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Smoldering myeloma

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https://www.readbyqxmd.com/read/29729982/c3-glomerulopathy-associated-with-monoclonal-ig-is-a-distinct-subtype
#1
Aishwarya Ravindran, Fernando C Fervenza, Richard J H Smith, Sanjeev Sethi
Monoclonal immunoglobulins (MIg) may play a causal role in C3 glomerulopathy (C3G) by impairing regulation of the alternative pathway of complement. Ninety-five patients with C3G were tested for MIg of which 36 were positive. Their mean age at diagnosis was 60 years and among patient 50 years and older, 65.1% had a MIg. At presentation, median serum creatinine and proteinuria were 1.9 mg/dL and 3.0 g/24 hours. Hematuria was present in 32 (88.9%) patients. Twelve (34.3%) patients had low C3 levels. C3 nephritic factor was detected in 45...
May 2, 2018: Kidney International
https://www.readbyqxmd.com/read/29721253/neurofibromatosis-type-i-and-multiple-myeloma-coexistence-a-possible-link
#2
Fabrizio Accardi, Valentina Marchica, Cristina Mancini, Elena Maredi, Costantina Racano, Laura Notarfranchi, Davide Martorana, Paola Storti, Eugenia Martella, Benedetta Dalla Palma, Luisa Craviotto, Massimo De Filippo, Antonio Percesepe, Franco Aversa, Nicola Giuliani
The association between Neurofibromatosis type I (NF1) and multiple myeloma (MM), a plasma cell, dyscrasia is very rare. Here we put to the attention of the scientific community two new cases. The first one is a patient with active MM whereas the second with smoldering MM. Both patients present typical features of NF1 but skeletal alterations were present only in the second case including dysplasia, marked scoliosis and osteoporosis. MM osteolytic lesions were absent in both patients. In addition to the clinical diagnosis of NF1, a molecular testing for NF1 gene mutations has been performed finding that patient one was heterozygous for the c...
March 2, 2018: Hematology Reports
https://www.readbyqxmd.com/read/29674497/plasma-cell-proliferative-index-predicts-outcome-in-immunoglobulin-light-chain-amyloidosis-treated-with-stem-cell-transplantation
#3
M Hasib Sidiqi, Mohammed Aljama, Dragan Jevremovic, William G Morice, Michael Timm, Francis K Buadi, Rahma Warsame, Martha Q Lacy, Angela Dispenzieri, David Dingli, Wilson I Gonsalves, Shaji Kumar, Prashant Kapoor, Taxiarchis Kourelis, Nelson Leung, William J Hogan, Morie Gertz
The plasma cell proliferative index provides an insight into plasma cell biology in plasma cell disorders and is an important prognostic marker in myeloma and smoldering myeloma. We analyzed the prognostic impact of the plasma cell proliferative index in 513 patients with systemic AL Amyloidosis undergoing stem cell transplantation at the Mayo Clinic between January 2003 and 31 August 2016. Two cohorts were identified; Low or Elevated plasma cell proliferative index. Patients with an Elevated plasma cell proliferative index had more cardiac involvement (56% vs 44%; p=0...
April 19, 2018: Haematologica
https://www.readbyqxmd.com/read/29616856/oncogene-induced-senescence-a-potential-breakpoint-mechanism-against-malignant-transformation-in-plasma-cell-disorders
#4
Nicola Lehners, Elena Ellert, Jing Xu, Jens Hillengass, Jonas Leichsenring, Albrecht Stenzinger, Hartmut Goldschmidt, Mindaugas Andrulis, Marc S Raab
Oncogene-induced senescence (OIS) is a cellular tumor-suppressive mechanism present in several premalignant conditions. Here, we analyze the possible impact of OIS on malignant transformation in plasma cell disorders. Tumor samples from 125 patients with different disease stages were analyzed immunohistochemically for expression of senescence markers. Protein expression of cyclin-dependent kinase inhibitor p21Cip1/Waf1 was significantly higher in smoldering multiple myeloma (SMM) compared to monoclonal gammopathy of undetermined significance (MGUS) (p = ...
April 4, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29582696/anti-cd38-and-anti-slamf7-the-future-of-myeloma-immunotherapy
#5
Elena Zamagni, Paola Tacchetti, Lucia Pantani, Michele Cavo
the high expression of a number of surface antigens on malignant plasma cells, the bone marrow micro-environment and immune effector T cells, makes these appealing targets for immune therapy with monoclonal antibodies (mAbs). Areas covered: Two mAbs, anti-CD38 daratumumab (Dara) and anti-SLAMF7 elotuzumab (Elo), have achieved recent regulatory approval for relapsed or refractory MM (RRMM) and are currently being explored as possible treatment options in novel combinations and different settings. This review discusses the current landscape and possible development of anti-CD38 and anti-SLAMF7 mAbs...
