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Amyloidosis AL

Sebastian Küchlin, Johannes Duffner, Sophia Scheubeck, Katja Schoeller, Lars Maruschke, Maximilian Seidl, Monika Engelhardt, Gerd Walz, Eric Peter Prager, Johannes Moritz Waldschmidt
Despite substantial improvements following the introduction of novel agents and antibodies, amyloid light-chain (AL)-amyloidosis still carries a grim prognosis. Here, we report on the case of a severely frail 86-year-old patient suffering from monoclonal gammopathy of renal significance (MGRS)-associated AL-amyloidosis with a diuretic-refractory nephrotic syndrome. In this patient, treatment with bortezomib-dexamethasone effectively induced a serological response, but was unfortunately poorly tolerated and failed to promote renal recovery fast enough to prevent secondary complications...
December 13, 2018: Hemodialysis International
Noemi Puig, Bruno Paiva, Marta Lasa, Leire Burgos, Jose J Perez, Juana Merino, Cristina Moreno, Maria-Belen Vidriales, Dolores Gómez Toboso, Maria-Teresa Cedena, Enrique M Ocio, Ramon Lecumberri, Alfonso García de Coca, Jorge Labrador, Maria-Esther Gonzalez, Luis Palomera, Mercedes Gironella, Valentin Cabañas, Maria Casanova, Albert Oriol, Isabel Krsnik, Albert Pérez-Montaña, Javier de la Rubia, Jose-Enrique de la Puerta, Felipe de Arriba, Felipe Prosper, Joaquin Martinez-Lopez, Quentin Lecrevisse, Javier Verde, Maria-Victoria Mateos, Juan-Jose Lahuerta, Alberto Orfao, Jesús F San Miguel
Early diagnosis and risk stratification are key to improve outcomes in light-chain (AL) amyloidosis. Here we used multidimensional-flow-cytometry (MFC) to characterize bone marrow (BM) plasma cells (PCs) from a series of 166 patients including newly-diagnosed AL amyloidosis (N = 94), MGUS (N = 20) and multiple myeloma (MM, N = 52) vs. healthy adults (N = 30). MFC detected clonality in virtually all AL amyloidosis (99%) patients. Furthermore, we developed an automated risk-stratification system based on BMPCs features, with independent prognostic impact on progression-free and overall survival of AL amyloidosis patients (hazard ratio: ≥ 2...
December 12, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Ann D Cohen, Susan M Landau, Beth E Snitz, William E Klunk, Kaj Blennow, Henrik Zetterberg
Alzheimer's disease (AD) is characterized by amyloid plaques and tau pathology (neurofibrillary tangles and neuropil threads). Amyloid plaques are primarily composed of aggregated and oligomeric β-amyloid (Aβ) peptides ending at position 42 (Aβ42). The development of fluid and PET biomarkers for Alzheimer's disease (AD), has allowed for detection of Aβ pathology in vivo and marks a major advancement in understanding the role of Aβ in Alzheimer's disease (AD). In the recent National Institute on Aging and Alzheimer's Association (NIA-AA) Research Framework, AD is defined by the underlying pathology as measured in patients during life by biomarkers (Jack et al...
December 8, 2018: Molecular and Cellular Neurosciences
M Hasib Sidiqi, Francis K Buadi, Angela Dispenzieri, Rahma Warsame, Martha Q Lacy, David Dingli, Nelson Leung, Wilson I Gonsalves, Prashant Kapoor, Taxiarchis V Kourelis, William J Hogan, Shaji K Kumar, Morie A Gertz
IgM related AL amyloidosis is a rare disease with patients presenting with more renal and neurological involvement and less cardiac involvement compared to those with non-IgM related disease. We retrospectively reviewed 38 patients receiving autologous stem cell transplant (ASCT) for IgM related AL amyloidosis at the Mayo Clinic between May 1999 and June 2018. Median age was 61 years and 71% were male. The most common organs involved were renal (63%), neurological (32%) and cardiac (26%). The median difference between involved and uninvolved free light chains (dFLC) was 6...
