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Rituximab resistance

Poorva Bindal, Sharif Aa Jalil, Lisa M Holle, Jessica M Clement
Nearly all men with prostate cancer who are treated with androgen deprivation therapy develop disease progression. There is considerable evidence to suggest that CXCL 13 released by tumor cells leads to B-cell infiltration into the prostate cells. This B-cell infiltration has been postulated to play a role in development of disease progression following androgen-deprivation therapies. We present a case of a patient who achieved remission of metastatic castrate-resistant prostate cancer after receiving rituximab and bendamustine for the treatment of follicular lymphoma...
August 9, 2018: Journal of Oncology Pharmacy Practice
Michela Cioni, Arcangelo Nocera, Augusto Tagliamacco, Sabrina Basso, Annalisa Innocente, Iris Fontana, Alberto Magnasco, Antonella Trivelli, Catherine Klersy, Antonella Gurrado, Miriam Ramondetta, Stella Boghen, Laura Catenacci, Enrico Verrina, Giacomo Garibotto, Gian Marco Ghiggeri, Massimo Cardillo, Fabrizio Ginevri, Patrizia Comoli
Current research is focusing on identifying bioclinical parameters for risk stratification of renal allograft loss, largely due to antibody-mediated rejection (AMR). We retrospectively investigated graft outcome predictors in 24 unsensitized pediatric kidney recipients developing HLA de novo donor-specific antibodies (dnDSAs), and treated for late AMR with plasmapheresis+low-dose IVIG+Rituximab or high-dose IVIG+Rituximab. Renal function and DSA properties were assessed before and longitudinally post-treatment...
August 4, 2018: Transplant International: Official Journal of the European Society for Organ Transplantation
Danka Pokrajac, Azra Hodzic Kamber, Zinaida Karasalihovic
Background: Nephrotic syndrome (NS) is one of the most frequent glomerular diseases among children. While most of the children with primary NS respond to steroid treatment, 10 to 20% of the patients are steroid-resistant, and the best therapy for such cases has never been defined. Objective: The present study aimed to evaluate steroid-resistant nephrotic syndrome (SRNS) patients. Materials and methods: Our research included 50 children (56% female and 44% male) with NS...
June 2018: Materia Socio-medica
Theo Pirich, Elisabeth Zwickl-Traxler, Martin Pecherstorfer, Josef Singer
Background & Aim: In randomised clinical trials, the type II anti-CD20 antibody obinutuzumab has been shown to be more effective than rituximab for therapy of chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL). However, this enhanced efficacy was linked with elevated rates of high-grade adverse events. The aim of this study was to assess the tolerability and toxicity profile of obinutuzumab treatment in routine patients with CLL and FL, of whom the majority had experienced toxicity or resistance to rituximab...
July 6, 2018: Oncotarget
S Keddie, S J Crisp, J Blackaby, A Cox, A Coles, M Hart, A J Church, A Vincent, M Zandi, M P Lunn
OBJECTIVE: To assess the therapeutic potential of bortezomib in treatment refractory NMDA receptor (NMDAR) antibody encephalitis and its potential in other immune mediated, B-cell driven neurological diseases. METHODS: Two cases of severe NMDAR-antibody encephalitis, resistant to first and second line therapy with steroids, IV immunoglobulins, plasma exchange, cyclophosphamide and rituximab were treated with 4 and 5 cycles of 1.3mg/m2 bortezomib at 350 and 330 days following initial presentation...
July 23, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
Jeffrey W Craig, Michael J Mina, Jennifer L Crombie, Ann S LaCasce, David M Weinstock, Geraldine S Pinkus, Olga Pozdnyakova
"Double-hit" and "double-expressor" lymphomas represent distinct but overlapping subsets of aggressive B-cell non-Hodgkin lymphoma. The high rates of bone marrow involvement by these lymphomas pose a major therapeutic challenge due to the chemotherapy-resistant nature of the bone marrow microenvironment and the limited utility of rituximab-based salvage regimens in patients with relapsed/refractory disease. Preclinical studies utilizing high-dose cyclophosphamide in combination with the anti-CD52 monoclonal antibody alemtuzumab have recently shown promise in the treatment of intramedullary disease, and a Phase I human trial is now underway...
2018: PloS One
Lekh N Dahal, Chie-Yin Huang, Richard J Stopforth, Abbie Mead, Keith Chan, Juliet X Bowater, Martin C Taylor, Priyanka Narang, H T Claude Chan, Jinny H Kim, Andrew T Vaughan, Francesco Forconi, Stephen A Beers
Rituximab is an anti-CD20 mAb used in the treatment of B cell malignancies. Loss of surface CD20 Ag from the surface of target cells is thought to be one mechanism governing resistance to rituximab, but how this occurs is not completely understood. Two explanations for this have been proposed: antigenic modulation whereby mAb:CD20 complexes are internalized in a B cell intrinsic process and shaving, in which mAb:CD20 complexes undergo trogocytic removal by effector cells, such as macrophages. However, there is conflicting evidence as to which predominates in clinical scenarios and hence the best strategies to overcome resistance...
