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https://www.readbyqxmd.com/read/27914971/once-weekly-ofatumumab-in-untreated-or-relapsed-waldenstr%C3%A3-m-s-macroglobulinaemia-an-open-label-single-arm-phase-2-study
#1
Richard R Furman, Herbert A Eradat, Christine G DiRienzo, Craig C Hofmeister, Suzanne R Hayman, John P Leonard, Morton Coleman, Ranjana Advani, Asher Chanan-Khan, Julie Switzky, Qiming M Liao, Damini Shah, Roxanne C Jewell, Steen Lisby, Thomas S Lin
BACKGROUND: The development of more effective and safer treatments, especially non-chemotherapeutics, is needed for patients with Waldenström's macroglobulinaemia. The aim of the study was to assess the safety and clinical activity of intravenous ofatumumab monotherapy for untreated and relapsed Waldenström's macroglobulinaemia. METHODS: We did a phase 2, open-label, single-arm study at six centres (hospitals and cancer clinics) in the USA. Patients aged at least 18 years who were diagnosed with untreated or relapsed Waldenström's macroglobulinaemia and required treatment, received up to three cycles of weekly ofatumumab for 5 weeks...
November 30, 2016: Lancet Haematology
https://www.readbyqxmd.com/read/27914970/ofatumumab-another-way-to-target-cd20-in-waldenstr%C3%A3-m-s-macroglobulinaemia
#2
Christian Buske
No abstract text is available yet for this article.
November 30, 2016: Lancet Haematology
https://www.readbyqxmd.com/read/27899193/genetic-predisposition-to-leukemia-and-other-hematologic-malignancies
#3
REVIEW
Simone Feurstein, Michael W Drazer, Lucy A Godley
In this review, we provide an overview of familial myelodysplastic syndromes (MDS)/acute leukemia (AL) and bone marrow failure syndromes, as well as insights into familial myeloproliferative neoplasms (MPNs), familial multiple myeloma (MM), familial Waldenström macroglobulinemia (WM), familial lymphoma, and cancer predisposition syndromes with increased risk of MDS/AL. This field will continue to accelerate as next-generation sequencing (NGS) techniques identify novel predisposition alleles in families with a genetic predisposition to hematologic malignancies...
October 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/27890075/clone-specific-myd88-l265p-and-cxcr4-mutation-status-can-provide-clinical-utility-in-suspected-waldenstr%C3%A3-m-macroglobulinemia-lymphoplasmacytic-lymphoma
#4
Bettina Burnworth, Zhixing Wang, Timothy P Singleton, Angela Bennington, Wayne Fritschle, Richard Bennington, Lisa Eidenschink Brodersen, Denise A Wells, Michael R Loken, Barbara K Zehentner
MYD88 L265P, a diagnostic marker for lymphoplasmacytic lymphoma (LPL)/Waldenström macroglobulinemia (WM) can also be detected in other hematopoietic malignancies. We demonstrate a novel approach to increase the specificity of this marker for WM/LPL diagnosis by combining flow cytometric cell sorting with molecular analysis. Clonal B-lymphocyte and co-occurring clonal plasma cell populations of low-grade B-cell lymphomas were sorted by flow cytometry and analyzed for immunoglobulin gene rearrangements (PCR), and for MYD88 and CXCR4 mutations...
December 2016: Leukemia Research
https://www.readbyqxmd.com/read/27872060/bdr-in-newly-diagnosed-patients-with-wm-final-analysis-of-a-phase-2-study-after-a-minimum-follow-up-of-6-years
#5
Maria Gavriatopoulou, Ramón García-Sanz, Efstathios Kastritis, Pierre Morel, Marie-Christine Kyrtsonis, Eurydiki Michalis, Zafiris Kartasis, Xavier Leleu, Giovanni Palladini, Alessandra Tedeschi, Dimitra Gika, Giampaolo Merlini, Pieter Sonneveld, Meletios A Dimopoulos
In this phase 2 multicenter trial, we evaluated the efficacy of the combination of bortezomib, dexamethasone and rituximab (BDR) in 59 previously untreated symptomatic patients with Waldenström's Macroglobulinemia, most of which were of advanced age and with adverse prognostic factors. BDR consisted of a single 21-day cycle of bortezomib alone (1.3 mg/m(2) IV days 1, 4, 8, and 11), followed by weekly IV bortezomib (1.6 mg/m(2) days 1, 8, 15, and 22) for 4 additional 35-day cycles, with IV dexamethasone (40 mg) and IV rituximab (375 mg/m(2)) on cycles 2 and 5, for a total treatment duration of 23 weeks...
