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https://www.readbyqxmd.com/read/28423722/the-importance-of-the-genomic-landscape-in-waldenstr%C3%A3-m-s-macroglobulinemia-for-targeted-therapeutical-interventions
#1
REVIEW
Antonio Sacco, Adriano Fenotti, Loredana Affò, Stefano Bazzana, Domenico Russo, Marco Presta, Michele Malagola, Antonella Anastasia, Marina Motta, Christopher J Patterson, Giuseppe Rossi, Luisa Imberti, Steven P Treon, Irene M Ghobrial, Aldo M Roccaro
The Literature has recently reported on the importance of genomics in the field of hematologic malignancies, including B-cell lymphoproliferative disorders such as Waldenström's Macrolgobulinemia (WM). Particularly, whole exome sequencing has led to the identification of the MYD88L265P and CXCR4C1013G somatic variants in WM, occurring in about 90% and 30% of the patients, respectively. Subsequently, functional studies have demonstrated their functional role in supporting WM pathogenesis and disease progression, both in vitro and in vivo, thus providing the pre-clinical evidences for extremely attractive targets for novel therapeutic interventions in WM...
March 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28397326/diagnosis-and-management-of-neuropathies-associated-with-plasma-cell-dyscrasias
#2
REVIEW
Evan Rosenbaum, Douglas Marks, Shahzad Raza
Neuropathies associated with plasma cell dyscrasias are a major cause of morbidity for patients managed by medical oncologists. Because of similarities in clinical presentation and on nerve conduction studies, identifying the underlying disease leading to a paraproteinemic neuropathy can often be difficult. In addition, the degree of neurologic deficit does not strictly correlate with the extent of abnormalities on common clinical laboratory testing. Fortunately, with increasing understanding into the biologic mechanisms of underlying hematologic diseases, additional biomarkers have recently been developed, thus improving our diagnostic capacity...
April 10, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28395585/a-phase-ii-bayesian-sequential-clinical-trial-in-advanced-waldenstr%C3%A3-m-macroglobulinemia-patients-treated-with-bortezomib-interest-of-addition-of-dexamethasone
#3
Véronique Leblond, Pierre Morel, Marie-Sarah Dilhuidy, Xavier Leleu, Carole Soussain, Stéphane Leprête, Brigitte Dreyfus, Caroline Dartigeas, Béatrice Mahé, Bruno Anglaret, Brigitte Pégourié, Caroline Besson, Thérèse Aurran, Anne Vekhoff, Olivier Tournilhac, Anne Banos, Hervé Oya, Julie Lejeune, Maya Ouzegdouh, Sylvie Chevret
In patients with advanced Waldenström macroglobulinemia (WM), overall response rate (ORR) and median progression-free survival (PFS) achieved with bortezomib alone and bortezomib rituximab combination were 27-85% and 7.9 months, and 81% and 16.4 months, respectively. We checked the role of dexamethasone in combination with bortezomib by enrolling in a phase II trial 34 patients with relapsed/refractory WM. Bortezomib (1.3 mg/m(2) IV D1, 4, 8, and 11 every 21 days) was used for six cycles. In non-responding patients, dexamethasone (20 mg daily for two days) was added to each infusion after the second cycle...
April 10, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28390781/clinical-disorders-responsible-for-plasma-hyperviscosity-and-skin-complications
#4
REVIEW
Gregorio Caimi, Melania Carlisi, Caterina Urso, Rosalia Lo Presti, Eugenia Hopps
In this brief review, we have examined some clinical disorders which are associated to an altered hemorheological profile and at times accompanied by skin ulcers. This skin condition may be, in fact, observed in patients with primary plasma hyperviscosity such as multiple myeloma, Waldenstrom macroglobulinemia, cryoglobulinemia, cryofibrinogenemia, dysfibrinogenemia and connective tissue diseases. It must be underlined that the altered hemorheological pattern is not the only responsible for this skin complication but, as it worsens the microcirculatory flow, it contributes to determine the occurrence of the skin ulcers...
April 5, 2017: European Journal of Internal Medicine
https://www.readbyqxmd.com/read/28390215/waldenstr%C3%A3-m-s-macroglobulinemia-masquerading-as-ovarian-cancer-with-peritoneal-carcinomatosis-ascites-and-elevated-ca-125
#5
Patrick Eulitt, Denise Fabian, Crystal Kelly, Jessica Hemminger, Basem M William
Waldenström's macroglobulinemia is a rare hematology malignancy which often presents with "B symptoms," anemia, and thrombocytopenia. A 46-year-old woman presented with 2 months of abdominal distension accompanied by an unintentional 20-lb weight loss. Her abdominal CT scan demonstrated diffuse carcinomatosis with bilateral ovarian lesions and screening labs revealed a markedly elevated CA-125, suggesting a diagnosis of ovarian cancer. Upon admission for workup, patient was found to have a significant protein gap, later attributed to a markedly elevated IgM...