July 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Katrin Kienzl-Wagner, Alejandra Rosales, Stefan Scheidl, Thomas Giner, Claudia Bösmüller, Michael Rudnicki, Rupert Oberhuber, Christian Margreiter, Afschin Soleiman, Dietmar Öfner, Stefan Schneeberger, Siegfried Waldegger
Primary focal segmental glomerulosclerosis (FSGS) recurs in up to 55% after kidney transplantation. Here, we report the successful management of recurrent FSGS. A 5-year old boy with primary FSGS received a deceased donor renal transplant. Immediate and fulminant recurrence of FSGS caused anuric graft failure resistant to plasmapheresis and rituximab. After exclusion of structural or immunological damage to the kidney by repeated biopsies, the allograft was retrieved from the first recipient on day 27 and transplanted into a 52-year old second recipient suffering from vascular nephropathy...
July 1, 2018: American Journal of Transplantation
Soumita Bagchi, Arun Kumar Subbiah, Dipankar Bhowmik, Sandeep Mahajan, Raj Kanwar Yadav, Mani Kalaivani, Geetika Singh, Amit Dinda, Sanjay Kumar Agarwal
Background: Persistent significant proteinuria has been associated with increased risk of progression to end-stage kidney disease in patients with idiopathic membranous nephropathy (IMN). Rituximab (RTX) therapy has given encouraging results in IMN, but most of the studies have used a higher dose, which is limited by the high cost as well as a potential increased risk of infections. Our study aimed to assess the efficacy and safety of low-dose RTX in patients with immunosuppression-resistant IMN...
June 2018: Clinical Kidney Journal
Diego Strianese
PURPOSE: To present an update on the efficacy and safety of immunosuppressive therapy for thyroid eye disease (TED) and to offer a general recommendation for management of TED, in light of these reports. METHODS: Data were retrieved from a literature search on PubMed, using the following words: thyroid eye disease, immunosuppressant, corticosteroid, methotrexate, azathioprine, cyclosporine, cyclophosphamide, rituximab, etanercept, adalimumab, tocilizumab, teprotumumab, adverse effects, side effects, and complications...
July 2018: Ophthalmic Plastic and Reconstructive Surgery
Biswanath Basu, Anja Sander, Birendranath Roy, Stella Preussler, Shilpita Barua, T K S Mahapatra, Franz Schaefer
Importance: Calcineurin inhibitors are an established first-line corticosteroid-sparing therapy for patients with corticosteroid-dependent nephrotic syndrome (CDNS), whereas B-lymphocyte-depleting therapy is mostly used as a rescue for calcineurin inhibitor-resistant cases. The positive efficacy and safety profile of rituximab raises the question of whether it could be used as a first-line alternative to calcineurin inhibitor therapy. Objective: To compare the efficacy of rituximab and tacrolimus in maintaining relapse-free survival among children with CDNS...
June 18, 2018: JAMA Pediatrics
Swathi Balaji, Makhdum Ahmed, Elizabeth Lorence, Fangfang Yan, Krystle Nomie, Michael Wang
Mantle cell lymphoma is an aggressive subtype of non-Hodgkin B cell lymphoma that is characterized by a poor prognosis determined by Ki67 and Mantle Cell International Prognostic Index scores, but it is becoming increasingly treatable. The majority of patients, especially if young, achieve a progression-free survival of at least 5 years. Mantle cell lymphoma can initially be treated with an anti-CD20 antibody in combination with a chemotherapy backbone, such as VR-CAP (the anti-CD20 monoclonal antibody rituximab administered with cyclophosphamide, doxorubicin, and prednisone) or R-CHOP (the anti-CD20 monoclonal antibody rituximab administered with cyclophosphamide, doxorubicin, vincristine, and prednisone)...
June 15, 2018: Journal of Hematology & Oncology
Chelsea C Pinnix, Andrea K Ng, Bouthaina S Dabaja, Sarah A Milgrom, Jillian R Gunther, C David Fuller, Grace L Smith, Zeinab Abou Yehia, Wei Qiao, Christine F Wogan, Mani Akhtari, Osama Mawlawi, L Jeffrey Medeiros, Hubert H Chuang, William Martin-Doyle, Philippe Armand, Ann S LaCasce, Yasuhiro Oki, Michelle Fanale, Jason Westin, Sattva Neelapu, Loretta Nastoupil
Dose-adjusted rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-R-EPOCH) has produced good outcomes in primary mediastinal B-cell lymphoma (PMBCL), but predictors of resistance to this treatment are unclear. We investigated whether [18 F]fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) findings could identify patients with PMBCL who would not respond completely to DA-R-EPOCH. We performed a retrospective analysis of 65 patients with newly diagnosed stage I to IV PMBCL treated at 2 tertiary cancer centers who had PET-CT scans available before and after frontline therapy with DA-R-EPOCH...