November 21, 2016: Blood
https://www.readbyqxmd.com/read/27870550/clinical-and-immunological-characteristics-of-autoimmune-addison-s-disease-a-nationwide-swedish-multicenter-study
#6
Frida Dalin, Gabriel Nordling Eriksson, Per Dahlqvist, Åsa Hallgren, Jeanette Wahlberg, Olov Ekwall, Stefan Söderberg, Johan Rönnelid, Per Olcén, Ola Winqvist, Sergiu-Bogdan Catrina, Berit Kriström, Maria Laudius, Magnus Isaksson, Maria Halldin Stenlid, Jan Gustafsson, Gennet Gebre-Medhin, Sigridur Björnsdottir, Annika Janson, Anna-Karin Åkerman, Jan Åman, Karel Duchen, Ragnhildur Bergthorsdottir, Gudmundur Johannsson, Emma Lindskog, Mona Landin-Olsson, Maria Elfving, Erik Waldenström, Anna-Lena Hulting, Olle Kämpe, Sophie Bensing
CONTEXT: Studies on clinical and immunological features of Autoimmune Addison's disease (AAD) are needed to understand the disease burden and increased mortality. OBJECTIVE: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles and cardiovascular risk factors. DESIGN, SETTING AND PARTICIPANTS: Cross sectional, population-based study. 660 AAD patients were included utilizing the Swedish Addison Registry (SAR) 2008-2014...
November 21, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27864891/3d-mri-quantification-of-femoral-head-deformity-in-legg-calv%C3%A3-perthes-disease
#7
Karen D Standefer, Molly Dempsey, ChanHee Jo, Harry K W Kim
The purpose of this study was to quantify femoral head deformity in patients with Legg-Calvé-Perthes disease (LCPD) using a novel three dimensional (3D) magnetic resonance imaging (MRI) reconstruction and volume based analysis. Bilateral femoral heads of 17 patients (mean age 9.9 ± 2.0 years; 12 boys, 5 girls) with LCPD were scanned 1-2 times (n= 33 LCPD heads, 20 normal heads) using a 1.5T MRI scanner. Fourteen patients had unilateral and three had bilateral LCPD with 5 hips in the Waldenström initial stage, 9 in the fragmentation stage, 14 in the reossification stage, and 5 in the healed stage...
November 19, 2016: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/27852906/assessment-of-femoral-head-revascularization-in-legg-calv%C3%A3-perthes-disease-using-serial-perfusion-mri
#8
Harry K W Kim, Jamie Burgess, Alec Thoveson, Paul Gudmundsson, Molly Dempsey, Chan-Hee Jo
BACKGROUND: Legg-Calvé-Perthes disease is a juvenile form of osteonecrosis of the femoral head. The purpose of this study was to use serial perfusion magnetic resonance imaging (MRI) to determine the pattern and rate of revascularization of the femoral heads of patients with the active stage of Legg-Calvé-Perthes disease. METHODS: We performed a prospective study of 29 patients (30 hips) with a mean age (and standard deviation) of 8.4 ± 1.9 years who were diagnosed with Waldenström Stage-1 or 2 Legg-Calvé-Perthes disease...
November 16, 2016: Journal of Bone and Joint Surgery. American Volume
https://www.readbyqxmd.com/read/27836860/prospective-multicenter-clinical-trial-of-everolimus-as-primary-therapy-in-waldenstrom-macroglobulinemia-wmctg-09-214
#9
Steven P Treon, Kirsten Meid, Christina Tripsas, Leonard T Heffner, Herbert Eradat, Ashraf Z Badros, Lian Xu, Zachary R Hunter, Guang Yang, Christopher J Petterson, Joshua Gustine, Jorge J Castillo, Jeffrey Matous, Irene M Ghobrial
PURPOSE: Everolimus inhibits mTOR, a component of PI3K/AKT pro-survival signaling triggered by MYD88 and CXCR4 activating mutations in Waldenstrom's Macroglobulinemia (WM). EXPERIMENTAL DESIGN: We evaluated everolimus in a prospective, multicenter study of 33 symptomatic, previously untreated WM patients. Intended therapy consisted of everolimus (10 mg/day) until progression or unacceptable toxicity. Dose de-escalation was permitted. The study was registered at www...
