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Waldenstrom macroglobulinemia

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https://www.readbyqxmd.com/read/28548645/waldenstrom-macroglobulinemia-cells-devoid-of-btk-c481s-or-cxcr4-whim-like-mutations-acquire-resistance-to-ibrutinib-through-upregulation-of-bcl-2-and-akt-resulting-in-vulnerability-towards-venetoclax-or-mk2206-treatment
#1
A Paulus, S Akhtar, H Yousaf, A Manna, S M Paulus, Y Bashir, T R Caulfield, M Kuranz-Blake, K Chitta, X Wang, Y Asmann, R Hudec, W Springer, S Ailawadhi, A Chanan-Khan
Although ibrutinib is highly effective in Waldenstrom macroglobulinemia (WM), no complete remissions in WM patients treated with ibrutinib have been reported to date. Moreover, ibrutinib-resistant disease is being steadily reported and is associated with dismal clinical outcome (overall survival of 2.9-3.1 months). To understand mechanisms of ibrutinib resistance in WM, we established ibrutinib-resistant in vitro models using validated WM cell lines. Characterization of these models revealed the absence of BTK(C481S) and CXCR4(WHIM-like) mutations...
May 26, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28536906/current-status-of-bruton-s-tyrosine-kinase-inhibitor-development-and-use-in-b-cell-malignancies
#2
REVIEW
Andrew Aw, Jennifer R Brown
The B-cell receptor (BCR) pathway plays an important role in the survival, proliferation and trafficking of cancer cells in a variety of B-cell malignancies. Recently, a number of agents have been developed to target various components of the BCR pathway. One such target is Bruton's tyrosine kinase (BTK), a Tec family kinase member found near the cell membrane that is involved in upstream BCR signaling. The biological function of BTK in several B-cell lymphoid malignancies has led to the development of the oral BTK inhibitor ibrutinib...
May 23, 2017: Drugs & Aging
https://www.readbyqxmd.com/read/28529201/bing-neel-syndrome-with-detectable-myd88-l265p-gene-mutation-as-a-late-relapse-following-autologous-hematopoietic-stem-cell-transplantation-for-waldenstr%C3%A3-m-s-macroglobulinemia
#3
Anna J Kopińska, Grzegorz Helbig, Anna Koclęga, Sławomira Kyrcz-Krzemień
No abstract text is available yet for this article.
June 5, 2017: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
https://www.readbyqxmd.com/read/28523957/clinical-case-idelalisib-induced-immunoglobulin-flare
#4
Jan Novak, Martin Havrda, Lubica Gaherova, Jan Spicka, Tomas Kozak
IgM flare is a transient, treatment-induced, increase of monoclonal IgM levels in lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) patients. Until recently this phenomenon was observed in patients treated with Cladribine and Rituximab. Here we report a case of a heavily pretreated chronic lymphocytic leukemia patient with an atypically high immunoglobulin production who developed clinically significant immunoglobulin flare following Idelalisib treatment.
May 19, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28520564/normothermic-cardiopulmonary-bypass-in-patient-with-waldenstr%C3%A3-m-s-macroglobulinemia-and-cryoglobulinemia-a-case-report
#5
Shiho Satomi, Asuka Kasai, Eisuke Hamaguchi, Yasuo M Tsutsumi, Katsuya Tanaka
Waldenström's macroglobulinemia (WM) manifests as hyperviscosity syndrome. Cryoglobulinemia, which may increase blood viscosity or induce thrombosis in association with decreased body temperature, can occur in combination with WM. We describe the management of an 82-year-old woman with WM, hyperviscosity syndrome, and cryoglobulinemia who required open aortic valve replacement. Decreased body temperature in this patient was prevented during cardiopulmonary bypass by using a forced air warming system and normothermic cardioplegia with continuous warm blood cardioplegia perfusion...