December 7, 2018: Biology of Blood and Marrow Transplantation
Karlijn H G Rutten, Reinier A P Raymakers, Bouke P C Hazenberg, Hans L A Nienhuis, Edo Vellenga, Monique C Minnema
BACKGROUND: Although survival has improved in recent decades, the short-term prognosis of patients with immunoglobulin light chain (AL) amyloidosis remains grim. We aimed to assess overall survival (OS) of AL amyloidosis patients by comparing cohorts in two consecutive time periods. METHODS: Data were collected and compared on 126 patients from two tertiary referral centres in The Netherlands during the time periods 2008-2012 and 2013-2016. RESULTS: There was a non-significant trend to improved 6-month OS in the last cohort (78% vs...
December 4, 2018: Amyloid: the International Journal of Experimental and Clinical Investigation
Panagiota Kyriakou, Dimitrios Mouselimis, Anastasios Tsarouchas, Angelos Rigopoulos, Constantinos Bakogiannis, Michel Noutsias, Vasileios Vassilikos
BACKGROUND: Cardiac Amyloidosis (CA) pertains to the cardiac involvement of a group of diseases, in which misfolded proteins deposit in tissues and cause progressive organ damage. The vast majority of CA cases are caused by light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR). The increased awareness of these diseases has led to an increment of newly diagnosed cases each year. METHODS: We performed multiple searches on MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews...
December 4, 2018: BMC Cardiovascular Disorders
Justin R Arnall, Saad Z Usmani, Hawawu Adamu, Joseph Mishkin, Manisha Bhutani
Systemic light-chain (AL) amyloidosis is a rare hematologic disorder where proteins infiltrate tissues leading to organ failure and death. Cardiac involvement, present in ∼70% of patients, determines stage and prognosis of the disease, with advanced involvement having a median survival of six months. The treatment of light-chain amyloidosis is directed at recovering organ function with therapeutic strategies following those of multiple myeloma with plasma cell-directed therapies. The use of single agent daratumumab has been reported in light-chain amyloidosis achieving rapid and deep responses...
November 26, 2018: Journal of Oncology Pharmacy Practice
Shun Manabe, Chihiro Iwasaki, Michiyasu Hatano, Fuyuki Kametani, Masahide Yazaki, Kosaku Nitta, Michio Nagata
BACKGROUND: Immunoglobulin heavy-and-light-chain amyloidosis (AHL amyloidosis) is a newly established disease entity where both the immunoglobulin heavy-chain and light-chain compose amyloid fibrils. The immunoglobulins responsible for the amyloid fibrils are generally identified by immunostaining and/or laser microdissection-liquid chromatography-tandem mass spectrometry (LMD-LC-MS/MS). However, both techniques do not biochemically differentiate immunoglobulins that formed amyloid fibrils from non-responsible immunoglobulins...
November 22, 2018: BMC Nephrology
Kar Wah Fuah, Christopher Thiam Seong Lim
BACKGROUND: Amyloidosis is a disorder caused by extracellular tissue deposition of insoluble fibrils which may result in a wide spectrum of symptoms depending upon their types, sites and amount of deposition. Amyloidosis can be divided into either systemic or localized disease. CASE PRESENTATION: We present a case of a middle-aged gentleman who presented with persistent nephrotic syndrome with worsening renal function. Repeated renal biopsies showed the presence of renal-limited AL amyloidosis...