May 2018: Expert Review of Hematology
https://www.readbyqxmd.com/read/29577600/quantification-of-number-of-cd38-sites-on-bone-marrow-plasma-cells-in-patients-with-light-chain-amyloidosis-and-smoldering-multiple-myeloma
#6
Katharina Kriegsmann, Tobias Dittrich, Brigitte Neuber, Mohamed H S Awwad, Ute Hegenbart, Hartmut Goldschmidt, Jens Hillengass, Dirk Hose, Anja Seckinger, Carsten Müller-Tidow, Anthony D Ho, Stefan Schönland, Michael Hundemer
BACKGROUND: Recent approaches in multiple myeloma (MM) treatment have targeted CD38. As antigen expression levels on plasma cells (PCs) were demonstrated to affect response to monoclonal antibody (mAb) treatment, a precise characterization of PC phenotype is warranted. METHODS: Anti-CD38 mAb (isatuximab) was tested for antibody-dependent cellular cytotoxicity (ADCC) in MM cell lines. Quantification of the number of sites (NOS) of CD38 on bone marrow PCs and other immune cells obtained from light chain (AL) amyloidosis (n=46) and smoldering multiple myeloma (SMM) patients (n=19) was performed with two different quantitative flow cytometry (QFCM) applications...
March 25, 2018: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/29576386/multiple-myeloma-clinical-updates-from-the-american-society-of-hematology-annual-meeting-2017
#7
REVIEW
Evangelos Terpos
The novel clinical data for myeloma that were presented in the 2017 Annual Meeting of the American Society of Hematology are summarized here. Studies with curative approach (CESAR) or prolonging progression-free survival (CENTAURUS) for patients with high-risk smoldering multiple myeloma (SMM) are described. Updated data from large phase III studies for patients with newly diagnosed MM (NDMM) who are eligible for autologous stem cell transplantation (ASCT) (EMN02, MRC XI) are described, along with the results of studies using novel anti-myeloma drug combinations for induction, consolidation, and maintenance as first-line therapy...
March 1, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29568990/necrobiotic-xanthogranuloma-a-30-year-single-center-experience
#8
Talal Hilal, David J DiCaudo, Suzanne M Connolly, Craig B Reeder
To characterize the clinical features, associated disorders, and treatment of necrobiotic xanthogranuloma (NXG), a rare non-Langerhans cell histiocytosis, we conducted a retrospective review of pathologically confirmed NXG at Mayo Clinic Arizona from 1987 to June 2017. Data on clinical findings, laboratory findings, associated disorders, therapy, and response to therapy were extracted. Nineteen patients were identified. Mean age was 54 years (range, 17-84) with equal gender distribution. Median follow-up was 5...
March 22, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29563136/the-pattern-of-mesenchymal-stem-cell-expression-is-an-independent-marker-of-outcome-in-multiple-myeloma
#9
Carolina Schinke, Pingping Qu, Syed J Mehdi, Antje Hoering, Joshua Epstein, Sarah Johnson, Frits van Rhee, Maurizio Zangari, Sharmilan Thanendrarajan, Bart Barlogie, Faith E Davies, Shmuel Yaccoby, Gareth Morgan
PURPOSE: Mesenchymal stem cells (MSCs) are an essential component of the bone marrow (BM) microenvironment and have shown to support cancer evolution in multiple myeloma (MM). Despite the increasing evidence that MM MSCs differ from their healthy counterparts, little knowledge exists as to whether MSCs independently influence disease outcome. The aim of the present study was to determine the importance of MSCs in disease progression and outcome in MM. EXPERIMENTAL DESIGN: To determine the impact of MSCs on MM outcome in an in vivo system, we first identified genes from cultured MSCs that were specific to MSC expression and were not or minimally expressed in PCs or other cells present in BM aspirates...
March 21, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29532268/monoclonal-gammopathy-in-rheumatic-diseases
#10
Yue Yang, Long Chen, Yuan Jia, Yang Liu, Lei Wen, Yaoxian Liang, Yuan An, Shi Chen, Yin Su, Zhanguo Li
To analyze the clinical spectrum, laboratory characteristics, and outcomes of monoclonal gammopathy (MG) in patients with rheumatic diseases. Screening for the presence of MG was performed in 872 inpatients with rheumatic diseases from January 2010 to July 2017. A total of 41 patients were enrolled. Their clinical and biological features in addition to outcomes were described. For each patient with primary Sjögren syndrome (pSS), 2 age- and sex-matched pSS patients without MG were selected as controls. Risk factors for the presence of MG and malignant hematological neoplasias were assessed...
