AL-PNP only (tibial: p = 0.0106; peroneal: p = 0.0070; sural: p = 0.0190). Tibial nerve caliber was higher in moderate (58.0 ± 8.8 mm3) vs mild AL-PNP (46.5 ± 2.5 mm3; p = 0.008) vs controls (39.1 ± 1.2 mm3; p < 0.0001). MRN detects and quantifies peripheral nerve injury in AL-PNP in vivo with high sensitivity and in close correlation with the clinical stage. Quantitative parameters are feasible new imaging biomarkers for the detection of early AL-PNP and might help to monitor microstructural nerve tissue changes under treatment.

Subcutaneous daratumumab (DARA SC) plus cyclophosphamide, bortezomib, and dexamethasone (CyBorD) in patients (Pts) with newly diagnosed amyloid light chain (AL) amyloidosis: Safety run-in results of andromeda.

8011Background: Systemic AL amyloidosis is characterized by disposition of insoluble amyloid fibrils into tissues and organs via clonal expansion of CD38+ plasma cells. The safety run-in of DARA SC...

AMYLOIDOSIS RESEARCH CONSORTIUM CARDIAC AMYLOIDOSIS SURVEY: RESULTS FROM PATIENTS WITH AL AND ATTR AMYLOIDOSIS AND THEIR CAREGIVERS

Background Cardiac amyloidosis (CA) is a severe, progressive, and fatal disease. Amyloid transthyretin (ATTR), due to the wild-type (wtATTR) or hereditary (hATTR) transthyretin, and amyloid light chain (AL) amyloidosis may result in CA. Nonspecific symptoms of CA can cause delays in diagnosis until the disease is advanced. We report the results of the largest international CA patient survey ever conducted analyzing delays and errors in the diagnostic pathway. Methods The Amyloidosis Research Consortium (ARC) developed an online survey, which was distributed to patient lists of ARC, the Amyloidosis Foundation, and Amyloidosis Support Groups in January 2017. The survey was designed for all forms of amyloidosis, but this report is limited to AL and ATTR amyloidosis, and included responses from the United States, United Kingdom, France, Netherlands, and Spain. The questions focused on diagnosis, barriers to healthcare, and patients’ disease state. Results At the time of this analysis, there were 581 total responders, 438 (233 patients, 205 caregivers) for AL amyloidosis and 143 (79 patients, 64 caregivers) for ATTR amyloidosis (89 hATTR, 54 wtATTR). There was alignment across responses from patients and caregivers. For all forms of amyloidosis, heart involvement was highly prevalent including in patients with wtATTR (94% [33/34]), hATTR (82% [37/45]), and AL amyloidosis (90% [210/233]) based on self-reported current heart involvement. With the exception of wtATTR that primarily has cardiac involvement, other organs were often affected including the kidney (52%) and GI (42%) in AL amyloidosis and nerves (76%) and GI (40%) in hATTR amyloidosis. Common initial symptoms were shortness of breath and fatigue. Delays and misdiagnosis was common. Many patients visited 3-5 different physicians before diagnosis, >40% of patients received a misdiagnosis, and many received treatment for the misdiagnosed condition. Conclusions This represents the largest patient survey of patients with CA. Multi-organ involvement, delays in diagnosis, and misdiagnosis are common. Disease awareness and understanding of common presenting symptoms is vital, especially among those to whom patients are initially referred.

Healthcare resource utilization and costs in amyloid light-chain amyloidosis: a real-world study using US claims data.

To estimate healthcare utilization and costs in amyloid light-chain (AL) amyloidosis. AL amyloidosis patients were identified in 2007-2015 claims databases if they had ≥1 inpatient/≥2 outpatient claims consistent with AL amyloidosis and received ≥1 AL-specific treatment. Descriptive statistics were reported. 50.1% (n=3670) were admitted ≥1 time during the year, 11.3% (n=827) ≥3times. From 2007 to2015, bortezomib use increased from 4.6to 25.3%; melphalan use decreased from 18.9to 2.0%; costs increased from 92,866 to $114,030. Among incident patients with at least 2years of follow-up, healthcare utilization and costs decreased from first to second year post-diagnosis. AL chemotherapy-based prescribing practices changed. Total annual healthcare costs increased over time among AL amyloidosis patients.

