scholarly journals Kinetic stability and sequence/structure studies of urine-derived Bence-Jones proteins from multiple myeloma and light chain amyloidosis patients

2017 ◽  
Vol 230 ◽  
pp. 89-98 ◽  
Author(s):  
Luis M. Blancas-Mejía ◽  
Emily B. Martin ◽  
Angela Williams ◽  
Jonathan S. Wall ◽  
Marina Ramirez-Alvarado
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Kinetic Stability ◽  
Sequence Structure ◽  
Light Chain Amyloidosis ◽  
Bence Jones Proteins

scholarly journals Prevalence and clinical implications of t(11;14) in patients with amyloid light-chain amyloidosis with or without concurrent multiple myeloma

2019 ◽  
Vol 49 (2) ◽  
pp. 195-198 ◽  
Author(s):  
Hiroki Kobayashi ◽  
Yoshiaki Abe ◽  
Daisuke Miura ◽  
Kentaro Narita ◽  
Akihiro Kitadate ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Clinical Implications ◽  
Light Chain Amyloidosis ◽  
Amyloid Light Chain

scholarly journals Diaphragmatic Amyloidosis Causing Respiratory Failure: A Case Report and Review of Literature

2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
Aleksey Novikov ◽  
Horatio Holzer ◽  
Robert A. DeSimone ◽  
Ghaith Abu-Zeinah ◽  
David J. Pisapia ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Respiratory Failure ◽  
Light Chain ◽  
Phrenic Nerve ◽  
Early Recognition ◽  
Pulmonary Function Tests ◽  
Rapid Progression ◽  
Immunoglobulin Light Chain ◽  
Light Chain Amyloidosis ◽  
Immunoglobulin Light Chain Amyloidosis

Neuromuscular respiratory failure is a rare complication of systemic immunoglobulin light chain amyloidosis. We describe a case of a 70-year-old Caucasian man with multiple myeloma who presented with worsening dyspnea. The patient was diagnosed with and treated for congestive heart failure but continued to suffer from hypercapnic respiratory insufficiency. He had restrictive physiology on pulmonary function tests and abnormal phrenic nerve conduction studies, consistent with neuromuscular respiratory failure. The diagnosis of systemic immunoglobulin light chain amyloidosis was made based on the clinical context and a cardiac biopsy. Despite treatment attempts, the patient passed away in the intensive care unit from hypercapnic respiratory failure. Autopsy revealed dense diaphragmatic amyloid deposits without phrenic nerve infiltration or demyelination or lung parenchymal involvement. Only 5 cases of neuromuscular respiratory failure due to amyloid infiltration of the diaphragm have been described. All cases, including this, were characterized by rapid progression and high mortality. Therefore, diaphragmatic amyloidosis should be on the differential for progressive neuromuscular respiratory failure in patients with multiple myeloma or any other monoclonal gammopathy. Given its poor prognosis, early recognition of this condition is essential in order to address goals of care and encourage pursuit of palliative measures.

Immunoglobulin light-chain amyloidosis shares genetic susceptibility with multiple myeloma

Leukemia ◽  
2014 ◽  
Vol 28 (11) ◽  
pp. 2254-2256 ◽  
Author(s):  
N Weinhold ◽  
A Försti ◽  
M I da Silva Filho ◽  
J Nickel ◽  
C Campo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Genetic Susceptibility ◽  
Light Chain ◽  
Immunoglobulin Light Chain ◽  
Light Chain Amyloidosis ◽  
Immunoglobulin Light Chain Amyloidosis

Role of oral examination in newly diagnosed multiple myeloma patients: A safe and simple way to detect light chain amyloidosis

Oral Diseases ◽  
2018 ◽  
Vol 24 (7) ◽  
pp. 1343-1348 ◽  
Author(s):  
Merav Leiba ◽  
Suha Jarjoura ◽  
Waseem Abboud ◽  
Arnon Nagler ◽  
Ran Yahalom ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Oral Examination ◽  
Newly Diagnosed ◽  
Light Chain Amyloidosis

scholarly journals The Occurrence of AL Amyloidosis (Light-Chain Amyloidosis) in Patients with Multiple Myeloma in Lower Silesia Region, Poland