March 13, 2018: Clinical Rheumatology
https://www.readbyqxmd.com/read/29467487/loss-of-heterozygosity-as-a-marker-of-homologous-repair-deficiency-in-multiple-myeloma-a-role-for-parp-inhibition
#11
Charlotte Pawlyn, Andrea Loehr, Cody Ashby, Ruslana Tytarenko, Shayu Deshpande, James Sun, Kyle Fedorchak, Tariq Mughal, Faith E Davies, Brian A Walker, Gareth J Morgan
PARP inhibitors can induce synthetic lethality in tumors characterized by homologous recombination deficiency (HRD), which can be detected by evaluating genome-wide loss of heterozygosity (LOH). Multiple myeloma (MM) is a genetically unstable tumor and we hypothesized that HRD-related LOH (HRD-LOH) could be detected in patient samples, supporting a potential role for PARP inhibition in MM. Using results from targeted next-generation sequencing studies (FoundationOne® Heme), we analyzed HRD-LOH in patients at all disease stages (MGUS (n = 7), smoldering MM (SMM, n = 30), newly diagnosed MM (NDMM, n = 71), treated MM (TRMM, n = 64), and relapsed MM (RLMM, n = 234)) using an algorithm to identify HRD-LOH segments...
February 2, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29463830/evolving-m-protein-pattern-in-patients-with-smoldering-multiple-myeloma-impact-on-early-progression
#12
Carlos Fernández de Larrea, Ignacio Isola, Arturo Pereira, Ma Teresa Cibeira, Laura Magnano, Natalia Tovar, Luis-Gerardo Rodríguez-Lobato, Xavier Calvo, Juan I Aróstegui, Tania Díaz, Ester Lozano, María Rozman, Jordi Yagüe, Joan Bladé, Laura Rosiñol
Smoldering multiple myeloma (SMM) is a biologically heterogeneous, clinically defined entity with a variable rate of progression to symptomatic multiple myeloma (MM). Reliable markers for progression are critical for the development of potential therapeutic interventions. We retrospectively evaluated the predictive value of the evolving pattern of serum M-protein among other progression risk factors in 206 patients with SMM diagnosed between 1973 and 2012. Median time from recognition of evolving type to progression into symptomatic MM was 1...
February 2, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29429818/undertreatment-of-older-patients-with-newly-diagnosed-multiple-myeloma-in-the-era-of-novel-therapies
#13
Bita Fakhri, Mark A Fiala, Sascha A Tuchman, Tanya M Wildes
BACKGROUND: With the expanding armamentarium of therapeutic agents for multiple myeloma (MM), it is important to identify any undertreated patient populations to mitigate outcome disparities. MATERIALS AND METHODS: We extracted the data for all plasma cell myeloma cases (International Classification of Disease for Oncology, third revision [ICD-O-3] code 9732) in the Surveillance, Epidemiology, End Results (SEER)-Medicare database from 2007 to 2011. The ICD-O-3 histologic code 9732 captures both active MM and smoldering/asymptomatic myeloma...
March 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29415936/-recurrent-invasive-pneumococcal-disease-in-a-patient-with-igg-%C3%AE%C2%BA-smoldering-multiple-myeloma
#14
Masahiro Chiba, Kazuo Oshimi, Toshihiro Matsukawa, Kouhei Okada, Takuto Miyagishima
A 68-year-old female with smoldering multiple myeloma (IgG-κ type) was admitted to the hospital owing to general fatigue, fever, and pain in the right leg. On the day following admission, she developed shock, and a blood culture revealed Streptococcus pneumoniae. She was diagnosed with septic shock and invasive pneumococcal disease (IPD). She received antibiotics and intravenous immunoglobulin and improved after several days. She had a history of recurrent IPD and had received the pneumococcal polysaccharide vaccine 23 (PPSV23) 2 years earlier...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29393672/functional-and-molecular-mri-of-the-bone-marrow-in-multiple-myeloma
#15
Vassilis Koutoulidis, Nickolas Papanikolaou, Lia A Moulopoulos
MRI plays an important role in the management of patients with plasma cell neoplasms and has been recognized as a biomarker of malignancy in the novel criteria for the diagnosis of multiple myeloma. Functional and molecular MRI techniques such as diffusion-weighted imaging (spinal or whole body), intravoxel incoherent motion, and dynamic contrast enhanced MRI, provide additional information related to tumor cellularity and angiogenesis, which may have prognostic implications for patients with smoldering and symptomatic myeloma...