November 6, 2018: BMC Nephrology
Richa Manwani, Ute Hegenbart, Shameem Mahmood, Sajitha Sachchithanantham, Charalampia Kyriakou, Kwee Yong, Rakesh Popat, Neil Rabin, Carol Whelan, Tobias Dittrich, Christoph Kimmich, Philip Hawkins, Stefan Schönland, Ashutosh Wechalekar
High-dose melphalan with autologous stem cell transplantation (ASCT) can induce durable haematological and organ responses in systemic AL amyloidosis (AL). Stringent selection criteria have improved safety of ASCT in AL but most patients are transplant-ineligible. We report our experience of deferred ASCT in AL patients who were transplant-ineligible at presentation but had improvements in organ function after induction chemotherapy, enabling them to undergo ASCT. Twenty-two AL patients underwent deferred ASCT from 2011 to 2017...
November 5, 2018: Blood Cancer Journal
M Hasib Sidiqi, Mohammed A Aljama, Eli Muchtar, Francis K Buadi, Rahma Warsame, Martha Q Lacy, Angela Dispenzieri, David Dingli, Nelson Leung, Wilson I Gonsalves, Prashant Kapoor, Taxiarchis V Kourelis, William J Hogan, Robert C Wolf, Shaji K Kumar, Morie A Gertz
High-dose melphalan is the standard conditioning regimen for patients with AL amyloidosis receiving autologous stem cell transplantation. Conventional formulations require propylene glycol (PG) as a co-solvent and melphalan has limited solubility and chemical stability after reconstitution, with potential risks for propylene glycol-related complications. Captisol-stabilized propylene glycol-free (PG-free) melphalan has been developed with improved solubility and chemical stability. We compared a cohort of patients with AL amyloidosis receiving PG melphalan (n = 96) to those receiving PG-free melphalan (n = 48) as conditioning for autologous stem cell transplantation...
November 2, 2018: Bone Marrow Transplantation
Divyesh P Engineer, Vivek B Kute, Himanshu V Patel, Pankaj R Shah
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...
September 2018: Saudi Journal of Kidney Diseases and Transplantation
Boris Brumshtein, Shannon R Esswein, Michael R Sawaya, Gregory Rosenberg, Alan T Ly, Meytal Landau, David S Eisenberg
Systemic light chain amyloidosis (AL) is a human disease caused by overexpression of monoclonal immunoglobulin light chains that form pathogenic amyloid fibrils. These amyloid fibrils deposit in tissues and cause organ failure. Proteins form amyloid fibrils when they partly or fully unfold and expose segments capable of stacking into β-sheets that pair and thereby form a tight, dehydrated interface. These structures, termed steric zippers, constitute the spines of amyloid fibrils. Here, using a combination of computational (with ZipperDB and Boston University ALBase), mutational, biochemical, and protein structural analyses, we identified segments within the variable domains of Ig light chains that drive the assembly of amyloid fibrils in AL...
October 24, 2018: Journal of Biological Chemistry
Tiffany P Quock, Eunice Chang, Jennifer S Munday, Anita D'Souza, Sohum Gokhale, Tingjian Yan
AIMS: Examine mortality and healthcare costs in Medicare beneficiaries with newly diagnosed immunoglobulin light chain (AL) amyloidosis. PATIENTS & METHODS: Cases were identified in 2012-2015 Medicare 5% data with ≥1 inpatient/≥2 outpatient claims consistent with AL amyloidosis and ≥1 AL-specific treatment. Cases were matched 3:1 with disease-free controls. Descriptive statistics were reported. RESULTS:  A total of 249 (33.3%) cases were matched to 747 (66...
November 2018: Journal of Comparative Effectiveness Research
Zuzanna Oruba, Tomasz Kaczmarzyk, Katarzyna Urbańczyk, Artur Jurczyszyn, Szymon Fornagiel, Krystyna Gałązka, Anna Bednarczyk, Maria Chomyszyn-Gajewska
We report the history of a 59-year old patient with systemic AL amyloidosis of intraoral manifestation. The patient first presented with complaints about dysphagia and remarkable enlargement of the tongue with highly reduced mobility, as well as bilateral submucosal thickenings on the cheeks. Histopathological examination of the incisional biopsy of the buccal mucosa and underlying tissues revealed AL amyloidosis. The microscopic presentation was, however, unique, as the amyloid deposits were present intracellularly in the striated muscles...