March 31, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28370087/myd88-l265p-mutation-in-cutaneous-involvement-by-waldenstr%C3%A3-m-macroglobulinemia
#6
Victoria Alegría, Lucía Prieto-Torres, Carlos Santonja, Raul Córdoba, Rebeca Manso, Luis Requena, Socorro María Rodríguez-Pinilla
Cutaneous manifestations of Waldenström macroglobulinemia may occur due to several mechanisms, the least common being direct skin infiltration by neoplastic cells. We report a case of patient that after 4-year history of indolent Waldenström macroglobulinemia developed skin infiltration by lymphoplasmacytoid cells in the form of a small, mildly indurated plaque on the anterior chest. MYD88 L265P mutation was detected both in the previous bone marrow biopsy and in the cutaneous lesion. We review the impact of this new genetic tool in the diagnosis and treatment of lymphoplasmacytic proliferations...
March 30, 2017: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/28366781/waldenstr%C3%A3-m-macroglobulinemia-review-of-pathogenesis-and-management
#7
REVIEW
Seongseok Yun, Ariel C Johnson, Onyemaechi N Okolo, Stacy J Arnold, Ali McBride, Ling Zhang, Rachid C Baz, Faiz Anwer
Waldenström macroglobulinemia (WM) is a low-grade B-cell clonal disorder characterized by lymphoplasmacytic bone marrow involvement associated with monoclonal immunoglobulin M. Although WM remains to be an incurable disease with a heterogeneous clinical course, the recent discovery of mutations in the MYD88 and CXCR4 genes further enhanced our understanding of its pathogenesis. Development of new therapies including monoclonal antibodies, proteasome inhibitors, and Bruton tyrosine kinase inhibitors have made the management of WM increasingly complex...
March 7, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28335825/canine-tick-borne-diseases-in-pet-dogs-from-romania
#8
Martin O Andersson, Conny Tolf, Paula Tamba, Mircea Stefanache, Jonas Waldenström, Gerhard Dobler, Lidia Chițimia-Dobler
BACKGROUND: Tick-borne diseases are of substantial concern worldwide for animals as well as humans. Dogs have been a human companion for millennia, and their significant impact on human life renders disease in dogs to be of great concern. Tick-borne diseases in dogs represent a substantial diagnostic challenge for veterinarians in that clinical signs are often diffuse and overlapping. In addition, co-infections with two or more pathogens enhance this problem further. Molecular methods are useful to disentangle co-infections and to accurately describe prevalence and geographical distribution of tick-borne diseases...
March 23, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28333850/multimodality-ocular-imaging-in-a-case-report-of-hyperviscosity-syndrome-associated-with-lymphoplasmacytic-leukemia-the-images-tell-the-story
#9
Rene Y Choi, Rachel Jacoby, Akbar Shakoor
PURPOSE: To report the clinical course of a patient with ocular manifestations of hyperviscosity syndrome associated with Waldenström macroglobulinemia, and for the first time, video imaging of mobile emboli in the conjunctival and retinal vasculature. METHODS AND PATIENT: A 60-year-old woman with newly diagnosed Waldenström macroglobulinemia, with no visual complaints was evaluated by the Ophthalmology service for a baseline ocular examination. RESULTS: At presentation, ocular examination revealed a visual acuity of 20/25 in each eye...
March 22, 2017: Retinal Cases & Brief Reports
https://www.readbyqxmd.com/read/28331368/new-developments-in-the-management-of-waldenstr%C3%A3-m-macroglobulinemia
#10
REVIEW
Jithma P Abeykoon, Uday Yanamandra, Prashant Kapoor
Waldenström macroglobulinemia (WM) is a rare, immunoglobulin M -associated lymphoplasmacytic lymphoma. With the recent discoveries of CXCR warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) and MYD88 mutations, our understanding of the biology of WM has expanded substantially. While WM still remains incurable, the field is rapidly evolving, and a number of promising agents with significant activity in this malignancy are being evaluated currently. In this review, we discuss the new developments that have occurred in WM over the past 15 years, with a focus on the role of ibrutinib, an oral Bruton's tyrosine kinase inhibitor that has recently been approved for WM in the United States, Europe, and Canada...