February 13, 2018: British Journal of Radiology
https://www.readbyqxmd.com/read/29326807/heavy-chain-diseases-and-myeloma-associated-fanconi-syndrome-an-update
#16
REVIEW
Roberto Ria, Franco Dammacco, Angelo Vacca
The heavy chain diseases (HCDs) are rare B-cell malignancies characterized by the production of a monoclonal immunoglobulin heavy chain without an associated light chain. There are three types of HCD, defined by the class of immunoglobulin heavy chain produced: IgA (α-HCD), IgG (γ-HCD), and IgM (μ-HCD). Alpha-HCD is the most common and usually occurs as intestinal malabsorption in a young adult from a country of the Mediterranean area. Gamma- and μ-HCDs are rarer and associated with a B-cell non-Hodgkin lymphoma that produces an abnormal Ig heavy chain...
2018: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/29321378/glutamine-derived-2-hydroxyglutarate-is-associated-with-disease-progression-in-plasma-cell-malignancies
#17
Wilson I Gonsalves, Vijay Ramakrishnan, Taro Hitosugi, Toshi Ghosh, Dragan Jevremovic, Tumpa Dutta, Dhananjay Sakrikar, Xuan-Mai Petterson, Linda Wellik, Shaji K Kumar, K Sreekumaran Nair
The production of the oncometabolite 2-hydroxyglutarate (2-HG) has been associated with c-MYC overexpression. c-MYC also regulates glutamine metabolism and drives progression of asymptomatic precursor plasma cell (PC) malignancies to symptomatic multiple myeloma (MM). However, the presence of 2-HG and its clinical significance in PC malignancies is unknown. By performing 13C stable isotope resolved metabolomics (SIRM) using U[13C6]Glucose and U[13C5]Glutamine in human myeloma cell lines (HMCLs), we show that 2-HG is produced in clonal PCs and is derived predominantly from glutamine anaplerosis into the TCA cycle...
January 11, 2018: JCI Insight
https://www.readbyqxmd.com/read/29296837/baseline-mutational-patterns-and-sustained-mrd-negativity-in-patients-with-high-risk-smoldering-myeloma
#18
Sham Mailankody, Dickran Kazandjian, Neha Korde, Mark Roschewski, Elisabet Manasanch, Manisha Bhutani, Nishant Tageja, Mary Kwok, Yong Zhang, Adriana Zingone, Laurence Lamy, Rene Costello, Candis Morrison, Malin Hultcrantz, Austin Christofferson, Megan Washington, Martin Boateng, Seth M Steinberg, Maryalice Stetler-Stevenson, William D Figg, Elli Papaemmanuil, Wyndham H Wilson, Jonathan J Keats, Ola Landgren
Early results of a prospective phase 2 clinical trial of carfilzomib, lenalidomide, and dexamethasone followed by lenalidomide maintenance in high-risk smoldering myeloma showed promising results that were previously published. Here, we provide novel insights into the genetic landscape of high-risk smoldering myeloma and information on sustained minimal residual disease (MRD) negativity with an expanded cohort of patients. Eighteen patients with high-risk smoldering myeloma were enrolled between 29 May 2012, and 14 January 2014...
October 10, 2017: Blood Advances
https://www.readbyqxmd.com/read/29222256/shall-we-treat-smoldering-multiple-myeloma-in-the-near-future
#19
REVIEW
Ola Landgren
In recent years, several new drugs have been approved for the treatment of multiple myeloma. Many of these newer drugs are highly efficacious and less toxic than older chemotherapy drugs. In 2014, the diagnostic criteria for multiple myeloma were revised. The intent with the new criteria was to identify patients who require therapy at an earlier stage than at manifestation of organ complications. A subset of patients who were previously defined as having high-risk smoldering multiple myeloma was redefined as having multiple myeloma...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29159320/immunogenicity-and-persistence-of-the-13-valent-pneumococcal-conjugate-vaccine-pcv13-in-patients-with-untreated-smoldering-multiple-myeloma-smm-a-pilot-study
#20
Mathilde Bahuaud, Hélène Bodilis, Marion Malphettes, Anaïs Maugard Landre, Caroline Matondo, Didier Bouscary, Frédéric Batteux, Odile Launay, Jean-Paul Fermand
Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder that frequently progress to multiple myeloma (MM), a disease at high risk of pneumococcal infections. Moreover, if the polysaccharide vaccine is poorly immunogenic in MM, the 13-valent conjugated vaccine has never been tested in clonal plasma cell disorders. We evaluated its immunogenicity for 7 serotypes in 20 patients ≥ 50 years of age with smoldering multiple myeloma (SMM) pre and post routine-vaccination with PCV13. Concentrations of IgG specific for 7 serotypes were measured at baseline, 1, 6, and 12 months after vaccination by standardized ELISA and an Opsonophagocytic Assay (OPA)...
November 2017: Heliyon
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