Validity of Amyloidosis in the Danish National Patient Registry.

P-019: Real-world treatment patterns, clinical outcomes, and healthcare resource utilization of individuals with light chain (AL) amyloidosis in Alberta, Canada: a population-based study

The Clinical Impact of Proteomics in Amyloid Typing

P-020: Altered mRNA splicing identifies novel biomarkers and therapeutic targets in AL (Amyloid light-chain) Amyloidosis

Objectives: To describe FDG-PET/CT in amyloid light-chain (AL) amyloidosis. Methods: We describe a French multicenter study which included patients with AL amyloidosis who had undergone a FDG-PET/CT during follow-up. Results: Ten patients with AL amyloidosis (median age 62 years [59–85]) were analyzed. AL amyloidosis was of λ-type in 7/10 cases (70%) and localized amyloidosis in 4/10 cases (40%). AL amyloidosis was primary in 7/10 (70%) cases and associated with Waldenstrom’s macroglobulinemia (n = 2) and plasmocytoma (n = 1) in the remaining cases. Median delay between diagnosis and PET was 1 month [0–51]. PET was positive in seven (70%) patients and showed a median FDG SUV of 6.5 []. FDG uptakes with positive PET were localized in seven patients, namely in the nasopharynx (n = 3), bronchopulmonary (n = 2), duodenal, cutaneous, bone, joint and muscular areas (n = 1, each). FDG uptakes on PET were concordant with the known organ impairment in 6/7 cases (86%) and showed unknown nasopharyngeal and mesenteric localization in one case each. PET was negative in the patient with cardiac amyloidosis and two patients with pulmonary amyloidosis. Conclusion: High FDG uptake may be present in patients with AL amyloidosis, however prospective studies are needed in order to determine the place of FDG PET in AL amyloidosis.

Purpose: Gastric symptoms from Amyloid Light-chain (AL) amyloidosis are rare. This is a patient with hematemesis found to have a massive gastric mucosal tear secondary to gastric AL amyloidosis. Case Report: A 47-year-old woman presented with hematemesis, epigastric and chest pain. She had no prior symptoms, no known past medical, surgical, or family history. She denied use of medications. Vital signs were normal. She had a right eye ecchymosis (post-emesis), chest and epigastric tenderness, but no crepitus. Esomeprazole drip was initiated. Hemoglobin was 9.0 g/dL, platelets 222 K/uL, total protein 9.5 g/dL, albumin 3.5 g/dL, and INR was 1.2. Chest x-ray was unremarkable. Upper endoscopy revealed a large deep mucosal tear along the lesser curvature of the gastric body oozing blood with friable mucosa (Figure 1A). Chest CT showed a gastric submucosal hematoma, and no perforation (Figure 1B). She had no further major events. Repeat endoscopy showed a nodular mucosa with linear scarring. Air insufflation caused superficial mucosal tearing in the gastric body and antrum (Figure 1C). Biopsy results showed submucosal amorphous material deposition, and positive Congo Red stain consistent with amyloid (Figure 1D). Results of serum electrophoresis and bone marrow biopsy revealed a diagnosis of AL amyloidosis with IgG Lambda multiple myeloma. She was treated with bortezomib, cyclophosphamide, and dexamethasone.Figure 1: A. Retroflexed view of the lesser curve gastric hematoma / tear (arrow). B. CT-gastric hematoma (arrow). C. Tearing on insufflation. D. Biopsy-Congo Red stain.Discussion: Incidence of AL amyloidosis in the U.S. is 6-10 cases per million personyears, with 10-15% of multiple myeloma patients having AL amyloid. Only 1% have symptoms from gastric involved AL amyloidosis. Patients can present with peri-orbital pinch purpura. Endoscopic features include ulcerations, granular and friable mucosa, irregular gastric folds, submucosal hemorrhage, and hematomas. Bleeding in AL amyloidosis is due to capillary fragility from amyloid deposition, coagulation factor deficiency, especially low factor X, and abnormal platelets. The goal of therapy is to suppress the synthesis of light chains by treating the underlying disorder.

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Kidney and liver involvement in monoclonal light chain disorders

Identification of clonal immunoglobulin λ light-chain gene rearrangements in AL amyloidosis using next-generation sequencing

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.

Amyloid light-chain (AL) amyloidosis is the most common type of systemic amyloidosis and is a multi-organ disease affecting mostly the heart and kidneys. AL amyloidosis is a protein misfolding disorder characterized by the tissue deposition of monoclonal light chains (LCs) produced by neoplastic plasma cells. Measurement of circulating free LC (FLC) is an important tool for diagnosis, risk stratification, and management of AL amyloidosis and can be performed through antibody-based methods or mass spectrometry. Furthermore, correct identification of LC deposits in tissues is essential to diagnose AL amyloidosis. Together with antibody-based techniques, methods relying on mass spectroscopy are now available.