Subcapsular Hepatic Hematoma Resulting From Hepatic Microaneurysms in a Patient With Systemic Amyloidosis

A 64-year-old woman presented with acute onset of epigastric pain. Her history was significant for extensive amyloid light-chain amyloidosis and known hepatic amyloidosis substantiated by prior liver biopsy. Computed tomography of the abdomen demonstrated a large subcapsular perihepatic hematoma along the posterior margin of the left hepatic lobe measuring 19 × 6 × 13 cm (Figure A, arrow). Hepatic arteriography was performed and demonstrated hepatic microaneurysms involving the left hepatic artery (Figure B, arrows), a rare but recognized complication of systemic amyloidosis. In this case, multiple hepatic microaneurysms involving the left hepatic artery were identified on angiography. Management with left hepatic artery particle embolization resulted in enduring symptomatic resolution and hemodynamic stability. Spontaneous hemorrhage is a well-recognized manifestation of primary (amyloid light-chain) amyloidosis. Impaired platelet function, amyloid angiopathy, hyperfibrinolysis, and acquired coagulation factor deficiencies predispose to hemorrhagic events in patients with this condition. Vascular infiltration by amyloid fibrils serves as the likely basis for aneurysmal formation as supported by biopsy-proven hepatic amyloidosis. This case highlights spontaneous hemorrhage as a possible cause for acute abdominal pain and anemia in the setting of systemic amyloidosis.

Clinical and laboratory profile of renal amyloidosis: A single-center experience

The kidney is the most common organ involved in systemic amyloidosis. We aimed to study etiology and clinicopathological profile of renal amyloidosis. This was a retrospective study of 40 consecutive adult patients with biopsy-proven renal amyloidosis evaluated over a period of two years. Emphasis was given to describing the clinical presentation, renal function, proteinuria, type of amyloidosis, and its etiology. Mean age of the study cohort was 44 ± 15 years (with a male-to-female ratio of 3:1). Amyloid A (AA) amyloidosis was the most common type of amyloidosis observed in 72.5% of cases. Amyloid light chain (AL) amyloidosis accounted for 17.5% of cases, and the rest remained undetermined. AA amyloidosis had widespread age distribution while AL amyloidosis was confined to those >40 years. Proteinuria was the most common renal manifestation observed in all patients. Nephrotic syndrome was seen in 70% of patients. Mean 24 h proteinuria was 6.4 g. Renal failure was the second most common manifestation seen in 70% of patients, of whom 21.4% required hemodialysis. Tuberculosis (TB) accounted for 90% cases of AA amyloidosis. The most prevalent form was pulmonary TB while the rest accounted for by rheumatoid arthritis and bronchiectasis. Among patients with TB induced amyloidosis, 61.5% had received adequate treatment for TB in the past. All patients with AL amyloidosis had nephrotic range proteinuria, five had renal failure out of which two required dialysis. Cardiac involvement was seen in two patients. AA amyloidosis was the most common type of renal amyloidosis in the present study and pulmonary TB was the most common etiology.

Nationwide Survey of 741 Patients with Systemic Amyloid Light-chain Amyloidosis in Japan.

Objective To retrospectively investigate the clinical manifestations of systemic amyloid light-chain (AL) amyloidosis in Japanese patients and the treatment strategy for the condition. Methods We conducted a survey of Japanese AL amyloidosis patients, who were treated between January 1, 2012, and December 31, 2014. Results A total of 741 AL amyloidosis patients were included in this study (436 men and 305 women; median age: 65 years old, range: 31-93). The most frequently affected organ was the kidneys (n=542), followed by the heart (n=252), gastrointestinal (GI) tract (n=164), autonomic nervous system (n=131), liver (n=71), and peripheral nervous system (n=71). Diagnostic findings were most commonly detected in the GI tract (upper GI tract: 350 cases, lower GI tract: 167 cases), followed by the bone marrow and kidneys. An abdominal fat-pad biopsy was only conducted in 128 patients. Autologous stem cell transplants (ASCTs) and bortezomib were used to treat 126 and 276 patients, respectively. Conclusion The clinical features of Japanese patients with systemic AL amyloidosis are similar to those reported previously for cases in the US and Europe. Regarding treatment, a significant number of ASCTs were performed in Japan as well as in Western countries. Surprisingly, a marked number of patients received bortezomib as a treatment for AL amyloidosis.