November 11, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27825469/the-role-of-stem-cell-transplantation-in-waldenstrom-s-macroglobulinemia
#10
REVIEW
Rajshekhar Chakraborty, Eli Muchtar, Morie A Gertz
Waldenstrom's macroglobulinemia (WM) is an indolent B-cell lymphoma, which is highly chemosensitive, with an overall response rate over 90% to novel agents. However, most patients eventually relapse after response to first-line chemotherapy, necessitating further treatment. The possibility of long-lasting remission after high-dose cytotoxic chemotherapy followed by stem cell rescue is high in WM due to the chemosensitive nature of the disease and lower proliferative activity compared to multiple myeloma. In this paper, we have reviewed current evidence on autologous (auto-) and allogeneic (allo-) stem cell transplantation (SCT) in WM...
June 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27825468/novel-therapeutic-targets-in-waldenstrom-macroglobulinemia
#11
REVIEW
Aneel Paulus, Sikander Ailawadhi, Asher Chanan-Khan
Understanding of molecular mechanisms that drive Waldenstrom macroglobulinemia (WM) cell survival are rapidly evolving. This review briefly highlights emerging "WM-relevant" targets; for which therapeutic strategies are currently being investigated in preclinical and clinical studies. With the discovery of MYD88L265P signaling and remarkable activity of ibrutinib in WM, other targets within the B-cell receptor pathway are now being focused on for therapeutic intervention. Additional targets which play a role in WM cell survival include TLR7, 8 and 9, proteasome-associated deubiquitinating enzymes (USP14 and UCHL5), XPO1/CRM1 and AURKA...
June 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27825467/future-therapeutic-options-for-patients-with-waldenstr%C3%A3-m-macroglobulinemia
#12
REVIEW
Jorge J Castillo, Zachary R Hunter, Guang Yang, Kimon Argyropoulos, M Lia Palomba, Steven P Treon
Waldenström macroglobulinemia (WM) is a rare lymphoma characterized by the accumulation of IgM-producing lymphoplasmacytic cells. Although WM patients can experience prolonged remissions, the disease invariably recurs. Therefore, novel treatments associated with higher success rates and lower toxicity profiles are needed. The discovery of recurrent mutations in the MYD88 and CXCR4 genes has unraveled potential therapeutic targets in WM patients. As a result of these findings and based on the design and execution of a prospective clinical trial, the FDA granted approval to ibrutinib, an oral Bruton tyrosine kinase (BTK) inhibitor, to treat patients with symptomatic WM...
June 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27825466/current-therapy-guidelines-for-waldenstrom-s-macroglobulinaemia
#13
REVIEW
Efstathios Kastritis, Meletios A Dimopoulos
Waldenstrom's macroglobulinaemia (WM) is a B-cell neoplasm in which bone marrow is infiltrated by lymphoplasmacytic cells that secrete monoclonal immunoglobulin M (IgM). More than a decade ago, specific criteria were agreed to define diagnosis and symptomatic disease requiring therapy; however, treatment recommendations change as new options emerge. Treatment decisions consider specific disease characteristics (burden of disease, IgM levels, presence of cytopenias) and patient characteristics (age, comorbidities, toxicity)...
June 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27825465/monoclonal-gammopathy-of-undetermined-significance-and-waldenstr%C3%A3-m-s-macroglobulinemia
#14
REVIEW
Sham Mailankody, Ola Landgren
Since the initial identification of patients with monoclonal elevation of gamma globulin and associated clinical symptoms in 1944 by Jan Waldenström, several new insights have been gained using a range of approaches. For example, IgM monoclonal gammopathy of undetermined significance and smoldering Waldenström's macroglobulinemia are defined clinical precursor states to symptomatic Waldenström's macroglobulinemia. Epidemiologic studies have established the prevalence of these conditions and the estimated risk of progression to symptomatic disease...
June 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27825464/prognostic-factors-and-indications-for-treatment-of-waldenstr%C3%A3-m-s-macroglobulinemia
#15
REVIEW
Robert A Kyle, Stephen M Ansell, Prashant Kapoor
Waldenström's Macroglobulinemia (WM) is characterized by the presence of an IgM monoclonal protein regardless of its size, 10% or more bone marrow infiltration by small lymphocytes with a plasmacytoid or plasma cell differentiation. These cells usually have the following markers: IgM+, CD5(-), CD10(-), CD19(+), CD20(+) and CD23(-). Chronic lymphocytic leukemia as well as other lymphoproliferative disorders such as mantle cell, marginal zone and mucosa-associated lymphoid tissue (MALT) lymphoma must be excluded...
