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https://www.readbyqxmd.com/read/29122991/maternal-embryonic-leucine-zipper-kinase-is-a-novel-target-for-proliferation-associated-high-risk-myeloma
#1
Arnold Bolomsky, Roy Heusschen, Karin Schlangen, Kathrin Stangelberger, Joséphine Muller, Wolfgang Schreiner, Niklas Zojer, Jo Caers, Heinz Ludwig
Treatment of high-risk patients is a major challenge in multiple myeloma. This is especially true for patients assigned to the gene-expression-profiling defined proliferation subgroup. Although recent efforts have identified some key players of proliferative myeloma, genetic interactions and players that can be targeted with clinically effective drugs have to be identified to overcome the poor prognosis of these patients. We therefore examined maternal embryonic leucine zipper kinase (MELK) for its implications in hyper-proliferative myeloma and analysed the activity of the MELK inhibitor OTSSP167 in vitro and in vivo...
November 9, 2017: Haematologica
https://www.readbyqxmd.com/read/29070995/dramatic-response-with-single-agent-ibrutinib-in-multiply-relapsed-marginal-zone-lymphoma-with-myd88-l265p-mutation
#2
Ryan C Lynch, Ranjana H Advani
The B-cell receptor signaling pathway is important in the lymphomagenesis of many lymphomas, including marginal zone lymphoma (MZL). Herein we describe a case of extranodal MZL refractory to multiple lines of therapy. The presence of an IgM paraprotein prompted further evaluation, and the patient was found to have an MYD88(L265P) mutation. Treatment with ibrutinib led to a dramatic response with prompt resolution of symptoms and significant improvement in measurable sites of disease. The excellent response to ibrutinib in our patient with MYD88(L265P)-mutated refractory MZL supports a biological rationale for its use...
September 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/29057130/cutaneous-vasculitis-an-unusual-presentation-of-a-biclonal-nodal-plasma-cell-dyscrasia
#3
D Swan, M Murphy, E Elhassadi
We describe an unusual case of a biclonal nodal plasma cell dyscrasia, presenting with a vasculitic rash, end-organ damage, and cytopenias. Serum protein electrophoresis demonstrated a biclonal kappa-restricted paraprotein, with a negative skeletal survey and no bone marrow disease. Fluorodeoxyglucose-PET-CT (FDG-PET-CT) revealed nodal involvement, which was not appreciable clinically, and facilitated biopsy, confirming the diagnosis of a nodal plasmacytoma. Complete biochemical response and resolution of the vasculitic rash were achieved with bortezomib-based therapy...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/29043147/a-case-report-of-paraproteinemia-associated-pauci-immune-glomerulonephritis-a-new-form-of-monoclonal-gammopathy-of-renal-significance
#4
Robert Rope, Neeraja Kambham, Neiha Arora
BACKGROUND: Renal disease associated with paraproteinemias is classically predicated upon pathologic paraprotein deposition in the kidney. However, growing evidence suggests that paraproteins may be able to systemically activate complement or neutrophils to drive renal damage. This may provide an alternative pathologic mechanism for renal injury in rare cases. CASE REPORT: We report a case of a patient with crescentic pauci-immune glomerulonephritis presenting with rapidly progressive renal failure, polyarthropathy, and a purpuric rash in association with a monoclonal immunoglobulin G κ-light-chain producing multiple myeloma...
2017: Clin Nephrol Case Stud
https://www.readbyqxmd.com/read/29037891/chemotherapy-based-stem-cell-mobilization-does-not-result-in-significant-paraprotein-reduction-in-myeloma-patients-in-the-era-of-novel-induction-regimens
#5
Anthony Oyekunle, Evgenii Shumilov, Philippe Kostrewa, Andreas Burchert, Lorenz Trümper, Patrick Wuchter, Gerald Wulf, Ulrike Bacher, Nicolaus Kröger
Novel induction agents markedly improved remission rates in multiple myeloma (MM), and the continued use of chemotherapy for CD34(+) stem cell mobilization (SCM) has been questioned. We examined the additional effect of chemotherapy in SCM regarding remission status/morbidity. We reviewed 236 consecutive MM patients (aged 36 to 75 years) with first autologous stem cell transplantation from January 2009 to March 2016 after chemotherapy-based SCM. Responses were measured by changes in intact Ig and free light chain levels before and after chemomobilization (International Myeloma Working Group [IMWG] criteria)...
