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Rituximab resistance

A Ishiwatari, S Wakai, H Shirakawa, K Honda
Primary membranous nephropathy (MN) is an organ-specific autoimmune disease mainly caused by autoantibodies acting against the podocyte antigen M-type phospholipase A2 receptor 1 (PLA2R). Herein we present the clinical and histologic findings, including PLA2R staining, of early recurrent MN after kidney transplantation that was successfully treated with rituximab. A 60-year-old Japanese man had end-stage renal failure due to steroid-resistant primary MN and underwent ABO-incompatible living donor kidney transplantation...
October 2018: Transplantation Proceedings
Yunzi Liu, Yifan Shi, Rong Ren, Jingyuan Xie, Weiming Wang, Nan Chen
Focal segmental glomerulosclerosis (FSGS) is a glomerulonephritis with podocyte injury. The renal prognosis of FSGS is relative poor. The overall remission rate of the FSGS patients with nephrotic syndrome to immunosuppressive treatments was reported as 47-66%, highlighting its therapeutic challenge-lacking in sufficient evidence-based interventions. In first-line treatment of nephrotic syndrome, daily oral prednisolone is a commonly used drug, whereas optimal treatment strategies, like indications and duration, remain controversial...
October 2018: Nephrology
Ekkehard Genth
Idiopathic inflammatory myopathies (IIM) are a rare and clinically polymorphic and heterogenous group of myositis syndromes. Myositis is part of a systemic autoimmune disorder with various extramuscular manifestations affecting skin, lungs, joints, esophagus and other organ systems. Most myositis patients have autoantibodies against non organspecific antigens. More than 20 different autoantibodies are known. They are associated with different clinical phenotypes of adult or juvenile dermatomyositis or myositis-overlap syndromes and different genetic markers...
October 2018: Deutsche Medizinische Wochenschrift
Paolo Fraticelli, Colomba Fischetti, Fausto Salaffi, Marina Carotti, Massimo Mattioli, Giovanni Pomponio, Armando Gabrielli
OBJECTIVES: To describe a single centre experience using combination therapy with rituximab (RTX) and mycophenolate mofetil (MMF) in a prospective series of systemic sclerosis (SSc) patients with pulmonary and cutaneous involvement, rapidly progressive or resistant to conventional therapy. METHODS: RTX was administered in two different regimens (1000 mg fortnightly x 2 or 375 mg/m2/week for 4 consecutive weeks) at baseline and after 6 months, associated with MMF 2000 mg/day continuously...
July 2018: Clinical and Experimental Rheumatology
Manuela Colucci, Rita Carsetti, Simona Cascioli, Jessica Serafinelli, Francesco Emma, Marina Vivarelli
BACKGROUND: A pathogenic role of B cells in non-genetic nephrotic syndrome has been suggested by the efficacy of rituximab, a B cell depleting antibody, in maintaining a prolonged remission. However, little information is available on B cell homeostasis in nephrotic syndrome patients. METHODS: We retrospectively analyzed by flow cytometry the distribution of different B cell subpopulations in 107 steroid-sensitive and in 6 genetic steroid-resistant nephrotic syndrome pediatric patients, compared with age- and sex-matched controls...
September 28, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Ashwin Agarwal, Russell P Hall, Lionel L Bañez, Adela R Cardones
BACKGROUND: Rituximab is a promising steroid sparing agent used in the treatment of moderate to severe pemphigus vulgaris. Its exact place in the algorithm of pemphigus treatment, vis-à-vis other, conventional adjuvant therapy (CAT) is not known. OBJECTIVE: To describe and compare disease course outcomes and morbidity among patients with moderate to severe pemphigus who received rituximab therapy (RT) in addition to prednisone and CAT, versus those who were treated with prednisone and CAT alone...
2018: PloS One
Chunfa Huang, Yifan Tu, Carl E Freter
Fludarabine (flu) -containing regimens such as flu, cyclophosphamide and rituximab have been established as one of the standard first line therapy in medically-fit chronic lymphocytic leukemia (CLL) patients. Therefore, flu-refractory (primary flu-insensitivity or flu-caused relapse) remains a major problem causing treatment failure for CLL patients. We isolated the peripheral blood mononuclear cells (PBMCs) from CLL patients and treated with flu to find flu-refractory cases, and established flu-resistant clonal cells to study molecular mechanism of flu-resistance...