The treatment of paraprotein-related kidney disease.

Myeloma kidney and amyloid light-chain (AL) amyloidosis remain the principal kidney complications of paraproteins. In this review, we update readers to many of the recent advances which have occurred in the care and outcomes for patients with these presentations. Myeloma kidney has historically caused a severe acute kidney injury with very poor outcomes. The combination of new diagnostic techniques, enabling a rapid diagnosis and novel chemotherapy agents has transformed these poor outcomes for the better. Two multicentre randomized controlled trials have recently evaluated if the removal of free light chains by high cut-off haemodialysis improves renal outcomes beyond effective chemotherapy alone. Although we await the full articles of these studies to be published, abstracts suggested the studies will have contradictory primary results. In the field of AL amyloidosis, there are now novel criteria for the risk stratification of kidney outcomes which can be used in combination with markers of early kidney response to provide clinicians with powerful tools to guide patient discussions. Across both AL amyloidosis and myeloma kidney patient outcomes continue to improve. Principally this improvement has been driven by the continuing development of novel chemotherapy agents in this field.

Abnormal Coronary Flow Velocity Reserve and Decreased Myocardial Contractile Reserve Are Main Factors in Relation to Physical Exercise Capacity in Cardiac Amyloidosis

The aim of the present study was to evaluate the clinical importance of echocardiographic coronary flow velocity reserve (CFVR), resting and exercise left ventricular global longitudinal strain (LVGLS), and myocardial work efficiency (MWE) in patients with cardiac amyloidosis (CA). The study population comprised 69 subjects: group A, 27 patients with CA confirmed by endomyocardial biopsy (CA positive); group B, 42 healthy control subjects. The amyloid phenotype in group A was as follows: patients with wild-type transthyretin-related amyloidosis (n=10), carriers of the Danish familial transthyretin amyloidosis mutation with cardiac involvement (n=5), and patients with amyloid light chain amyloidosis with cardiac involvement (n=12). All subjects underwent comprehensive echocardiographic evaluation during rest and during symptom-limited, semisupine exercise testing. Furthermore, CFVR was assessed using Doppler echocardiography. Patients with CA had significantly lower CFVR (1.7±0.6 vs 3.9±0.8, P<.0001), MWE (1.9±1.0 vs 3.0±0.7, P<.0001), and LVGLS magnitude (11% [10%-14%] vs 20% [18%-21%], P<.0001) than control subjects. Patients with CA showed severely reduced deformation and efficiency reserve compared with control subjects (ΔLVGLS 0.9±2.8% vs 5.6±2.3%, P<.0001; ΔMWE 2.5±2.8 vs 8.8±2.6, P<.0001). In patients with CA, a strong relation was seen between physical capacity by the metabolic equivalent of tasks test and CFVR (r=0.55, P<.01), peak exercise LVGLS (r=0.64, P<.0001), and peak exercise MWE (r=0.60, P<.01). Patients with CA had a profound lack of CFVR and longitudinal myocardial deformation reserve compared with healthy control subjects. Both parameters were significantly associated with exercise capacity and may prove useful for evaluating cardiac performance in patients with CA.

Intramyocardial inflammation predicts adverse outcome in patients with cardiac AL amyloidosis.