2014 ◽  
Vol 23 (2) ◽  
pp. 235-244
Author(s):  
Lidia Usnarska-Zubkiewicz ◽  
Jadwiga Hołojda ◽  
Michał Jeleń ◽  
Anna Zubkiewicz-Zarębska ◽  
Jakub Dębski ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Al Amyloidosis ◽  
Light Chain Amyloidosis ◽  
Lower Silesia

scholarly journals First Description of B Cell Maturation Antigen Expression in Light Chain Amyloidosis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5452-5452
Author(s):  
Susan Bal ◽  
Allison Sigler ◽  
Alexander Chan ◽  
David J. Chung ◽  
Ahmet Dogan ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
B Cell ◽  
Board Of Directors ◽  
Light Chain ◽  
Research Funding ◽  
Plasma Cells ◽  
Staining Intensity ◽  
Advisory Committees ◽  
Light Chain Amyloidosis ◽  
B Cell Maturation

Background B-cell maturation antigen (BCMA) is a transmembrane protein belonging to the tumor necrosis factor (TNF) superfamily involved in the regulation of B cell proliferation and survival as well as maturation/differentiation into plasma cells. In multiple myeloma cells, overexpression of BCMA has been shown to activate mitogen activated protein kinase pathways (AKT, ERK1/2, and NF-κB) and upregulates anti-apoptotic proteins (MCL1, BCL2, BCL-xL) resulting in cellular proliferation. Immunotherapeutic strategies targeting BCMA are showing great promise in heavily pre-treated refractory multiple myeloma. Light Chain Amyloidosis (AL) is a multisystem disorder of clonal plasma cells that results in the production of an abnormal light chain which misfolds and deposits in the organs leading to disruption of tissue architecture, cellular stress, dysfunction and eventually, death. The smaller burden and lower proliferative potential of the offending clonal plasma cells in amyloidosis may potentially lend itself favorably to immunotherapeutic strategies targeting BCMA. Given the efficacy of this approach in MM, the evaluation of BCMA expression on the surface of amyloidogenic plasma cells is warranted. Methods All patients diagnosed with Light chain Amyloidosis at Memorial Sloan Kettering Cancer Center, NY between January 1, 2012, and December 31, 2018, who had unstained bone marrow samples were identified. These unstained BM biopsy samples were prospectively stained for BCMA expression using Immunohistochemistry (IHC). We utilized a clinical-grade assay (clone D6; catalog sc-390147; company Santa-Cruz; monoclonal antibody; dilution 1:400) in a CLIA compliant setting. We scored the biopsies for BCMA expression, intensity, and site of staining. We also obtained their demographic details, staging, and cytogenetic information for the patients with available samples. Results During the queried period, 28 unstained samples were available for testing from the time of disease diagnosis. The median age of the population was 63 years (range 41-73). 64% of patients were male and consistent with the literature; a majority of patients (75%) had lambda-typic clonal plasma cells. Cytogenetic abnormalities using fluorescence in situ hybridization (FISH) were reviewed, t(11;14) was seen in 36% patients, and chromosome 1q and del 13q were each seen in 32% of patients. No patient had t(4;14) or del 17p. The median clonal PC burden in BM at diagnosis was 10% (range2-80%) and 36% had > 10% plasma cells. In clonal PCs, the median BCMA expression was 80% (range 20-100%). Only one patient had a staining intensity under 50% (20%). Membranous staining was noted in 82% of patients and a Golgi pattern in 11%. The median staining intensity was 2 (range 1-3). Of the patients with baseline diagnostic samples available for testing, six patients had additional unstained bone marrow samples for staining at the time of relapse. The majority of patients (83%) who relapsed had >10% plasma cells with a higher median plasma cell burden of 35% (range 10-80). The median BCMA expression was 65% (range 50-80) with no patient having <50% expression. The staining pattern was membranous in 50%, Golgi in 17%, and Golgi-membranous in 33%. At the time of relapse, the median clonal PC burden was 13% (range 5-30). BCMA expression continued to be present at the time of relapse with a median 75% (range 50-100) with predominantly membranous staining (83%). The median staining intensity in both diagnostic and relapsed tissue within the six samples studied was 1. Conclusions Our study represents the first description of BCMA expression on the surface of amyloidogenic plasma cells to our knowledge. BCMA is uniformly expressed by pathologic PCs in AL amyloidosis both at the time of diagnosis and relapse. Given the efficacy of BCMA directed therapy in multiple myeloma, further investigation of these agents in light-chain amyloidosis are warranted and may provide an effective therapeutic strategy in this devastating disease. Figure Disclosures Dogan: Corvus Pharmaceuticals: Consultancy; Celgene: Consultancy; Seattle Genetics: Consultancy; Novartis: Consultancy; Takeda: Consultancy; Roche: Consultancy, Research Funding. Giralt:Takeda: Consultancy, Research Funding; Johnson & Johnson: Consultancy, Research Funding; Kite: Consultancy; Novartis: Consultancy; Actinium: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy; Celgene: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Miltenyi: Research Funding; Spectrum Pharmaceuticals: Consultancy. Hassoun:Novartis: Consultancy; Janssen: Research Funding; Celgene: Research Funding. Landau:Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees; Caelum: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Clinical Analysis of Cardiac Involvement in 53 Patients With Multiple Myeloma Coexistent With Light Chain Amyloidosis