September 4, 2018: Oncotarget
Guosheng Li, Shuang Wang, Na Li, Yang Liu, Qi Feng, Xinyi Zuo, Xin Li, Yu Hou, Linlin Shao, Chunhong Ma, Chengjiang Gao, Ming Hou, Jun Peng
Primary immune thrombocytopaenia (ITP) is the most common haemorrhagic disease. Although most patients respond initially to mainstream therapies, such as corticosteroids, immunosuppressants or rituximab, a large proportion of patients fail to respond or relapse. These treatments only affect B lymphocytes or short-lived plasma cells, but not already existing long-lived plasma cells (LLPCs) which persistently secrete antibodies. We hypothesized that LLPCs may play a role in the corticosteroid-resistant or relapsed ITP patients, and bortezomib, a proteasome inhibitor, may act on plasma cells and offer a therapeutic effect...
October 2018: Thrombosis and Haemostasis
Tanja Falter, Stephanie Herold, Veronika Weyer-Elberich, Carina Scheiner, Veronique Schmitt, Charis von Auer, Xavier Messmer, Philipp Wild, Karl J Lackner, Bernhard Lämmle, Inge Scharrer
BACKGROUND:  Autoimmune thrombotic thrombocytopenic purpura (iTTP) is caused by autoantibody-mediated severe a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13 (ADAMTS13) deficiency leading to micro-angiopathic haemolytic anaemia (MAHA) and thrombocytopenia with organ damage. Patients survive with plasma exchange (PEX), fresh frozen plasma replacement and corticosteroid treatment. Anti-CD20 monoclonal antibody rituximab is increasingly used in patients resistant to conventional PEX or relapsing after an acute bout...
October 2018: Thrombosis and Haemostasis
Emanuela Zappulo, Laura Ambra Nicolini, Carmen Di Grazia, Alida Dominietto, Teresa Lamparelli, Francesca Gualandi, Patrizia Caligiuri, Bianca Bruzzone, Emanuele Angelucci, Claudio Viscoli, Malgorzata Mikulska
PURPOSE: Hepatitis B virus (HBV) reactivation during immunosuppressive therapy is common in patients with hematological malignancies, even in case of resolved infection. Prophylaxis of HBV reactivation is universally recommended in stem cell transplant (SCT) recipients and patients treated with anti-CD20 agents (i.e., rituximab). Despite its well-established favorable safety profile, lamivudine (LAM) use in prophylaxis has been debated because of the possible emergence of resistant viral strains...
September 19, 2018: Infection
Elodie Nattes, Danièle Karaa, Laurène Dehoux, Michel Peuchmaur, Theresa Kwon, Georges Deschênes
AIM: Complete or partial resistance to prednisone and calcineurin inhibitors in children with idiopathic nephrotic syndrome often leads to end stage renal disease. The aim of the study was to report the outcome of patients with multidrug resistant nephrotic syndrome treated with an association of immunoglobulin immunoadsorption, intravenous immunoglobulins and B cell depletion. METHODS: At treatment initiation, patients received 10 sessions of immunoglobulin immunoadsorption and intravenous immunoglobulins in two weeks followed by one rituximab in case of remission...
September 19, 2018: Acta Paediatrica
Alexandros Makis, Zoi Kanta, Dimitrios Kalogeropoulos, Nikoloaos Chaliasos
Autoimmune hemolytic anemia (AIHA) is a relatively uncommon hematological entity in children and sometimes is characterized by a severe course requiring more than one line course therapy. Treatment decisions depend on the severity and chronicity of the anemia and the characteristics of the autoantibodies. Immunosuppression with corticosteroids is the first-line treatment, especially in warm-reactive AIHA. Refractory cases are treated with immunosuppressive drugs, cytotoxic agents, androgens, or splenectomy, with various side effects and questionable efficacy...
2018: Case Reports in Hematology
Xiaolong Tang, Chunmei Xie, Zhenyou Jiang, Amin Li, Shiyu Cai, Changhao Hou, Jian Wang, Yong Liang, Dong Ma
The mTOR signal pathway is often highly activated in B-cell non-Hodgkin's lymphoma (NHL) and promotes cancer progression and chemo-resistance. Therefore, the pathways of mTOR are an important target for drug development in this disease. In the current study, we developed a rituximab (anti-CD20)-modified mTOR inhibitor, AZD-2014, loaded into nanoparticles (Ab-NPs-AZD-2014) for trial of its anti-NHL effect. In a cultured NHL cell line, Ab-NPs-AZD-2014 inhibited cancer cell growth, induced cell apoptosis, and blocked activation of mTORC1 and mTORC2 in Raji cells...