2017: Cancer Management and Research
https://www.readbyqxmd.com/read/28321094/lymphoplasmacytic-lymphoma-accompanied-by-transformed-diffuse-large-b-cell-lymphoma-with-the-myd88-l265p-mutation
#11
Toru Kida, Akira Tanimura, Akihiro Ono, Takahiro Matsui, Keiichiro Honma, Jiro Fujita, Tetsuo Maeda, Hirohiko Shibayama, Kenji Oritani, Eiichi Morii, Yuzuru Kanakura
The gene mutation occurring with transformation in lymphoplasmacytic lymphoma (LPL) /Waldenström macroglobulinemia (WM) has not been fully elucidated. Herein, we report a 61-year-old man with LPL/WM. In this case, the MYD88 gene mutation appeared with transformation to diffuse large B-cell lymphoma (DLBCL). Bone marrow biopsy revealed the involvement of CD20 positive small plasmacytoid lymphocytes, indicating LPL/WM. However, the samples taken from both the cervical lymph node and the pleural effusion provided a pathological diagnosis of DLBCL...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28295729/targeting-of-b-cell-receptor-signalling-in-b-cell-malignancies
#12
M Jerkeman, M Hallek, M Dreyling, C Thieblemont, E Kimby, L Staudt
Pharmacological agents that inhibit enzymes of the B-cell receptor (BCR) pathway are of increasing importance in the treatment of B-cell malignancies. These include inhibitors of Bruton tyrosine kinase (BTK), phosphatidylinositol 3-kinase (PI3K), splenic tyrosine kinase and protein kinase Cβ. Two agents are already approved in the USA and Europe: ibrutinib, a BTK inhibitor, for the treatment of chronic lymphatic leukaemia (CLL), mantle cell lymphoma (MCL) and Waldenström's macroglobulinemia; and idelalisib, a PI3Kδ inhibitor, for the treatment of CLL and follicular lymphoma...
March 14, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28294689/genomics-signaling-and-treatment-of-waldenstr%C3%A3-m-macroglobulinemia
#13
Zachary R Hunter, Guang Yang, Lian Xu, Xia Liu, Jorge J Castillo, Steven P Treon
Next-generation sequencing has revealed recurring somatic mutations in Waldenström macroglobulinemia (WM). Commonly recurring mutations include MYD88 (95% to 97%), CXCR4 (30% to 40%), ARID1A (17%), and CD79B (8% to 15%). Diagnostic discrimination of WM from overlapping B-cell malignancies is aided by MYD88 mutation status. Transcription is affected by MYD88 and CXCR4 mutations and includes overexpression of genes involved in VDJ recombination, CXCR4 pathway signaling, and BCL2 family members. Among patients with MYD88 mutations, those with CXCR4 mutations show transcriptional silencing of tumor suppressors associated with acquisition of mutated MYD88...
February 13, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28287298/pneumocystis-jirovecii-induced-chronic-interstitial-lung-disease-in-waldenstr%C3%A3-m-s-macroglobulinemia
#14
Wolfram Windisch, Axel Meissner, Axel Goßmann, Michael Brockmann, Verena Schildgen, Oliver Schildgen
Infections with Pneumocystis jirovecii can result in asymptomatic colonization or induce life threatening clinical symptoms. However, there appears to be a 'gray area' between colonization and severe pneumonia that remains underestimated so far. We describe a case with chronic interstitial lung disease and chronic cough that was attributed to P. jirovecii. The patient's history of chronic cough, although very likely being fostered by the underlying Waldenström's macroglobulinemia and interstitial lung disease, was most likely caused by P...