Background and aimIt is well established that cancer patients have an increased risk of venous thromboembolism (VTE). However, no previous study has examined the quality of VTE diagnoses related to cancer patients in the Danish National Registry of Patients (DNRP). To support future studies on cancer and risk of VTE, this study aimed to estimate the positive predictive value (PPV) of VTE diagnoses among prostate cancer (PC) patients registered in the DNRP.Materials and methodsWe conducted a validation study using data from hospitals within the Central Denmark Region, which covers a population of 1.3 million people. Using the DNRP, we identified a total of 120 PC patients registered with VTE within the period 1995–2012. We also identified a random sample of 120 PC patients with no VTE registration within the same period. Therefore, a total of 240 patients were selected for medical chart review. We compared data from the DNRP to data collected from medical record review (ie, reference standard). We then computed PPV, sensitivity, and specificity with corresponding 95% confidence intervals (CIs) using the Jeffreys method.ResultsThe final study sample included 232 PC patients, of which 115 were registered with VTE and 117 had no registration of VTE in the DNRP. We found the overall PPV of VTE diagnoses in the DNRP to be 86.1% (95% CI 78.9%–91.5%). Sensitivity was 98.0% (95% CI 93.8%–99.6%), and specificity was 87.8% (95% CI 81.4%–92.6%). We also found the PPV of incident PC diagnoses in the DNRP to be 98.3% (95% CI 96.1%–99.4%).ConclusionFor PC patients, the registration of VTE diagnoses in the DNRP is associated with a high PPV. We provide evidence that data from the DNRP are valid for studies on risk of VTE among cancer patients.

Autologous stem cell transplantation (ASCT) has improved the prognosis of selected patients with immunoglobulin amyloid light-chain (AL) amyloidosis. However, there exist little data regarding Asian patients receiving ASCT. We retrospectively analyzed 24 patients who were treated with ASCT for AL amyloidosis between 2007 and 2012. The median age at the time of ASCT was 56 years (range: 40–62 years), and in 63% of patients, the AL amyloidosis involved two or more organs. All patients except one received induction treatment such as cyclophosphamide, dexamethasone or thalidomide before ASCT, but only approximately half of these patients showed a hematologic response. After ASCT, the overall hematologic response was increased to 92% (22/24), which translated into increased organ response in 58% of patients (14/24). There was no transplantation-related mortality (0%) even though cardiac amyloidosis patients were included in our series. In conclusion, our results of ASCT in patients with AL amyloidosis were comparable to that of Western countries in terms of response and survival outcomes. Therefore, ASCT is an effective and feasible treatment approach for Asian patients with AL amyloidosis.

Background: Patients with amyloid light-chain (AL) amyloidosis who have advanced cardiac damage are at risk of premature mortality. Currently, bortezomib is the mainstay in the treatment of AL amyloidosis, but the benefits of bortezomib in patients with ultra-high-risk (2004 Mayo stage IIIb or 2012 Mayo stage IV) AL amyloidosis have not been proved definitively.Methods: We performed a retrospective analysis of patients newly diagnosed with ultra-high-risk AL amyloidosis who received a bortezomib-based regimen or supportive treatment. We aimed to establish the effects of bortezomib on early mortality and long-term outcomes in this high-risk population.Results: Patients receiving bortezomib-containing chemotherapy (n = 62) and patients receiving no chemotherapy (n = 24) were included. Median overall survival (OS) was 30 months in the bortezomib group and 2 months in the control group (p < .001), and median progression-free survival (PFS) was 15.8 months (bortezomib) and 2 months (control; p < .001). The early-death rate (within 6 months of treatment) was 32.3% (bortezomib) and 66.7% (control; p < .001). In a landmark analysis assessing outcomes in patients surviving beyond 6 months, the 2-year OS and PFS in the bortezomib group were 77.3% and 65.8%, respectively.Conclusions: Bortezomib-based regimens can help to reduce early mortality and improve long-term survival in patients with ultra-high-risk AL amyloidosis.

BackgroundThe incidence of acromegaly is uncertain, since population-based studies are few. In the absence of a specific acromegaly registry, the Danish National Registry of Patients (DNRP) becomes a potential source of data for studying the epidemiology of acromegaly, by linking all hospital discharge diagnoses to the personal identification numbers of individual Danish inhabitants. The validity of the DNRP with respect to acromegaly, however, remains to be tested. The aim of this study was to validate the International Classification of Diseases (ICD) codes for acromegaly (ICD-8: 25300, 25301. ICD-10: E22.0) as used in the DNRP, and to assess the influence of various registration patterns on the accuracy of registry data.MethodsWe identified patients registered with ICD codes for the diagnosis of acromegaly or other pituitary disorders during the period 1991–2009. Data on the institutional origin of each registration and the number of relevant DNRP registrations were recorded, and systematic patient chart reviews were performed to confirm the diagnosis.ResultsIn total, 110 cases of acromegaly were confirmed, compared with 275 registered cases, yielding a positive predictive value (PPV) of 40%. When restricting the search to the regional highly specialized department of endocrinology, the PPV increased to 53% with no loss of cases with confirmed acromegaly. With a requirement of at least one, two, or three DNRP registrations, the PPV increased, but with a concurrent loss of confirmed cases.ConclusionThe DNRP seems to be a useful source for identifying new cases of acromegaly, especially when restricting the search to a relevant regional highly specialized department. The PPV of DNRP data used for this purpose can be increased by including only cases with several registrations. A similar approach may be successfully applied to other rare diseases in which continuity of care is provided by highly specialized departments.

The Efficacy and Safety of Daratumumab-Based Regimens in the Initial Treatment of Amyloid Light-Chain Amyloidosis