June 12, 2018: Blood Advances
Tarek Alhamad, John Manllo Dieck, Usman Younus, Dany Matar, Sami Alasfar, Vikas Vujjini, Devin Wall, Bilal Kanawati, Reiser Jochen, Daniel C Brennan, Nada Alachkar
BACKGROUND: Treatment of focal segmental glomerular sclerosis (FSGS) after kidney transplantation is challenging with unpredictable outcomes. The objective was to investigate the use of adrenocorticotropic hormone (ACTH) analogue gel in kidney transplant recipients with de novo or recurrent FSGS resistant to therapeutic plasma exchange and/or rituximab. METHODS: We performed a retrospective review of cases of de novo or recurrent resistant FSGS at 2 large U.S. transplant centers between April 2012 and December 2016...
June 12, 2018: Transplantation
Warren H Chan, Daniel J Lewis, Esther J Kim, Phyu P Aung, Madeleine Duvic
Generalized morphea is associated with epoxy resin vapors and is characterized by the development of lesions shortly after exposure. Morphea presenting along with eosinophilic fasciitis (EF), or morphea/EF overlap, is rare and an indicator of poor prognosis and resistance to treatment. Here we present a case of generalized morphea/EF overlap linked to epoxy exposure. Our patient received multiple therapies-ultraviolet A1 phototherapy, prednisone, methotrexate, azathioprine, mycophenolate mofetil, cyclophosphamide, cyclosporine, and rituximab-none of which led to a significant response...
March 2018: JAAD Case Reports
J Decaux, I Ferreira, P Van Eeckhout, C Dachelet, M Magremanne
Paraneoplastic pemphigus is a rare autoimmune blistering disease generally associated with malignancy. The clinical presentation consists typically of painful and diffuse erosive stomatitis that may be accompanied by polymorphic skin lesions and systemic involvement. Diagnosis is based on clinical manifestations and confirmed by histology and immunological testing. The current first-line treatment is systemic corticosteroids and adjuvant therapies, including immunosuppressive agents. We report a case of buccal paraneoplastic pemphigus resistant to ibrutinib and rituximab successfully treated with azathioprine and polyclonal immunoglobulins...
June 8, 2018: Journal of Stomatology, Oral and Maxillofacial Surgery
Junji Suzumiya
Chronic lymphocytic leukemia (CLL) is the most common hematological malignancy in the Western countries. Although a multi-step model has been proposed for the pathogenesis of CLL as well as other malignancies, the precise mechanism underlying the development of CLL remains complicated and unclear. In addition, several studies have investigated adverse prognostic factors, including gene abnormalities and the evolution of clones with the disease progression. FCR (fludarabine, cyclophosphamide, and rituximab) has been the standard first-line therapy for "fit" younger patients without TP53 abnormality/17p deletion...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Mitchell R Smith, Robert F Weiss
Novel agents are changing therapy for patients with CLL, but their optimal use remains unclear. We model the clinical situation in which CLL responds to therapy, but resistant clones, generally carrying del17p, progress and lead to relapse. Sub-clones of varying growth rates and treatment sensitivity affect predicted therapy outcomes. We explore effects of different approaches to starting novel agent in relation to bendamustine-rituximab induction therapy: at initiation of therapy, at the end of chemo-immunotherapy, at molecular relapse, or at clinical detection of relapse...
May 7, 2018: Leukemia Research
Paola Tatangelo, Francesco Londrino, Giorgio Di Vasta, Giuliana Guido, Alessia Centi, Sara Dominijanni, Eleonora Bernabei, Maria Stella Caramiello, Damiano Di Franco, Roberto Palumbo
A 39-year man with primary steroid resistant focal segmental glomerulosclerosis (FSGS) was treated with mycophenolate mofetil and ACE-inhibitors. After six months a different therapeutics approach was mandatory due to the worsening of renal function and the relapse of proteinuria at the nephrotic range. The combination of cascade plasmafiltration and single dose of rituximab (375 mg/m²) achieved clinical remission and improved renal function in six months follow up. Cascade plasmafiltration in association with rituximab can be considered as a salvage method for primary steroid-resistant FSGS...
May 2018: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
Sophie Béliard, Mathilde Di Filippo, Gilles Kaplanski, René Valéro
We report the first case of an autoimmune hypertriglyceridemia successfully treated with rituximab, an anti-CD20-targeted monoclonal antibody. A 45-year-old man, with prior autoimmune conditions, developed severe, acquired hypertriglyceridemia resistant to traditional triglyceride lowering therapies. After the elimination of secondary or genetic causes, we detected the presence of anti-LPL-IgG by immunoblot. After 3 infusions of rituximab, we observed a marked improvement of his hypertriglyceridemia, concomitant with a reduction in plasma anti-LPL antibody titer and B-lymphocytes counts...
April 30, 2018: Journal of Clinical Lipidology
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