June 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27825463/preclinical-models-of-waldenstr%C3%A3-m-s-macroglobulinemia-and-drug-resistance
#16
REVIEW
Sikander Ailawadhi, Aneel Paulus, Asher Chanan-Khan
Newer therapeutic strategies are emerging in Waldenström's Macroglobulinemia (WM), which has traditionally been an orphan disease diagnosis. Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor was FDA-approved in 2015 as the first ever drug for the treatment of WM. This being a targeted therapy, has given rise to increased research into novel agents and pathways that can be exploited for clinical benefit in WM. In order to understand the underlying mechanisms of disease behavior as well as to test the benefit of various drugs, appropriate preclinical models are required...
June 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27825462/targeting-cell-adhesion-and-homing-as-strategy-to-cure-waldenstr%C3%A3-m-s-macroglobulinemia
#17
REVIEW
Steven T Pals, Marie José Kersten, Marcel Spaargaren
Most B-cell malignancies strictly depend on signals from the microenvironment for their survival and proliferation. This niche-dependency can be regarded as their Achilles' heel and provides an excellent target for therapy. Waldenström's macroglobulinemia (WM) is characterized by the accumulation of neoplastic post-germinal center B cells within the bone marrow (BM). Interestingly, one third of the patients carry activating mutations in the chemokine receptor CXCR4, a key mediator of B cell and plasma cell homing to the BM...
June 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27825461/epigenomics-in-waldenstrom-s-macroglobulinaemia
#18
REVIEW
Antonio Sacco, Adriano Fenotti, Stefano Bazzana, Luisa Imberti, Giuseppe Rossi, Christopher J Patterson, Steven P Treon, Irene M Ghobrial, Aldo M Roccaro
Epigenomics refers to study of the epigenome, which represents changes in gene expression that are not induced by DNA sequence aberrations. For instance, DNA methylation, histone acetylation and microRNAs may modulate gene expression without altering the gene sequence. Waldenström's macroglobulinaemia (WM) is a low-grade B-cell lymphoma, classified as lymphoplasmacytic lymphoma, characterized by the presence of clonal lymphoplasmacytic cells in the bone marrow and serum monoclonal immunoglobulin-M in the circulation...
June 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27825460/bone-marrow-microenvironment-in-waldenstrom-s-macroglobulinemia
#19
REVIEW
Shahrzad Jalali, Stephen M Ansell
Waldenstrom Macroglobulinemia (WM) is a low-grade B-cell lymphoma defined firstly by infiltration of lymphoplasmacytic cells into the bone marrow (BM), the milieu where the cells acquire signals that promote malignant growth and proliferation. A second characteristic associated with WM is the increased synthesis of monoclonal immunoglobulin M (IgM) by lymphoplasmacytic cells, which is secreted in the serum and often results in hyperviscosity. Advanced genomic tools have improved our understanding of the genetic events that contribute to malignant transformation in WM, but the role of BM microenvironment is also emerging as having an essential role in WM disease progression...
June 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27825459/origin-of-waldenstrom-s-macroglobulinaemia
#20
REVIEW
Ramón García-Sanz, Cristina Jiménez, Noemí Puig, Bruno Paiva, Norma C Gutiérrez, Paula Rodríguez-Otero, Julia Almeida, Jesús San Miguel, Alberto Orfão, Marcos González, Martín Pérez-Andrés
Waldenstrom's macroglobulinaemia (WM) is an MYD88(L265P)-mutated lymphoplasmacytic lymphoma that invades bone marrow and secretes monoclonal immunoglobulin M (IgM). WM cells are usually unable to undergo class switch recombination, and have mutated IGHV, with a typical immunophenotype CD19(+)/CD22(low+)/CD23(-)/CD25(+)/CD27(+)/CD45(+)/CD38(low+)/SmIgM(+) (negative for CD5, CD10, CD11c, CD103). This immunophenotype matches memory B cells (smIgM(-/+)/CD10(-)/CD19(+)/CD20(+)/CD27(+)/CD38(low+)/CD45(+)), representing 30% of B cells in the blood...
June 2016: Best Practice & Research. Clinical Haematology
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