To evaluate the influence of endomyocardial biopsy (EMB)-proven intramyocardial inflammation on mortality in patients with cardiac transthyretin amyloid (ATTR) or amyloid light-chain (AL) amyloidosis. We included 54 consecutive patients (mean age 68.83 ± 9.59 years; 45 men) with EMB-proven cardiac amyloidosis. We followed up patients from first diagnostic biopsy to as long as 36 months (mean 11.5 ± 12 months) and compared their outcome with information on all-cause mortality with or without proof of inflammation on EMB. Intramyocardial inflammation was assessed by quantitative immunohistology. Patients suffering from amyloidosis revealed a significant poor prognosis with proof of intramyocardial inflammation in contrast to those without inflammation (log-rank P = 0.019). Re-grouping of patients indicated AL amyloidosis to have a significant impact on all-cause mortality (log-rank P = 0.012). The detailed subgroup analysis showed that patients suffering from AL amyloidosis with intramyocardial inflammation have a significantly worse prognosis compared with AL amyloidosis without inflammation and ATTR with or without inflammation, respectively (log-rank P = 0.014, contingency Fisher's exact test, P = 0.008). Our study reports for the first time a high incidence (48.1%) of intramyocardial inflammation in a series of patients with EMB-proven cardiac amyloidosis and could show that in patients with AL amyloidosis, intramyocardial inflammation correlated significantly with increased mortality. Our data have a direct clinical impact because one can hypothesize that additional immunomodulating/anti-inflammatory treatment regimens in patients with biopsy-proven inflammation of heart muscle tissue could be beneficial for patients suffering from cardiac AL amyloidosis.

Platelet Count before Peripheral Blood Stem Cell Mobilization Is Associated with the Need for Plerixafor But Not with the Collection Result

Background: A low platelet count before mobilization has recurrently been identified as risk factor for poor mobilization. Methods: To determine the relevance of this finding for peripheral blood stem cell (PBSC) mobilization, including pre-emptive or rescue plerixafor in the case of poor mobilization, we retrospectively analyzed all patients undergoing PBSC collection at our institution between January 2014 and December 2015 (n = 380). Results: In total, 99% of the patients (377/380) successfully collected a minimum of 2 × 10⁶ CD34+ cells/kg body weight sufficient for a single transplant. Rescue or pre-emptive plerixafor was administered to 11% of the patients (42/380). No correlations between the platelet count before mobilization and the number of peripheral blood CD34+ cells or the CD34+ cell collection result were detected in the entire population or the subgroups according to diagnosis (newly diagnosed multiple myeloma, relapsed multiple myeloma, lymphoma, amyloid light-chain amyloidosis, sarcoma, or germ cell tumor). However, patients requiring pre-emptive or rescue plerixafor had a significantly lower platelet count before mobilization (217/nl vs. 245/nl; p = 0.004). Conclusion: With the current state of the art PBSC mobilization strategies, the platelet count before mobilization was not associated with the CD34+ cell collection result but was associated with the need for pre-emptive or rescue application of plerixafor.

Colonic Amyloidoma: A Rarely Encountered Finding

Amyloidosis is a systemic disease characterized by the extracellular deposition of abnormal protein fibrils throughout the body that disrupts normal tissue architecture and function. It can present in many different forms, but the most common form that affects the gastrointestinal tract (GIT) is amyloid light-chain (AL) amyloidosis. Although amyloid deposition in the GIT is not uncommon, less than 50% will develop GI symptoms including GI dysmotility, malabsorptive diarrhea, spontaneous hemorrhage, and pseudo-obstruction. Early diagnosis of AL amyloidosis is essential because most cases are diagnosed late and associated with a poor prognosis. If left untreated it can carry median 1-year mortality rate of approximately 50%. Identifying the classic findings of AL amyloidosis during endoscopy should prompt further evaluation for disease. Our patient is a 54-year-old man with a past medical history significant for AL amyloidosis diagnosed on renal biopsy, who presented with worsening hematochezia. He also reported recurrent abdominal pain, a 60-pound weight loss, chronic diarrhea, and recurrent syncope for the last 4 months. Hemoglobin was 8.4 g/dL on admission. Colonoscopy revealed multiple large and small hemorrhagic polypoid lesions. The largest lesion filled approximately 75% of the colon. Multiple blood clots were also identified, but no active bleeding was seen during endoscopy. Endoscopic biopsies were not pursued given significant bleeding risk and prior diagnosis of AL amyloidosis. AL amyloid deposition within the vascular walls of the GIT increases vessel fragility and can result in hemorrhage beneath the lamina propria, forming submucosal hematomas. During endoscopy, submucosal hematomas appear purple and have a polypoid appearance with a shelf-like base. Other common findings during endoscopy include: mucosal ulcerations, intestinal erosions, yellowish plaque-like infiltrative lesions, and thickened mucosal folds. Rarely, as evident in our case, patients may have tumor-forming deposits of amyloid called amyloidomas, which can be wrongly diagnosed as a primary or metastatic GI malignancy. Given the poor prognosis associated with AL amyloidosis, recognizing common endoscopic findings should prompt the endoscopist to maintain a high index of suspicion and diagnose amyloidosis to improve overall prognosis.Figure: Endoscopy Findings.