September 8, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Johannes Gutsch, Paul G Werthmann, Andreas Rosenwald, Gunver S Kienle
BACKGROUND: A nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) is a lymphoproliferative neoplasm with a fair prognosis, but the possibility of a malignant transformation into a diffuse large B-cell lymphoma (DLBCL) is high. DLBCL progresses aggressively. Introduction of rituximab into therapy had led to improved outcomes. The use of Viscum album extracts (VAE) in cancer is established, but their application in lymphoma are rare. CASE PRESENTATION: A 65-year-old patient was diagnosed with DLBCL stage IIa with splenomegaly, transformed from a NLPHL, after a 30-year history of repeatedly enlarged inguinal lymph nodes...
September 2018: Anticancer Research
Jaroslav Čermák, Martin Písačka
Autoimmune hemolytic anemia (AIHA) is caused by auto-antibodies directed against self red blood cell (RBC) surface antigens. A consequence may be an intravascular hemolysis mediated by activated complement or extravascular hemolysis caused by destruction of complex of RBC with autoantibody in spleen and liver. The basic classification subdivides AIHA in primary/idiopathic and secondary with known underlying disease. A classification according to the thermal range of antibody recognizes warm AIHA, cold aglutinin disease (CAD), mixed AIHA and paroxysmal cold hemoglobinuria...
2018: Vnitr̆ní Lékar̆ství
Anne Bordron, Cristina Bagacean, Audrey Mohr, Adrian Tempescul, Boutahar Bendaoud, Stéphanie Deshayes, Florence Dalbies, Caroline Buors, Hussam Saad, Christian Berthou, Jacques-Olivier Pers, Yves Renaudineau
The anti-CD20-specific monoclonal antibody rituximab (RTX), in combination with chemotherapy, is commonly used for primary treatment in chronic lymphocytic leukemia (CLL). However, relapses remain important and activation of the complement pathway is one of the mechanisms by which RTX generates the destruction of B cells directly by complement-dependent cytotoxicity (CDC), or indirectly by antibody-dependent cellular phagocytosis. In this study, the RTX capacity to induce CDC was established in 69 untreated CLL patients, this cohort including 34 patients tested before the initiation of RTX-chemotherapy...
August 3, 2018: Oncotarget
M L Hung, H T Liao, W S Chen, M H Chen, C C Lai, C Y Tsai, D M Chang
Objective The objective of this paper is to analyze the clinical features, outcomes, mortality risk factors, and all-cause mortalities of invasive aspergillosis (IA) in patients with systemic lupus erythematosus (SLE). Methods Medical records were reviewed to identify SLE patients with IA from January 2006 to June 2017, at Taipei Veterans General Hospital, Taiwan. A total of 6714 SLE patients were included. Clinical/laboratory parameters and treatment outcomes were analyzed. Results Four patients (19.0%) had definite and 17 had probable (81...
August 29, 2018: Lupus
Yuko Wada-Shimosato, Junji Ikeda, Shin-Ichi Tsujimoto, Koji Sasaki, Masakatsu Yanagimachi, Ryosuke Kajiwara, Norio Shiba, Hidetoshi Murata, Nobutaka Kawahara, Shoji Yamanaka, Reo Tanoshima, Shuichi Ito
Primary central nervous system lymphoma (PCNSL) is a rare and aggressive type of extranodal non-Hodgkin lymphoma that carries an unsatisfactory prognosis. Treating refractory PCNSL is challenging because of resistance to conventional cytotoxic and intrathecal chemotherapies. Therefore, novel therapeutic approaches are needed. Here, we report a 12-year-old boy with CD20-positive PCNSL, which was refractory to combination chemotherapy and intravenous rituximab. However, the patient achieved complete remission after repeated intraventricular rituximab administration...
August 17, 2018: Journal of Pediatric Hematology/oncology
Mukesh Patekar, Ajay Gogia, Akash Tiwari, Lalit Kumar, Atul Sharma, Soumya Ranjan Mallick, Mehar Chand Sharma, Sanjay Thulkar, Ritu Gupta
Background: Burkitt lymphoma (BL) is treated with short, intensive, noncross resistant multidrug chemotherapy regimens. The management of this aggressive lymphoma is a challenge in our resource-limited setting, and the published data from India is scarce. Aim: This retrospective study aims to evaluate the clinical features and treatment outcomes in adult patients with BL treated with uniform chemotherapy, cyclophosphamide, vincristine, doxorubicin, methotrexate, ifosfamide, etoposide, cytarabine (CODOX-M/IVAC) protocol (± Rituximab)...
July 2018: South Asian Journal of Cancer
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
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