March 2017: Future Microbiology
https://www.readbyqxmd.com/read/28286680/utility-of-myd88-in-the-differential-diagnosis-and-choice-of-second-line-therapy-in-a-case-of-nonsecretory-lymphoplasmacytic-lymphoma-versus-free-light-chain-waldenstrom-s-macroglobulinemia
#15
D Kazmierski, M L Palomba, C Barsigian
The MYD88 L265P somatic variant (MYD88) has a high prevalence in Waldenstrom's Macroglobulinemia (WM), a form of lymphoplasmacytic lymphoma (LPL) associated with monoclonal IgM. Although the role of MYD88 in WM was initially reported in 2012, it was not until 2016 that MYD88 testing was included in the National Cancer Care Network (NCCN) Guidelines. We present a case illustrating the utility of MYD88 status in distinguishing atypical forms of WM from marginal zone lymphoma (MZL) and in selecting second-line therapy with ibrutinib...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28284031/immunoparesis-in-igm-gammopathies-as-a-useful-biomarker-to-predict-disease-progression
#16
Marcio Andrade-Campos, Ilda Murillo-Flórez, Ramón García-Sanz, Pilar Giraldo
BACKGROUND: The management of IgM monoclonal gammopathies undetermined significance (IgM-MGUS) and Waldenstrom's macroglobulinemia (WM) may be challenging. Modern immunoassays that quantify specific monoclonal heavy and light chain immunoglobulins are promising for their use in these applications. METHODS: Ninety consecutive patients (39 IgM-MGUS, 32 indolent WM [iWM], and 19 WM) seen between January 2007 and March 2014 were analyzed. Heavy/light chain (HLC) and serum free light chains assays (FLC) were determined at diagnosis to study their utility as biomarkers in IgM monoclonal gammopathies...
March 11, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28280994/detection-of-myd88-l265p-and-whim-like-cxcr4-mutation-in-patients-with-igm-monoclonal-gammopathy-related-disease
#17
Xin-Xin Cao, Qi Meng, Hao Cai, Tian-Hua He, Cong-Li Zhang, Wei Su, Jian Sun, Yue Li, Wei Xu, Dao-Bin Zhou, Jian Li
A broad spectrum of diseases are associated with IgM monoclonal gammopathy, including Waldenstrom macroglobulinemia (WM), various types of B cell non-Hodgkin's lymphoma (NHL), multiple myeloma (MM), primary amyloidosis (AL), and monoclonal gammopathy of undetermined significance (MGUS); these are called IgM monoclonal gammopathy related diseases (IgM-RD). We investigated MYD88 L265P and WHIM-like CXCR4 mutations in various IgM-RD. Patients with serum immunofixation electrophoresis confirmed IgM monoclonal gammopathy who had enough material for DNA extraction and presented between January 2008 and October 2016 at Peking Union Medical College Hospital were enrolled in this cohort...
March 9, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28277849/targeting-indolent-non-hodgkin-lymphoma
#18
Lori A Leslie, Alan P Skarbnik, Coleen Bejot, Susan Stives, Tatyana A Feldman, Andre H Goy
Due to recent advancements in the understanding of the molecular pathogenesis of B-cell malignancies, there has been an explosion of innovative agents in development. The purpose of this review is to efficiently summarize novel therapies with activity in indolent non-Hodgkin lymphoma (iNHL) targeting surface antigens, signaling pathways, and the tumor microenvironment. Areas covered: A literature search was performed to identify preclinical data and clinical trials focused on the use of targeted therapies in iNHL subtypes including follicular lymphoma, marginal zone lymphoma, small lymphocytic lymphoma, and lymphoplasmacytic lymphoma/Waldenström macroglobulinemia...
March 15, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28273184/-how-can-we-treat-waldenstr%C3%A3-m-s-macroglobulinemia
#19
Anna Orsolya Mucsi, Zsolt Nagy
Waldenström's macroglobulinemia is a rare, low-grade non-Hodgkin lymphoma of B cell origin, most common in elderly male patients with a median age of 64 years at diagnosis. It accounts for approximately 2% of hematologic malignancies. The disease is incurable now with a median overall survival of 6.2 years. In the past decade growing evidence suggests the role of the complex signaling pathways and microenvironment as a potential target of the therapy in the lymphoproliferative disorders as well as Waldenström's macroglobulinemia...
March 8, 2017: Magyar Onkologia
https://www.readbyqxmd.com/read/28273183/-the-pathology-and-genetic-background-of-lymphoplasmacytic-lymphoma-waldenstr%C3%A3-m-macroglobulinaemia
#20
Botond Timár
Lymphoplasmacytic lymphoma is a rare low-grade B-cell lymphoma, which is composed of a mixture of small lymphocytes, plasmacytoid cells and plasma cells that typically infiltrate the bone marrow, but lymph nodes and rarely other organs can be involved as well. Waldenström macroglobulinaemia is a lymphoplasmacytic lymphoma with typical bone marrow involvement and is associated with detectable IgM paraproteins. The diagnosis of lymphoplasmacytic lymphoma/Waldenström macroglobulinaemia (LPL/WM) can be challenging, due to similarities to other small B-cell lymphomas with plasmacytic differentiation and/or with IgM paraproteins...
March 8, 2017: Magyar Onkologia
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