October 13, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29034435/advances-in-the-treatment-of-paraproteinemic-neuropathy
#6
REVIEW
Eduardo Nobile-Orazio, Mariangela Bianco, Andrea Nozza
Purpose of review Several advances have been made on the pathogenesis and therapy of neuropathies associated with paraproteinemia (monoclonal gammopathy). It is important for the neurologist to understand the pathogenetic relevance of this association especially when the hematological disease does not require per se any therapy. Recent findings Treatment of the neuropathy in patients with malignant paraproteinemia is mainly addressed by the hematologist while the neurologist is mainly involved in the initial diagnosis and in deciding whether the neuropathy is caused by the disease or by the chemotherapy used for the disease...
October 16, 2017: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/29029605/monitoring-multiple-myeloma-by-idiotype-specific-peptide-binders-of-tumor-derived-exosomes
#7
Enrico Iaccino, Selena Mimmi, Vincenzo Dattilo, Fabiola Marino, Patrizio Candeloro, Antonio Di Loria, Danilo Marimpietri, Antonio Pisano, Francesco Albano, Eleonora Vecchio, Simona Ceglia, Gaetanina Golino, Antonio Lupia, Giuseppe Fiume, Ileana Quinto, Giuseppe Scala
Tumor-derived exosomes (TDEs) play a pivotal role in tumor establishment and progression, and are emerging biomarkers for tumor diagnosis in personalized medicine. To date, there is a lack of efficient technology platforms for exosome isolation and characterization. Multiple myeloma (MM) is an incurable B-cell malignancy due to the rapid development of drug-resistance. MM-released exosomes express the immunoglobulin B-cell receptor (Ig-BCR) of the tumor B-cells, which can be targeted by Idiotype-binding peptides (Id-peptides)...
October 13, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28985955/paraprotein-deposits-in-the-skin
#8
REVIEW
Victoria Alegría-Landa, Lorenzo Cerroni, Heinz Kutzner, Luis Requena
Cutaneous manifestations secondary to paraprotein deposits in the skin include a group of different disorders that although rare, may be the first clinical manifestation of the underlying hematologic dyscrasia. In this article we review the clinical manifestations and histopathologic findings of the processes that result from specific deposition of the paraprotein in different structures of the skin. Paraneoplastic processes frequently associated with hematologic malignancies will not be covered in this review...
October 3, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28903575/diagnostic-tools-of-waldenstr%C3%A3-ms-macroglobulinemia-best-possibilities-for-non-invasive-and-long-term-disease-monitoring
#9
K Growkova, Z Kufová, T Sevcikova, J Filipová, M Kascak, T Jelínek, S Grosicki, A Barchnicka, Ľ Roziaková, M Mistrík, M Simicek, R Hájek
Waldenströms macroglobulinemia (WM) is a B-cell malignancy characterized by high level of monoclonal immunoglobulin M (IgM) paraprotein in blood serum and associated with the bone marrow infiltration by malignant cells with lymphoplasmacytic differentiation. WM remains incurable advances in therapy. Most of WM cases are associated with a somatic point mutation L265P in MYD88. Significantly higher risk of progression from the IgM monoclonal gammopathy of undetermined significance (IgM MGUS) to WM for patients with mutated MYD88 gene suggests that this mutation is an early oncogenic event and plays a central role in development of malignant clones...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28893029/poems-syndrome-with-biclonal-gammopathy-a-rare-association
#10
Dibyendu De, Sandeepan Halder, Suvro Sankha Datta
Polyneuropathy, Organomegaly, Endocrinopathy, M protein and Skin changes (POEMS) syndrome is rare plasma cell dyscrasia with multisystem involvement. The name comes from the five characteristic features: Polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes. The presence of biclonal M band is a rare manifestation. Here, we are describing the cases of a 60-year-old lady, presented with bilateral pedal oedema and pericardial effusion and peripheral neuropathy. She also had hepatosplenomegaly, hyperpigmented rash and hypothyroidism and hyperparathyroidism...