2020 ◽  
Vol 20 (8) ◽  
pp. 519-525.e1
Author(s):  
Yuanyuan Yu ◽  
Zhongxia Huang ◽  
Wanli Hu ◽  
Xin Li ◽  
Man Shen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Cardiac Involvement ◽  
Clinical Analysis ◽  
Light Chain Amyloidosis

scholarly journals Near tetrapoloid karyotype with translocation t(11;14) in a Moroccan patient with amyloid light-chain amyloidosis and multiple myeloma

2020 ◽  
Vol 14 ◽  
pp. 100217
Author(s):  
Hasna Hamdaoui ◽  
Abdelhafid Natiq ◽  
Oumaima Benlarroubia ◽  
Thomas Liehr ◽  
Hind Dehbi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Light Chain Amyloidosis ◽  
Amyloid Light Chain ◽  
Moroccan Patient

Daratumumab, pomalidomide, and dexamethasone as a bridging therapy to autologous stem cell transplantation in a case of systemic light-chain amyloidosis with advanced cardiac involvement

2018 ◽  
Vol 25 (4) ◽  
pp. 1021-1025 ◽  
Author(s):  
Justin R Arnall ◽  
Saad Z Usmani ◽  
Hawawu Adamu ◽  
Joseph Mishkin ◽  
Manisha Bhutani
Keyword(s):  
Multiple Myeloma ◽  
Abdominal Pain ◽  
Light Chain ◽  
Cardiac Involvement ◽  
Single Agent ◽  
Al Amyloidosis ◽  
Light Chain Amyloidosis ◽  
Hematologic Disorder ◽  
Complete Hematologic Response ◽  
Paradoxical Worsening

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. The combination of daratumumab, pomalidomide, and dexamethasone (DaraPomD) is particularly interesting for severe AL based on success in multiple myeloma. A 43-year-old female with light-chain amyloidosis and concomitant multiple myeloma presented with severe bowel dysmotility causing abdominal pain, anemia, and a 100-pound unintentional weight loss. A combination of cyclophosphamide, bortezomib, and dexamethasone was initiated but after five cycles her symptoms were progressing and therapy was switched to DaraPomD to optimize response. At the conclusion of two cycles she had achieved an amyloid complete-hematologic response, with her recurring ileus and abdominal pain significantly improved. Additionally, cardiac markers also suggested a rapid response without a common paradoxical worsening of congestive heart failure, and was overall well tolerated. Given the severe symptoms and refractory nature of our patient's disease DaraPomD was reasonable. With the tolerability and response seen, this patient experience supports a formal clinical trial evaluating the safety and efficacy of DaraPomD in light-chain amyloidosis.

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