2018: Polish Journal of Pathology: Official Journal of the Polish Society of Pathologists
Anthony L Nguyen, Muhammad Kamal, Ravi Raghavan, Gayathri Nagaraj
A 52 year-old male presented with neck pain after undergoing thyroidectomy for a goiter three weeks prior which was complicated by a neck hematoma requiring evacuation. Computed tomography (CT) scan showed a neck hematoma requiring evacuation and he received desmopressin with cessation of bleeding. Coagulation studies were normal. He returned eighteen months later with severe oral mucosal bleeding after a dental procedure and required transfusions with red blood cells, platelets, and fresh frozen plasma (FFP) in addition to desmopressin, Humate-P, aminocaproic acid, and surgical packing...
September 5, 2018: Hematology Reports
Juan Gonzalez, Ahsan Wahab, Kavitha Kesari
Dysphagia is an uncommon presentation of systemic immunoglobulin light-chain (AL) amyloidosis with multiple myeloma (MM). Gastrointestinal (GI) involvement usually manifests with altered motility, malabsorption or bleeding. Furthermore, patients identified with GI amyloidosis, without previous diagnosis of a plasma cell disorder, are extremely rare. We report an elderly woman who presented with acute on chronic cardiac dysfunction, sick sinus syndrome and acute renal failure. While admitted, she developed intermittent dysphagia to both solids and liquids...
October 21, 2018: BMJ Case Reports
Luis M Blancas-Mejia, Pinaki Misra, Christopher J Dick, Marta Marin-Argany, Keely R Redhage, Shawna A Cooper, Marina Ramirez-Alvarado
Common biophysical techniques like absorption and fluorescence spectroscopy, microscopy, and light scattering studies have been in use to investigate fibril assembly for a long time. However, there is sometimes a lack of consensus from the findings of an individual technique when compared in parallel with the other techniques. In this chapter, we aim to provide a concise compilation of techniques that can effectively be used to obtain a comprehensive representation of the structural, aggregation, and toxicity determinants in immunoglobulin light chain amyloidosis...
2019: Methods in Molecular Biology
Brett W Sperry, Bryan A Reyes, Asad Ikram, Joseph P Donnelly, Dermot Phelan, Wael A Jaber, David Shapiro, Peter J Evans, Steven Maschke, Scott E Kilpatrick, Carmela D Tan, E Rene Rodriguez, Cecilia Monteiro, W H Wilson Tang, Jeffery W Kelly, William H Seitz, Mazen Hanna
BACKGROUND: Patients with cardiac amyloidosis often have carpal tunnel syndrome that precedes cardiac manifestations by several years. However, the prevalence of cardiac involvement at the time of carpal tunnel surgery has not been established. OBJECTIVES: The authors sought to identify the prevalence and type of amyloid deposits in patients undergoing carpal tunnel surgery and evaluate for cardiac involvement. The authors also sought to determine if patients with soft tissue transthyretin (TTR) amyloid had abnormal TTR tetramer kinetic stability...
October 23, 2018: Journal of the American College of Cardiology
Brian Lilleness, Frederick L Ruberg, Roberta Mussinelli, Gheorghe Doros, Vaishali Sanchorawala
Immunoglobulin light chain amyloidosis (AL amyloidosis) is caused by misfolded light chains which form soluble toxic aggregates that deposit in tissues and organs leading to organ dysfunction. The leading determinant of survival is cardiac involvement. Current staging systems use N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponins (TnT and TnI) for prognostication, but many centers do not offer NT-proBNP. We sought to derive a new staging system using brain natriuretic peptide (BNP) that would correlate with the Mayo 2004 staging system and be predictive for survival in AL amyloidosis...
October 17, 2018: Blood
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