July 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28886228/the-serum-heavy-light-chain-immunoassay-a-valuable-tool-for-sensitive-paraprotein-assessment-risk-and-disease-monitoring-in-monoclonal-gammopathies
#11
Christine Greil, Gabriele Ihorst, Felix Gaiser, Ulrich Salzer, Emanuel Bisse, Efstathios Kastritis, Heinz Ludwig, Ralph Wäsch, Monika Engelhardt
OBJECTIVE: The heavy/light chain (HLC)-immunoassay quantifies light chain types of each immunoglobulin class in patients with monoclonal gammopathies. METHODS: We assessed 147 consecutive patients with different forms and stages of plasma cell dyscrasias (PCD) who received standard tests (serum and urine protein electrophoresis [SPEP, UPEP], immunofixation [IFE], serum-free light chain [SFLC]), and HLC-immunoassay. Patients with multiple myeloma (MM, n = 102), smoldering MM (SMM, n = 5), monoclonal gammopathy of undetermined significance (MGUS, n = 28), and Waldenström's macroglobulinemia (WM, n = 12) were included...
September 8, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28885714/monoclonal-gammopathy-of-undetermined-significance-mgus-as-viewed-by-haematology-healthcare-professionals
#12
Charlene M McShane, Blain Murphy, Kah Heng Lim, Lesley A Anderson
OBJECTIVES: To investigate the words and descriptions used by haematology healthcare professionals (HCPs) to describe monoclonal gammopathy of undetermined significance (MGUS) to their patients. METHODS: A cross-sectional survey of haematology HCPs attending an annual haematology conference was undertaken. Content analysis was applied to the returned qualitative responses. RESULTS: In total, 55 people, many of whom were doctors (n=32; 58.2%) responded...
September 8, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28885307/the-treatment-of-paraprotein-related-kidney-disease
#13
Colin A Hutchison, Fei Xiong, Peter Mollee
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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...
November 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28879698/undetectable-vancomycin-concentrations-utilizing-a-particle-enhanced-turbidimetric-inhibition-immunoassay-in-a-patient-with-an-elevated-igm-level
#14
April A Cooper, Kevin Cowart, Amanda Clayton, Josee Paul
BACKGROUND: A case of undetectable vancomycin concentrations with the use of a particle enhanced turbidimetric inhibition immunoassay is reported. METHODS: A 73-year-old woman with B-cell lymphoma, chronic neutropenia with myelodysplastic syndrome and elevated IgM levels displayed repeated undetectable vancomycin concentrations, despite appropriate empiric vancomycin dosing. The vancomycin concentrations were processed utilizing a particle enhanced turbidimetric inhibition immunoassay (PETINIA)...
September 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28875888/concomitant-hiv-infection-in-newly-diagnosed-multiple-myeloma-patients-is-hard-to-recognise-and-should-be-tested-for-routinely-in-areas-of-high-endemicity
#15
J J B De Groot, M J Webb, J E Raubenheimer, M C Struwig, V J Louw
BACKGROUND: Over the past three decades much has changed in the treatment and outcomes of patients suffering concurrently from both multiple myeloma (MM) and HIV. While the prevalence of MM appears to be higher in HIV-positive individuals than in those who are uninfected, early recognition of patients suffering from both diseases is difficult and little information is available on their demographics and clinical presentation. OBJECTIVE: To compare the presenting features of HIV-positive patients diagnosed with MM with those of HIV-negative patients...