Czech Registry of Monoclonal Gammopathies - Technical Solution, Data Collection and Visualisation.

The Registry of Monoclonal Gammopathies (RMG) was established by the Czech Myeloma Group in 2007. RMG is a registry designed for the collection of clinical data concerning diagnosis, treatment, treatment results and survival of patients with monoclonal gammopathies. Data on patients with monoclonal gammopathy of undetermined significance (MGUS), Waldenström macroglobulinaemia (WM), multiple myeloma (MM) or primary AL ("amyloid light-chain") amyloidosis are collected in the registry. Nineteen Czech centres and four Slovak centres currently contribute to the registry. The registry currently contains records on more than 5,000 patients with MM, almost 3,000 patients with MGUS, 170 patients with WM and 26 patients with primary AL amyloidosis, i.e. more than 8,000 records on patients with monoclonal gammopathies altogether. This paper describes technology employed for the collection, storage and subsequent online visualisation of data. The CLADE-IS platform is introduced as a new system for the collection and storage of data from the registry. The form structure and functions of the new system are described for all diagnoses in general; these functions facilitate data entry to the registry and minimise the error rate in data. Publicly available online visualisations of data on patients with MGUS, WM, MM or primary AL amyloidosis from all Czech or Slovak centres are introduced, together with authenticated visualisations of data on patients with MM from selected centres. The RMG represents a data basis that makes it possible to monitor the disease course in patients with monoclonal gammopathies on the population level.Key words: Registry of Monoclonal Gammopathies - RMG - registries - monoclonal gammopathies - CLADE-IS - data visualisation - database.

Presence of fluorescent in situ hybridization abnormalities is associated with plasma cell burden in light chain amyloidosis

Objective/BackgroundTo assess abnormalities found on CD138-enriched fluorescent in situ hybridization (FISH) studies on pre-treatment bone marrow in systemic amyloid light-chain amyloidosis (AL) and correlate findings between these abnormalities with organ involvement and 1-year survival. MethodsWe reviewed 107 patients with systemic AL to identify the impact of a diagnostic FISH study done on plasma cell-enriched bone marrow in our institution between January 2010 and January 2015; 77 had pre-treatment testing performed. ResultsA total of 77 (61%) patients had abnormal FISH including: hyperdiploidy (29%), t(11;14), (20%), hypodiploidy (16%), t(4;14), (1%), del17p (5%), and+1q21 (5%). Abnormal FISH studies were more likely in those patients with plasma cell involvement≥10% (p=.002). FISH abnormalities were not shown to correlate with stage, cardiac involvement, or survival at 1year. One-year survival was significantly affected by stage at diagnosis and presence of cardiac and hepatic amyloid involvement. ConclusionWe conclude that in AL, FISH abnormalities are associated with clonal burden. We found no impact of these markers on the type of organ involvement or 1-year survival.

Contribution of human smooth muscle cells to amyloid angiopathy in AL (light-chain) amyloidosis