May 17, 2017: A & A Case Reports
https://www.readbyqxmd.com/read/28508985/light-chain-fanconi-syndrome-in-a-patient-with-acute-myeloid-leukemia-and-monoclonal-gammopathy-of-undetermined-significance
#6
Daniel W Ross, Rimda Wanchoo, Adriana Guigova, Cristina Ghiuzeli, Steven L Allen, Kenar D Jhaveri
Proximal tubules are a target for paraproteinemic diseases. Cast nephropathy, light chain deposition diseases, and amyloidosis are frequently encountered in patients with multiple myeloma. Rarely, a subset of patients develop light chain Fanconi syndrome (LCFS). LCFS has been reported with multiple myeloma, monoclonal gammopathy of renal significance (MGRS), chronic lymphocytic leukemia, Waldenstrom's macroglobulinemia and diffuse large B-cell lymphoma. No cases have been described with other hematologic malignancies...
November 2016: CEN Case Reports
https://www.readbyqxmd.com/read/28482711/the-presence-of-monoclonal-gammopathy-in-ph-negative-myeloproliferative-neoplasms-is-associated-with-a-detrimental-effect-on-outcomes
#7
Lenaïg Le Clech, Mehdi Sakka, Ahmed Meskar, Helene Kerspern, Jean-Richard Eveillard, Christian Berthou, Caroline Buors, Eric Lippert, Gaelle Guillerm, Isabelle Quintin-Roué, Jean-Luc Carré, Jean-Christophe Ianotto
Many case reports have indicated the occurrence of monoclonal gammopathy of uncertain significance (MGUS) or multiple myeloma (MM) in patients with Ph-negative myeloproliferative neoplasms (MPN), but few cohorts of patients have been published. This study concerns 667 patients newly diagnosed with polycythemia vera (PV) or essential thrombocythemia (ET) who were tested for monoclonal (M) protein at diagnosis (13.9% of patients). The overall survival of patients with M protein was dramatically lower than that of patients without M protein (12...
May 9, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28473042/monoclonal-gammopathy-associated-peripheral-neuropathy-diagnosis-and-management
#8
REVIEW
Hafsa M Chaudhry, Michelle L Mauermann, S Vincent Rajkumar
Monoclonal gammopathies comprise a spectrum of clonal plasma cell disorders that include monoclonal gammopathy of undetermined significance, multiple myeloma, and Waldenström macroglobulinemia. In this review, we outline the epidemiology, etiology, classification, diagnosis, and treatment of monoclonal gammopathy-associated peripheral neuropathy. Monoclonal gammopathy of undetermined significance is relatively common in the general population, with a prevalence of 3% to 4% among individuals older than age 50 years...
May 2017: Mayo Clinic Proceedings
https://www.readbyqxmd.com/read/28469834/ibrutinib-associated-skin-toxicity-a-case-of-maculopapular-rash-in-a-79-year-old-caucasian-male-patient-with-relapsed-waldenstrom-s-macroglobulinemia-and-review-of-the-literature
#9
Anders Bisgaard Jensen, Birgitte Stausbøl-Grøn, Rikke Riber-Hansen, Francesco d'Amore
Waldenstrom's macroglobulinamia (WM) is a rare malignant lymphoproliferative disorder, characterized by monoclonal IgM paraproteinemia and neoplastic proliferation of malignant lymphoplasmacytoid cells in the bone marrow. Traditionally, WM has been treated with modalities similar to those used in the management of other indolent lymphomas. Just recently, based on impressive clinical trial results in heavily pretreated WM patients, a new Bruton Tyrosine Kinase-inhibitor, Ibrutinib, has been approved for the treatment of this disorder...
March 13, 2017: Dermatology Reports
https://www.readbyqxmd.com/read/28423722/the-importance-of-the-genomic-landscape-in-waldenstr%C3%A3-m-s-macroglobulinemia-for-targeted-therapeutical-interventions
#10
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...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28397326/diagnosis-and-management-of-neuropathies-associated-with-plasma-cell-dyscrasias
#11
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
#12
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
#13
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
#14
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
#15
Victoria Alegría-Landa, Lucía Prieto-Torres, Carlos Santonja, Raul Córdoba, Rebeca Manso, Luis Requena, Socorro M Rodríguez-Pinilla
Cutaneous manifestations of Waldenström macroglobulinemia (WM) may occur because of 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 WM 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
#16
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...
May 2017: Clinical Lymphoma, Myeloma & Leukemia
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
#17
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
#18
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
#19
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
#20
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
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