August 25, 2017: South African Medical Journal, Suid-Afrikaanse Tydskrif Vir Geneeskunde
https://www.readbyqxmd.com/read/28825948/11c-methionine-avid-plasmablastic-lymphoma
#16
Salvatore Annunziata, Annarosa Cuccaro, Carmelo Caldarella, Lucia Leccisotti, Stefan Hohaus
A 73-year-old woman had a diagnosis of a plasmablastic lymphoma by the excision of the right parotid gland. Two years after the diagnosis, the patient underwent a whole-body C-methionine PET/CT in order to evaluate the amino acid avidity of a scalp metastasis and for plasmablastic lymphoma restaging. C-methionine uptake was detected in the scalp, in several bone sites, and in the cricoid cartilage. Plasmablastic lymphoma is a subtype of B-cell lymphoma with an aggressive behavior and a poor prognosis. C-methionine appears to be a promising tracer for paraprotein-producing neoplasms...
August 19, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28803241/gender-specific-aspects-in-patients-with-multiple-myeloma-undergoing-autologous-stem-cell-transplantation-a-single-center-experience
#17
Doris Posch, Werner Rabitsch, Philipp Wohlfarth, Michael Leiner, Edit Porpaczy, Johannes Drach, Markus Raderer, Wolfgang Lamm
OBJECTIVE: Limited data exist on gender-specific aspects in hematologic malignancies and have been obtained mostly in non-Hodgkin lymphomas. The objective of this study was to investigate gender-specific aspects in patients with multiple myeloma (MM) undergoing autologous stem cell transplantation (ASCT). METHODS: A retrospective data analysis of 191 patients with MM who underwent ASCT was performed. Data collected from clinical records included age, sex, stage, induction therapy, outcome of induction, kind of stem cell mobilization, response to induction therapy and ASCT, cytogenetic aberrations, progression-free survival, and overall survival...
August 12, 2017: Oncology
https://www.readbyqxmd.com/read/28801984/low-dose-bortezomib-and-dexamethasone-as-primary-therapy-in-elderly-patients-with-waldenstr%C3%B3-m-macroglobulinemia
#18
Ya-Ping Zhang, Xi Yang, Zeng-Hua Lin, Xin-Feng Wang, Xin Cao, Xue-Fen You, Hong-Ming Huang, Wen-Yu Shi, Hong Liu
OBJECTIVE: This retrospective study was designed to determine the efficacy and safety of low-dose bortezomib and dexamethasone (lBD) in elderly Chinese patients with Waldenstrӧm macroglobulinemia (WM). METHODS: Ten patients with WM aged over 60 years received first-line treatment with lBD. RESULTS: The median age was 70 years (range, 61-77 years). The overall response rate was 80%, including 1 patient who achieved a complete response, 1 patient with very good partial response, and 6 patients with a partial response...
August 12, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28748903/immunoglobulin-a-nephropathy-in-a-patient-with-igg-kappa-light-chain-myeloma
#19
Abhilash Chandra, Anupama Kaul, Vinita Aggarwal
Paraproteins can cause a variable set of pathologic changes in the kidney. The introduction of novel anti-plasma cell agents capable of reversing renal failure have revolutionized the management of paraprotein-mediated kidney injury. Activation of the transcription factor nuclear factor kB (NF-kB) has been shown to be involved in the development of human glomerulonephritis (GN). Inhibitors of NF-kB may provide potential agents for treatment of immune complex GN. In this paper, we report a patient with IgA nephropathy and IgG kappa myeloma, who responded dramatically to chemotherapy targeted toward myeloma...
July 2017: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/28747620/chronic-inflammatory-demyelinating-polyneuropathy-variant-with-creatine-kinase-elevation-and-vanishing-effect-of-immunoglobulins
#20
Josef Finsterer, Rahim Aliyev
BACKGROUND Whether creatine-kinase (CK) is elevated or not in chronic inflammatory demyelinating polyneuropathy (CIDP) and its variants is not comprehensively investigated. CASE REPORT We report the case of a 47-year-old male who developed weakness of the left lower leg and the right index finger at age 42 years. At age 44 years, paresthesias and dysesthesias of both lower legs and mild right lower leg weakness additionally developed. CK was recurrently elevated since age 42 years but paraprotein and anti-myelin-associated glycoprotein (MAG)-antibodies were negative...
July 27, 2017: American Journal of Case Reports
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