ABSTRACTObjective: Amyloid light-chain (AL) amyloidosis is a disease process that often compromises the peripheral vascular system and leads to systemic end-organ dysfunction. Although amyloid formation in vessel walls is a multifaceted process, the assembly of the native light chains (LCs) into amyloid fibrils is central to its pathogenesis. Recent evidence suggests that endocytosis and endolysosomal processing of immunoglobin LCs by host cells is essential to the formation of amyloid fibrils that are deposited in at least some tissues. The aim of this study was to elucidate the role of vascular smooth muscle in amyloid angiopathy. Methods: Human coronary artery smooth muscle cells (SMCs) were grown on coverslips, four chamber glass slides, and growth factor-reduced Matrigel matrix in the presence of 10 µg/ml of ALs (λ and κ isotypes), nonamyloidogenic LCs, and culture medium (negative control) for 48 and 72 hours. Thereafter, a detailed light microscopic, immunohistochemical, and ultrastructural evaluation was conducted to verify amyloid deposition and characterize the role of SMCs in the formation of amyloid deposits in the various experimental conditions. Results: Amyloid deposits were detected extracellulary as early as 48 hours after exposure of vascular smooth muscle cells (VSMCs) to AL-LCs (amyloidogenic light chains) as confirmed by affinity to Congo red dye, thioflavin T fluorescence, and transmission electron microscopy. No amyloid was present in the cultures of SMCs treated with medium alone or nonamyloidogenic LCs. SMCs associated with amyloid deposits exhibited CD68, lysosome-associated membrane protein 1-1, and intracellular lambda light chain expression and only focal smooth muscle actin and muscle-specific actin positivity. Electron microscopy revealed these cells to have an expanded mature lysosomal compartment closely associated with deposits of newly formed amyloid fibrils. Conclusions: The interaction of amyloidogenic LCs with VSMCs is necessary for the formation of amyloid fibrils that are deposited in peripheral vessels. VSMCs participate in the formation of amyloid by the intracellular processing of AL-LCs, which is possible due to their transformation from a smooth muscle to a macrophage phenotype. The formation of amyloid fibrils occurs in the mature lysosomal compartment of transformed cells. The amyloid that is formed is then extruded into the extracellular matrix.

AL amyloidosis patients with low amyloidogenic free light chain levels at first diagnosis have an excellent prognosis

AbstractThe difference between involved minus uninvolved serum free light chains (dFLC) has been established as an invaluable hematologic parameter in systemic amyloid light chain (AL) amyloidosis. However, patients with an initial dFLC level <50 mg/L are currently deemed not evaluable for response to therapy. Therefore, we aimed to characterize this subgroup of patients and to define novel hematologic response parameters. We retrospectively analyzed 783 AL patients newly diagnosed at our center between 2002 and 2016. Patients with a dFLC level <50 mg/L showed smaller bone marrow plasmacytosis compared to patients with a dFLC level ≥50 mg/L (7% vs 10%, P < .001), but no significant differences in all analyzed chromosomal aberrations. Cardiac involvement was less frequent (45% vs 80%, P < .001) and less severe (Mayo 2004 stage III: 18% vs 51%, P < .001), whereas kidney involvement was more prevalent (83% vs 53%, P < .001) and proteinuria was higher (7.3 g/L vs 5.0 g/L, P < .001). In multivariate analyses, a dFLC level <50 mg/L appeared to be an independent prognostic factor with respect to overall survival (hazard ratio [HR] = 0.50, P = .003) and renal survival (HR = 0.56, P = .020). Patients with a dFLC level <50 mg/L showed a higher proportion of complete hematologic response after first-line therapy compared to patients with a dFLC level ≥50 mg/L (39% vs 9%, P < .001). Receiver-operating characteristics analysis identified a low-dFLC partial response (dFLC <10 mg/L for patients with a dFLC between 20 and 50 mg/L), which predicted overall and renal survival already at 3 months after the start of therapy. Importantly, a parallel Italian study validated this new hematologic remission parameter. The outcome of prospective clinical trials might be adversely influenced by exclusion of the favorable clinical subgroup with an initial dFLC <50 mg/L. We propose the appreciation of dFLC in hematologic response assessment for all patients with a baseline dFLC >20 mg/L.

Plasma cell neoplasm as a risk factor for early thrombosis of arteriovenous fistula.

We hypothesized that presence of plasma cell neoplasms might be a risk for thrombosis of arteriovenous fistulas (AVFs) as well as other well-known factors including age, sex, race, and presence of diabetes mellitus or certain vascular disorders. In this single-center, retrospective study based on medical record data, we investigated the influence of plasma cell neoplasms and the above-mentioned factors on the occurrence of complete occlusive thrombosis of the AVF within 30 days after surgery for creation of the AVF. Thrombosis was defined as the absence of bruit or thrill on auscultation and palpation, throughout systole and diastole. We retrospectively assessed the medical records of 91 patients with end-stage renal failure, including 8 patients with plasma cell neoplasm (5 with multiple myeloma and 3 with amyloid light-chain amyloidosis), who underwent surgical creation of an AVF at the wrist or anatomical snuff box for the first time between April 2014 and December 2016. Early thrombosis (i.e., within 30 days of surgery) occurred in 50.0% (4/8) and 10.8% (9/83) of patients with and without plasma cell neoplasm, respectively (P = 0.013). Multivariate analysis revealed that, after adjusting for baseline characteristics, plasma cell neoplasm was the only significant risk factor for early AVF thrombosis (odds ratio, 38.8; 95% confidence interval, 4.0-378.9; P = 0.0017). Considering the poor prognosis of plasma cell neoplasm and its association with higher risk for AVF thrombosis, another type of vascular access is likely to be more suitable than AVF in such patients.

Myocardial Deformation in Cardiac Amyloid Light-chain Amyloidosis: Assessed with 3T Cardiovascular Magnetic Resonance Feature Tracking

Clinically, assessment of myocardial function is essential in patients with amyloid light-chain cardiac amyloidosis (AL-CA) to predict outcome and determine therapeutic approach. The aim of this study was to investigate the feasibility of cardiovascular magnetic resonance (CMR)-derived feature tracking algorithm for assessing left ventricular (LV) myocardial deformation in AL-CA, and to determine if these abnormal myocardial deformation parameters are correlated to impaired LV myocardial microvascular dysfunction. A total of 42 AL-CA patients, including 26 with preserved systolic function and 16 with impaired LVEF, and 35 healthy controls were enrolled and underwent CMR examination. Our result indicated that AL-CA patients had significantly reduced global peak strain (PS) (longitudinal, circumferential, and radial) (all P < 0.05). AL-CA patients with normal LVEF showed preserved longitudinal PS at apical and significantly reduced longitudinal PS at mid and basal segments. By Spearman’s rank correlation analysis, the LV regional radial, circumferential, and longitudinal myocardial deformation values were correlated to myocardial upslope and MaxSI in CA, regardless of LVEF. This study indicated that the abnormal LV myocardial deformation of AL-CA patients can be monitored using feature tracking CMR, even in those with preserved LVEF; and the myocardial deformation was associated with coronary microvascular dysfunction.

Ixazomib for Relapsed or Refractory Light-Chain Amyloidosis

Amyloid light-chain (AL) amyloidosis is initially treated with melphalan and dexamethasone or cyclophosphamide, dexamethasone, and bortezomib.

Addition of cyclophosphamide and higher doses of dexamethasone do not improve outcomes of patients with AL amyloidosis treated with bortezomib

Bortezomib, in combination with dexamethasone (VD) or with the addition of cyclophosphamide (VCD), is highly effective in patients with amyloid light-chain (AL) amyloidosis. Currently, VCD is considered as a primary regimen for patients with AL, but it is not clear whether the addition of cyclophosphamide to VD further and significantly improves efficacy, given the substantial activity of bortezomib itself. We retrospectively compared the outcomes of 101 patients with AL amyloidosis who received VD (n=59) or VCD (n=42) in two consecutive periods. Early mortality after adjustment for Mayo stage was similar. On intent to treat, a hematologic response rate was 68% for patients treated with VD and 78% for VCD (P=0.26), while complete response+very good partial response (CR+VGPR) rate was 47.5% and 35%, respectively. Higher doses of dexamethasone or twice-weekly bortezomib were not associated with significantly higher CR+VGPR rates. Organ responses occurred in similar rates between the two groups. Median survival was similar (33 vs 36 months, P=0.45) even after adjustment for Mayo stage and dose and schedule of bortezomib and dexamethasone. In conclusion, bortezomib even with low doses of dexamethasone is effective for the treatment of AL amyloidosis; higher doses of dexamethasone and addition of cyclophosphamide do not seem to have a profound effect on efficacy and survival.